Acute skin irritant effects of cyanobacteria (blue-green algae) in healthy volunteers

Objective : To assess the skin irritant potential of a range of laboratory grown cyanobacterial species using skin-patch testing on human volunteers.
Methods : Cell suspensions and extracts of cyanobacterial cultures of Microcystis aeruginosa (non-toxic strain), Anabaena circinalis and Nodularia spumigena were applied to 64 volunteers in one trial, and Microcystis aeruginosa (toxic strain), Apanocapsa incerta and Cylindrospermopsis raciborskii were applied to 50 volunteers in a second trial. Six cell concentrations of each organism in the range from less than 5,000 to greater than 200,000 cells/ml were applied in random order using adhesive skin patches (Finn Chambers). In addition, the applications included two treatments of each cyanobacterial species, involving whole and lysed cells, and positive (sodium lauryl sulphate) and negative (culture media) controls. Patches were removed after 24 hours and assessment of erythema was made by a dermatologist blinded to the species, cell type and concentration.
Results : On average, between 20% and 24% of individuals with 95% confidence interval ±8% reacted across the concentration range tested for these cyanobacterial species. The reaction rates were lower (11% to 15%) among the subset of subjects not reacting to negative controls. The reaction was mostly mild, and in all cases was resolved without treatment. This was the case for both whole and lysed cells with little difference in reaction rates between these two treatments. There was also no dose-response across the concentration range for any of the cyanobacterial species tested.
Conclusion : A small proportion of healthy people (around 20%) may develop a skin reaction to cyanobacteria in the course of normal water recreation, but the reaction is mild and resolved without treatment.     

Cochlear implant outcomes and quality of life in the elderly: Manchester experience over 13 years1

Objectives: To objectively evaluate the clinical and functional outcomes of cochlear implantation in an elderly population. Design: Retrospective comparative study. Setting: Neurotology unit at Manchester Royal Infirmary, a supraregional tertiary referral centre in collaboration with Adult Cochlear Implant Programme at The University of Manchester. Participants: All cochlear implant procedures (38) undertaken on post‐lingually deafened elderly patients (age range at the time of implantation 65–80 years, n = 34) in the period from 1989 to 2002. Main outcome measures: Medical and surgical outcomes. Audiological performance outcomes for isolated words, words in sentences in quiet and noise. Functional outcome measures used are self‐reported measures of the social, psychological and emotional aspects of quality of life, and the differences between expectations for functional outcomes and the realization of functional outcomes. They included expectation profiles, Glasgow Benefit inventory (GBI) and Glasgow Health Status Inventory Questionnaire (GHSI). Results: There was statistically significant improvement post‐implantation of both open and closed set test scores (P < 0.01). Eighty‐two percentage of patients were completely satisfied with their cochlear implants. Patients judged that implantation restored half the loss of quality of life that they had experienced as a result of severe‐profound deafness with a highly significant (P < 0.001) improvement in overall quality of life after implantation. The commonest post‐operative observation was transient mild pyrexia. Conclusions: The age of a cochlear implant candidate should not be a factor in the candidacy decision‐making process. The quality of life of our elderly recipients was significantly improved after cochlear implant.     

Inhibition of cell cycle and induction of apoptosis by 2‐oxoheksyl isothiocyanate and alyssin in cell lines carrying various inherited BRCA1 mutations

An important aspect of the chemopreventive activity of isothiocyanates (ITC) is their ability to induce cell growth inhibition and apoptosis. In this study, the effect of two sulforaphane analogues, 2‐oxoheksyl isothiocyanate and alyssin, on lymphoblastoid cells, derived from people carrying four different germ‐line mutations in BRCA1 gene, was tested and compared to the effect on wild type cells. The mutations studied were: C61G; 3819del5; 4153delA, and 5382INSC. Changes in cell viability and density after 2‐oxoheksyl isothiocyanate and alyssin treatment were evaluated, as well as cell cycle progression, mitochondrial membrane potential changes, and phosphatidylserine externalization. Both isothiocyanates were shown to reduce cell viability and density in all cell lines tested, as well as the change in cell cycle phase's distribution. The response of cells to two ITC tested was various, as well as mutation type‐modulated. We found that change of cellular maintenance by chemopreventive agents can be modulated by single allele BRCA1 mutation. Drug Dev. Res. 65:84–92, 2005. © 2005 Wiley‐Liss, Inc.     

Synergistic antinociceptive interaction between acetaminophen or metamizol and B vitamins in the formalin test

There is evidence that B vitamins produce antinociception in animals. However, potentiation of NSAID‐induced antinociception by B vitamins is unclear. The current study was designed to investigate the antinociceptive interaction between a mixture of B vitamins and either acetaminophen or metamizol. Acetaminophen (56–316 mg/kg), metamizol (32–178 mg/kg), and the mixture of B vitamins (32–178 mg/kg of thiamine, pyridoxine, and cyanocobalamin in a 100:100:1 proportion, respectively) or a combination of each drug with the B vitamins mixture was administered orally to female Wistar rats, and the antinociceptive effect determined in the formalin test. Isobolographic analyses were used to define the nature of the interaction between NSAIDs and B vitamins. Oral administration of either drug produced a dose‐related antinociceptive effect. Isobolographic analyses revealed that both acetaminophen or metamizol and the B vitamins mixture interacted synergistically in the formalin test, suggesting that these two combinations could be useful in treating inflammatory pain states. Drug Dev. Res. 66:286–294, 2006. © 2006 Wiley‐Liss, Inc.     

Vascular modulation through exercise improves chemotherapy efficacy in Ewing sarcoma

Recent studies in mouse models of cancer have shown that exercise improves tumor vascular function, thereby improving chemotherapy delivery and efficacy. However, the mechanisms underlying this improvement remain unclear and the effect of exercise on Ewing sarcoma (ES), a pediatric bone and soft tissue cancer, is unknown. The effect of exercise on tumor vascular hyperpermeability, which inversely correlates with drug delivery to the tumor, has also not been evaluated. We hypothesized that exercise improves chemotherapy efficacy by enhancing its delivery through improving tumor vascular permeability. We treated ES‐bearing mice with doxorubicin with or without moderate treadmill exercise. Exercise did not significantly alter ES tumor vessel morphology. However, compared to control mice, tumors of exercised mice had significantly reduced hyperpermeability, significantly decreased hypoxia, and higher doxorubicin penetration. Compared to doxorubicin alone, doxorubicin plus exercise inhibited tumor growth more efficiently. We evaluated endothelial cell sphingosine‐1‐phosphate receptors 1 and 2 (S1PR1 and S1PR2) as potential mediators of the improved vascular permeability and increased function afforded by exercise. Relative to tumors from control mice, vessels in tumors from exercised mice had increased S1PR1 and decreased S1PR2 expression. Our results support a model in which exercise remodels ES vasculature to reduce vessel hyperpermeability, potentially via modulation of S1PR1 and S1PR2, thereby improving doxorubicin delivery and inhibiting tumor growth more than doxorubicin alone does. Our data suggest moderate aerobic exercise should be tested in clinical trials as a potentially useful adjuvant to standard chemotherapy for patients with ES.