Inflammatory mediators in nasal lavage, induced sputum and serum of employees with rheumatic and respiratory disorders.

Exposure to microbes present in mould-damaged buildings has been linked to increased frequency of various inflammatory diseases. The current study examined differences in inflammatory mediators in nasal lavage (NAL), induced sputum (IS) and serum of occupants with rheumatic or respiratory disorders and their controls, all working in the same moisture-damaged building. Exhaled nitric oxide (NO) measurements, lung function tests, skin-prick tests and health data collection by questionnaire were performed. Concentrations of NO, interleukin (IL)-1, IL-4, IL-6 and tumour necrosis factor-alpha in NAL, IS and serum (excluding NO and IL-1) of the subjects were measured during an occupational exposure period and the vacation period without such exposure. The concentrations of IL-4 in NAL fluid were significantly higher among all occupants during the working period (geometric mean 8.5 microg x mL(-1), range 0-206.5 microg x mL(-1)), as compared to that during vacation (0.4 microng x mL(-1) range 0-3.7 pg x mL(-1)) (p = 0.008). Absence from the work environment also significantly diminished reporting of symptoms. IL-4 levels in the serum of case subjects were significantly higher than in controls. Moreover, employees with respiratory symptoms had markedly higher exhaled NO values than their controls (p = 0.028). In summary, these data suggest that mediators in nasal lavage samples reflect the occupational exposure to moulds, whereas possible indicators of existing disorders are detectable in serum.

A bioassay using Artemia salina for detecting phototoxicity of plant coumarins.

Artemia salina (brine shrimp) has been successfully used for toxicity testing, and a screening test for phototoxicity has been developed based on this method. The ability of the method to test the phototoxic potential of seven known compounds was investigated. Athamantin (an angular furanocoumarin) and umbelliferone (a simple coumarin) showed no phototoxicity, while linear furanocoumarins exhibited phototoxic activity in the following order: psoralen > bergapten > peucedanin > xanthotoxin. The applicability of this method was also tested in screening the phototoxicity of plant material. Six plants from Apiaceae [Aegopodium podagraria L., Anethum graveolens L., Angelica archangelica L., Levisticum officinalis Koch, Petroselinum crispum (P. Mill) A. W. Hill., and Peucedanum palustre (L.) Moench] and one from Rutaceae (Ruta graveolens L.) were selected, all of them known to contain furanocoumarins. Extracts from leaves collected at different times during the growth period were used in the screening. Our results were in accordance with the furanocoumarin content of these plants and with the results of other phototoxicity tests. The Artemia salina method proved to be rapid, simple and inexpensive, and is therefore ideal in the initial biological screening of large numbers of samples for simultaneous detection of both toxicity and phototoxicity.

Volatile constituents of wild and in vitro cultivated Gloeophyllum odoratum.

The brown-rot fungus Gloeophyllum odoratum was collected from spruce stumps in southern Finland. The volatiles in the fruiting body and fungal cultures grown in malt extract and liquid medium were investigated. Chitin, chitosan and D-(+)-glucosamine at a concentration of 450 mgl-1 medium were used as elicitors. Chitosan completely inhibited growth in the solid medium. The main volatile(s) according to GC and GC-MS analysis were either linalool, citronellol, geraniol and methyl p-methoxyphenylacetate or drimenol depending on the culture type and elicitor. The composition of volatiles in the natural fungus differed slightly from that of the cultivated fungus since the major compound was methyl p-methoxyphenylacetate. The volatile oils were toxic to larvae of the brine shrimp, Artemia salina, indicating that they may possess insecticidal and cytotoxic activity.

Bioactivity of certain Egyptian Ficus species.

The fruit extracts of Ficus sycomorus L., F. benjamina L., F. bengalensis L. and F. religiosa L. were screened for bioactivity. F. bengalensis and F. religiosa demonstrated activity in the brine shrimp test (Artemia salina) which indicates toxicity, whereas F. sycomorus and F. benjamina showed no activity. All the fruit extracts exhibited antitumor activity in the potato disc bioassay. None of the tested extracts showed any marked inhibition on the uptake of calcium into rat pituitary cells GH4C1. The extracts of the four tested Ficus species had significant antibacterial activity, but no antifungal activity. The results of this preliminary investigation support the traditional use of these plants in folk medicine for respiratory disorders and certain skin diseases.

Toxicity of the blue-green alga Oscillatoria agardhii to the mosquito Aedes aegypti and the shrimp Artemia salina.

The cyanobacterium Oscillatoria agardhii 27, which does not produce mammalian neuro- or hepatotoxins, was highly toxic to the larval stages of the yellow fever mosquito Aedes aegypti: its 24-h LC50 values against fourth-and second-instar larvae of A. aegypti were 8.7 and 6.1 µg live cells/ml, respectively. The toxin was water-soluble and was partially purified but the chemical nature of the toxic compound(s) is still unknown. Aqueous solutions were also toxic to the newborn larvae of the brine shrimp, Artemia salina, used for the bioassay. The toxic activity of these solutions decreased markedly on heating to ≧90°C for 15 min.

Algae in mosquito breeding sites and the effectiveness of the mosquito larvicide Bacillus thuringiensis H-14.

The presence of cyanobacteria generally decreased the effectiveness of Bacillus thuringiensis H-14 (BTI) as a mosquito larvicide. The effect was more pronounced when the mosquito larvae were exposed to BTI in the presence of several cyanobacterial strains. No synergistic or antagonistic effect between the δ-endotoxin from BTI and the hepatotoxin from cyanobacteria was seen. Neurotoxic cyanobacterial strains caused very fast paralysis in mosquito larvae; the decreases in the effectiveness of BTI when tested in combination with a neurotoxic strain might be due to the effect of this paralytic action on the feeding rate of the mosquito larvae.

Structure determination and toxicity of a new microcystin from Microcystis aeruginosa strain 205.

A new hepatotoxic microcystin was isolated from the cyanobacterium Microcystis aeruginosa strain 205. Its structure was found to be [Dha7]microcystin-RR as determined by amino acid analysis, mass spectrometry and 1H NMR spectroscopy. LD50 value (i.p. mouse) of this toxin was 180 micrograms/kg. The 48 hr lethal concentration (48-hr-LC50) of the toxin for larvae of the yellow fever mosquito, Aedes aegypti, was 14.9 micrograms/ml.

Prognosis of transitional cell bladder cancer: a multivariate prognostic score for improved prediction.

Clinical and histological prognostic factors were evaluated by means of Cox's analysis in 265 bladder cancer patients with a mean followup of 10 years. The parameters studied were obtained from the primary biopsies, which included clinical stage, World Health Organization grade, papillary status, morphometrically measured mean nuclear area, standard deviation of nuclear area, mean nuclear area of the 10 largest nuclei, mitotic activity index and volume corrected mitotic index. In univariate survival analysis all of the parameters predicted survival (p less than 0.001). In Cox's analysis the clinical stage was the most important prognosticator (p less than 0.001) followed by papillary status (p less than 0.001), volume corrected mitotic index (p = 0.011) and nuclear area of the 10 largest nuclei (p = 0.091). In stages Ta to T2, grades 1 to 2 tumors the papillary status (p = 0.001), mitotic activity index (p = 0.021) and T category (p = 0.029) showed independent prognostic value. Among the stages Ta to T1 tumors the papillary status included all of the available prognostic information (p = 0.001). In a separate analysis of histological features in all papillary tumors histological grade (p less than 0.001) and mitotic activity index (p = 0.021) were related independently to survival in Cox's analysis. In papillary stages Ta to T2, grades 1 to 2 tumors (mitotic activity index, p = 0.029) and in papillary stages Ta to T1 tumors (volume corrected mitotic index, p = 0.054) mitotic indexes showed independent prognostic value. In grade 2 tumors the papillary status p = 0.004) and mitotic activity index (p = 0.090) had independent prognostic value. The mitotic indexes predicted progression among stages Ta to T1 tumors (p less than 0.001) and within World Health Organization grades significantly. The combination of prognostic parameters into prognostic scores gave a more accurate estimate of survival than the single parameter approach. The results suggest morphometric grading of bladder tumors. However, papillary and nonpapillary tumors require different grade limits.

Classic prognostic factors, flow cytometric data, nuclear morphometric variables and mitotic indexes as predictors in transitional cell bladder cancer.

One hundred and eighty-seven patients with a transitional cell bladder cancer were followed by retrospectively for a mean of 9.5 years. Clinical stage (p less than 0.0001), histological grade (p less than 0.0001), papillary (p less than 0.0001), SPF (p less than 0.0001), M/V index (p less than 0.0001), MAI (p less than 0.0001), DNA index (p = 0.0001) SDNA (p = 0.0004), NA10 (p = 0.0023), NA (p = 0.0044) and G2% (p = 0.0158) were significantly correlated with survival in univariate analysis. In Cox's analysis T-category, papillarity and MAI had independent prognostic value and in combination they predicted bladder cancer-related survival significantly (X2 = 117.5, p less than 0.0001). When histological parameters only were analysed, WHO grade, SPF and papillarity were independent predictors and their combined prognostic significance was high (X2 = 76.6, p less than 0.0001). In papillary tumours SPF (p v 0.0005), MAI (p = 0.0009), DNA index (p = 0.0010) and M/V index (p = 0.0021) predicted survival significantly in addition to stage (P less than 0.0001) and grade (p = 0.0003) in univariate analysis. In Cox's analysis T-category, MAI and M/V index were independent predictors and their combined prognostic value was high (X2 = 54.1, p less than 0.0001). In Ta-T1 and in T2-T3 tumours, WHO grade, papillarity, SPF, mitotic indexes and DI were significant predictors in univariate analysis. In Cox's analysis of Ta-T1 tumours papillarity had independent prognostic value, whereas in papillary Ta-T1 tumours mitotic activity included all prognostic information. In T2-T3 tumours WHO grade and SPF were independent predictors. In conclusion, in papillary bladder tumours T-category is the most important predictor of survival followed by parameters reflecting proliferative activity of cancer cells.

Occurrence of the hepatotoxic cyanobacterium Nodularia spumigena in the Baltic Sea and structure of the toxin.

Water blooms formed by potentially toxic species of cyanobacteria are a common phenomenon in the Baltic Sea in late summer. Twenty-five cyanobacterial bloom samples were collected from open and coastal waters of the Baltic Sea during 1985 to 1987, and their toxicity was determined by mouse bioassay. All of 5 bloom samples from the southern Baltic Sea, 6 of 6 from the open northern Baltic Sea (Gulf of Finland), and 7 of 14 Finnish coastal samples were found to contain hepatotoxic cyanobacteria. Nodularia spumigena and Aphanizomenon flos-aquae occurred together in high amounts in blooms from the open-sea areas. In addition, coastal samples contained the species Anabaena lemmermannii, Microcystis aeruginosa, and Oscillatoria agardhii. Eighteen hepatotoxic N. spumigena cultures were isolated from water bloom and open-sea water samples. High-pressure liquid chromatographic analysis of both hepatotoxic bloom samples and Nodularia strains showed a single toxic fraction. The toxin concentrations of the blooms were less than or equal to 2.4 mg/g of freeze-dried material, and those of laboratory-grown cultures were 2.5 to 8.0 mg/g of freeze-dried cells. A single toxin was isolated from three N. spumigena-containing bloom samples and three N. spumigena laboratory isolates. Amino acid analysis and low- and high-resolution fast-atom bombardment mass spectroscopy indicated that the toxin from all of the sources was a cyclic pentapeptide (molecular weight, 824) containing glutamic acid, beta-methylaspartic acid, arginine, N-methyldehydrobutyrine, and 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid.(ABSTRACT TRUNCATED AT 250 WORDS)