TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls.

Particles in exhaled air (PEx) may reflect the composition of respiratory tract lining fluid (RTLF); thus, there is a need to assess their potential as sources of biomarkers for respiratory diseases. In the present study, we compared PEx from patients with asthma and controls using time-of-flight-secondary ion mass spectrometry (TOF-SIMS) and multivariate analysis. Particles were collected using an instrument developed in-house. 15 nonsmoking subjects with physician-diagnosed asthma and 11 nonsmoking healthy controls performed 10 consecutive forced exhalations into the instrument. Particle concentrations were recorded and samples of particles collected on silicon plates were analysed by TOF-SIMS. Subjects with asthma exhaled significantly lower numbers of particles than controls (p=0.03) and the ratio of unsaturated to saturated phospholipids was significantly lower in samples from subjects with asthma (0.25 versus 0.35; p=0.036). Orthogonal partial least squares-discriminant analysis models showed good separation between both positive and negative spectra. Molecular ions from phosphatidylcholine and phosphatidylglycerol, and protein fragments were found to discriminate the groups. We conclude that analysis of PEx is a promising method to examine the composition of RTLF. In the present explorative study, we could discriminate between subjects with asthma and healthy controls based on TOF-SIMS spectra from PEx.

Microbe-like inclusions in tree resins and implications for the fossil record of protists in amber.

During the past two decades, a plethora of fossil micro-organisms have been described from various Triassic to Miocene ambers. However, in addition to entrapped microbes, ambers commonly contain microscopic inclusions that sometimes resemble amoebae, ciliates, microfungi, and unicellular algae in size and shape, but do not provide further diagnostic features thereof. For a better assessment of the actual fossil record of unicellular eukaryotes in amber, we studied equivalent inclusions in modern resin of the Araucariaceae; this conifer family comprises important amber-producers in Earth history. Using time-of-flight secondary ion mass spectrometry (ToF-SIMS), we investigated the chemical nature of the inclusion matter and the resin matrix. Whereas the matrix, as expected, showed a more hydrocarbon/aromatic-dominated composition, the inclusions contain abundant salt ions and polar organics. However, the absence of signals characteristic for cellular biomass, namely distinctive proteinaceous amino acids and lipid moieties, indicates that the inclusions do not contain microbial cellular matter but salts and hydrophilic organic substances that probably derived from the plant itself. Rather than representing protists or their remains, these microbe-like inclusions, for which we propose the term 'pseudoinclusions', consist of compounds that are immiscible with the terpenoid resin matrix and were probably secreted in small amounts together with the actual resin by the plant tissue. Consequently, reports of protists from amber that are only based on the similarity of the overall shape and size to extant taxa, but do not provide relevant features at light-microscopical and ultrastructural level, cannot be accepted as unambiguous fossil evidence for these particular groups.

Systemic quinine photosensitivity.

A 72-year-old woman developed a photodistributed skin eruption while taking quinine hydrochloride (250 mg) once or twice weekly for recumbency cramps. The histopathology showed an eczematous reaction. Phototesting after quinine therapy had been discontinued for one month revealed normal erythema thresholds for ultraviolet (UV) light in the A range (17 J/cm2) and UV light in the B range (20 mJ/cm2). A second phototest after a ten-day period of reexposure to quinine hydrochloride (250 mg daily) showed a drastically lowered threshold for UV light in the A range (less than 1.0 J/cm2), while the test for UV light in the B range was unchanged. The patient's dermatitis also exacerbated with pronounced itching. The histopathologic results from a positive test site were similar to those of her eczematous lesions. We believe this to be the first documented case of systemic quinine photosensitivity. The clinical picture, the results of the phototests, and the histopathology suggest a photoallergic mechanism.

Ancient microbial activity recorded in fracture fillings from granitic rocks (Äspö Hard Rock Laboratory, Sweden).

Fracture minerals within the 1.8-Ga-old Äspö Diorite (Sweden) were investigated for fossil traces of subterranean microbial activity. To track the potential organic and inorganic biosignatures, an approach combining complementary analytical techniques of high lateral resolution was applied to drill core material obtained at -450 m depth in the Äspö Hard Rock Laboratory. This approach included polarization microscopy, time-of-flight secondary ion mass spectrometry (ToF-SIMS), confocal Raman microscopy, electron microprobe (EMP) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The fracture mineral succession, consisting of fluorite and low-temperature calcite, showed a thin (20-100 µm), dark amorphous layer lining the boundary between the two phases. Microscopic investigations of the amorphous layer revealed corrosion marks and, in places, branched tubular structures within the fluorite. Geochemical analysis showed significant accumulations of Si, Al, Mg, Fe and the light rare earth elements (REE) in the amorphous layer. In the same area, ToF-SIMS imaging revealed abundant, partly functionalized organic moieties, for example, C(x)H(y)⁺, C(x)H(y)N⁺, C(x)H(y)O⁺. The presence of such functionalized organic compounds was corroborated by Raman imaging showing bands characteristic of C-C, C-N and C-O bonds. According to its organic nature and the abundance of relatively unstable N- and O- heterocompounds, the organic-rich amorphous layer is interpreted to represent the remains of a microbial biofilm that established much later than the initial cooling of the Precambrian host rock. Indeed, δ¹³C, δ¹8O and 87Sr/86Sr isotope data of the fracture minerals and the host rock point to an association with a fracture reactivation event in the most recent geological past.

Sample cooling or rotation improves C60 organic depth profiles of multilayered reference samples: results from a VAMAS interlaboratory study.

We demonstrate two methods to improve the quality of organic depth profiling by C(60) sputtering using multilayered reference samples as part of a VAMAS (Versailles project on Advanced Materials and Standards) interlaboratory study. Sample cooling was shown previously to be useful in extending the useful depth over which organic materials can be profiled. We reinforce these findings and demonstrate that cooling results in a lower initial sputtering yield to approximately -40 degrees C, but the improvement in useful profiling depth continues as the sample is cooled further, even though there is no further reduction in the initial sputtering yield. We report, for the first time, the use of sample rotation in organic depth profiling and demonstrate that the initial sputtering yield at room temperature is maintained throughout the depth of the samples used in this study. Useful profiling depth and good depth resolution are both associated with a constant sputtering yield. The fact that rotation results in the maintenance of depth resolution underlines the fact that depth resolution is often limited by the development of ion-beam-induced topography. Constant sputtering yield results in a constant secondary-ion yield, after transient processes have occurred, and this allows simple quantification methods to be applied to organic depth profiling data.

Analysis of hopanes and steranes in single oil-bearing fluid inclusions using time-of-flight secondary ion mass spectrometry (ToF-SIMS).

Steranes and hopanes are organic biomarkers used as indicators for the first appearance of eukaryotes and cyanobacteria on Earth. Oil-bearing fluid inclusions may provide a contamination-free source of Precambrian biomarkers, as the oil has been secluded from the environment since the formation of the inclusion. However, analysis of biomarkers in single oil-bearing fluid inclusions, which is often necessary due to the presence of different generations of inclusions, has not been possible due to the small size of most inclusions. Here, we have used time-of-flight secondary ion mass spectrometry (ToF-SIMS) to monitor in real time the opening of individual inclusions trapped in hydrothermal veins of fluorite and calcite and containing oil from Ordovician source rocks. Opening of the inclusions was performed by using a focused C(60)(+) ion beam and the in situ content was precisely analysed for C(27)-C(29) steranes and C(29)-C(32) hopanes using Bi(3)(+) as primary ions. The capacity to unambiguously detect these biomarkers in the picoliter amount of crude oil from a single, normal-sized (15-30 mum in diameter) inclusion makes the approach promising in the search of organic biomarkers for life's early evolution on Earth.

Analysis of archaeal core ether lipids using Time of Flight-Secondary Ion Mass Spectrometry (ToF-SIMS): Exploring a new prospect for the study of biomarkers in geobiology.

The capability of Time of Flight-Secondary Ion Mass Spectrometry (ToF-SIMS) of analysing molecular archaeal biomarkers in geobiological samples was tested and demonstrated. Using a bismuth cluster primary ion source, isopranyl glycerol di- and tetraether core lipids were detected in small amounts of total organic extracts from methanotrophic microbial mats, simultaneously and without further chemical treatment and chromatographic separation. ToF-SIMS was also employed to track the distribution of fossilized ether lipids in a massive carbonate (aragonite) microbialite that precipitated as a result of the microbial anaerobic oxidation of methane. An unambiguous signal was obtained when analysing a freshly broken rock surface (base of a microdrill core). Though some limitation occurred due to µm-topographical effects (sample roughness), it was possible to display the abundance of high molecular weight (C86 ) of tetraethers exposed in particular regions of the rock surface. 'Molecular mapping' revealed that a part of these molecules was encased within the rock fabric in a cluster-like distribution that might trace the arrangement of the calcifying microbial colonies in the once active mat system. The results reveal promising perspectives of ToF-SIMS for (i) the quasi-nondestructive analysis of lipids in extremely small geobiological samples at low concentrations; (ii) resolving the spatial distribution of these compounds on a µm2 - to cm2 -scale; and (iii) the more exact assignment of lipid biomarkers to their biological source.

The influence of locally administered ultraviolet light (UVB) on the allergic contact dermatitis in the mouse.

A quantitative model of contact allergy to picryl chloride in the mouse was used to evaluate the influence of locally administered ultraviolet light (UVB) on sensitization and challenge. UVB was given in three different doses immediately before and 24 h before sensitization and challenge, respectively. A suppressive effect was demonstrated on the afferent as well as on the efferent limb of the allergic reaction.

Oral hyposensitization in allergic contact dermatitis.

In this review, the concepts of hyposensitization, tolerance and hardening are defined. Studies concerning hyposensitization by different routes of allergen administration are mentioned. The most important studies in humans, as well as in experimental animals, regarding oral hyposensitization are then gone into more thoroughly. The possible mechanisms of hyposensitization are discussed. It is concluded that oral hyposensitization in humans is indeed possible. Furthermore, the reaction is antigen-specific, diminishes quickly, and it is probably the dose administered at a certain moment rather than the total amount of allergens ingested that is crucial when receiving hyposensitization. However, further performed studies do not justify the routine use of oral hyposensitization.

Local and systemic effect of ultraviolet irradiation (UVB and UVA) on human allergic contact dermatitis.

In subjects hypersensitive to nickel we have investigated local and systemic effect of whole body exposure of cumulative suberythema UVB doses as well as solarium-UVA exposure. UVB possesses both locally and systemically a suppressive effect on human allergic contact dermatitis, but UVA has no such effect. The systemic suppressive effect of UVB might be of therapeutic importance in patients with severe chronic dermatitis of the hands when adding this effect to a local suppressive effect. Also, patch testing should not be performed during UVB and/or overt sun exposure.

Treatment of chronic hand eczema with UV-B Handylux in the clinic and at home.

The efficacy of UV-B irradiation, administered by a new unit, Handylux, in patients with chronic hand eczema was investigated. 15 patients were treated in the clinic and 11 patients at home. Treatments were performed 4-5 x weekly for approximately 10 weeks. According to the strict criteria used for clearing, none of the patients cleared during the study, but 18 of the 26 patients were defined as much improved by the investigator, while 17 of the patients considered themselves as > 80% improved. The compliance in both groups was very good and side-effects limited and dose-related. According to our experience, the effect of high dose UV-B in chronic hand eczema is almost comparable to PUVA, and offers an opportunity for patients to treat themselves at home.

Local and systemic effect of UVB irradiation in patients with chronic hand eczema.

The effect of local as well as whole body irradiation with UVB was investigated in patients with chronic hand eczema not responding to conventional topical treatment. UVB irradiation of the hands was significantly more effective than placebo. Whole body UVB irradiation combined with additional irradiation of the hands proved to be even more effective than local treatment in clearing chronic hand eczema. Due to the relatively fast relapse of the hand eczema after the UVB treatment period maintenance treatment is warranted. This could possibly be carried out by the patients at home, but under surveillance by a dermatologist.

Oral hyposensitization in nickel allergy.

In two controlled studies, each including 24 patients with contact allergy to nickel, different protocols were designed in an attempt to diminish the patients' hypersensitivity by oral administration of the antigen. With doses of 5.0 mg nickel sulfate taken once a week for 6 weeks, but not with 0.5 mg daily, the degree of contact allergy was significantly lowered, measured as patch test reactions before and after nickel administration.

Single exposure to ultraviolet irradiation and elicitation of human allergic contact dermatitis.

Ultraviolet radiation has been stated to inhibit afferent as well as efferent phases of allergic contract dermatitis. In this controlled study 17 female patients with nickel allergy were studied by three different protocols after an initial determination of their degree of hypersensitivity. They were patch tested with nickel sulfate immediately after UVB, 4-6 days after UVB, or immediately after external PUVA. Neither depressing nor enhancing of the allergic reaction was observed when compared to non-irradiated controls. The role of Langerhans cells as antigen-presenting cell playing an important role in the elicitation phase of allergic contract dermatitis is discussed and questioned.

An open study of efficacy and safety of long-term treatment with mometasone furoate fatty cream in the treatment of adult patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis is a severe chronic skin disease often deteriorated by the presence of microorganisms and often responds well to treatment with potent corticosteroids. However, the long-term use of potent topical corticosteroids are accompanied by side-effects such as skin atrophy. OBJECTIVE: To study the effect and safety of prophylactic treatment with mometasone furoate fatty cream (contains hexylene glycol) for 6 months in patients with atopic dermatitis. RESULTS: Sixty-one of 68 (90%) patients were still free of their disease after 6 months of twice weekly treatment and only one showed possible treatment related signs of skin atrophy. The number of Staphylococcus aureus and Pityrosporum ovale were significantly reduced in cleared patients. CONCLUSIONS: Mometasone furoate fatty cream is effective and safe both for treatment and as a prophylaxis in patients with atopic dermatitis.