Diversity and comparability--towards a common European Higher Education Area.
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Journal Article↗
Biomedical subjects
Martin Vogel
Publications and source records attributed to Martin Vogel.
Determination of airborne isocyanates.
Isocyanates are important in industrial hygiene and workplace monitoring. Owing to their severe acute toxicity and sensitizing properties, analytical methods with high sampling efficiency and sensitivity in the low ppb to ppt range are required. The reactivity of isocyanates necessitates initial derivatization with nucleophilic agents--usually amines--for stabilization and enrichment; this is often followed by chromatographic separation with spectroscopic, electrochemical, or mass spectrometric detection. Sampling strategies for airborne isocyanates comprise active, i.e. pumped, or passive, i.e. diffusive, methods; the method selected depends on the application. Whereas active methods rely mainly on impingers, reagent-coated filters, or sampling tubes, passive samplers make use of reagent-coated filters, the surface of which is connected to the air sample by diffusion channels. Because airborne isocyanates are prone to occur in different forms, i.e. as vapors, as aerosols, or adsorbed on particulate matter, denuder sampling has been introduced, thus enabling simultaneous collection of gaseous and aerosol isocyanates. The first part of this review summarizes chemical methods and reagents which have been introduced for derivatization of airborne isocyanates. The advantages and drawbacks of the individual derivatization procedures and their combination with different detection principles are evaluated. In the second part, the most recent developments in air sampling for isocyanates, with special focus on diffusive sampling, are reviewed and critically discussed.
Journal Article↗
Validation of a diffusive sampling method for airborne low-molecular isocyanates using 4-nitro-7-piperazinobenzo-2-oxa-1,3-diazole-impregnated filters and liquid chromatography-tandem mass spectrometry.
A diffusive sampling method for the determination of low-molecular isocyanates as their 4-nitro-7-piperazinobenzo-2-oxa-1,3-diazole (NBDPZ) derivatives using tandem mass spectrometry (MS/MS) after atmospheric pressure chemical ionisation (APCI) is presented. Isocyanic acid (ICA), methyl isocyanate (MIC), ethyl isocyanate (EIC) and phenyl isocyanate (PhIC) are collected on NBDPZ-impregnated polystyrene divinyl benzene (SDB) filter tapes. The method was validated for MIC, EIC and PhIC for concentrations between 0.5 and 50 ppb at relative humidity (RH) conditions from 10 up to 90%. Validation was carried out by active sampling using 1-(2-methoxyphenyl)piperazine (2-MP) as derivatising agent. Sampling periods applied were between 15 min and more than 8 h. The sampling rates were determined to be 21.0 mL/min for MIC with a relative standard deviation (RSD) of 9.0% for 184 samplers, 15.6 mL/min for EIC (RSD 11.6%; N = 154) and 11.5 mL/min for PhIC (RSD 8.4%; N = 87). The limits of quantification were 1.4 ppb for MIC and 1.3 ppb for EIC and PhIC applying 15 min sampling periods. Owing to high background signals, isocyanic acid could only be determined when it was present in concentrations in the high ppb range.
Air↗
Passive sampling of airborne peroxyacetic acid.
The first passive sampling device for the determination of airborne peroxyacetic acid (PAA) is presented. 2-([3-{2-[4-Amino-2-(methylsulfanyl)phenyl]-1-diazenyl}phenyl]sulfonyl)-1-ethanol (ADS) is used to impregnate glass fiber filters, and the reagent is oxidized by PAA to the corresponding sulfoxide ADSO. After elution of the filters, ADS and ADSO are separated by reversed-phase HPLC and detected by UV/visible absorbance. Limit of detection is 30 ppb, limit of quantification is 90 ppb (for 30 min sampling), and the linear range comprises 2 orders of magnitude. Thorough investigations were carried out with respect to the selectivity of the method toward hydrogen peroxide, and air samples were analyzed successfully after disinfection of a laboratory area.
Air Pollutants, Occupational↗
Recent methods for the determination of peroxide-based explosives.
In the last few years, the need to determine peroxide-based explosives in solid samples and air samples has resulted in the development of a series of new analytical methods for triacetonetriperoxide (TATP, acetone peroxide) and hexamethylenetriperoxidediamine (HMTD). In this review, after a short introduction describing the state of the art in the field, these new analytical methods are critically discussed. Particular emphasis is placed on spectroscopic and mass spectrometric methods as well as on chromatographic techniques with selective detection schemes. The potential of these methods to analyse unknown solid samples that might contain one or more of the explosives and to analyse peroxide-based explosives in air is evaluated.
Journal Article↗
Temperature change does not affect force between regulated actin filaments and heavy meromyosin in single-molecule experiments.
The temperature dependence of sliding velocity, force and the number of cross-bridges was studied on regulated actin filaments (reconstituted thin filaments) when they were placed on heavy meromyosin (HMM) attached to a glass surface. The regulated actin filaments were used because our previous study on muscle fibres demonstrated that the temperature effect was much reduced in the absence of regulatory proteins. A fluorescently labelled thin filament was attached to the gelsolin-coated surface of a polystyrene bead. The bead was trapped by optical tweezers, and HMM-thin filament interaction was performed at 20-35 degrees C to study the temperature dependence of force at the single-molecule level. Our experiments showed that there was a small increase in force with temperature (Q10 = 1.43) and sliding velocity (Q10 = 1.46). The small increase in force was correlated with the small increase in the number of cross-bridges (Q10 = 1.49), and when force was divided by the number of cross-bridges, the result did not depend on the temperature (Q(10) = 1.03). These results demonstrate that the force each cross-bridge generates is fixed and independent of temperature. Our additional experiments demonstrate that tropomyosin (Tm) in the presence of troponin (Tn) and Ca2+ enhances both force and velocity, and a truncated mutant, Delta23Tm, diminishes force and velocity. These results are consistent with the hypothesis that Tm in the presence of Tn and Ca2+ exerts a positive allosteric effect on actin to make actomyosin linkage more secure so that larger forces can be generated.
Actin Cytoskeleton↗
Sacking of CMAJ editors.
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Attitude of Health Personnel↗
Analysis of microperoxidases using liquid chromatography, post-column substrate conversion and fluorescence detection.
A liquid chromatographic method with on-line activity determination for microperoxidases has been developed. After enzymatic digestion of a cytochrome, possibly under formation of microperoxidases, the product mixture is separated by reversed-phase liquid chromatography. The products first pass a diode-array detector, and are then subjected to a reaction with 4-(N-methylhydrazino)-7-nitro-2,1,3-benzooxadiazole (MNBDH) and hydrogen peroxide. In a reaction coil, microperoxidases catalyze the reaction under formation of the fluorescent 4-(N-methylamino)-7-nitro-2,1,3-benzooxadiazole (MNBDA). Quantification of the microperoxidases is performed using a fluorescence detector at an excitation wavelength of 470 nm and an emission wavelength of 545 nm, respectively. For this LC-based detection system, limits of detection are 3 x 10(-8) mol/L, limits of quantification are 9 x 10(-8) mol/L, and a linear range from 9 x 10(-8) mol/L to 3 x 10(-6) mol/L is obtained for the microperoxidases MP-9 and MP-11. A highly active microperoxidase MP-6 was found in the reaction of cytochrome c from bovine heart with protease from streptomyces griseus.
Animals↗
Photoaffinity labeling with 8-azidoadenosine and its derivatives: chemistry of closed and opened adenosine diazaquinodimethanes.
The reactive intermediate produced upon photolysis of 8-azidoadenosine was studied by chemical trapping studies, laser flash photolysis with UV-vis and IR detection, and modern computational chemistry. It is concluded that photolysis of 8-azidoadenosine in aqueous solution releases the corresponding singlet nitrene which rapidly tautomerizes to form a closed adenosine diazaquinodimethane in less than 400 fs. A perbenzoylated derivative of 8-azidoadenosine cannot undergo this tautomerization, and instead, it fragments upon photolysis to form an opened adenosine diazaquinodimethane. The singlet nitrene is too short-lived to be observed and, thus, to relax to the lowest triplet state or to become covalently attached to targeted biological macromolecules. The pivotal closed adenosine diazaquinodimethane, the product of nitrene tautomerization, has a lifetime of ca. 1 min or longer in water and in HEPES buffer at ambient temperature. However, this intermediate reacts rapidly with good nucleophiles such as amines, thiols, and phenolates, and significantly more slowly with weak nucleophiles such as alcohols and water. On the basis of these studies, it is clear that the closed adenosine diazaquinodimethane, and not the singlet or triplet nitrene, is the pivotal reactive intermediate involved in photolabeling and cross-linking studies using the 8-azidoadenosine family of photoaffinity labeling reagents.
Adenosine↗
Orthotopic liver transplantation in human immunodeficiency virus (HIV)-positive patients: outcome of 7 patients from the Bonn cohort.
The outcome and clinical features of 7 HIV-positive patients who were liver transplanted at Bonn University in the era of highly active antiretroviral therapy (HAART) between 1997 and 2004, analyzed by retrospective chart review, are reported. Reasons for orthotopic liver transplantation (OLT) were end-stage liver disease due to chronic hepatitis C (n = 4) or hepatitis B (n = 1) or acute liver failure due to fulminant hepatitis B (n = 2). Immunosuppression was based on cyclosporine A and prednisone. HAART was reinitiated 1 month after transplantation, and immunosuppression was carefully adapted to account for drug-drug interactions between cyclosporine A and protease inihibitors. Prednisone was withdrawn 5 months (median) after OLT when immunosuppression had been reliably established in the presence of HAART. One patient died 95 days after OLT due intrathoracic hemorrhage, whereas 6 patients were alive at a median of 24 months. A single episode of acute rejection was observed. The spectrum of postoperative complications was no different from HIV-negative patients apart from Kaposi's sarcoma and multicentric Castleman's disease in a single patient. Recurrent hepatitis B infection was efficiently prevented, whereas hepatitis C reinfection occurred in all 4 patients who had preexisting hepatitis C. Earlier reports on fatal courses of recurrent hepatitis C infection, high rates of organ rejection, and HAART-related liver toxicity were not observed in our patients. In conclusion, even though preliminary, our data suggest that outcomes after liver transplantation of HIV-infected patients can be improved.
Adult↗
Sampling of airborne pollutants: strategies and developments.
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Air Pollutants↗
Clinical outcomes of HIV-HCV co-infection in a large cohort of hemophiliac patients.
OBJECTIVE: To determine the disease progression of HIV-HCV co-infected hemophiliacs in a large cohort of patients (n = 288) cared for at a single medical institution. PATIENTS AND METHODS: Annual mortality rates for AIDS- and liver-related death were calculated and Kaplan-Meier survival plots were drawn to determine the progression to AIDS and death. RESULTS: Between January 1985 and December 2002, 179 (62.2%) and 195 (67.7%) of these patients had developed AIDS or died, respectively. Overall, AIDS accounted for 128 deaths, which almost entirely (93.7%) occurred prior to the introduction of highly active antiretroviral therapy (HAART) at the end of 1995. A total of 29 patients died of liver failure, most of them (69%) during the years 1991-1996. Since 1997, only five cases of fatal liver failure were reported. Non-HIV-HCV related reasons were responsible for 38 deaths and occurred predominantly (47%) in the years 1997-2002. Starting November 1995, 72 patients were treated with HAART. However, by December 2002, only 52.5% and 83% of all HAART-treated patients had a stable viremia (<400 copies/ml) and a sufficient CD4(+) T-cell count (>200/microl), respectively. CONCLUSION: These data indicate that liver-related mortality peaked in the years 1991-1996, but subsequently tended to decline. Moreover, despite widespread treatment of patients with HAART, a significant proportion of individuals had an unsatisfactory immunological and virological status at the end of 2002.
Acquired Immunodeficiency Syndrome↗
Hepatitis C-associated autoimmunity in patients coinfected with HIV.
BACKGROUND: Hepatitis C virus (HCV) infection is associated with multiple extrahepatic manifestations. It is unclear to what extent extrahepatic manifestations occur in HIV/HCV coinfection. METHODS: We prospectively assessed cross-sectional frequencies of autoimmune manifestations in HIV/HCV-coinfected patients (n=98), HIV-mono-infected (n=45) and HCV-mono-infected patients (n=78). Diagnostic vasculitis scores, HCV and HIV loads, CD4 cell counts, thyroid-, cardiolipin-, non-organ-specific tissue antibodies (nuclear, smooth muscle, anti-liver-kidney-microsome, neutrophil-cytoplasmic) and cryoglobulins were determined. RESULTS: Synergistic effects of HCV and HIV infection were observed with respect to the prevalence of antibodies against thyroglobulin (HCV infection 15.4%, HIV infection 8.8%, HIV/HCV coinfection 30.6%; P<0.001) and cardiolipin antibodies (HCV infection 9.0%, HIV infection 31%, HIV/HCV coinfection 46%; P<0.001). Cryoglobulinemia type III, was significantly associated with HCV infection (HCV, 25.6%; HIV/HCV, 20.4%) but not with HIV infection (4.4%, P<0.05). Rheumatoid factor was commonly detected in patients with HCV infection (48%), but occurred considerably less frequently in patients with HIV infection (4.4%) or HIV/HCV coinfection (9.5%, P<0.01). CONCLUSION: HIV coinfection appears to differentially modulate the frequency of HCV-related autoimmunity. However, autoimmunity is rarely accompanied by clinical manifestations.
Adult↗
Safety of lopinavir/ritonavir for the treatment of HIV-infection.
Kaletra, a fixed-dose co-formulation of lopinavir/ritonavir, was the first boosted protease inhibitor developed for the treatment of HIV-infection. In September 2000, the US FDA granted Kaletra fast-track approval as data showed a higher efficacy in the treatment of HIV-infection than standard protease inhibitors of that time. Although potency was of major concern in the early years of highly active antiretroviral therapy (HAART), presently, with the perspective of HIV-infection becoming a chronic but well controllable disease, other issues begin to draw increased attention in the long-term management of HIV-infected patients. Among general health issues such as cardiovascular disease, metabolic disorders or hepatitis co-infection, the long-term toxicity and safety of HAART is an important concern when choosing antiretroviral drugs for each individual patient. In this review, the authors report on the safety of lopinavir/ritonavir in the treatment of HIV-infected patients, and focus on special patient groups and relevant safety issues.
Anti-HIV Agents↗
Successful therapy of hepatitis B with tenofovir in HIV-infected patients failing previous adefovir and lamivudine treatment.
Three HIV-infected patients with chronic hepatitis B (genotype A) were switched to adefovir therapy after unsuccessful lamivudine treatment. Surprisingly, adefovir therapy failed, although none of the virus isolates displayed mutations known to be associated with adefovir resistance (A181V, N236T). In two isolates we identified hepatitis B virus DNA polymerase mutation L217R, in one case we found multiple frameshifts in the same region. In all cases adefovir was replaced by tenofovir, resulting in a significant drop in the viral load.
AIDS-Related Opportunistic Infections↗
Development of multinuclear giant cells during the degradation of Bioglass particles in rabbits.
Bioglass particles of the compositions 45s5, 52s, and 55s were implanted in the distal femoral epiphysis of rabbits. Animals were sacrificed at 7, 28, and 84 days postoperatively and specimens investigated using electron microscopy and electron dispersive X-ray analysis. The intention was to correlate the finding of different types of multinuclear giant cells (MNGC) in the center of the implantation bed with earlier hypothesized accumulated particle eluates and changed particle compositions. The distribution of Si, Na, Ca, P, O, S, and Cl throughout the implantation bed was analyzed. Bioglass particles degraded either in Si-rich remnants or in CaP-shells. MNGC of foreign body giant cell type in high numbers as well as of osteoclast-like type at later time intervals in small numbers were found on the surface of Si-rich as well as on Ca- and P-rich particle remnants. Osteoclast-like cells were detected on the particles after transformation in CaP-shells. It is concluded that the formation of different types of MNGC is determined by the composition of the substrate, that is, osteoclast-like cells develop exclusively on resorbable substrates. The absolute number of MNGC depended on the time after implantation and the solubility of the implant. Bone bonding, however, only occurred on Ca- and P-rich surfaces.
Animals↗
Intrauterine onset of acute neuropathic type 2 Gaucher disease: identification of a novel insertion sequence.
A subset of patients with type 2 Gaucher disease is characterized by intrauterine onset of rapidly progressive neuropathic disease, arthrogryposis, hydrops fetalis and in some cases restrictive dermopathy. beta-Glucocerebrosidase (beta-glucosidase) activity is usually low or undetectable. In most cases death ensues either in-utero or within hours or days after birth. We report on an infant born to non-consanguineous parents of Caucasian origin presenting at birth with hydrops, arthrogryposis, severe respiratory distress, hepatosplenomegaly, and liver failure. Death occurred within several hours after delivery and autopsy revealed typical Gaucher cells in multiple organs in combination with severe apoptotic neurodegeneration throughout the brain. beta-Glucocerebrosidase activity was 1% of the norm in fibroblasts and a novel heterozygous insertion c.1515_1516insAGTGAGGGCAAT was identified by genomic sequencing and an insertion-specific seminested PCR. In addition, molecular studies revealed a previously described in type 1 Gaucher disease missense mutation c.476G --> A which results in a heterozygous substitution of R120Q. Our observations confirm considerable genotypic heterogeneity in patients with type 2 Gaucher disease. The transheterozygous combination of a mutation, previously described in type 1 Gaucher disease, together with a newly identified insertion may result in this severe phenotype.
Age of Onset↗
Management of drug-to-drug interactions between cyclosporine A and the protease-inhibitor lopinavir/ritonavir in liver-transplanted HIV-infected patients.
Highly active antiretroviral therapy (HAART) has improved the life expectancy of HIV-infected patients, allowing orthotopic liver transplantation as a reasonable treatment option for selected patients with terminal liver disease. Both non-nucleoside reverse transcriptase inhibitors and protease inhibitors, key elements of HAART, give rise to substantial drug-to-drug interactions with immunosuppressive drugs such as tacrolimus and cyclosporine A. After studying 12-hour pharmacokinetic profiles in 3 HIV-positive patients after liver transplantation, we describe how dosing of cyclosporine A can be adjusted to maintain effective immunosuppressive drug levels on a daily dosing schedule when ritonavir-boosted indinavir or lopinavir-based antiretroviral therapy is given. To avoid toxic drug levels, we used an orally available cyclosporine A formulation prepared from the commercial available intravenous solution, which enabled dose adjustments in 1-mg increments. Under ritonavir-boosted HAART, cyclosporine A levels showed markedly altered absorption/elimination characteristics with more or less constant blood-levels throughout the dosing interval and prolonged elimination half-lives up to 38 hours. To obtain equivalent areas under the curve of cyclosporine A, daily doses were reduced to 5-20% of the individual standard doses given before initiation of ritonavir-boosted HAART. Because of the flat absorption/elimination profiles under ritonavir-boosted HAART cyclosporine A, dosing could be reliably monitored long term by measuring cyclosporine A trough-levels.
Adult↗