Fast Peroxy Radical Isomerization and OH Recycling in the Reaction of OH Radicals with Dimethyl Sulfide.

Dimethyl sulfide (DMS), produced by marine organisms, represents the most abundant, biogenic sulfur emission into the Earth's atmosphere. The gas-phase degradation of DMS is mainly initiated by the reaction with the OH radical forming first CH3SCH2O2 radicals from the dominant H-abstraction channel. It is experimentally shown that these peroxy radicals undergo a two-step isomerization process finally forming a product consistent with the formula HOOCH2SCHO. The isomerization process is accompanied by OH recycling. The rate-limiting first isomerization step, CH3SCH2O2 → CH2SCH2OOH, followed by O2 addition, proceeds with k = (0.23 ± 0.12) s-1 at 295 ± 2 K. Competing bimolecular CH3SCH2O2 reactions with NO, HO2, or RO2 radicals are less important for trace-gas conditions over the oceans. Results of atmospheric chemistry simulations demonstrate the predominance (≥95%) of CH3SCH2O2 isomerization. The rapid peroxy radical isomerization, not yet considered in models, substantially changes the understanding of DMS's degradation processes in the atmosphere.

The inverse electron-demand Diels-Alder reaction as a new methodology for the synthesis of 225Ac-labelled radioimmunoconjugates.

The inverse electron-demand Diels-Alder reaction between tetrazine (Tz) and trans-cyclooctene (TCO) facilitates the efficient radiosynthesis of 225Ac-labelled radioimmunoconjugates in a two-step method, outperforming conventional approaches based on isothiocyanate couplings.

Ultrastructural Aspects of the Prenatal Bovine Ovary Differentiation with a Special Focus on the Interstitial Cells.

The aim of this investigation was to study the ultrastructural features during the development of fetal bovine ovaries (crown rump length ranging from 11.4 to 94.0 cm). An interesting observation was the occurrence of big elongated cells containing a variety of electron dense granules and light homogenous vacuoles/bodies. They were located between the stroma cells surrounding the germ cell cord ends, adjacent to the first formed primordial follicles, typically situated near blood vessels. ER alpha and ER beta receptor positive cells could be detected in the same regions by means of immunohistochemistry. Intercellular bridges linked the germ cells nests oogonia. Germ cell cords consisted of centrally located, large, pale oogonia, surrounded by elongated somatic cells with very long cytoplasm extensions. Primordial follicles with flat pale follicular cells could be observed on the inner end of the cords. Extrusions of the outer nuclear membrane could often been recognised in voluminous oocytes.

Development and prospective evaluation of a multimedia teaching course on aortic valve replacement.

BACKGROUND: Participation in heart surgery requires procedural and factual knowledge and intensive preparation. There is evidence in the literature that multimedia driven learning has advantages in medical fields where an understanding of complex temporal and spatial events plays an important role. This work describes the development and evaluation of a multimedia driven, online teaching course on aortic valve replacement for students and residents. METHODS: The instructional model followed a methodological approach with scalable information for different user groups. Various interactive multimedia development tools were employed. In a prospective study, 20 students and 10 residents were exposed to the program in a standardized environment. Both groups completed a 20-item multiple choice pre- and post-test. Psychometric evaluation with HILVE (Heidelberg inventory for the evaluation of teaching courses, 50 items) was performed. RESULTS: The multimedia course integrates more than 200 high quality surgical video and audio sequences, interactive 2 D and 3 D models, as well as illustrations and text. It is available at www.lamedica.de. Study time in the student group was 103 +/- 11 min and 70 +/- 10 min in the resident group. Mean number of correct responses to the knowledge pre-test was 6.23 +/- 2.71 in the student group and 12.2 +/- 2.66 in the resident group. Mean number of correct responses to the knowledge post-test was 15.24 +/- 2.06 in the student group ( p < 0.0001 vs. pre-test) and 17 +/- 2.98 in the resident group ( p = 0.004 vs. pre-test). The HILVE test showed positive results for teaching conditions, the program's instructional competence, student motivation and individual learning. CONCLUSION: Our data demonstrate that multimedia driven training can adapt to the individual needs of learners and improves procedural knowledge required for open heart surgery. Consequently, the whole course forms part of the training of residents and students.

Desalination of mixed tannery effluent with membrane bioreactor and reverse osmosis treatment.

A limiting factor for the reuse and recycling of treated tannery wastewater for irrigation and other uses is the high salt content, which persists even after conventional treatment. Reverse osmosis (RO) membrane treatment has been shown to significantly reduce the salt contents of tannery effluents. However, the high organic content of tannery effluent leads to rapid scaling and biofouling of RO membranes with a consequent reduction in flux rates and performance. Membrane bioreactors (MBR) have been shown to be highly effective in the removal of organic pollutants and suspended solids from tannery effluent. This research investigated the use of a combined MBR and RO treatment process to treat tannery effluents to an acceptable level for irrigation purposes. The MBR was operated at 17-20 h retention time, at a F/M ratio of 0.52 kg COD x kg SS(-1) x day(-1) and a volumetric loading rate of 3.28 kg COD x m(-3) x day(-1). This treatment reduced the COD, BOD, and ammonia concentrations of the effluent by 90-100%. The MBR was shown to be an excellent pretreatment prior to RO technology, due to the high removal efficiency of organic compounds and suspended solids, with average concentrations of 344 mg x L(-1) COD and 20 mg x L(-1) BOD achieved in the permeate. RO treatment reduced the salt content of the MBR permeate by up to 97.1%. The results of the research demonstrated that the MBR system developed was appropriate for the treatment of tannery effluents and, in combination with the RO treatment, reduced the salt content to acceptable levels for irrigation. The MBR pretreatment reduced bio-fouling and scaling of subsequent RO treatment and improved the overall performance of the RO unit. It is believed that this is the first investigation of a combined MBR and RO treatment for tannery effluents. This research provided data for an outline design of a full-scale MBR and RO plant with a treatment capacity of 5000 m3 per day for mixed tannery effluents.

Techno-economic evaluation of membrane filtration for the recovery and re-use of tanning chemicals.

The majority of pollution generated from leather manufacturing can be contributed to the inefficiency of chemical use in leather processing and to organic substances derived from the hides during processing. In particular, the overall tanning processes performed in drums can be characterized by a high consumption of water and chemicals, most of which are found in the final wastewater. To ensure full penetration and reaction of chemicals with collagen, chemicals are added in excess and are only partly up-taken by the leather. Significant savings of chemicals can be achieved by recovery and recycling of chemicals and water from part streams, thus reducing environmental impacts. This research formed an integrated approach to investigate and exploit the potential of a closed loop operation for various part streams of tanneries. Each of the process streams was separately collected, treated and purified by membrane technologies to obtain a recyclable liquor which can be re-used operationally. In this way a complete recovery of process liquors can be achieved for immediate operational re-use. Membrane technology has been applied to recover chemicals from un-hairing, vegetable tanning, chrome liquors and to polish saline part streams for re-use. By applying membrane filtration up to 90% of the treated liquors can be recovered giving a remaining concentrate volume of only 10%. The permeate obtained from several process areas contained to a high extent chemicals, which were re-used for leather processing.

[Not Available]. / Bildung von Ochratoxin A bei der Lagerung von Triticale nach künstlicher Infektion mitPenicillium verrucosum in Abhängigkeit unterschiedlicher Feuchtegehalte.

Triticale is a frequently cultivated and used in feed rations because of high yields of kernels and straw. Furthermore triticale is cosidered in a culturelandscape program. The storage of triticale and storage conditions become more and more important. In our study Triticale was remoistered to a watercontent of 14, 16, 18, und 19% as well, inoculated withP verrucosum and stored for 28 weeks from november till july in a research granary (tower silo). This experiment should simulate the storage situation in farmscale from cold wintermonths to warm spring times. Every four weeks CO2 was measured, and samples for moisture, OTA- and CT-analysis were taken. At week 20 and a MC of 19 % 22 µg OTA/kg triticale were found. The maximum of OTA-production in this humidity stage was at week 28 with 635 µg/kg. Also at a MC of 18 % OTA could be found with levels near to the detection limit. In contrast to former investigations with oatsP verrucosum produced in triticale no citrinin even when the OTA concentrations were higher than in our investigations.

Na(+)/H(+) exchange inhibition with HOE642 improves postischemic recovery due to attenuation of Ca(2+) overload and prolonged acidosis on reperfusion.

BACKGROUND: Na(+)/H(+) exchange inhibition with HOE642 (cariporide) improves postischemic recovery of cardiac function, but the mechanisms of action remain speculative. Because Na(+)/H(+) exchange is activated on reperfusion, it was hypothesized that its inhibition delays realkalinization and decreases intracellular Na(+) and, via Na(+)/Ca(2+) exchange, Ca(2+) overload. Attenuated Ca(2+) overload and prolonged acidosis are known to be cardioprotective. METHODS AND RESULTS: Left ventricular developed and end-diastolic pressures were measured in isolated buffer-perfused rat hearts subjected to 30 minutes of no-flow ischemia and 30 minutes of reperfusion (37 degrees C) with or without 1 micromol/L HOE642 added to the perfusate 15 minutes before ischemia. Intracellular Ca(2+) concentration ([Ca(2+)](i)) and pH(i) were measured with aequorin (n=10 per group) and (31)P NMR spectroscopy (n=6 per group), respectively. HOE642 did not affect preischemic mechanical function, [Ca(2+)](i), or pH(i). Mechanical recovery after 30 minutes of reperfusion was substantially improved with HOE642: left ventricular developed pressure (in percent of preischemic values) was 92+/-3 versus 49+/-7 and left ventricular end-diastolic pressure was 16+/-3 versus 46+/-5 mm Hg (P<0.05 for HOE642-treated versus untreated hearts). End-ischemic [Ca(2+)](i) was significantly lower in HOE642-treated than in untreated hearts (1.04+/-0.06 versus 1.84+/-0. 02 micromol/L, P<0.05). Maximal intracellular Ca(2+) overload during the first 60 seconds of reperfusion was attenuated with HOE642 compared with untreated hearts: 2.0+/-0.3 versus 3.2+/-0.3 micromol/L (P<0.05). pH(i) was not different at end ischemia ( approximately 5.9+/-0.05). Realkalinization was similar in the first 90 seconds of reperfusion and significantly delayed in the next 3 minutes (eg, 6.8+/-0.07 in HOE642-treated hearts compared with 7. 2+/-0.07 in untreated hearts; P<0.05). CONCLUSIONS: HOE642 improves postischemic recovery by reducing Ca(2+) overload during ischemia and early reperfusion and by prolonging postischemic acidosis.

Inhibition of endogenous nitric oxide synthase potentiates ischemia-reperfusion-induced myocardial apoptosis via a caspase-3 dependent pathway.

OBJECTIVE: Apoptosis of cardiomyocytes may contribute to ischemia-reperfusion injury. The role of nitric oxide (NO) in apoptosis is controversial. Therefore, we investigated the effect of NO synthase inhibition on apoptosis of cardiomyocytes during ischemia and reperfusion and elucidated the underlying mechanisms. METHODS AND RESULTS: Isolated perfused rat hearts (n = 6/group) were subjected to ischemia (30 min) and reperfusion (30 min) in the presence or absence of the NO synthase inhibitor NG-mono-methyl-L-arginine. Reperfusion induced cardiomyocyte apoptosis as assessed by immunohistochemistry (TUNEL-staining) and the demonstration of the typical DNA laddering. Apoptosis during reperfusion was associated with the cleavage of caspase-3, the final down-stream executioner caspase, whereas the protein levels of the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax were unchanged. Inhibition of the NO synthase drastically increased ischemia and reperfusion-induced apoptosis of cardiomyocytes. Moreover, the NO synthase inhibitor enhanced the activation of caspase-3, suggesting that NO interferes with the activation of caspases in ischemia-reperfusion. CONCLUSION: The results of the present study demonstrate that inhibition of endogenous NO synthesis during ischemia and reperfusion leads to an enhanced induction of apoptosis, suggesting that the endogenous NO synthesis protects against apoptotic cell death. Inhibition of NO synthesis thereby activates the caspase cascade, whereas the Bcl-2/Bax protein levels remained unchanged.

Deoxynivalenol, zearalenone, ochratoxin A: Quality of feed cereals.

In order to determine the distribution of mycotoxin contamination in Bavaria, Germany, and to control the quality of feed cereals the three toxins, deoxynivalenol (DON), ochratoxin A (OTA), and zearalenone (ZEA) from 5 different cereals out of 5 districts were analysed. Our investigation demonstrates that all data are near the discussed guide values thus the quality of cereals was not affected seriously in 1999. Calculating the medians for the 5 districts separately it was possible to establish a rough grid revealing a more detailed view on the mycotoxin situation in Bavaria.

Adsorption of ochratoxin A, deoxynivalenol and zearalenonein vitro at different pH and adsorbents.

The adsorption of standards of 100 µg/kg Ochratoxin A (OTA), 30 mg/kg Deoxynivalenol (DON) and 30 mg/kg Zearalenone (ZEA) from 2.5 ml phosphate buffer (pH 3.0 and pH 7.0) and pure destilled water were studiedin vitro after addition of 0.1, 0.25, 0.5, 1.0 and 2.5 % (w/v) activated charcoal and four adsorbents (A I-A IV). Adsorbent A I was 1.0, 2.5 and 5.0 % modified yeast cell wall+vitamin mixture+plant oil refined. A II was modified yeast cell wall. A III was bentonite+enzymes+modified yeast cell wall+vitamin E+trace elements. A IV was bentonite. The adsorption for OTA and ZEA were 100 % by 0.1 % activated charcoal, but DON adsorption ranged from 47 to 99 % depending on the concentration of charcoal and pH value. However, adsorption of DON by 0.5, 1.0 and 2.5 % charcoal did not differ significantly by different pH buffers. Adsorption of OTA by A I, A II and A III (1.0 and 2.5 %) was higher in pH 7.0 buffer and pure destilled water compared to pH 3.0 buffer. A IV and 5.0 % A II showed an opposite trend. However, adsorption of OTA was by A II>A III>A IV (at pH 7.0 and water). The overall means of adsorption were higher by A II>A III>A IV>A I. Generally, the adsorption ranged from 15 to 60 % depending on kind and concentration of adsorbents and pH values. DON adsorption (30, 16 and 5 mg/kg) was not affected by A I, A II, A III and A IV. Adsorption of ZEA was highest by A I, and the lowest by A III. The means of adsorption at different pH were by A I>A II>A IV (2.5 and 5.0 %)>A III. The overall means show the same trend. Generally, the adsorption ranged from 13 to 57 %.

Dose-dependent reduction of myocardial infarct mass in rabbits by the NHE-1 inhibitor cariporide (HOE 642).

The aim of this study was to investigate the dose-dependent effect of pretreatment with the selective sodium-hydrogen exchange NHE-subtype 1 inhibitor cariporide on myocardial infarct mass in a rabbit model of coronary ligation and reperfusion. Furthermore, in a second part of the study, we tested the effect of cariporide in the rabbits when given prior to reperfusion. Rabbits (n=49) were randomized in 7 groups: saline vehicle, cariporide: 0.01, 0.03, 0.1 and 0.3 mg/kg, and subjected to a 30 min occlusion of a branch of the left coronary artery followed by 2 h reperfusion. Cariporide was given as a bolus intravenously 10 min before occlusion or 5 min before reperfusion. After reperfusion, myocardial infarct mass was determined by triphenyl tetrazolium chloride staining and expressed as a percent of area at risk. Cariporide given intravenously 10 min before occlusion in doses of 0.01, 0.03, 0.1, 0.3 mg/kg, led to a dose-dependent reduction in infarct mass from 58+/-6% in controls to 48+/-4% (-17%, NS), 36+/-5% (-38%, p<0.05), 26+/-6% (-55%, p<0.05), 11+/-4% (-81%, p<0.05) respectively, whereas area at risk did not differ in between the groups. The effect of the lowest dose of 0.01 mg/kg did not reach significance. Plasma levels at different doses of cariporide were correlated to the respective infarct mass. After coronary occlusion left ventricular end-diastolic pressure (LVEDP) significantly increased throughout occlusion and reperfusion. Cariporide in the doses of 0.3, 0.1 and 0.03 mg/kg normalized LVEDP when measured after 2 h reperfusion. In controls hemodynamic parameters such as mean arterial blood pressure (MAP), heart rate (HR), left ventricular pressure (LVP) and LV dP/dt(max) were not significantly changed by ischemia/reperfusion with the exception of MAP, LVP and LV dP/dt(max) which were significantly decreased after 120 min reperfusion. Cariporide at doses of 0.1, 0.03 and 0.01 mg/kg did not significantly influence these parameters, whereas the highest dose of 0.3 mg/kg prevented the decrease of MAP and LVP. Cariporide (0.3 mg/kg i.v.) administered 5 min before reperfusion significantly reduced infarct mass by 31%. Under these conditions the increase of LVEDP after coronary occlusion was not influenced by cariporide. As in the pretreatment experiments, the decrease of MAP and LVP was prevented when measured 2 h after reperfusion. The results show that pretreatment with the NHE-subtype 1 inhibitor cariporide is cardioprotective by reducing infarct mass in rabbits in a dose-dependent manner. While the cardioprotective effect of pretreatment could be demonstrated over a broad range of doses, the efficacy of the compound when given only on reperfusion was significant but more limited.

[Verification of MR thermometry by means of an in vivo intralesional, fluoroptic temperature measurement for laser-induced thermotherapy ov liver metastases]. / Verifizierung der MR-Thermometrie mittels in vivo intraläsionaler, fluoroptischer Temperaturmessung für die laserinduzierte Thermotherapie von Lebermetastasen.

PURPOSE: To evaluate the correlation of MR-measured changes of signal intensity and invasive fluoroptic temperature measurements during MR-guided LITT of liver metastases. MATERIALS AND METHODS: In 15 patients with proven liver metastases of colorectal carcinoma, MR-guided LITT was performed with a percutaneous approach in a multiapplicator technique. Two temperature sensitive T1-weighted sequences (FLASH-2D- and TurboFLASH-sequences) were used to map the spatial and temporal distribution of Nd:YAG laser effects. Parallel fluoroptic temperature measurements were carried out by means of an inserted probe in a distance of 5-26 mm (mean: 14 mm) from the laser applicator. RESULTS: In both sequences a gradually increasing signal loss could be documented during laser application which proved to be reversible after cessation of energy deposition. the percentage of decrease in signal intensity correlated directly with the measured increase of temperature. Invasive fluoroptical evaluation of temperature distribution after 10 min exposure time showed at 5 mm distance from the applicator an increase of temperature of 35 degrees C, in 10 mm distance a mean increase of 9 degrees C +/- 1.7, in 15 mm a mean increase of 7 degrees C +/- 1.6 and in 20 mm a mean increase of 3 degrees C +/- 0.5. This is evidence of thermal tissue damage up to 3 cm in diameter with laser monoapplication. The qualitative evaluation revealed a reproducible correlation of the extent of signal loss around the applicator and the finally induced degree of necrosis. CONCLUSION: Invasive fluoroptical temperature measurements prove the diagnostic reliability of MR thermometry for the online monitoring of LITT of liver metastases.

Activation of Ca2+/calmodulin-dependent protein kinase II by extracellular calcium in cultured hippocampal pyramidal neurons.

The ability of various stimuli to convert Ca2+/calmodulin-dependent protein kinase II (CaMKII) into a Ca2+-independent (autonomous) form was examined in cultured embryonic rat hippocampal pyramidal neurons. The most effective stimulation by far was observed when cells were equilibrated in buffer containing low extracellular [Ca2+] ([Ca2+]o) (approximately 50 nM) and then shifted to normal [Ca2+]o (approximately 1.26 mM) by addition of CaCl2 (referred to as "Ca2+ stimulation"). Virtually complete (>90%) conversion of the kinase to the autonomous form occurred within 30-50 s, with a return to baseline within 5 min. By contrast, depolarization of cells with high [K+] or treatment with glutamate or a Ca2+ ionophore caused insignificant increases (<10%) in levels of the autonomous form. The Ca2+-stimulated increase in CaMKII autonomy coincided with a two- to threefold increase in kinase subunit phosphorylation. In the first 40 s of Ca2+ stimulation, 32P incorporation into the immunoprecipitated subunits of CaMKII occurred exclusively on threonine residues, including Thr286Thr287 of the alpha/beta subunits. Longer incubation of cells resulted in a decline of phosphothreonine content, whereas levels of phosphoserine-containing peptides showed a significant increase. The activation of CaMKII by Ca2+ stimulation was accompanied by only a small rise in intracellular [Ca2+]. Inhibitor studies showed that Na+-dependent action potentials and Ca2+ influx through glutamate receptors or voltage-sensitive Ca2+ channels did not contribute to the activation. Moreover, CaMKII was not activated by extracellular addition of other cations, including Mn2+, Mg2+, Co2+, or Gd3+. Although the mechanism of Ca2+ stimulation is presently unclear, it may involve either activation of extracellular calcium receptors or capacitative calcium entry. The dramatic rise in CaMKII autonomy and the Ca2+ selectivity of the response suggest a direct and specific relationship between [Ca2+]o and the state of activation of the kinase in intact neurons.

Inhibition of p130cas tyrosine phosphorylation by calyculin A.

P130cas is a dominant tyrosine phosphorylated protein in v-src-and v-crk-transformed cells. Tyrosine phosphorylation also occurs in response to integrin-mediated cell adhesion. P130cas has a unique structure with multiple SH2 and SH3 binding sites, which makes it a candidate docking protein that might be involved in several signal transduction pathways. Little is known about how p130cas itself is regulated. In this report we present evidence that tyrosine phosphorylated p130cas was rapidly dephosphorylated in several lymphatic cell lines after treatment with calyculin A, a serine/threonine phosphatase inhibitor. A similar result was obtained with okadaic acid, but higher concentrations and longer incubation times were required. Constitutive phosphorylation as well as receptor-cross linking-induced p130cas phosphorylation was inhibited. Furthermore, the p130cas-Crk association was disrupted by treatment of cells with calyculin A. However, the p130cas-Lyn association was not affected. These results suggest that calyculin A specifically affects SH2 domain-mediated protein-protein interactions and that Lyn does not bind to a susceptible SH2 domain. Furthermore, the data presented is consistent with the existence of a calyculin A-sensitive phosphatase or tyrosine kinase that may be a critical regulator of p130cas tyrosine phosphorylation.

[Cost of illness in Parkinson disease. A retrospective 3-month analysis of direct costs]. / Krankheitskosten der Parkinson-Erkrankung. Eine retrospektive dreimonatige Analyse der direkten Kosten.

Parkinson's disease (PD) causes significant expense for the national health care system due to its chronic progressive course, the duration of the disease, the high prevalence and the devastating prognosis. In Germany more than DM 320 million are spent for drugs to alleviate parkinsonian symptoms. The aim of this study was to calculate the economic burden of PD by assessing direct medical costs. Forty patients suffering from idiopathic PD were interviewed at an office of neurological specialists and at an outpatient movement disorder clinic about their use of health care resources 3 months prior to the study. The total annual costs reported were DM 14,500, consisting of DM 6500 for drug therapy and DM 8000 for other medical services, including hospital inpatient care (DM 5600), outpatient care (DM 700), medical sundries (DM 1100) and physiotherapy (DM 600). The costs were positively correlated to the extent of the disease (Hoehn and Yahr stage; HY) and the occurrence of motor fluctuations/dyskinesias. We found that both drug-therapy expenses and total medical costs doubled from HYI to HYIV. The rarely employed s.c. therapy with apomorphine additionally increased the costs of drug therapy in HYV. The occurrence of fluctuations/ dyskinesias also increased medical expenses by approximately a factor of two. Indirect burden due to increased days off of work, unemployment and earlier retirement are also significant in Parkinson's disease. This study includes that a treatment which could prevent or retard disease progression as well as a treatment that delays or reduces motor complications would not only ameliorate the situation of patients suffering from PD, but would also lead to significant reductions in cost for the national health care system.

Synthesis of the highly selective Na+/H+ exchange inhibitors cariporide mesilate and (3-methanesulfonyl-4-piperidino-benzoyl) guanidine methanesulfonate.

The syntheses of cariporide mesilate ((4-isopropyl-3-methanesulfonyl-benzoyl) guanidine methanesulfonate, HOE 642, CAS 159138-81-5), currently being clinically investigated as a protective drug in cardiac ischemia and reperfusion states, and of HOE 694 ((3-methanesulfonyl-4-piperidino-benzoyl)guanidine methanesulfonate, CAS 149725-40-6), widely used as a physiological and pharmacological research tool in studies comprising Na+/H+ exchange (NHE) inhibition, are described. Additionally, their selectivity on the different subtypes is disclosed.