Growth of semi-polar GaN on high index silicon (11h) substrates by metal organic vapor phase epitaxy

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2014

Cytochemical characterization of gill and hepatopancreatic cells of the crab Ucides cordatus (Crustacea, Brachyura) validated by cell metal transport

Ucides cordatus (Linnaeus, 1763) is a hypo-hyper-regulating mangrove crab possessing gills for respiratory and osmoregulatory processes, separated in anterior and posterior sections. They also have hepatopancreas, which is responsible for digestion and absorption of nutrients and detoxification of toxic metals. Each of these organs has specific cells that are important for in vitro studies in cell biology, ion and toxic metals transport. In order to study and characterize cells from gills and hepatopancreas, both were separated using a Sucrose Gradient (SG) from 10 to 40% and cells in each gradient were characterized using the vital mitochondrial dye DASPEI (2-(4-dimethylaminostyryl)-N- ethylpyridinium iodide) and Trichrome Mallory's stain. Both in 20 and 40% SG for gill cells and 30% SG for hepatopancreatic cells, a greater number of cells were colored with DASPEI, indicating a larger number of mitochondria in these cells. It is concluded that the gill cells present in 20% and 40% SG are Thin cells, responsible for respiratory processes and Ionocytes responsible for ion transport, respectively. For hepatopancreatic cells, the 30% SG is composed of Fibrillar cells that possess larger number of membrane ion and nutrient transporters. Moreover, the transport of toxic metal cadmium (Cd) by isolated hepatopancreatic cells was performed as a way of following cell physiological integrity after cell separation and to study differences in transport among the cells. All hepatopancreatic cells were able to transport Cd. These findings are the first step for further work on isolated cells of these important exchange epithelia of crabs, using a simple separation method and to further develop successful in vitro cell culture in crabs.

Determinació de la ubicació estructural dels ions Yb3+ i Nb3+ en Yb:RTP, Nb:RTP i (Nb,Yb):RTP

Estudi elaborat a partir d’una estada al Stony Brook University al juliol del 2006. El RbTiOPO4 (RTP) monocristal•lí és un material d' òptica no lineal molt rellevant i utilitzat en la tecnologia làser actual, químicament molt estable i amb unes propietats físiques molt destacades, entre elles destaquen els alts coeficients electro-òptics i l'alt llindar de dany òptic que presenta. En els últims anys s’està utilitzant tecnològicament en aplicacions d'òptica no lineal en general i electro-òptiques en particular. En alguns casos ja ha substituït, millorant prestacions, a materials tals com el KTP o el LNB(1). Dopant RTP amb ions lantànids (Ln3+) (2-4), el material es converteix en un material làser auto-doblador de freqüència, combinant les seves propietats no lineals amb les de matriu làser. El RTP genera radiació de segon harmònic (SHG) a partir d’un feix fonamental amb longituds d’ona inferiors a 990 nm, que és el límit que presenta el KTP.La determinació de la ubicació estructural i l’estudi de l'entorn local del ions actius làser és de fonamental importància per a la correcta interpretació de les propietats espectroscòpiques d’aquest material. Mesures de difracció de neutrons sobre mostra de pols cristal•lí mostren que els ions Nb5+ i Ln3+ només substitueixin posicions de Ti4+ (8-9). Estudis molt recents d'EPR (electron paramagnetic resonance) semblen indicar que quan la concentració d'ió Ln3+ es baixa, aquest ió presenta la tendència a substituir l'ió alcalí present a l'estructura (10).Després dels resultats obtinguts en el present treball a partir de la tècnica EXAFS a la instal•lació sincrotò del Brookhaven National Laboratory/State University of New York (Stony Brook) es pot concloure definitivament que els ions Nb s’ubiquen en la posició Ti (1) i que els ions Yb3+ es distribueixen paritariament en les dues posicions del Ti (1 i 2). Aquests resultats aporten una valuosa informació per a la correcta interpretació dels espectres, tant d’absorció com d’emissió, del material i per la avaluació dels paràmetres del seu comportament durant l'acció làser.

Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response.

RATIONALE: A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a well-documented neurobiological finding in major depression. Moreover, clinically effective therapy with antidepressant drugs may normalize the HPA axis activity. OBJECTIVE: The aim of this study was to test whether citalopram (R/S-CIT) affects the function of the HPA axis in patients with major depression (DSM IV). METHODS: Twenty depressed patients (11 women and 9 men) were challenged with a combined dexamethasone (DEX) suppression and corticotropin-releasing hormone (CRH) stimulation test (DEX/CRH test) following a placebo week and after 2, 4, and 16 weeks of 40 mg/day R/S-CIT treatment. RESULTS: The results show a time-dependent reduction of adrenocorticotrophic hormone (ACTH) and cortisol response during the DEX/CRH test both in treatment responders and nonresponders within 16 weeks. There was a significant relationship between post-DEX baseline cortisol levels (measured before administration of CRH) and severity of depression at pretreatment baseline. Multiple linear regression analyses were performed to identify the impact of psychopathology and hormonal stress responsiveness and R/S-CIT concentrations in plasma and cerebrospinal fluid (CSF). The magnitude of decrease in cortisol responsivity from pretreatment baseline to week 4 on drug [delta-area under the curve (AUC) cortisol] was a significant predictor (p<0.0001) of the degree of symptom improvement following 16 weeks on drug (i.e., decrease in HAM-D21 total score). The model demonstrated that the interaction of CSF S-CIT concentrations and clinical improvement was the most powerful predictor of AUC cortisol responsiveness. CONCLUSION: The present study shows that decreased AUC cortisol was highly associated with S-CIT concentrations in plasma and CSF. Therefore, our data suggest that the CSF or plasma S-CIT concentrations rather than the R/S-CIT dose should be considered as an indicator of the selective serotonergic reuptake inhibitors (SSRIs) effect on HPA axis responsiveness as measured by AUC cortisol response.

Cadmium hyperaccumulation and genetic differentiation of Thlaspi caerulescens populations

Although the knowledge on heavy metal hyperaccumulation mechanisms is increasing, the genetic basis of cadmium (Cd) hyperaccurnulation remains to be elucidated. Thlaspi caerulescens is an attractive model since Cd accumulation polymorphism observed in this species suggests genetic differences between populations with low versus high Cd hyperaccumulation capacities. In our study, a methodology is proposed to analyse at a regional scale the genetic differentiation of T. caerulescens natural populations in relation to Cd hyperaccumulation capacity while controlling for different environmental, soil, plant parameters and geographic origins of populations. Twenty-two populations were characterised with AFLP markers and cpDNA polymorphism. Over all loci, a partial Mantel test showed no significant genetic structure with regard to the Cd hyperaccumulation capacity. Nevertheless, when comparing the marker variation to a neutral model, seven AFLP fragments (9% of markers) were identified as presenting particularly high genetic differentiation between populations with low and high Cd hyperaccurnulation capacity. Using simulations, the number of outlier loci was showed to be significantly higher than expected at random. These loci presented a genetic structure linked to Cd hyperaccumulation capacity independently of the geography, environment, soil parameters and Zn, Pb, Fe and Cu concentrations in plants. Using a canonical correspondence analysis, we identified three of them as particularly related to the Cd hyperaccumutation capacity. This study demonstrates that populations with low and high hyperaccurnulation capacities can be significantly distinguished based on molecular data. Further investigations with candidate genes and mapped markers may allow identification and characterization of genomic regions linked to factors involved in Cd hyperaccumulation.

Evaluation of cumulative PCB exposure estimated by a job exposure matrix versus PCB serum concentrations.

Although polychlorinated biphenyls (PCBs) have been banned in many countries for more than three decades, exposures to PCBs continue to be of concern due to their long half-lives and carcinogenic effects. In National Institute for Occupational Safety and Health studies, we are using semiquantitative plant-specific job exposure matrices (JEMs) to estimate historical PCB exposures for workers (n = 24,865) exposed to PCBs from 1938 to 1978 at three capacitor manufacturing plants. A subcohort of these workers (n = 410) employed in two of these plants had serum PCB concentrations measured at up to four times between 1976 and 1989. Our objectives were to evaluate the strength of association between an individual worker's measured serum PCB levels and the same worker's cumulative exposure estimated through 1977 with the (1) JEM and (2) duration of employment, and to calculate the explained variance the JEM provides for serum PCB levels using (3) simple linear regression. Consistent strong and statistically significant associations were observed between the cumulative exposures estimated with the JEM and serum PCB concentrations for all years. The strength of association between duration of employment and serum PCBs was good for highly chlorinated (Aroclor 1254/HPCB) but not less chlorinated (Aroclor 1242/LPCB) PCBs. In the simple regression models, cumulative occupational exposure estimated using the JEMs explained 14-24% of the variance of the Aroclor 1242/LPCB and 22-39% for Aroclor 1254/HPCB serum concentrations. We regard the cumulative exposure estimated with the JEM as a better estimate of PCB body burdens than serum concentrations quantified as Aroclor 1242/LPCB and Aroclor 1254/HPCB.

Increased clozapine plasma concentrations and side effects induced by smoking cessation in 2 CYP1A2 genotyped patients.

Clozapine, an atypical antipsychotic, depends mainly on cytochrome P4501A2 (CYP1A2) for its metabolic clearance. CYP1A2 is inducible by smoking, and lower plasma concentrations of clozapine are measured in smokers than in nonsmokers. Case reports have been published on the effects of discontinuing smoking in patients receiving clozapine, which might lead to elevated plasma concentrations and severe side effects. We present 2 cases on the consequences of smoking cessation in patients receiving this drug. In the first patient, smoking cessation resulted, within 2 weeks, in severe sedation and fatigue, with an approximately 3-fold increase of plasma clozapine concentrations. In the second patient, a very high plasma concentration of clozapine (3004 ng/mL) was measured 6 days following a 16-day stay in a general hospital, during which smoking was prohibited. In the latter patient, the replacement of omeprazole, a strong CYP1A2 inducer, by pantoprazole, a weaker CYP1A2 inducer, could have contributed, in addition to smoking cessation, to the observed strong increase of plasma clozapine concentrations. Genotyping of the 2 patients revealed that they were carriers of the AA genotype for the -164C>A polymorphism (CYP1A2*1F) in intron 1 of CYP1A2 gene, which has previously been shown to confer a high inducibility of CYP1A2 by smoking. Thus, at the initiation of clozapine treatment, smoking patients should be informed that, if they decide to stop smoking, they are encouraged to do so but must inform their prescriber beforehand. Also, because of the increased use of no-smoking policies in many hospitals, studies examining the consequences of such policies on the pharmacokinetics/pharmacodynamics of drugs metabolized by CYP1A2, taking into account different CYP1A2 genotypes, are needed.

Evaluation of different Cypermethrin formulations and concentrations in the control of Musca domestica

Cypermethrin (4 g/l, 5 g/l wettable powder and 7 ml/l, 10 ml/l emulsifiable concentrate) was tested, under laboratory conditions, against the adult Musca domestica. As a standard for comparison, a 6 ml/l concentrate suspension formulation of deltamethrin was used. One and twenty-four hours after application, mortality counts showed that the substances under test killed, respectively, more than 80% and 85% of the exposed insects. Under the conditions of the test, cypermethrin was considered effective in the control of the house fly.

Plasma levels of trimipramine and metabolites in four patients: determination of the enantiomer concentrations of the hydroxy metabolites.

A two-step high-performance liquid chromatography method is described, using a CN column and an alpha 1-acid glycoprotein column, which allows the measurement of the enantiomers of the hydroxy metabolites of trimipramine in plasma of trimipramine-treated patients. Of the four patients analyzed, three showed approximately equimolar concentrations of the (D)- and (L)-enantiomers of the hydroxy metabolites (2-hydroxy-trimipramine and 2-hydroxy desmethyltrimipramine), and one was found to have roughly twice as much of the (L)-form and of the (D)-form of 2-hydroxy trimipramine and 2-hydroxy desmethyltrimipramine. From the data available on the pharmacological effects of the enantiomers of trimipramine, it is postulated that this interindividual variability in its pharmacokinetics is another factor that could contribute to the interindividual variability in its pharmacodynamics.

The effect of subminimal inhibitory concentrations of penicillin on growth rate and haemolysin activity of group G Streptococcus

The influence of the subminimal inhibitory concentrations (1/3 and 1/4 of the MIC) of penicillin on growth rate and on haemolysin production of a strain of group G Streptococcus was studied. It was shown that 1/3 of the MIC almost completely inhibited the bacterial growth, but it was not able to inhibit haemolysin activity in the culture supernate. The generation time of bacteria grown in 1/4 of the MIC was approximately twice longer than that of the control culture. In all cultures, the haemolysin, after being produced (or liberated), reached a peak and decreased to low levels, which could suggest that group G Streptococcus produces some end products of metabolism that are able to inhibit haemolysin activity.

Correlation between plasma and urine phenylalanine concentrations.

In this pilot study, we show that plasma phenylalanine concentration can be predicted from urine concentration if the age of the patient is taken into consideration. This observation could open the way to a new monitoring of phenylketonuric patients in which painful frequent blood sampling, mandatory to adapt the low phenylalanine diet, could be mostly replaced by urinalysis. Compliance to treatment would be improved and hence also the ultimate mental development. Since this study was based on a small number of patients, validation of the model in a large multicentric survey is needed before it can be recommended.

Suivi thérapeutique des concentrations d'inhibiteurs de tyrosine kinase et d'autres médicaments oncologiques = Therapeutisches Drug-Monitoring der Konzentration von Tyrosinkinase-Inhibitoren und anderen Onkologika

Les médicaments anticancéreux sont souvent caractérisés par une importante variabilité pharmacocinétique interindividuelle, des relations entre concentration et réponse clinique et une marge thérapeutique étroite. Pourtant, le suivi thérapeutique des concentrations de ces médicaments (TDM) est encore rare en oncologie. Les bases scientifiques justifiant un TDM des nouvelles thérapies ciblées orales sont encore très hétérogènes. Cependant, d'assez solides évidences existent pour l'imatinib et certaines apparaissent progressivement pour d'autres composés. A côté de cela, le TDM est aussi pratiqué dans des situations spécifiques de traitement par certaines chimiothérapies conventionnelles. Des efforts considérables restent toutefois à réaliser pour mieux caractériser la pharmacocinétique de ces médicaments, pour préciser leurs relations concentration-effet et pour conduire des études prospectives randomisées évaluant le bénéfice clinique de l'approche TDM en oncologie.

Hydrocarbon biomarkers in the Topla-Mezica zinc-lead deposits, northern Karavanke/Drau Range, Slovenia: Paleoenvironment at the site of ore formation

The Mississippi Valley-type zinc and lead deposits at Topla (250,150 metric tons (t) of ore grading 1.0 wt % Zn and 3.3 wt % Pb) and Mezica (19 million metric tons (Mt) of ore grading 5.3 wt % Pb and 2.7 wt % Zn) occur within the Middle to Upper Triassic platform carbonate rocks of the northern Karavanke/Drau Range geotectonic units of the Eastern Alps, Slovenia. The ore and host rocks of these deposits have been investigated by a combination of inorganic and organic geochemical methods to determine major, trace, and rare earth element (REE) concentrations, hydrocarbon distribution, and stable isotope ratios of carbonates, kerogen, extractable organic matter, and individual hydrocarbons. These data combined with sedimentological evidence provide insight into the paleoenvironmental conditions at the site of ore formation. The carbonate isotope composition, the REE patterns, and the distribution of hydrocarbon biomarkers (normal alkanes and steranes) suggest a marine depositional environment. At Topla, a relatively high concentration of redox sensitive trace elements (V, Mo, U) in the host dolostones and REE patterns parallel to that of the North American shale composite suggest that sediments were deposited in a reducing environment. Anoxic conditions enhanced the preservation of organic matter and resulted in relatively higher total organic carbon contents (up to 0.4 wt %). The isotopic composition of the kerogen (delta C-13(kerogon) = -29.4 to -25.0 parts per thousand, delta N-15(kerogen) = -.13.6 to 6.8 parts per thousand) suggests that marine algae and/or bacteria were the main source of organic carbon with a very minor contribution from detrital continental plants and a varying degree of alteration. Extractable organic matter from Topla ore is generally depleted in C-13 compared to the associated kerogen, which is consistent with an indigenous source of the bitumens. The mineralization correlates with delta N-15(kerogen) values around 0 per mil, C-13 depleted kerogen, C-13 enriched n-heptadecane, and relatively high concentrations of bacteria] hydrocarbon biomarkers, indicating a high cyanobacterial biomass at the site of ore formation. Abundant dissimilatory sulfate-reducing bacteria, feeding on the cyanobacterial remains, led to accumulation of biogenic H2S in the pore water of the sediments. This biogenic H2S was mainly incorporated into sedimentary organic matter and diagenetic pyrite. Higher bacterial activity at the ore site also is indicated by specific concentration ratios of hydrocarbons, which are roughly correlated with total Pb plus Zn contents. This correlation is consistent with mixing of hydrothermal metal-rich, fluids and local bacteriogenic sulfide sulfur. The new geochemical data provide supporting evidence that Topla is a low-temperature Mississippi Valley-type deposit formed in an anoxic supratidal saline to hypersaline environment. A laminated cyanobacterial mat, with abundant sulfate-reducing bacteria was the main site of sulfate reduction.