Low Correlated Sequences & Architectures and Algorithms for Analog-to-Information Converters: Theory, Design, Implementation and Applications.

Most electronic systems can be described in a very simplified way as an assemblage of analog and digital components put all together in order to perform a certain function. Nowadays, there is an increasing tendency to reduce the analog components, and to replace them by operations performed in the digital domain. This tendency has led to the emergence of new electronic systems that are more flexible, cheaper and robust. However, no matter the amount of digital process implemented, there will be always an analog part to be sorted out and thus, the step of converting digital signals into analog signals and vice versa cannot be avoided. This conversion can be more or less complex depending on the characteristics of the signals. Thus, even if it is desirable to replace functions carried out by analog components by digital processes, it is equally important to do so in a way that simplifies the conversion from digital to analog signals and vice versa. In the present thesis, we have study strategies based on increasing the amount of processing in the digital domain in such a way that the implementation of analog hardware stages can be simplified. To this aim, we have proposed the use of very low quantized signals, i.e. 1-bit, for the acquisition and for the generation of particular classes of signals.

Aufbau und Charakterisierung eines flugzeuggetragenen Einzelpartikel-Massenspektrometers

Im Rahmen dieser Arbeit wurde ein flugzeuggetragenes Laserablations-Einzelpartikel-Massenspektrometer von Grund auf entworfen, gebaut, charakterisiert und auf verschiedenen Feldmesskampagnen eingesetzt. Das ALABAMA (Aircraft-based Laser ABlation Aerosol MAss Spectrometer) ist in der Lage die chemische Zusammensetzung und Größe von einzelnen Aerosolpartikeln im submikrometer-Bereich (135 – 900 nm) zu untersuchen.rnNach dem Fokussieren in einer aerodynamischen Linse wird dafür zunächst derrnaerodynamische Durchmesser der einzelnen Partikel mit Hilfe einer Flugzeitmessung zwischen zwei Dauerstrichlasern bestimmt. Anschließend werden die zuvor detektierten und klassifizierten Partikel durch einen gezielten Laserpuls einzeln verdampft und ionisiert. Die Ionen werden in einem bipolaren Flugzeit-Massenspektrometer entsprechend ihrem Masse zu- Ladungs Verhältnisses getrennt und detektiert. Die entstehenden Massenspektren bieten einen detaillierten Einblick in die chemische Struktur der einzelnen Partikel.rnDas gesamte Instrument wurde so konzipiert, dass es auf dem neuen Höhenforschungsflugzeug HALO und anderen mobilen Plattformen eingesetzt werden kann. Um dies zu ermöglichen wurden alle Komponenten in einem Rahmen mit weniger als 0.45 m³ Volumen untergebracht. Das gesamte Instrument inklusive Rahmen wiegt weniger als 150 kg und erfüllt die strengen sicherheitsvorschriften für den Betrieb an Bord von Forschungsflugzeugen. Damit ist ALABAMA das kleinste und leichteste Instrument seiner Art.rnNach dem Aufbau wurden die Eigenschaften und Grenzen aller Komponenten detailliert im Labor und auf Messkampagnen charakterisiert. Dafür wurden zunächst die Eigenschaften des Partikelstrahls, wie beispielsweise Strahlbreite und –divergenz, ausführlich untersucht. Die Ergebnisse waren wichtig, um die späteren Messungen der Detektions- und Ablationseffizienz zu validieren.rnBei den anschließenden Effizienzmessungen wurde gezeigt, dass abhängig von ihrer Größe und Beschaffenheit, bis zu 86 % der vorhandenen Aerosolpartikel erfolgreich detektiert und größenklassifiziert werden. Bis zu 99.5 % der detektierten Partikel konnten ionisiert und somit chemisch untersucht werden. Diese sehr hohen Effizienzen sind insbesondere für Messungen in großer Höhe entscheidend, da dort zum Teil nur sehr geringe Partikelkonzentrationen vorliegen.rnDas bipolare Massenspektrometer erzielt durchschnittliche Massenauflösungen von bis zu R=331. Während Labor- und Feldmessungen konnten dadurch Elemente wie Au, Rb, Co, Ni, Si, Ti und Pb eindeutig anhand ihres Isotopenmusters zugeordnet werden.rnErste Messungen an Bord eines ATR-42 Forschungsflugzeuges während der MEGAPOLI Kampagne in Paris ergaben einen umfassenden Datensatz von Aerosolpartikeln innerhalb der planetaren Grenzschicht. Das ALABAMA konnte unter harten physischen Bedingungen (Temperaturen > 40°C, Beschleunigungen +/- 2 g) verlässlich und präzise betrieben werden. Anhand von charakteristischen Signalen in den Massenspektren konnten die Partikel zuverlässig in 8 chemische Klassen unterteilt werden. Einzelne Klassen konnten dabei bestimmten Quellen zugeordnet werden. So ließen sich beispielsweise Partikel mit starkerrnNatrium- und Kaliumsignatur eindeutig auf die Verbrennung von Biomasse zurückführen.rnALABAMA ist damit ein wertvolles Instrument um Partikel in-situ zu charakterisieren und somit verschiedenste wissenschaftliche Fragestellungen, insbesondere im Bereich der Atmosphärenforschung, zu untersuchen.

Development and applications of hollow fiber flow field-flow fractionation in the bioanalytical field. Studies of aggregation phenomena in complex protein samples

Recent advances in the fast growing area of therapeutic/diagnostic proteins and antibodies - novel and highly specific drugs - as well as the progress in the field of functional proteomics regarding the correlation between the aggregation of damaged proteins and (immuno) senescence or aging-related pathologies, underline the need for adequate analytical methods for the detection, separation, characterization and quantification of protein aggregates, regardless of the their origin or formation mechanism. Hollow fiber flow field-flow fractionation (HF5), the miniaturized version of FlowFFF and integral part of the Eclipse DUALTEC FFF separation system, was the focus of this research; this flow-based separation technique proved to be uniquely suited for the hydrodynamic size-based separation of proteins and protein aggregates in a very broad size and molecular weight (MW) range, often present at trace levels. HF5 has shown to be (a) highly selective in terms of protein diffusion coefficients, (b) versatile in terms of bio-compatible carrier solution choice, (c) able to preserve the biophysical properties/molecular conformation of the proteins/protein aggregates and (d) able to discriminate between different types of protein aggregates. Thanks to the miniaturization advantages and the online coupling with highly sensitive detection techniques (UV/Vis, intrinsic fluorescence and multi-angle light scattering), HF5 had very low detection/quantification limits for protein aggregates. Compared to size-exclusion chromatography (SEC), HF5 demonstrated superior selectivity and potential as orthogonal analytical method in the extended characterization assays, often required by therapeutic protein formulations. In addition, the developed HF5 methods have proven to be rapid, highly selective, sensitive and repeatable. HF5 was ideally suitable as first dimension of separation of aging-related protein aggregates from whole cell lysates (proteome pre-fractionation method) and, by HF5-(UV)-MALS online coupling, important biophysical information on the fractionated proteins and protein aggregates was gathered: size (rms radius and hydrodynamic radius), absolute MW and conformation.

Hyperbranched polyether polyols as building blocks for complex macromolecular architectures

The present thesis deals with the development of new branched polymer architectures containing hyperbranched polyglycerol. Materials investigated include hyperbranched oligomers, hyperbranched polyglycerols containing functional initiator-cores at the focal point, well-defined linear-hyperbranched block copolymers and also negatively charged hyperbranched polyelectrolytes.rnHyperbranched oligoglycerols (DPn = 7 and 14) have been synthesized for the first time. The materials show narrow polydispersity (Mw/Mn ca. 1.45) and a very low content in cyclic homopolymers. 13C NMR evidences the dendritic structure of the oligomers and the DB could be calculated (44% and 52%). These new oligoglycerols were compared with the industrial products obtained by polycondensation which exhibit narrow polydispersity (Mw/Mn<1.3) butrnmultimodal distribution in SEC. Detailed 13C NMR and Maldi-ToF studies reveal the presence of branched units and cyclic compounds. In comparison, the hyperbranched oligoglycerols comprise a very low proportion of cyclic homopolymer which render them very interesting materials for biomedical applications for example.rnThe site isolation of the core moiety in dendritic structure offers intriguing potential with respect to peculiar electro-optical properties. Various initiator-cores (n-alkyl amines, UVabsorbing amines and benzophenone) for the ROMBP of glycidol have been tested. The bisglycidolized amine initiator-cores show the best control over the molecular weight and the molecular weight distribution. The photochemical analyses of the naphthalene containingrnhyperbranched polyglycerols show a slight red shift, a pronounced hypochromic effect (decrease of the intensity of the band) compared with the parent model compound and the formation of a relative compact structure. The benzophenone containing polymers adopt an open structure in polar solvents. The fluorescence measurements show a clear “dendritic effect” on the fluorescence intensities and the quantum yield of the encapsulated benzophenone.rnA convenient 3-step strategy has been developed for the preparation of well-defined amphiphilic, linear-hyperbranched block copolymers via hypergrafting. The procedure represents a combination of carbanionic polymerization with the alkoxide-based, controlled ring-opening multibranching polymerization of glycidol. Materials consisting of a polystyrene linear block and a hyperbranched polyglycerol block exhibit narrow polydispersity (1.01-1.02rnfor 5.4% to 27% wt. PG and 1.74 for 52% wt. PG) with a high grafting efficiency. The strategy was also extended to materials with a linear polyisoprene block.rnDetailed investigations of the solution properties of the block copolymers with linear polystyrene blocks show that block copolymer micelles are stabilized by the highly branched block. The morphology of the aggregates is depending on the solvent: in chloroform monodisperse spherical shape aggregates and in toluene ellipsoidal aggregates are formed. On graphite these aggregates show interesting features, giving promising potential applications with respect to the presence of a very dense, functional and stable hyperbranched block.rnThe bulk morphology of the linear-hyperbranched block copolymers has been investigated. The materials with a linear polyisoprene block only behave like complex liquids due to the low Tg and the disordered nature of both components. For the materials with polystyrene, only the sample with 27% wt. hyperbranched polyglycerol forms some domains showing lamellae.rnThe preparation of hyperbranched polyelectrolytes was achieved by post-modification of the hydroxyl groups via Michael addition of acrylonitrile, followed by hydrolysis. In aqueous solution materials form large aggregates with size depending on the pH value. After deposition on mica the structures observed by AFM show the coexistence of aggregates andrnunimers. For the low molecular weight sample (PG 520 g·mol-1) extended and highly ordered terrace structures were observed. Materials were also successfully employed for the fabrication of composite organic-inorganic multilayer thin films, using electrostatic layer-bylayer self-assembly coupled with chemical vapor deposition.

Liquid crystalline cellulose derivatives for mirrorless lasing

In this thesis cholesteric films made of liquid crystalline cellulose derivatives with improved optical properties were prepared. The choice of the solvent, hydrogen bond influencing additives, the synthetic realization of a very high degree of substitution on the cellulosic polymer and the use of mechanical stirring at the upper concentration limit of the liquid crystalline range were the basis for an improved alignment of the applied cellulose tricarbamates. In combination with a tuned substrate treatment and film preparation method, cholesteric films were obtained, with optical properties that were theoretically predicted and only known from low molecular weight liquid crystals so far. Subsequent polymerization allowed a permanent fixing of the alignment and the fabrication of free standing and insensitive films.rnThe incorporation of inorganic nanorods into the cholesteric host material was mediated with tailored block copolymers, available via controlled radical polymerization methods. In addition to the shape match between the rodlike mesogens of the host and the nanorods it was possible to increase the miscibility of both materials. Nevertheless, the size of the nanorods, in comparison to the mesogens, in these densely packed liquid crystalline phases as well as their long equilibration times were the reasons for phase separation. Nanorods are, in principle, valuable substitutes for organics, but their utilization in cellulosic CLC was not to be combined with a high quality alignment of the cholesteric structure.rnA swelling process of polymerized films in a dye solution or dissolving dyes in non-polymerized CLC was used for incorporation of the organic chromophores. With the first method the CLC could be aligned and polymerized without any disturbance due to dye molecules. The optical properties of dye and CLC were matched, with regard to mirrorless lasing devices. The dye was optically excited and laser emission supported by the cholesteric cavity was obtained. The polarization and wavelength of the emitted radiation as well as its bandwidth, the obtained interference pattern and threshold behavior of the emission proofed the feedback mechanism that was not believed to be realizable in liquid crystalline polymers. rnUtilization of a microfluidic co-flow injection device enabled us to transfer the properties of cellulosic CLC from the planar film shape to spherical micrometer sized particles. The pure material yielded particles with distorted mesogen alignment similar to films prepared by capillary flow. Dilution of the CLC with a solvent that migrated into the carrier phase during particle preparation provided the basis for particles with well ordered areas. rnAlthough cellulose derivatives were known for their liquid crystalline behavior for decades and synthesized in mass production, their application as feedback material was affected by bad optical properties. In comparison to low molar mass compounds, the low degree of order in the CLC phase was the cause. With the improved material, defined lasing emission was shown and characterized. Derivatives of cellulose are desirable materials, because, as a renewable resource, they are available in large amounts for a low price and need only simple derivatization reactions. The fabrication of CLC films with tunable lasing emission, for which this thesis can provide a starting point, is in good agreement with today's requirements of modern technology and its miniaturization.rn

Molekulare und supramolekulare Eigenschaften von neuen Donor-Akzeptor-Polymeren

Die organische Halbleitertechnologie befindet sich seit Jahrzehnten im Focus des Interesses, da sie eine kostengünstige und umweltverträgliche Alternative zu anorganischen Silizium-basierten Halbleitern darstellt. Die Möglichkeit der gezielten Funktionalisierung von definierten Strukturen durch synthetische Methoden, welche eine große Vielfalt an Materialien ermöglicht, steht dabei besonders im Vordergrund. Die Modifikation von physikalischen Eigenschaften ermöglicht dabei eine stark erleichterte Anpassung für den geplanten Anwendungsbereich. Im Rahmen der vorliegenden Dissertation wurden organische Halbleitermaterialien basierend auf Cyclopenta[2,1-b:3,4-b']dithiophen (CDT) dargestellt und hinsichtlich ihrer strukturellen und elektronischen Eigenschaften untersucht. In Kombination mit Benzo[c][1,2,5]thiadiazol (BTZ) und weiteren Akzeptoren wurden zunächst Donor(D)-Akzeptor(A)-Polymere synthetisiert und Struktur-Eigenschaft-Beziehungen aufgestellt. So konnte ein sehr hochmolekulares Polymer CDT-BTZ-Polymer (Mn = 36 kg mol-1, PDI = 2.6) erhalten werden, welches sich durch eine hohe lamellare Ordnung und eine gemessene Ladungsträgermobilität in FETs von über 5.0 cm2V-1s-1 bei Raumtemperatur auszeichnete; bei niedrigen Temperaturen (240 K) war letztgenannte 6.5 cm2V-1s-1. Aufgrund dieses hohen Ladungstransports und der Abwesenheit niedermolekularer Polymerketten innerhalb des Polymers konnte erstmals eine Messung eines HALL-Effektes bewerkstelligt werden. Dies war der erste Beweis eines Band-artigen Ladungstransportes an einem Polymerhalbleiter. Des Weiteren wurde durch synthetische Veränderung der Grundstruktur des Polymers zu längeren Alkylketten eine anisotrope Anordnung der Polymerketten erreicht und die Ladungsträgermobilität (6.5 cm2V-1s-1 bei Raumtemperatur) weiter gesteigert. Darauf aufbauend wurde der Einfluss von stereoisomeren Seitenketten an CDT-BTZ-Polymeren auf Packungsverhalten, Parametern (Sperrstrom, Einschaltstrom) in FETs und Löslichkeit in organischen Lösungsmitteln untersucht. Durch cis-trans-Isomerisierung der Seitenketten wurde hier eine neue Methode zur Optimierung des Packungsverhaltens von Polymeren in dünnen Filmen und Lösung gefunden. Zuletzt wurden D-π-A-Farbstoffen, welche CDT als Verbrückungseinheit (π) beinhalten, dargestellt. Durch Variation von D und A konnten Struktur-Eigenschaft-Beziehungen in der Anwendung in Solarzellen (Feststoffsolarzellen, Flüssigsolarzellen) gefunden werden. Die Untersuchungen der photoinduzierten Absorption und der Photolumisenzenzquantenausbeute lieferten dabei Erklärungen für physikalische Prozesse wie Ladungsinjektion- und rekombination.

Mortality and morbidity in the city of Bern, Switzerland, 1805-1815 with special emphasis on infant, child and maternal deaths

This article contributes to the research on demographics and public health of urban populations of preindustrial Europe. The key source is a burial register that contains information on the deceased, such as age and sex, residence and cause of death. This register is one of the earliest compilations of data sets of individuals with this high degree of completeness and consistency. Critical assessment of the register's origin, formation and upkeep promises high validity and reliability. Between 1805 and 1815, 4,390 deceased inhabitants were registered. Information concerning these individuals provides the basis for this study. Life tables of Bern's population were created using different models. The causes of death were classified and their frequency calculated. Furthermore, the susceptibility of age groups to certain causes of death was established. Special attention was given to causes of death and mortality of newborns, infants and birth-giving women. In comparison to other cities and regions in Central Europe, Bern's mortality structure shows low rates for infants (q0=0.144) and children (q1-4=0.068). This could have simply indicated better living conditions. Life expectancy at birth was 43 years. Mortality was high in winter and spring, and decreased in summer to a low level with a short rise in August. The study of the causes of death was inhibited by difficulties in translating early 19th century nomenclature into the modern medical system. Nonetheless, death from metabolic disorders, illnesses of the respiratory system, and debilitation were the most prominent causes in Bern. Apparently, the worst killer of infants up to 12 months was the "gichteren", an obsolete German term for lethal spasmodic convulsions. The exact modern identification of this disease remains unclear. Possibilities such as infant tetanus or infant epilepsy are discussed. The maternal death rate of 0.72% is comparable with values calculated from contemporaneous sources. Relevance of childbed fever in the early 1800s was low. Bern's data indicate that the extent of deaths related to childbirth in this period is overrated. This research has an explicit interdisciplinary value for various fields including both the humanities and natural sciences, since information reported here represents the complete age and sex structure of a deceased population. Physical anthropologists can use these data as a true reference group for their palaeodemographic studies of preindustrial Central Europe of the late 18th and early 19th century. It is a call to both historians and anthropologists to use our resources to a better effect through combination of methods and exchange of knowledge.

Air pollution during pregnancy and neonatal outcome: a review

There is increasing evidence of the adverse impact of prenatal exposure to air pollution. This is of particular interest, as exposure during pregnancy--a crucial time span of important biological development--may have long-term implications. The aims of this review are to show current epidemiological evidence of known effects of prenatal exposure to air pollution and present possible mechanisms behind this process. Harmful effects of exposure to air pollution during pregnancy have been shown for different birth outcomes: higher infant mortality, lower birth weight, impaired lung development, increased later respiratory morbidity, and early alterations in immune development. Although results on lower birth weight are somewhat controversial, evidence for higher infant mortality is consistent in studies published worldwide. Possible mechanisms include direct toxicity of particles due to particle translocation across tissue barriers or particle penetration across cellular membranes. The induction of specific processes or interaction with immune cells in either the pregnant mother or the fetus may be possible consequences. Indirect effects could be oxidative stress and inflammation with consequent hemodynamic alterations resulting in decreased placental blood flow and reduced transfer of nutrients to the fetus. The early developmental phase of pregnancy is thought to be very important in determining long-term growth and overall health. So-called "tracking" of somatic growth and lung function is believed to have a huge impact on long-term morbidity, especially from a public health perspective. This is particularly important in areas with high levels of outdoor pollution, where it is practically impossible for an individual to avoid exposure. Especially in these areas, good evidence for the association between prenatal exposure to air pollution and infant mortality exists, clearly indicating the need for more stringent measures to reduce exposure to air pollution.

Aberrant low expression level of bovine beta-lactoglobulin is associated with a C to A transversion in the BLG promoter region

Beta-lactoglobulin (beta-LG) is the major whey protein in cow's milk. It is well established that the predominant 2 genetic variants, beta-LG A and B, are differentially expressed. Extensive investigation of the genetic variation in the promoter region of the BLG gene revealed the existence of specific haplotypes associated with the A and B variants, respectively. However, the genetic basis for the differential expression of BLG A and B alleles is still elusive. We have previously reported a quantitative beta-LG B variant, characterized by a very low beta-LG protein expression level. Here, we report that the corresponding BLG allele (BLG B*) shows a correspondingly low mRNA expression level. Comparative DNA sequencing of 7,670 bp of the BLG B* allele and the established BLG B allele revealed a unique difference of a C to A transversion at position 215 bp upstream of the translation initiation site (g.-215C>A). This mutation segregated perfectly with the differential phenotypic expression in a paternal half-sib family and could be confirmed in 2 independent cases. The sequence of the BLG B allele in the region of the mutation is highly conserved among 4 related ruminant species. The site of the mutation corresponds to a putative consensus-binding sequence for the transcription factors c-Rel and Elk-1 as predicted by searching the TRANSFAC database. The beta-LG B* site might be relevant in the natural production of milk of low beta-LG content.

Expression of FGFRL1, a novel fibroblast growth factor receptor, during embryonic development

FGFRL1 is a novel member of the fibroblast growth factor receptor (FGFR) family. To investigate its expression during mammalian embryonic development, we have used the mouse system. Expression of Fgfrl1 is very low in mouse embryos of day 6 but steadily increases until birth. As demonstrated by in situ hybridization of 16-day-old embryos, the Fgfrl1 mRNA occurs in cartilaginous structures such as the primordia of bones and the permanent cartilage of the trachea, the ribs and the nose. In addition, some muscle types, including the muscles of the tongue and the diaphragm, express Fgfrl1 at relatively high level. In contrast, the heart and the skeletal muscles of the limbs, as well as many other organs (brain, lung, liver, kidney, gut) express Fgfrl1 only at basal level. It is conceivable that Fgfrl1 interacts with other Fgfrs, which are expressed in cartilage and muscle, to modulate FGF signaling.

A simple presurgical necrotizing enterocolitis-mortality scoring system

OBJECTIVE: To assess the relationship between early laboratory parameters, disease severity, type of management (surgical or conservative) and outcome in necrotizing enterocolitis (NEC). STUDY DESIGN: Retrospective collection and analysis of data from infants treated in a single tertiary care center (1980 to 2002). Data were collected on disease severity (Bell stage), birth weight (BW), gestational age (GA) and pre-intervention laboratory parameters (leukocyte and platelet counts, hemoglobin, lactate, C-reactive protein). RESULTS: Data from 128 infants were sufficient for analysis. Factors significantly associated with survival were Bell stage (P<0.05), lactate (P<0.05), BW and GA (P<0.01, P<0.001, respectively). From receiver operating characteristics curves, the highest predictive value resulted from a score with 0 to 8 points combining BW, Bell stage, lactate and platelet count (P<0.001). At a cutoff level of 4.5 sensitivity and specificity for predicting survival were 0.71 and 0.72, respectively. CONCLUSION: Some single parameters were associated with poor outcome in NEC. Optimal risk stratification was achieved by combining several parameters in a score.

Prospectively assessed incidence, severity, and determinants of respiratory symptoms in the first year of life

Respiratory symptoms are common in infancy. Nevertheless, few prospective birth cohort studies have studied the epidemiology of respiratory symptoms in normal infants. The aim of this study was to prospectively obtain reliable data on incidence, severity, and determinants of common respiratory symptoms (including cough and wheeze) in normal infants and to determine factors associated with these symptoms. In a prospective population-based birth cohort, we assessed respiratory symptoms during the first year of life by weekly phone calls to the mothers. Poisson regression was used to examine the association between symptoms and various risk factors. In the first year of life, respiratory symptoms occurred in 181/195 infants (93%), more severe symptoms in 89 (46%). The average infant had respiratory symptoms for 4 weeks and 90% had symptoms for less than 12 weeks (range 0 to 23). Male sex, higher birth weight, maternal asthma, having older siblings and nursery care were associated with more, maternal hay fever with fewer respiratory symptoms. The association with prenatal maternal smoking decreased with time since birth. This study provides reliable data on the frequency of cough and wheeze during the first year of life in healthy infants; this may help in the interpretation of published hospital and community-based studies. The apparently reduced risk in children of mothers with hayfever but no asthma, and the decreasing effect of prenatal smoke exposure over time illustrate the complexity of respiratory pathology in the first year of life.

Plasma S-nitrosothiol status in neonatal calves: ontogenetic associations with tissue-specific S-nitrosylation and nitric oxide synthase

Neonatal cattle and in part neonates of other species have manyfold higher plasma concentrations of nitrite plus nitrate than mature cows and subjects of other species, suggesting an enhanced and needed activation of the nitric oxide (NO) axis at birth. While the biological half-life of NO is short (<1 sec), its functionality can be prolonged, and in many regards more discretely modulated, when it reacts with low-molecular-weight and protein-bound thiols to form S-nitrosothiols (RSNO), from which NO subsequently can be rereleased. We used the calf as a model to test the hypothesis that plasma concentrations of RSNO are elevated at birth in mammals, correlate with ascorbate and urate levels, are selectively generated in critical tissue beds, and are generated in a manner temporally coincident with changes in tissue levels of active NO synthases (NOS). Plasma concentrations of RSNO, ascorbate, and urate were highest immediately after birth (Day 0), dropped >50% on Day 1, and gradually decreased over time, reaching a nadir in mature cattle. Albumin and immunoglobulin G were identified as major plasma RSNO. The presence of S-nitrosocysteine (SNC, a validated marker for S-nitrosylated proteins), inducible NOS (iNOS), and activated endothelial NOS (eNOS phosphorylated at Ser1177) in different tissues was analyzed by immunohistochemistry in another group of similar-aged calves. SNC, iNOS, and phosphorylated eNOS were detected in liver and ileum at the earliest timepoint of sampling (4 hrs after birth), increased between 4 and 24 hrs, and then declined to near-nondetectable levels by 2 weeks of life. Our data show that the neonatal period in the bovine species is characterized by highly elevated and coordinated NO-generating and nitrosylation events, with the ontogenetic changes occurring in iNOS and eNOS contents in key tissues as well as RSNO products and associated antioxidant markers.

[Pancytopenia and hemolysis--diagnosis, differential diagnosis and therapy of pernicious anemia]

Pernicious anemia and Vitamin B12 deficiency have a wide range of symptoms and are a common finding in the elderly. A 73 year old female is admitted to the hospital because of dyspnea, fatigue and loss of appetite and weight. While previous medical history and physical examination are inconspicuous, laboratory findings show severe pancytopenia with macrocytosis, low reticulocyte count and marked signs of hemolysis. A very low serum level of vitamin B12 and chronic atrophic type A gastritis upon endoscopy with presence of parietal cell antibodies in the serum lead to the diagnosis of pernicious anemia. Complete restitution is achieved by parenteral vitamin B12 substitution. Nowadays, severe pernicious anemia is only rarely seen. The differential diagnosis of pancytopenia (with macrocytic anemia) combined with hemolysis and the essential hints to the diagnosis of pernicious anemia are discussed, and thereby practical aspects including therapy actualized.

Serum lipoproteins during treatment with the antihypertensive agent indapamide

Considering the documented, potentially undesirable influence of various thiazide-type or loop diuretics on serum lipoproteins, we prospectively investigated in 69 men (mean age +/- SEM, 32 +/- 1 years) the metabolic effects of the new diuretic-antihypertensive compound indapamide. Compared to placebo, indapamide (2.5 mg/day) given for 6 to 8 weeks lowered (p less than 0.02 to less than 0.001) blood pressure (supine values from 148/98 +/- 3/2 to 137/93 +/- 3/2) in 29 men with mild to moderate essential hypertension, but not in 40 healthy men. In both groups, significant (p less than 0.05 to less than 0.001) decreases in body weight (-0.8 kg) and plasma potassium (-0.6 mmol/L), and increases in plasma uric acid (+20%), renin activity (+200%), and aldosterone documented good compliance. There were no significant changes in total cholesterol (in all subjects, from 208 +/- 6 to 213 +/- 6 mg/dl), low- or very low-density lipoprotein (VLDL) cholesterol (127 +/- 6 to 129 +/- 6 and 21 +/- 1 to 21 +/- 2 respectively), high-density lipoprotein cholesterol (50 +/- 1 to 51 +/- 1 mg/dl), total triglycerides (Tg) (108 +/- 5 to 112 +/- 6 mg/dl), VLDL-Tg, apoproteins A1 and A2, plasma glucose, epinephrine, norepinephrine, sodium, calcium, magnesium, and creatinine; apoprotein B (84 +/- 2 to 88 +/- 3 mg/dl) and plasma insulin after glucose loading dose tended to be increased minimally. The absence of distinct lipoprotein alterations after short-term indapamide treatment may be of clinical and epidemiological interest.