The liquidlike ordering of lipid A-diphosphate colloidal crystals: the influence of Ca2+, Mg2+, Na+, and K+ on the ordering of colloidal suspensions of lipid A-diphosphate in aqueous solutions.

A comprehensive study was performed on electrostatically stabilized aqueous dispersion of lipid A-diphosphate in the presence of bound Ca2+, Mg2+, K+, and Na+ ions at low ionic strength (0.10-10.0-mM NaCl, 25 degrees C) over a range of volume fraction of 1.0 x 10(-4)< or =phi< or =4.95 x 10(-4). These suspensions were characterized by light scattering (LS), quasielastic light scattering, small-angle x-ray scattering, transmission electron microscopy, scanning electron microscopy, conductivity measurements, and acid-base titrations. LS and electron microscopy yielded similar values for particle sizes, particle size distributions, and polydispersity. The measured static structure factor, S(Q), of lipid A-diphosphate was seen to be heavily dependent on the nature and concentration of the counterions, e.g., Ca2+ at 5.0 nM, Mg2+ at 15.0 microM, and K+ at 100.0 microM (25 degrees C). The magnitude and position of the S(Q) peaks depend not only on the divalent ion concentration (Ca2+ and Mg2+) but also on the order of addition of the counterions to the lipid A-diphosphate suspension in the presence of 0.1-microM NaCl. Significant changes in the rms radii of gyration (R2G) 1/2 of the lipid A-diphosphate particles were observed in the presence of Ca2+ (24.8+/-0.8 nm), Mg2+ (28.5+/-0.7 nm), and K+ (25.2+/-0.6 nm), whereas the Na+ salt (29.1+/-0.8 nm) has a value similar to the one found for the de-ionized lipid A-diphosphate suspensions (29.2+/-0.8 nm). Effective particle charges were determined by fits of the integral equation calculations of the polydisperse static structure factor, S(Q), to the light-scattering data and they were found to be in the range of Z*=700-750 for the lipid A-diphosphate salts under investigation. The light-scattering data indicated that only a small fraction of the ionizable surface sites (phosphate) of the lipid A-diphosphate was partly dissociated (approximately 30%). It was also discovered that a given amount of Ca2+ (1.0-5.0 nM) or K+ (100 microM) influenced the structure much more than Na+ (0.1-10.0-mM NaCl) or Mg2+ (50 microM). By comparing the heights and positions of the structure factor peaks S(Q) for lipid A-diphosphate-Na+ and lipid A-diphosphate-Ca2+, it was concluded that the structure factor does not depend simply on ionic strength but more importantly on the internal structural arrangements of the lipid A-diphosphate assembly in the presence of the bound cations. The liquidlike interactions revealed a considerable degree of ordering in solution accounting for the primary S(Q) peak and also the secondary minimum at large particle separation. The ordering of lipid A-diphosphate-Ca2+ colloidal crystals in suspension showed six to seven discrete diffraction peaks and revealed a face-centered-cubic (fcc) lattice type (a=56.3 nm) at a volume fraction of 3.2 x 10(-4)< or =phi< or =3.9 x 10(-4). The K+ salt also exhibited a fcc lattice (a=55.92 nm) at the same volume fractions, but reveals a different peak intensity distribution, as seen for the lipid A-diphosphate-Ca2+ salt. However, the Mg2+ and the Na+ salts of lipid A-diphosphate showed body-centered-cubic (bcc) lattices with a=45.50 nm and a=41.50 nm, respectively (3.2 x 10(-4)< or =phi< or =3.9 x 10(-4)), displaying the same intensity distribution with the exception of the (220) diffraction peaks, which differ in intensity for both salts of lipid A-diphosphate.

Fast perfluorocarbon imaging using 19F U-FLARE.

The application of an ultra-fast low angle RARE technique for the 19F imaging of perfluorocarbons (PFCs) used as temporary blood substitutes is described. This sequence is attractive for fast 19F imaging studies that measure the biodistribution of PFCs in vivo, due to its high signal-to-noise ratio. Extensions of this technique for the chemical shift selective measurement of fluorine T1 values are presented. Using the linear dependence between the oxygen partial pressure (pO2) and the T1 relaxation rate of PFC resonances this technique makes possible the fast in vivo measurement of oxygen tension. Using the sequence in a diffusion sensitized form 19F measurements of the diffusion constants of PFCs are also presented. Phantom experiments to test the methods, and in vivo images obtained in rat studies are given and discussed.

Blood substitutes made on the basis of perfluorocarbons inhibit intracellular energy generation.

Although perfluorocarbons (PFC) are chemically inert, toxic reactions are observed on using them as fluorocarbon emulsions in blood substitutes. Six to twelve hours after exchanging about half of the circulating blood of conscious rats pathobiochemical reactions occur despite a high interarterial oxygen pressure. They indicate the disturbance of intracellular energy generation, which is characterized by a decrease in ATP, increase in ADP, inorganic phosphate and potassium, increase in NADH and lactate. Impurities of perfluorocarbons and effects of the surfactant were excluded to be causes of this disturbance. The following hypotheses were proposed: Storing of perfluorocarbons in the mitochondrial membrane decreases the ATP-forming proton gradient on the membrane and the electron transport in cytochromes is disturbed, respectively.

Phospholipid vesiculated fluorocarbons--promising trend in blood substitutes.

Dispersions of fluorocarbons (PFC's) made with phospholipids have unusual properties, e.g. very high stability, due to the formation of thermodynamically stable vesicles. They can be used for high PFC concentrations as well as e.g. for ESR imaging.

Interaction of beta-carboline with chick embryo spontaneous motility.

The effect of beta-carboline (beta-CCE) on spontaneous motility and its development was studied in chick embryos between the 11th and 19th day of incubation. 1. Acutely administered beta-CCE (7.5 mg/kg e.w.) already induced significant activation of motility in 11-day-old embryos. From the 17th day of incubation activation acquired a paroxysmal character. 2. In spinal embryos (decapitated on the second day of incubation) there was no such activating effect, demonstrating that it is associated with supraspinal components of the CNS. 3. In chronic administration from the fourth day of incubation (1.55 +/- 0.24 mg/kg e.w./24h), beta-CCE led to reduced development of spontaneous motility. The effect was concentrated in the period between the fourth and eighth day of incubation. The chronic administration of beta-CCE augmented the activating effect of metrazol and weakened GABA-inhibition of spontaneous motility. 4. On the basis of their findings, the authors express the hypothesis that the benzodiazepine beta-CCE-sensitive component of the complex GABA receptor evidently already functions from the beginning of the second half of incubation of chick embryos.

[Rheological behavior of blood substitutes with a perfluorocarbon base]. / Untersuchungen zum rheologischen Verhalten von Blutersatzmitteln auf Perfluorcarbonbasis.

Oxygen uptake and desoxygenation in blood take place in the capillary system of the organism so that flow characteristics of blood substitutes should be adapted to that of microcirculation. Therefore, appropriate viscosity of blood substitutes is required. In addition to this, studies on the viscosity of blood substitutes made on the basis of perfluorocarbons are also of interest for considering the deemulsificability during circulation. Viscosity measurements carried out on highly polymerized dextran solutions determining the colloid osmotic pressure in blood substitutes, perfluorocarbon emulsions as oxygen carriers, blood as well as mixtures of these components showed that the rheological behaviour of blood substitutes examined did not lead to organic disorders.

[The standardization of colloid osmotic pressure of blood substitutes with a perfluorocarbon base]. / Untersuchungen zur Einstellung des kolloidosmotischen Druckes von Blutersatzmitteln auf Perfluorcarbonbasis.

Besides a number of other characteristic features the colloidal osmotic pressure of blood substitutes is of importance, since it regulates the physiological balance between the intra- and extravascular fluid content. The colloidal osmotic pressure in blood is determined predominantly by the albumin fraction. The entropy increase on diluting albumin which, can't pass semipermeable vascular walls of the intravascular substances are used in blood substitutes to maintain the colloidal osmotic pressure. Their selection and appropriate are of great importance for the efficiency of blood substitutes.

[The toxicity of surface-active substances for emulsifying perfluorocarbon compounds as components of blood substitute preparations]. / Untersuchungen zur Toxizität oberflächenaktiver Substanzen zur Emulgierung von Perfluorcarbonverbindungen als Bestandteil von Blutersatzmitteln.

Perfluorocarbons are insoluble in water. For being used as oxygen carriers in blood substitutes they therefore have to be emulsified. Using surfactants in the living organism a compromise on the emulsifying effect and toxicity is to be made, since good emulsifiers do also affect biological membranes. The influence of molecule parameters of surfactants on toxicity was studied in this paper.

[The dynamics of bone apposition in different animal species--a comparative study]. / Untersuchungen zur Dynamik der Knochenapposition bei verschiedenen Tierspezies--eine vergleichende Studie.

The time of the bone apposition was compared in rats, rabbits and guinea pigs with the aid of enzyme-activity measurements, determination of the proportion of minerals and the judgment of the cell generation. For this intention a defect was made in the distal femur epiphyses at the three species. The animals were observed for a term of 15 weeks. The results showed little differences with regard to the speed of the bone apposition in the three called species. The bone metabolism of rats was higher than those of the other ones. A clear reference value for the enzyme activity to a define point of time of the mineralization could not be ascertained.

[Efficacy of Pygeum africanum extract in the medical therapy of urination disorders due to benign prostatic hyperplasia: evaluation of objective and subjective parameters. A placebo-controlled double-blind multicenter study]. / Wirksamkeit eines Extraktes aus Pygeum africanum in der medikamentösen Therapie von Miktionsstörungen infolge einer benignen Prostatahyperplasie: Bewertung objektiver und subjektiver Parameter. Eine placebokontrollierte doppelblinde Multizenterstudie.

The efficacy of an extract of Pygeum africanum in the treatment of micturitional disorders due to benign prostatic hyperplasia was tested in a multicentre double-blind trial versus placebo. Capsules containing 50 mg of Pygeum africanum extract or placebo were administered at a dosage of 1 capsule in the morning and 1 capsule in the evening over a period of 60 days. 263 patients were included in this study, which was carried out in 8 centres in Germany, France, and Austria. Evaluation was mainly based on quantitative parameters such as residual urine, uroflowmetry and the precise monitoring of diurnal and nocturnal pollakiuria. Treatment with the Pygeum africanum extract led to a marked clinical improvement: a comparison of the quantitative parameters showed a significant difference between the Pygeum africanum group and the placebo group with respect to therapeutic response. The characteristic subjective symptoms of micturitional disorders, which were evaluated by the patients in a qualitative manner, were also significantly improved by administration of Pygeum africanum extract. Overall assessment at the end of therapy, showed that micturition improved in 66% of the patients treated with Pygeum africanum extract, as compared with an improvement of 31% in the placebo group. The difference was significant at the statistical level of p less than 0.001. During therapy with Pygeum africanum extract, gastrointestinal side effects occurred in 5 patients. Treatment was discontinued in three of those cases.

[Bilateral symmetrical obliteration syndrome of the subclavian-brachial system in the elderly female]. / Bilateral-symmetrisches Obliterationssyndrom des Subklavia-Brachialis-Systems bei der älteren Frau.

The case of an elderly woman is reported, presenting with a bilateral-symmetrical occlusive disease of the subclavian-brachialis-axis in combination with Horton's arteriitis. Early intraarterial thrombolysis may be an appropriate first-line treatment to favourably influence complicated coagulation phenomena.

[The place of nuclear medicine procedures in clarifying the state of gastrointestinal bleeding--radionuclide monitoring]. / Stellenwert nuklearmedizinischer Verfahren in der Abklärung gastrointestinaler Blutungsaktivität--Radionuklid Monitoring.

Radionuclide studies today can specify the actual state of gastrointestinal bleeding. "Radionuclide monitoring" characterises a method that allows a long-term surveillance of the patient for hours or even days (sequential scintigraphy). Labelling of the intravasal space is best met by in vivo/vitro labelling of the red blood cells with 99mTc, "Radionuclide monitoring" may positively influence current concepts of diagnosis or treatment control of patients suffering from gastrointestinal bleeding.

[Schwannomas of the stomach]. / Schwannome des Magens.

One benign and one malignant schwannoma of the stomach are presented. The gross appearance, degree of local invasion and the complications are demonstrated by double-contrast radiology technique and CT. Benign schwannomas can only be distinguished from the malignant ones on the basis of histological and immunohistochemical criteria.

[Abscess of the cervical soft tissues and the mediastinum resulting from an infected jaw cyst]. / Abszess der Halsweichteile und des Mediastinums ausgehend von einer infizierten Kieferzyste.

A woman is described in whom an infected radicular cyst of the mandible resulted in a cervical phlegmon with abscess formation and spreading into the superior mediastinum.

[Automatic blood group determination in the ABO- and Rh-system using conductometry]. / Automatisierte Blutgruppenbestimmung im AB0- und Rh-System mittels Konduktometrie.

A method was developed and tested on the basis of conductometry for determining blood group-specific agglutinates in the AB0 and Rh-system (D). By comparing the measured particle numbers before and after administration of specific antisera or test erythrocytes and objective evaluation can be made whether agglutination has occurred or not. The calculated degrees of agglutination were compared depending on the method, sex, and age of patients. The method can be automated.

[An atypical finding in a bone cyst]. / Atypischer Befund einer Knochenzyste.

Atypical radiologic and scintigraphic findings of a benign bone cyst in a 49-year old male are presented. The cyst is surrounded by a polygonal thick uneven sclerotic rim and shows radionuclide uptake.

[The development of drug utilization with special reference to demographic factors]. / Die Entwicklung des Arzneimittelverbrauchs unter besonderer Berücksichtigung demographischer Faktoren.

Possible influences of demographic changes in the Federal Republic of Germany on future expenditures for medication have been investigated using population models from the Federal Statistical Office and data concerning the structure of current drug expenditures of the health insurance system. In addition the former contribution of demographic changes to the development of drug expenditures has been estimated using retrospective analysis. The study demonstrates that a constant supply with medicines would require an increase of expenses of 0.6% per year until 2,000 AD due to demographic changes, assuming other conditions remain constant. Development since 1957, however, shows that demographic influences are of relatively low importance for the development of total drug expenditures. During the last decade the total growth of costs for medicines was 6 times higher than that which would have been expected due to demographic changes alone. Further comparisons with the growth rate of the gross national product (GNP) demonstrate that since 1975 growth of drug expenditures parallels growth of GNP. The price indices for pharmaceutical products and for cost of living developed in a parallel way during the same period of time.

[Chemoluminescence study of the influence of phagocytosis of peripheral blood leukocytes using a perfluorocarbon-containing blood substitute]. / Chemolumineszenzuntersuchungen zur Beeinflussung der Phagozytose der Leukozyten des periphern Blutes durch perfluorcarbonhaltige Blutersatzmittel.

In an animal experimental model (rats) the influence of which model substances for blood substitution of GDR origin may have on the phagocytosis behaviour of leukocytes of the peripheral blood was investigated by means of luminol-amplified chemoluminescence. After applying the model substance in an amount corresponding to 10% of the circulating blood volume a reversible increase of luminol-amplified chemoluminescence could be observed. The values referred to the portion of neutrophilic granulocytes, however, showed no significant differences compared to the control groups. The opsonizing capacity of the serum towards cymosan revealed a temporary deficit after applying blood substitution substances of GDR origin. The conclusion is drawn that the functions of leukocytes of the peripheral blood recorded by the applied method are not depressed by the model substances used.