Ultrafast spectroscopy of RuII polypyridine complexes in the gas phase and the liquid phase: [Ru(2,2'-bipyridine)2(nicotinamide)2]2.

[Ru(bipyridine)2(nicotinamide)2]2+ (1) and its monoaqua-complex [Ru(bipyridine)2(nicotinamide)(H2O)]2+ (2) were spectroscopically studied for the first time in the gas phase by static and time resolved UV photodissociation spectroscopy, observing nicotinamide and H2O ligand dissociation for 1 and 2, respectively. Both processes and their ultrafast dynamics were investigated in parallel by transient absorption spectroscopy in aqueous solution. The latter data were newly acquired for the long-wavelength MLCT band excitation of 1 and provide novel ultrafast ligand dissociation results for 2, confirming the gas phase results, i.e., exclusive H2O cleavage over nicotinamide loss. Similar apparent time constants in the sub-ps and few ps ranges were obtained for 1 in both phases, whereas a larger time constant of ca. two hundreds of ps for the ground state recovery was observed exclusively in the solution phase. Our reaction scheme accounts for faster dissociation dynamics in the gas phase by energetical lowering of the 3MC vs. the 3MLCT states by lack of solvent stabilization of the latter. Based on the apparent time constants, we favour, for the solution dynamics, a fast bimodal vibrational deactivation in the 3MLCT/3MC manifolds and a slow dissociation obfuscated by the ground state recovery. This is substantiated by a similar reaction scheme proposed for the ultrafast dynamics of 2, resulting in a new assignment for transient absorption features with λ > 550 nm to the 3MC manifold, and a common kinetic description for 1 and 2. Computations at the TD-DFT/cc-PVTZ/MDF28 level support our spectroscopic findings and the suggested deactivation pathways.

Ultrafast excited-state relaxation of a binuclear Ag(i) phosphine complex in gas phase and solution.

The binuclear complex [Ag2(dcpm)2](PF6)2 (dcpm = bis(dicyclohexylphosphino)methane) exhibits a structure with a close silver-silver contact mediated by the bridging ligand and thus a weak argentophilic interaction. Upon electronic excitation this cooperative effect is strongly increased and determines the optical and luminescence properties of the compound. We have studied here the ultrafast electronic dynamics in parallel in gas phase by transient photodissociation and in solution by transient absorption. In particular, we report the diverse photofragmentation pathways of isolated [Ag2(dcpm)2]2+ in an ion trap and its gas phase UV photodissociation spectrum. By pump-probe fragmentation action spectroscopy (λex = 260 nm) in the gas phase, we have obtained fragment-specific transients which exhibit a common ultrafast multiexponential decay. This is fitted to four time constants (0.6/5.8/100/>1000 ps), highlighting complex intrinsic photophysical processes. Remarkably, multiexponential dynamics (0.9/8.5/73/604 ps) are as well found for the relaxation dynamics in acetonitrile solution. Ab initio calculations at the level of approximate coupled-cluster singles-doubles (CC2) theory of ground and electronically excited states of the reduced model system [Ag2(dmpm)2]2+ (dmpm = bis(dimethylphosphino)methane) indicate a shortening of the Ag-Ag distance upon excitation by 0.3-0.4 Å. In C2 geometry two close-lying singlet states S1 (1MC(dσ*-pπ), 1B, 4.13 eV) and S2 (1MC(dσ*-pσ), 1A, 4.45 eV) are found. The nearly dark S1 state has not been reported so far. The excitation of the S2 state carries a large oscillator strength for the calculated vertical transition (266 nm). Two related triplets are calculated at T1 (3.87 eV) and T2 (3.90 eV). From these findings we suggest possible relaxation pathways with the two short time constants ascribed to ISC/IVR and propose from the obtained similar values in gas phase that the fast solution dynamics is dominated by intramolecular processes. A further relaxation by IC/IVR in the triplet manifold is likely to account for the observed intermediate time constants. For the acetonitrile relaxation dynamics additional modifications are invoked based on solvent-induced shifts of the energy levels and the possible formation of solvent and counterion exciplexes on a longer timescale.

[Partial response of solar urticaria to omalizumab therapy]. / Partielles Ansprechen einer Lichturtikaria auf Omalizumab.

The treatment of solar urticaria is regarded as difficult. In some cases good responses to the anti-IgE antibody omalizumab (Xolair®), approved for treatment of chronic spontaneous urticaria, have been reported. We report on a 50-year-old Caucasian woman who for the last 5 years has developed localized itching and stinging erythemas following exposure to sunlight accompanied sometimes by anaphylactic reactions. Oral antihistamines in three- to four-fold doses and a topical sun screen had been only partially effective in long-term use. Positive immediate-type reactions with whealing appeared in phototesting with low doses of UVB and UVA. Three weeks after s. c. injection of 300 mg omalizumab, the minimal urticarial dose (MUD) for UVB was increased at least 20-fold (from <0.001 to 0.02 J/cm2) and for UVA four-fold (from 0.1 to 0.4 J/cm2) and the patient reported no itching at the test area. On the other hand, MUD for UVA1 remained unchanged (5.0 J/cm2). The weekly urticarial activity score (UAS7) was reduced from 30 points before omalizumab administration to 14 points in weeks two and three. Overall, a partial response of solar urticaria to omalizumab therapy could be observed in the present case.

Generation of a zinc and rhodium containing metallomacrocycle by rearrangement of a six-coordinate precursor complex.

Two pentadentate N3,P2 ligands coordinate zinc(ii) by their N3 pocket. Four free phosphine donors allow the coordination of four AuCl moieties leading to a pentanuclear ZnAu4 complex. In contrast, the attempt to use the phosphines for chelating coordination of two Rh(CO)Cl units results in a well-organized rearrangement that ends up with the formation of a metallomacrocycle in high yields.

[Development, situation and perspective of self-help support in Germany]. / Entwicklung, Situation und Perspektiven der Selbsthilfeunterstützung in Deutschland.

Self-help groups and self-help associations are an important part of the social security system. In Germany, self-help contact points, senior citizen centers, volunteer agencies, citizen centers and multi-generation houses combine citizen participation with innovative professional services. Unfortunately, there is no guarantee of continuous financial support for these important, locally administered institutions. There are about 280 self-help contact points and more than 400 federal self-help associations that support and promote self-help in Germany. Healthy communities, healthy workplaces and healthy people need a decentralized system of self-help programs operated at local and regional levels, in districts and towns. Thereby, professional support systems that operate self-help programs and promote citizen participation in the self-help programs must be managed in a similar regional format. New forms of cooperation from the regional and local governments, private companies, and citizen engagement already exist. Additionally, regional projects of integrated maintenance systems with the regional health maintenance institutions have been established. Currently, the central challenges of the self-help programs are quality development, inclusion of people with social disadvantages and of people with migrational background. The essential prerequisites for this work are continuous financial support and a politically supported infrastructure, which is in fact an important health investment.

Nonradiative deexcitation dynamics of 9H-adenine: an OM2 surface hopping study.

The nonradiative relaxation of 9H-adenine was studied at the semiempirical OM2/MR-CI level using the surface-hopping approach. Geometry optimizations of energy minima and conical intersections as well as single-point calculations of excitation energies at critical points were performed to characterize the relevant potential energy surfaces of 9H-adenine and to assess the accuracy of the OM2 results. Surface-hopping calculations were performed to describe the nonradiative dynamics of 9H-adenine after vertical excitation into the optically active state. They showed that the deexcitation process is mainly governed by a two-step relaxation consisting of an ultrashort component and a longer component. These findings compare well with experimental results from time-resolved photoelectron spectroscopy.

Playing with Pearson's concept: orthogonally functionalized 1,4-diaza-1,3-butadienes leading to heterobinuclear complexes.

By reacting 1,2-diketones and ortho- diphenylphosphinoyl aniline in the presence of zinc(ii) as a templating agent, cationic zinc(ii) complexes of novel phosphine oxide functionalized 1,4-diaza-1,3-butadiene ligands are acessible. Herein the zinc(ii) site is bound to all four donor atoms of the ligand. Depending on the flexibility of the 1,4-diaza-1,3-butadiene backbone, the bonds to zinc(ii) from the 1,4-diaza-1,3-butadiene donors can be broken. Reaction with oxalate cleaves the zinc(ii) coordination completely and makes accessible the free ligands possessing orthogonal (N,N: soft; O,O: hard) sets of donor sites. This allows for the specific coordination of soft and hard Lewis acids and thus for the generation of heterobimetallic complexes, here exemplarily shown for the combination of palladium(ii) (soft) and zinc(ii) (hard) centres.

A direct access to heterobimetallic complexes by roll-over cyclometallation.

Complexes of the type [Cp*Ir(N,N')Cl]+ (N,N' = 2-(2-dialkylaminopyrimidin-4-yl)pyrimidine) can undergo roll-over cyclometallation leading to a novel N,N'-donor site. Following this strategy heterobimetallic complexes including iridium(iii) and a Group X metal centre in the oxidation state +II were achieved.

Calculating absorption shifts for retinal proteins: computational challenges.

Rhodopsins can modulate the optical properties of their chromophores over a wide range of wavelengths. The mechanism for this spectral tuning is based on the response of the retinal chromophore to external stress and the interaction with the charged, polar, and polarizable amino acids of the protein environment and is connected to its large change in dipole moment upon excitation, its large electronic polarizability, and its structural flexibility. In this work, we investigate the accuracy of computational approaches for modeling changes in absorption energies with respect to changes in geometry and applied external electric fields. We illustrate the high sensitivity of absorption energies on the ground-state structure of retinal, which varies significantly with the computational method used for geometry optimization. The response to external fields, in particular to point charges which model the protein environment in combined quantum mechanical/molecular mechanical (QM/MM) applications, is a crucial feature, which is not properly represented by previously used methods, such as time-dependent density functional theory (TDDFT), complete active space self-consistent field (CASSCF), and Hartree-Fock (HF) or semiempirical configuration interaction singles (CIS). This is discussed in detail for bacteriorhodopsin (bR), a protein which blue-shifts retinal gas-phase excitation energy by about 0.5 eV. As a result of this study, we propose a procedure which combines structure optimization or molecular dynamics simulation using DFT methods with a semiempirical or ab initio multireference configuration interaction treatment of the excitation energies. Using a conventional QM/MM point charge representation of the protein environment, we obtain an absorption energy for bR of 2.34 eV. This result is already close to the experimental value of 2.18 eV, even without considering the effects of protein polarization, differential dispersion, and conformational sampling.

Quantitative assessment of soluble fibrin in plasma by affinity chromatography--a comparative study with desAA-fibrin, desAABB-fibrin and fibrinogen.

A quantitative determination of soluble fibrin in plasma was carried out by affinity chromatography. For this purpose, desAA-fibrin and fibrinogen immobilized on Sepharose 4B were used at the stationary side whereas batroxobin-induced 125I-desAA-fibrin or thrombin-induced 125I-desAABB-fibrin mixed with plasma containing 131I-fibrinogen represented the fluid phase. The binding characteristics of these mixtures to the immobilized proteins were compared at 20 degrees C and 37 degrees C. Complete binding of both types of fibrin to the immobilized desAA-fibrin was always seen at 20 degrees C as well as at 37 degrees C. However, binding of soluble fibrin was accompanied by substantial binding of fibrinogen that was more pronounced at 20 degrees C. Striking differences depending on the temperature at which the affinity chromatography was carried out, were documented for the fibrinogen-fibrin interaction. At 20 degrees C more than 90% of the applied desAA-fibrin was bound to the immobilized fibrinogen whereas at 37 degrees C only a mean of 17% were retained at the fibrinogen-Sepharose column. An opposite finding with regard to the tested temperature was made with the desAABB-fibrin. Nearly complete binding to insolubilized fibrinogen was found at 37 degrees C (95%) but only 58% of the desAABB-fibrin were bound at 20 degrees C. The binding patterns did not change when the experiments were performed in the presence of calcium ions. The opposite behaviour of the two types of soluble fibrin to immobilized fibrinogen at the different temperatures, together with the substantial binding of fibrinogen in the presence of soluble fibrin to insolubilized fibrin in every setting tested, devaluates affinity chromatography as a tool in the quantitative assessment of soluble fibrin in patient's plasma.

Crosslinking of fibrinogen to immobilized DesAA-fibrin.

DesAA-fibrin Sepharose was produced by treating fibrinogen-Sepharose with batroxobin. DesAA-fibrin Sepharose was mixed with different concentrations of fibrinogen and at different ratios, and incubated with preactivated FXIII. After 2 hours at 37 degrees C, the Sepharose beads were separated by centrifugation and non-crosslinked fibrinogen was removed by twice times washing with guanidinium chloride, pH 4.1. Under these experimental conditions specific crosslinking of fibrinogen to immobilized desAA-fibrin by FXIIIa was found. These results support the concept of a specific interaction between fibrinogen and fibrin involving polymerization which enables FXIIIa to crosslink fibrin to fibrinogen being in an half-staggered overlap position but not in DD-long contact.

Fibrillation power, an alternative method of ECG spectral analysis for prediction of countershock success in a porcine model of ventricular fibrillation.

BACKGROUND: Noninvasive prediction of defibrillation success after cardiac arrest and cardiopulmonary resuscitation (CPR) may help in determining the optimal time for a countershock, and thus increase the chance for survival. METHODS: In a porcine model (n=25) of prolonged cardiac arrest, advanced cardiac life support was provided by administration of two or three doses of either vasopressin or epinephrine after 3 or 8 min of basic life support. After 4 min of ventricular fibrillation and 18 min of life support, defibrillation was attempted. The denoised power spectral density of 10 s intervals of the ventricular fibrillation electrocardiogram (ECG) was estimated from averaged and smoothed Fourier transforms. We have eliminated the spectral contribution of artifacts from manual chest compressions and provide a definition for the contribution of ventricular fibrillation to the power spectral density. This contribution is quantified and termed "fibrillation power". RESULTS: We tested fibrillation power and two established methods in their discrimination of survivors (n=16) vs. non-survivors (n=9) in the last minute before the countershock. A fibrillation power > or =79 dB predicted successful defibrillation with sensitivity, specificity, positive predictive value and negative predictive value of 98%, 98%, 99% and 97% while a mean fibrillation frequency > or =7.7 Hz was predictive with 85%, 83%, 90% and 77% and a mean amplitude > or =0.49 mV was predictive with 95%, 90%, 94% and 91%. CONCLUSIONS: We suggest that fibrillation power is an alternative source of information on the status of a fibrillating heart and that it may match the established mean frequency and amplitude analysis of ECG in predicting successful countershock during CPR.

Fluidized bed film coating of an ordered powder mixture to produce microencapsulated order units.

Very finely divided particulate salicylic acid (2-5 micrometers) was microencapsulated using conventional fluidized bed coating techniques. The process involved spray coating a preformed ordered mixture, in which the micronized particles are adsorbed on the surface of a coarser carrier material. The mixtures contained 0.1, 1.0 and 5.0% weight of microfine model drug (salicylic acid). Between 75 and 95% of the micronized particles were retained on the carrier surface beneath the film. This process offers a novel method of microencapsulating very fine particulate materials, which may find an application in the production of enteric coated and sustained release microdose products. A recent publication on electrostatic charge interactions in ordered mixtures reported that the addition of a third component can affect the stability of a binary ordered mixture. Addition of 2% talc increased the stability of some mixtures during coating and resulted in the microencapsulation of a significantly greater amount of micronized model drug. A 0.1% salicylic acid binary ordered mixture retained 74% of model drug beneath the film, the 0.1% ternary mixture (2% talc) gave a mean retention of 99%.

Fluidized bed film coating of an interactive powder mixture to produce microencapsulated 2-5 microns particles.

Previous work has shown an interactive (ordered) powder mixture, formed from 2-5 microns salicylic acid and a coarse spray-dried sugar, is stable when fluidized. The micronized material adheres to the carrier during fluid bed air suspension and may be film coated with a polymer. This process offers a novel method of microencapsulating very fine particulates, providing a way of manufacturing enteric-coated and sustained release microdose drug delivery systems. Different processing conditions were used in an attempt to optimize the retention of micronized model drug beneath the film. The effect of altering the following variables was investigated; polymer spray rate, addition of a third component which adhered to the binary adhesion units, and different materials of construction for the mixer used to form the interactive mixture. The microencapsulated adhesion units retained 90-95% of the micronized model drug. A statistical evaluation of the content uniformity showed that a very uniform dispersion was formed (CV less than 5%, 99% confidence). Multilayer film-coated adhesion units were also produced using a sequence of mixing and coating operations. This process offers a method of film coating microdose quantities of a drug, to produce a free flowing product, possessing excellent content uniformity.

Fluidized bed granulation of an ordered powder mixture.

The phenomenon of ordered unit segregation is of paramount importance in determining the homogeneity of an ordered mixture. This problem can be avoided by using a monodisperse carrier, but it is uneconomic. The fluidized bed granulation of a 0.1% ordered mixture has been studied as a method of reducing the effects of segregation. The ordered units were stable when fluidized and no significant loss of the microfine adsorbed material occurred during processing. The distribution of the minor component in the granules was significantly more uniform than in the original ordered mixtures. The demixing potential (formula: see text) (where p = proportion of cohesive minor component and w is the weight % of carrier material in a particular size range) was used to quantify the distribution of the minor component as a function of particle size. DP is a coefficient of variation and can be directly compared with the specification standard deviation sigma A. Batches of granules were compressed into 100 or 350 mg tablets, containing approximately 100 and 350 micrograms of model drug substance. The weight and content coefficients of variation (c.v.) were determined for 20 tablets. All batches had a weight c.v. less than or equal to 1.5% and a content c.v. less than or equal to 4.6%. Granulation of an ordered mixture greatly reduces the potential for segregation to decrease the mixture homogeneity. It also provides a solution to the problems which may be encountered when the mixing of small quantities of cohesive materials during conventional fluidized bed granulation is attempted.

Content uniformity of microdose tablets (dosage 1 microgram--10 mg) produced by fluid bed granulation of interactive mixtures.

Tablets (100 mg), containing microdose quantities of micronized model drug (1 microgram--10 mg), were produced from interactive powder mixtures which had been fluid bed granulated. Granulation prevents adhesion unit and constituent segregation occurring during compression. Single tablet assays were performed on 100 tablets from each batch. The content of tablets fell within +/- 15% of the mean, and the coefficient of variation was less than 5% (99% confidence) for all batches. Skewness in the content distribution showed little evidence of superpotent tablets and indicated the absence of significant agglomerates of particles of the micronized component. However, there was some indication that the mixtures produced were not totally agglomerate free. These results demonstrate that the true potential of interactive mixing may be realized, provided segregation in the mixture can be eliminated. The distribution of micronized model drug, as a function of carrier particle size, was determined for the different concentration mixtures before and after granulation. When 0.1-2% interactive mixtures were sieved gently, the proportions of micronized material adhering to the different size fractions of carrier were similar. However, the very low concentration mixtures (0.001-0.03%) proved to be relatively unstable, a significant proportion of the micronized component being transferred from the mixtures to the metal surfaces of the sieves. Granulation of the mixtures in a fluidized bed produced a uniform distribution of micronized material throughout the different sized granules. These granules were stable during vibration on the sieves and when compressed. All samples of tablets met the United States Pharmacopeia XXI content uniformity requirements.

Particulate contamination of Australian ampoules.

Theoretical predictions and computer simulations indicate that it may be impossible to achieve values of the coefficient of variation usually found in large volume parenterals (LVP) when the intrinsic particulate contamination in small volume parenterals (SVP) is investigated. Snap-opened ampoules from Australian manufacturers containing 5, 10 or 20 ml Water for Injections or Sodium Chloride Injection had a high level of particulate contamination, although within the USP XXI SVP limits. Heat-opened ampoules had much lower levels of contamination which were generally below the official LVP limits. Counts ml-1 were typically less than 10 and less than 1 for 5 and 20 micron particles, respectively. Coefficients of variation of the 5 micron data from an ampoule in any batch examined, typically ranged over 30-70%. Statistical analysis of the 5 micron data indicates significant differences between batches. Occasional ampoules had higher 5 micron counts than others in the same batch. At no time were the particulate contamination levels considered to be clinically important.

[The preservation of the whole corpse with natural color]. / Die Konservierung ganzer Leichen in natürlichen Farben.

An especially low-odor embalming technique was developed over a 30-years-period using a total of 977 complete cadavers, numerous cadavers after autopsy, and in vitro series of fresh beef. The color, consistency, and transparency of the tissue were very well preserved. The technique met high standards of preservation without releasing harmful substances into the environment. Concentrations of formaldehyde in room air remained under the limit of detection by Dräger capillaries. The efficacy for disinfection of the method was confirmed by bacteriologic tests. None of the cadavers or samples developed molds.

[An arterial substance for subsequent injection during the preservation of the whole corpse]. / Eine Arterienmasse zur Nachinjektion bei der Konservierung ganzer Leichen.

Masses for arterial injection were evaluated in 360 whole cadavers that had been injected with preservation fluid. A mass consisting of dextrin, latex, and lead tetroxide produced the best results. This mass provided high radiopacity at large distances from the injection site and ideal firmness for dissection. The easy application of the mass makes it suitable for research purposes as well as for teaching dissections.

[Resistance of blood culture isolates in vitro to 4 aminoglycoside antibiotics in Austria--1982/83]. / Resistenz von Blutkulturisolaten in vitro gegenüber 4 Aminoglykosidantibiotika in Osterreich--1982/83.

Over the period September 1982 to February 1983 268 blood culture isolates were consecutively collected in 4 microbiological laboratories in Austria (Linz, Vienna, Graz, Feldkirch) and 251 of these strains (streptococci excluded) were tested for resistance to Gentamicin (G), Tobramycin (T), Netilmicin (N) and Amikacin (A) using a microtitre broth dilution method. This investigation was part of an international study. Of the bacterial strains examined 57% were staphylococci (34% Staphylococcus aureus) and 43% gram-negative rods (18% E. coli, 17% other enterobacteriaceae and 5% Pseudomonas aeruginosa etc.). 25% of all strains tested were resistant to Gentamicin (MIC greater than 4 mg/l), 27% to Tobramycin (MIC greater than 4 mg/l), 6% to Netilmicin (MIC greater than 4 mg/ml) and 5% to Amikacin (MIC greater than 8 mg/l). The resistance rate of staphylococci was markedly greater towards Gentamicin (35%) and Tobramycin (39%) than Netilmicin (4%) and Amikacin (6%). The respective percentages of resistant gram-negative rods were considerably smaller, except in the case of Netilmicin (G 13%, T 11%, N 8%, A 4%). Regional differences were observed between Linz and Vienna in the resistance of staphylococci to Gentamicin (24% versus 49%) and Tobramycin (33% versus 53%). On a weight basis Netilmicin was the most active substance in combating nearly all groups of bacteria. Also in strains sensitive to the other aminoglycosides the MIC values of Netilmicin were considerably lower than for the other substances. A noteworthy feature in comparison with the results of other countries participating in this international study was the distinctly higher incidence of staphylococci among the blood culture isolates and the considerably higher percentage of aminoglycoside-resistant strains in Austria. Analysis of the data suggests that the high resistance rates among staphylococci are a consequence of selection by frequently used antibiotics. Hence, it appears essential to observe the development of aminoglycoside resistance in Austria closely and to recommend that these substances, of extreme value in the treatment of severe infections, should be used solely for the most stringent indications.