Fast electrically assisted regeneration of on-chip SERS substrates.

A microfluidic chip approach utilising integrated electrically connected stationary SERS targets based on inkjet-printed silver nanoparticles is presented. It enables multiple interference-free consecutive surface-enhanced Raman measurements inside chip channels by electrically assisted regeneration of the stationary SERS substrate. Thereby it circumvents common adsorption and memory effect problems associated with stationary SERS targets allowing multiple consecutive measurements in a continuous-flow system.

Prospective, multi-centre, randomised evaluation of the safety and efficacy of five dosing regimens of viscosupplementation with hylan G-F 20 in patients with symptomatic tibio-femoral osteoarthritis: a pilot study.

INTRODUCTION: Viscosupplementation by repeated intra-articular injections of hyaluronic acid (HA) is used widely in the treatment of symptomatic knee osteoarthritis (OA). The number of injections required can limit the availability of treatment and affect patient compliance. The aim of this study was to assess different dosing regimens of hylan G-F 20, a high molecular-weight cross-linked derivative of HA, in the treatment of pain due to knee OA. MATERIALS AND METHODS: Pilot, prospective, multi-centre, open-label, randomised trial in 100 patients with unilateral, symptomatic, tibio-femoral OA (Kellgren-Lawrence grade II or III), aged > or =40 years. Patients were randomised to receive varying dosing regimens of hylan G-F 20 (1 x 6 mL, 1 x 4 mL, 2 x 4 mL 2 weeks apart, 3 x 4 mL 1 week apart, or 3 x 2 mL 1 week apart). Adverse events (AE's) were monitored throughout the study. The primary efficacy endpoint was the change from baseline in the patient-rated knee OA pain assessment (100 mm visual analogue scale (VAS)) at 24 weeks. The secondary efficacy criteria included the WOMAC index, patient and physician global assessments using a 100 mm VAS, and knee OA pain assessment at all other visits. Concomitant use of permitted rescue medications (paracetamol) was also assessed. RESULTS: The treatment was well tolerated overall. Patients in the 3 x 4 mL group reported the highest percentage of device-related local AE's (30%) while patients in the 1 x 6 mL and 3 x 2 mL groups reported only 10%. There were no serious device-related AEs. There was a statistically significant improvement from baseline at week 24 in all efficacy endpoints for all treatment regimens. The 1 x 6 and 3 x 4 and 3 x 2 mL treatment groups showed the greatest mean improvements (-34.9, -32.6 and -36.7 mm respectively) in the patient-rated knee OA pain assessment VAS. CONCLUSION: This study suggests that a single 6 mL injection of hylan G-F 20 may be as efficacious, and as well tolerated, as 3 x 2 mL one week apart. A double-blind, controlled trial is needed to confirm these data.

[Willow bark extract--effects and effectiveness. Status of current knowledge regarding pharmacology, toxicology and clinical aspects]. / Weidenrindenextrakt--Wirkungen und Wirksamkeit. Erkenntnisstand zu Pharmakologie, Toxikologie und Klinik.

New pharmacological and clinical studies show that standardized willow bark extracts (WRE) is not only the natural form of salicylic acid. Willow bark extract has comparable antiinflammatory activities as higher doses of acetylsalicylic acid (ASS), and it shows antinociceptive and antipyretic activities. Under the pharmacologically active doses, no adverse effects regarding the stomach mucosa was observed, in contrast to acetylsalicylic acid. A daily dose of 1572 mg willow bark extract of a proprietary preparation (Assalix; standardised to 15.2% salicin, i.e. 240 mg salicin per day) was significantly superior to placebo in patients with osteoarthritis of the hip and the knee and in patients with exacerbations of chronic low back pain. In 2 open studies against active treatments as controls, willow bark extract exhibited advantages against a routinely prescribed treatment scheme of orthopedic specialists based on nonsteroidal antirheumatic drugs and rather similar efficacy as the COX-2-inhibitor refecoxib. Willow bark extract also displays an activity regarding the thrombocyte function, but the activity is clearly weaker.

Detection of carbonates in dust shells around evolved stars.

Carbonates on large Solar System bodies like Earth and Mars (the latter represented by the meteorite ALH84001) form through the weathering of silicates in a watery (CO3)2- solution. The presence of carbonates in interplanetary dust particles and asteroids (again, represented by meteorites) is not completely understood, but has been attributed to aqueous alteration on a large parent body, which was subsequently shattered into smaller pieces. Despite efforts, the presence of carbonates outside the Solar System has hitherto not been established. Here we report the discovery of the carbonates calcite and dolomite in the dust shells of evolved stars, where the conditions are too primitive for the formation of large parent bodies with liquid water. These carbonates, therefore, are not formed by aqueous alteration, but perhaps through processes on the surfaces of dust or ice grains or gas phase condensation. The presence of carbonates which did not form by aqueous alteration suggests that some of the carbonates found in Solar System bodies no longer provide direct evidence that liquid water was present on large parent bodies early in the history of the Solar System.

[Planning, realization and evaluation of post-marketing surveillance studies. Recommendations of the Society for Phytotherapy]. / Planung, Durchführung und Auswertung von Anwendungsbeobachtungen. Empfehlungen der Gesellschaft für Phytotherapie (GPHY).

Post-marketing-surveillance studies with herbal drugs usually are prospective prescription-epidemiological studies, which should allow statements on quality, efficacy and safety. Until now neither laws nor concrete normative guidelines for the methodology and the evaluation of post-marketing-surveillance studies are existing which could be used for pharmacovigilance. In the present paper guidelines for planning, realisation and evaluation are presented which should allow studies of high quality. The essential components required for the investigational plan are focussed. Also recommendations on the obligatory, optional and special components of the study protocols are made. Additionally statistical methods which allow the evaluation of the therapeutic efficacy are presented.

[Foreigners in Germany: ethnic diversity and regional patterns]. / Auslander in Deutschland: ethnische Vielfalt und regionale Schwerpunkte.

PIP: "This contribution gives an overview of the development of ethnic minorities and foreign population-groups in Germany within a regional perspective. Following a discussion of the complex terminology used to describe residential groups of foreigners, immigrants, and ethnic minorities, the recent history of immigration to West and East Germany is outlined. As a consequence of the succession of different ¿waves' of migrants, the ethnic diversity has strikingly risen during the last decades. Whereas guest-workers from most Mediterranean countries of Europe decreased, a strong increase is typical of refugees (former Yugoslavia) and asylum applicants (selected Third World countries), of migrants from Eastern Europe as well as of highly-skilled migrants from industrialized countries. For some of these groups, the spatial patterns are compared in the final part of the paper." (EXCERPT)^ieng

Analysis of the components of Lycopus europaeus L. in body fluids during metabolism studies. Comparison of capillary electrophoresis and high-performance liquid chromatography.

During pharmacokinetic studies with extracts obtained from medicinally used plants, analysis in body fluids is mainly performed by HPLC, an established separation method. In this paper high-performance capillary electrophoresis (HPCE) is investigated for its ability to separate such complex extracts. Crude extracts of Lycopus europaeus L. (Lamiaceae) are traditionally used against mild forms of hyperthyroidism. The metabolism of a 70% ethanolic extract with respect to some of its individual main components (rosmarinic and caffeic acid, luteolin-7-glucoside) and a mixture of the pure compounds were investigated using isolated perfused rat liver. After solid-phase extraction metabolites were determined using HPCE and HPLC separation techniques. A buffer solution composed of 0.05 mol l-1 Na2HPO4 at pH 7.0 with 30% acetonitrile was found to be the most suitable electrolyte for HPCE separation. The best mobile phase for isocratic HPLC was 0.03% TFA-acetonitrile (82:18, v/v). Data obtained with HPCE are in good accordance with those from HPLC; HPCE, however, is clearly more rapid and simple to perform.

The effect of Chelidonium majus herb extract on choleresis in the isolated perfused rat liver.

The total ethanolic extract, the phenolic and the alkaloidal fraction of the herb of Chelidonium majus L. (Papaveraceae) were tested for their choleretic activity using the isolated perfused rat liver. The total extract significantly caused chloresis by increasing the bile acid independent flow (BAIF); the observed weak activity of both fractions, tested each and as combination, however, was not significant.

Endocrine effects of Lycopus europaeus L. following oral application.

Lycopus extracts are used in folk medicine for the treatment of hyperthyroid symptoms. Diverse effects on the pituitary thyroidal system as well as on the pituitary gonadal system could be confirmed in experimental studies. But till now endocrine effects of Lycopus extracts in experimental animals were observed after parenteral application only. Therefore in this investigation an ethanolic extract of Lycopus europaeus was applied orally to rats, diverse endocrine parameters were measured between 3 and 24 h later and the effects compared to an i.p. treated group. The plant extract given p.o. caused a long lasting (for a period of more than 24 h) decrease of T3 levels, presumably as a consequence of a reduced peripheral T4 deiodination. A pronounced reduction of T4 and thyroid stimulating hormone (TSH) concentrations was observed 24 h after application of the test solution by gavage. The luteinizing hormone (LH) decrease as well as the TSH decrease, which was pronounced in spite of reduced T4 and T3 levels indicate a central point of attack of the plant extract. Differences in the biological activity in dependence on the route of application may be explained e.g. by differences in absorption of plant constituents.

Human organ specimen banking--15 years of experience.

As a reaction to the lack of information concerning ranges of a 'normal xenobiotic burden' within the population and also the aquatic, terrestrial and atmospheric environments, the sampling and storage of environmental materials in Germany in 1974 as a possible tool for environmental observation and early recognizing of hazards was proposed. During subsequent years the collection of human specimens was undertaken in Münster. In a pilot phase (1978-1983) conditions of optimized storage were investigated, including reliable storage temperature and container materials. Since 1985 the Environmental Specimen Bank for Human Tissue in Münster has been institutionalized under the auspices of the Federal Ministry of Environment, Nature Protection and Nuclear Safety as well as the Federal Environmental Agency in Berlin. Up to 1991 about 300,000 samples had been collected and stored at -85 degrees C in a walk-in deep-freezer of 34 m3 comprising autopsy material as well as 'available' organs form living persons (e.g. blood, urine, hair, human milk, saliva, seminal plasma, sweat). Having fulfilled the tasks within the scope of environmental banking the Münster institution has proved to be an adequate scientific tool. It has been integrated into the logistic system of the Environmental Specimen Bank in Germany having the following main tasks (a) the development of Standard Operation Procedures (SOP) for sampling and sample handling, (b) evaluation of reliable analytical methods for inorganic and organic sample characterization, (c) collection of a sufficient data pool for reference ranges of xenobiotics, which are essential for environmental risk assessment, and (d) the evaluation of the efficacy of legislative xenobiotic restrictions: this could be proved for lead and some organochlorine pesticides.

Environmental specimen banking and poisons control--a new challenge.

Today clinical toxicology and poisons control are widely lacking objective criteria, e.g., analytical data, figures of kinetics and metabolism in acute and chronic poisoning. Co-operation between clinical toxicology and an environmental specimen bank for human tissue will help to overcome many difficulties and complement one another. The possible power of such a co-operation is demonstrated by the example of the institutions in Münster, Germany. The successful strategies used for setting-up an environmental specimen bank for human tissue may also be applied in clinical toxicology and experimental toxicology. The frame of a university medical clinic seems to be the ideal basis of an effective co-operation of an Environmental Specimen Bank for Human Tissue, a Poisons Control Centre and clinical toxicology. In general a co-operation of an environmental specimen bank for human tissue and a poisons control centre will be cost-saving and beneficial to both and an environmental specimen bank for human tissue will gain the status of a unique tool for risk assessment of xenobiotics.

Influence of 3,5-dimethyl-3'-isopropyl-L-thyronine on thyroid state and gestational outcome in the Wistar rat.

3,5-Dimethyl-3'-isopropyl-L-thyronine (DIMIT, CAS 26384-44-1), a non-halogenated, artificial analogue of the thyroid hormone T3, was administered once daily by intragastric gavage to pregnant Wistar rats on days 17-20 of gestation to elucidate the effects of DIMIT on maternal and foetal thyroid state and gestational outcome under the influence of low iodine or iodine excess nutrition. Doses of 20 micrograms.kg-1.d-1 and 150 micrograms.kg-1.d-1 DIMIT were applied. Throughout pregnancy the animals were kept on low iodine diet and either on iodine free drinking water or iodine excess. There was no statistically significant effect on maternal body weight, weight of living foetus, the rate of intra-uterine death before day 16 of gestation, water and food consumption, and no hint of maternal thyrotoxicosis. The vital off-spring did not reveal any signs of gross malformation. DIMIT decreased serum TSH both in dams and foetus, and diminished the TSH stock of the pituitary gland of the dams. T3-levels were also lowered in maternal serum by DIMIT. These DIMIT induced effects were observed irrespective of iodine deficiency or excess. There was no difference in foetal mortality before onset of DIMIT-treatment, but the gestational death rate increased in a dose-related manner by the administration of DIMIT. This serious adverse effect became apparent at a DIMIT-dose that is not sufficient for a complete compensation of foetal hypothyroidism in utero. The higher prenatal mortality was accompanied by a decreased placental weight, but not by a reduced body weight of surviving foetus.

The NSAID sulindac reverses rectal adenomas in colectomized patients with familial adenomatous polyposis: clinical results of a dose-finding study on rectal sulindac administration.

After colectomy with ileorectal anastomosis (IRA) for treatment of familial adenomatous polyposis (FAP), the rectal mucosa remains, with the risk of malignant change. Locoregional (rectal) sulindac has been applied, with initial higher-dose therapy and subsequent low-dose maintenance therapy to minimise side-effects. The dose-finding study with sulindac suppositories started with a dose of 300 mg sulindac daily per patient over 6 weeks. Depending on proctoscopical evaluation of regression of polyposis, sulindac doses were reduced in predefined steps. Ten of 15 patients developed a complete remission following 42 weeks of treatment, while the rest had partial remission. Responses were recorded 6-24 weeks after beginning sulindac treatment. After 36 weeks, 13/15 patients received 25-50 mg sulindac daily. An increase in the number of partial remissions after 42 weeks of treatment at doses of 100 mg sulindac daily may indicate the first approach to a reduced dose between 100 mg to 25 mg sulindac daily, but may also point to the importance of long-term treatment rather than dose-intense therapy.

Shearing of the plastic coating of a hydrophilic guide wire in a right femoropopliteal bypass graft: removal from the contralateral side.

The plastic coating of a hydrophilic guide wire tore off during introduction through a beveled single wall arterial entry needle in a 75 year old male. The sheared piece of coating got stuck in his femoropopliteal bypass. It was removed by means of a modified arterial filter set from the contralateral side. The technique of its removal is described.

Embryotoxicity study of propenoic acid, 3-(4-methoxyphenyl)-3-methylbutylester in the Wistar rat.

3-(4-methoxyphenyl)-3-methylbutylester, propenoic acid (MPMBE; CAS no. 71617-10-2), a UVB-light filter used for sun protection of the skin, was administered once daily by intragastric gavage to pregnant Wistar rats on days 6-15 of gestation. Doses of 0.25 ml/kg/day (study group: D0.25), 0.75 ml/kg/day (D0.75) and 2.25 ml MPMBE/kg/day (D2.25) were applied. A positive control group (Pos) received 15 mg (all trans) retinoic acid/kg/day. MPMBE revealed some toxic effects in the dams of the group receiving the highest dose (D2.25): marked loss of body weight, polydipsia, reduced food consumption and intensified loss and thinning of hair. Only thinning or partial loss of hair without any other harmful effects was seen in the dams of group D0.75. An increase in embryonic deaths was striking in group D2.25; the living foetuses revealed signs of retarded development, but no major external or internal anomalies as signs of teratogenicity. This study was not able to present any teratogenic effects induced by MPMBE in the offspring, even at very high oral doses (> 2 g/kg/day) that caused substantial toxicity in the dams. In conclusion, concerning embryotoxicity an oral dose of 250 mg/kg/day MPMBE is regarded as a safe no-observed-effect level, whereas even 750 mg/kg/day MPMBE--following acknowledged rules--can be judged as a borderline no-observed-adverse-effect level.

Metabolism of garlic constituents in the isolated perfused rat liver.

The metabolic and kinetic behaviour of different garlic (Allium sativum L., Alliaceae) constituents were investigated in the isolated perfused rat liver, using aqueous extracts of garlic powder as well as isolated allicin, the main product of the enzymatic degradation of alliin. Allicin (allyl thiosulfinate) showed a remarkable first pass effect and passed the liver unmetabolized only at high concentrations which caused considerable cell injuries. Diallyl disulfide and allyl mercaptan were identified as metabolites of allicin, whereby diallyl disulfide probably is the metabolic precursor of allyl mercaptan as shown by perfusion with diallyl disulfide alone. The metabolites diallyl disulfide and allyl mercaptan could be determined in the perfusion medium as well as in the bile and the liver tissue. Other degradation products of garlic were also investigated in this model. Ajoenes and vinyldithiins were detected in perfusion medium after liver passage but no metabolites of them could be identified up to now.

Recurrence of stenoses following balloon angioplasty and Simpson atherectomy of the femoro-popliteal segment. A randomised comparative 1-year follow-up study using colour flow duplex.

The results of balloon angioplasty (BA) and atherectomy (AT) with the Simpson atherocath, were compared in a randomised prospective study. Thirty-one patients were randomised to one of these methods for the treatment of symptomatic stenotic or occlusive lesions in the superficial femoral and popliteal arteries. One patient died after randomisation but before the procedure, thus 30 patients were available for analysis. All patients had intermittent claudication and BA was used in 14 and AT in 16 limbs. A surveillance protocol included colour flow duplex scanning of the femoro-popliteal arteries after 6 weeks and then at 3-monthly intervals during the 1st year and every 6 months thereafter. The average duration of follow-up was 9.7 months. For confirmation intra-arterial digital subtraction angiography (DSA) was performed in all patients at 1 year following the intervention, when clinical symptoms occurred or when colour flow duplex indicated greater than 49% restenosis. Three small dissections were the only postoperative complications and residual stenoses greater than 20% diameter reduction (DR) were observed in two patients following BA and in two after AT. Improvement of clinical category according to the "Standards for evaluating results of interventional therapy for peripheral vascular disease" occurred in 13 of 14 BA patients and in 15 of 16 AT patients. Follow-up results were expressed as cumulative patency and clinical success. Endpoints for patency were recurrence of the stenosis at the treated segment or new lesions in different segments and endpoints for clinical success were a drop in clinical category (symptoms, ankle pressure indices and post-exercise ankle pressures). One-year patency (no restenosis greater than 49% DR) was 77% in patients with BA and 25% in patients with AT (p = 0.017).(ABSTRACT TRUNCATED AT 250 WORDS)

[Causes, progress, and consequences of migration in West Germany. On the state of research on migration]. / Ursachen, Ablaufe und Folgen von Wanderungen in Westdeutschland. Zum Stand der Migrationsforschung.

PIP: Literature on migration in West Germany is reviewed. The author examines migration in general, the extent of mobility, interregional migration, and the human capital approach to the study of migration. Rural areas that attract in-migrants are identified, as are densely populated regions. Some attention is also paid to international flows and to research concepts and methods.^ieng