Electrogenic Na-K pump in denervated mouse soleus muscles: prolonged activation by briefly applied acetylcholine.

Thin preparations of mouse soleus muscles denervated for 3-11 days were bathed in Cl-free solutions. The membrane potential (microelectrode technique) was an average of -65.6 mV. On application of 10 microM acetylcholine (ACh) the membrane potential fell to -2 to -8 mV. Following the washout of ACh it returned to values 9-24 mV more negative than before ACh. The membrane potential gradually returned toward the initial level during the ensuing 40-60 min. No hyperpolarization occurred when Na ions were absent during the application and washout of ACh or in the presence of 0.1 mM ouabain. The hyperpolarization was enhanced by replacing the Na ions by Li or Tris ions following an application of ACh in the presence of Na+. The hyperpolarization was suppressed by ouabain irrespective of whether the drug was applied in the presence or absence of Na+. The membrane potential was diminished by reducing [K+] from 4 to 1 mM in the absence of Na+ before ACh, but it was increased by the same procedure by up to 20 mV following the application of ACh. This indicates that the hyperpolarization was not entirely due to a K-depleting action of the Na-K pump at the membrane surface.

[MCI-plus: mild cognitive impairment with rapid progression. Part II: Biomarkers and research methods]. / MCI-plus: leichte kognitive Beeinträchtigung mit rascher Progredienz. Teil II: Biomarker und Untersuchungsmethoden.

Long-term studies will be pivotal in order to examine the efficacy of preventive and early therapeutic interventions during the preclinical phase of dementia. Biomarkers will be of importance due to the large sample sizes and the necessary logistic efforts, high drop-out rates and slow clinical progression. The validity of functional and even structural imaging methods is currently investigated with early and promising results; it is presently unclear whether conventional csf-markers of Alzheimer's disease (beta-amyloid and tau-proteins) are sufficiently sensitive to monitor the effects of early interventions. It also remains doubtful whether modifications of these methods will ever be useful and available for practical purposes.

[MCI-plus: mild cognitive impairment with rapid progression. Part I: prevention and therapy]. / MCI-plus: leichte kognitive Beeinträchtigung mit rascher Progredienz. Teil I: Prävention und Therapie.

Mild Cognitive Impairment (MCI) is a prevalent problem in the elderly and many patients show predictors of rapid cognitive decline ("MCI-plus"). MCI-plus represents a syndrome with growing importance in an ageing society, which will increasingly affect primary medicine and most other clinical specialties. We will have to face the dilemma of fast progress in the field of neurodiagnostics with innovative therapeutic strategies lagging behind. Psychological and medical co-morbidity in MCI-plus will therefore offer important opportunities to delay and to avoid the manifestation of dementia. We will review and discuss current training and treatment options including symptomatic and causal interventions.

[Pharmaco-economic evaluation of Ginkgo special extract EGb 761 for dementias in Austria]. / Pharmakoökonomische Bewertung von Ginkgo-Spezialextrakt EGb 761 im Indikationsgebiet dementielle Erkrankungen bezogen auf Osterreich.

The aim of the study was to carry out an economic evaluation of the therapeutic effects achievable with ginkgo special extract Egb 761 in dementia in Austria. The care-cost savings that could be achieved with ginkgo special extract Egb 761 therapy were estimated on the basis of the extent to which it delayed growing dependency and an increasing need for care--this being ascertained from the active treatment/placebo differences on GERRI after 6 months of treatment with Egb 761 and evaluated using the rates of the Austrian Federal Care Allowance Law--and compared with the cost of this therapy. The duration of illness, the start and duration of treatment, and the Egb 761 dose were varied in a series of scenarios in a sensitivity analysis. In all the scenarios the care-cost savings exceed the costs of the ginkgo special extract Egb 761 therapy. The cost/savings ratio is most favourable when the treatment is started early and when it is used in patients with dementia of the Alzheimer type. For every month by which the transition from the stage requiring a small to moderate amount of care to the stage requiring considerable or very considerable care can be delayed, one can save 812 [symbol: see text]. Prescribing ginkgo special extract Egb 761 for dementia makes sense from the national economic viewpoint because the product can yield care-cost savings that exceed the cost of the treatment itself.

[Effectiveness of brief infusions with Ginkgo biloba Special Extract EGb 761 in dementia of the vascular and Alzheimer type]. / Wirksamkeit kurzdauernder Infusionsbehandlungen mit Ginkgo-biloba-Spezialextrakt EGb 761 bei Demenz vom vaskulären und Alzheimer-Typ.

In a placebo-controlled, randomized, double-blind clinical trial, 40 patients with a mean age of 68 (+/- 12.5) years suffering from moderate dementia (Alzheimer, vascular, or mixed type) according to DSM-III-R criteria were included. Severity of the disease had to correspond to stages 4 or 5 of Reisberg's Global Deterioration Scale. Infusions of either EGb 761 or placebo were administered 4 days per week for 4 weeks. Primary outcome measure was the activities of daily living as assessed by the Nürnberger-Alters-Beobachtungsskala (NAB). The Clinical Global Impressions of change (CGI, item 2) and the actual intelligence as assessed by the Kurztest für Allgemeine Intelligenz (KAI) were further target variables. No relevant group differences could be detected at baseline. After therapy, patients of the active substance group scored significantly better (p < 0.05) on each outcome measure than those who received placebo. Using a sequential testing procedure, a global significance level of p < 0.05 could be assured. Superiority of EGb 761 therapy was also found with respect to a self-rating scale for instrumental activities of daily living (Nürnberger-Alters-Alltagsaktivitätenskala), the improvement of the most prominent symptom of illness, and the decrease of depression. Thus clinical efficacy of EGb 761 could be shown on three planes of assessment: the behavioral, the psychopathologic and the psychometric plane. It could be confirmed that, in patients with moderate dementia, short-term intravenous infusion therapy with EGb 761 results in an improvement of psychopathology and cognitive performance, which is reflected in an increased ability to cope with the demands of daily living.

Proof of efficacy of the Ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia.

The efficacy of the Ginkgo biloba special extract EGb 761 in outpatients with presenile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) according to DSM-III-R was investigated in a prospective, randomized, double-blind, placebo-controlled, multi-center study. After a 4-week run-in period, 216 patients were included in the randomized 24-week treatment period. These received either a daily oral dose of 240 mg EGb 761 or placebo. In accordance with the recommended multi-dimensional evaluation approach, three primary variables were chosen: the Clinical Global Impressions (CGI Item 2) for psychopathological assessment, the Syndrom-Kurztest (SKT)(1) for the assessment of the patient's attention and memory, and the Nürnberger Alters-Beobachtungsskala (NAB)(2) for behavioral assessment of activities of daily life. Clinical efficacy was assessed by means of a responder analysis, with therapy response being defined as response in at least two of the three primary variables. The data from the 156 patients who completed the study in accordance with the study protocol were taken into account in the confirmatory analysis of valid cases. The frequency of therapy responded in the two treatment groups differed significantly in favor of EGb 761, with p<0.005 in Fisher's Exact Test. The intent-to-treat analysis of 205 patients led to similar efficacy results. Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type and multi-infarct dementia was confirmed. The investigational drug was found to be well tolerated.

Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia.

The efficacy of the ginkgo biloba special extract EGb 761 in outpatients with presenile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infarct dementia (MID) according to DSM-III-R was investigated in a prospective, randomized, double-blind, placebo-controlled, multi-center study. After a 4-week run-in period, 216 patients were included in the randomized 24-week treatment period. These received either a daily oral dose of 240 mg EGb 761 or placebo. In accordance with the recommended multi-dimensional evaluation approach, three primary variables were chosen: the Clinical Global Impressions (CGI Item 2) for psychopathological assessment, the Syndrom-Kurztest (SKT) for the assessment of the patient's attention and memory, and the Nürnberger Alters-Beobachtungsskala (NAB) for behavioral assessment of activities of daily life. Clinical efficacy was assessed by means of a responder analysis, with therapy response being defined as response in at least two of the three primary variables. The data from the 156 patients who completed the study in accordance with the study protocol were taken into account in the confirmatory analysis of valid cases. The frequency of therapy responders in the two treatment groups differed significantly in favor of EGb 761, with p < 0.005 in Fisher's Exact Test. The intent-to-treat analysis of 205 patients led to similar efficacy results. Thus, the clinical efficacy of the ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type and multi-infarct dementia was confirmed. The investigational drug was found to be well tolerated.

Two-Dimensional detection in ion chromatography: sequential conductometry after suppression and passive hydroxide introduction.

An improved method that uses sequential suppressed and nonsuppressed IC for the sensitive detection of both common anions and very weak acid anions is described. After suppressed conductometric detection of an electrolytically generated hydroxide eluent and an electrolytic suppressor, the eluent is passed into a membrane device where KOH is passively introduced into the eluent stream using Donnan forbidden leakage. A second conductivity detector then measures the conductivity of the stream. The background conductance of the second detector is typically maintained at a relatively low level of 20-30 microS/ cm. The weak acids are converted to potassium salts that are fully ionized and are detected against a low KOH background as negative peaks. The applicability of different commercially available cation exchange membranes was studied. Device configurations investigated include planar, tubular, and a filament-filled annular helical (FFAH) device. The FFAH device provided more effective mixing of the penetrated hydroxide with the eluent stream, resulting in a noise level of < or = 7 nS/cm and a band dispersion value of less than 82 microL. Optimal design and performance data are presented.

Luminescence detection with a liquid core waveguide.

A new fluoropolymer tube is proposed as the basis of a novel class of liquid core waveguide-based luminescence detectors. Both chemiluminescence and photoluminescence detectors are possible. In the latter case, illumination is transverse to the main axis of the tube. With such a geometry, it is even possible to operate without monochromators, although limits of detection do improve with the incorporation of monochromators. The nature of the design is such that it is particularly simple to fabricate detectors in a flow-through configuration and where the light from the cell is coupled to a photodetector by an optical fiber. No focusing optics are necessary. A number of applications are illustrated. Attainable limits (LODs, S/N = 3) of detection include 150 pM fluorescein with a 254-nm excitation source, 200 amol of fluorescein in a capillary electrophoresis setup with excitation by two blue light-emitting diodes, 35 nM NH(3) as the isoindole derivative in a flow injection analysis system using a photodiode detector, 50 nM methylene blue and 1 nM Rhodamine 560 using respectively red and green LED arrays and an avalanche photodiode and a PMT in a FIA configuration, 100 parts per trillion by volume gaseous formaldehyde as the Hantzsch reaction product with cyclohexanedione using a diffusion scrubber, 2.7 µM and 17 nM hypochlorite based on its chemiluminescence reaction with luminol with photodiode and PMT detectors, respectively, and 1 ppm SO(4)(2)(-) based on nephelometric detection at 470 nm. The approach described herein leads to particularly simple and inexpensive luminescence detectors with excellent sensitivity.