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Biomedical subjects

M Eckert

Publications and source records attributed to M Eckert.

At least 19 recordsLinked to original sources

[Therapy of neuropathies with a vitamin B combination. Symptomatic treatment of painful diseases of the peripheral nervous system with a combination preparation of thiamine, pyridoxine and cyanocobalamin].

STUDY DESIGN: In an open, multicentric observational study involving 234 doctors in private practice, the evolution of symptoms and the tolerability of a vitamin B preparation (Neurotrat forte) used as treatment in 1,149 patients with polyneuropathy, neuralgia, radiculopathy and neuritis associated with pain and paresthesias, were observed. The form of administration (ampoules, dragées), dosage and duration of treatment were left to the individual care-providing physician. The target symptoms evaluated were intensity of pain, muscle weakness affecting the legs, and paresthesia. RESULTS: Under treatment, there was a clear improvement in these symptoms. At a second examination approximately three weeks after initiation of treatment, a positive effect on pain in particular was observed in 69% of the cases. Similar observations were also made for paresthesias and muscular weakness in the legs.

Diabetic Neuropathies

A new specific antibody reveals octopamine-like immunoreactivity in cockroach ventral nerve cord.

An antiserum was raised in rabbits immunized with octopamine conjugated to thyroglobulin. The specificity of this antiserum for octopamine is shown by dot blot immunoassay analysis. The antiserum does not crossreact with dopamine, noradrenaline, and serotonin, but slight crossreactivity with the amine tyramine at high concentrations was observed. The tyramine crossreactivity could be eliminated by preabsorption with a tyramine-glutaraldehyde-BSA conjugate. Using this antiserum, we describe the topographical distribution of octopamine-immunoreactive (ir) neuronal elements in wholemounts and paraffin sections of the ventral nerve cord of the American cockroach. The pattern of octopamine immunostaining is completely different from that obtained with an antidopamine serum, and can be blocked by preabsorbing the antioctopamine serum with BSA-conjugated octopamine. Cell bodies and dendritic processes of putatively octopaminergic dorsal (DUM) and ventral (VUM) unpaired median neurons were clearly octopamine-ir in all ganglia examined. The numbers of stained DUM somata in the mesothoracic, metathoracic, and terminal ganglion of females correspond to those of peripherally projecting DUM cells revealed previously by retrograde tracing (Gregory, Philos Trans R Soc Lond [Biol] 306:191, 1984; Tanaka and Washio, Comp Biochem Physiol 91A:37, 1988; Stoya et al., Zool Jb Physiol 93:75, 1989). In addition, various, previously unknown, paired cells with octopamine-like immunoreactivity were found in all ventral ganglia except abdominal ganglia 3-6. Some of these probably project intersegmentally.

Animals

Octopamine immunoreactive cell populations in the locust thoracic-abdominal nervous system.

We describe octopamine-immunoreactive somata and their projections in the pro- meso-, meta- and pregenital abdominal-ganglia of locusts. Immunoreactive midline somata were identified as dorsal- and ventral- unpaired median (DUM- and VUM-, respectively) neurones due to their: characteristic large size and positions of somata, primary neurites in DUM-tracts giving rise to T-junctions, and bilaterally projecting axons. In the prothoracic ganglion there are most likely 8 such cells; in the meso- and metathoracic, some 20 each; and in each individual pregenital abdominal ganglion, typically 3. All appear to project to peripheral nerves and their numbers correspond to the number of peripherally projecting DUM-cells identified to date in each ganglion. We suggest that probably all peripherally projecting DUM-cells are octopaminergic in the examined ganglia. Presumptive DUM-interneurones are not octopamine-immunoreactive, but, confirming other studies, are shown to label with an antiserum to gamma-amino butyric acid (GABA). Other octopamine-immunoreactive neurones include a pair of midline, prothoracic, anterior medial cells, not necessarily DUM-cells, and a pair of ventral lateral somata in each thoracic- and the first abdominal ganglion. The latter project intersegmentally in ventral tracts. Intersegmentally projecting octopamine-immunoreactive fibers in dorsal tracts probably arise from a prothoracic DUM-cell, which leaves through suboesophageal nerves, or descending suboesophageal DUM-cells. Thus, the octopamine-immunoreactive system of thoracic and pregenital abdominal ganglia in locust comprises all peripherally projecting DUM-cells and a plurisegmental network.

Abdomen

Expression and function of the neural cell adhesion molecule L1 in mouse leukocytes.

The neural cell adhesion molecule L1 is a cell surface glycoprotein of the immunoglobulin superfamily which mediates adhesion between neural cells. The possibility that similar cell-cell recognition mechanisms may be shared by the nervous and immune systems prompted us to study the expression and function of L1 in cells of the hematopoietic system. Immunofluorescence analysis using monoclonal L1 antibody revealed that the molecule is expressed in the bone marrow, spleen, and thymus of the mouse. This observation was confirmed by amplifying cDNA derived from these organs by the polymerase chain reaction with L1-specific oligonucleotide primers. Two-color fluorescence analysis indicated that bone marrow lymphoid and granulocyte precursor cells express low and high levels of L1, respectively. In the thymus L1 is primarily expressed by mature cells that have a strong expression of CD3 and in the spleen both B cells and T cells express L1. The possible function of L1 in lymphoid cells was studied using subcloned ESb-MP lymphoma cells having high or low densities of L1 on the cell surface as well as activated splenic B lymphoblasts. Parental and subcloned ESb-MP cells that strongly expressed L1 could form homotypic aggregates in the presence of low Ca2+ levels, whereas subcloned ESb-MP cells with a weak expression of L1 did not aggregate, suggesting that L1 mediates the Ca(2+)-independent aggregation of the parental ESb-MP cells. Furthermore, the aggregation of activated B lymphoblasts under physiological concentrations of Ca2+ and Mg2+ was inhibited by 30% in the presence of Fab fragments of polyclonal L1 antibodies, implying that L1 also mediates adhesion among normal lymphoid cells. A possible role of L1 on lymphocytes in stimulating the innervation of lymphoid organs is discussed.

Animals

Nectadrin, the heat-stable antigen, is a cell adhesion molecule.

Nectadrin, the cell surface glycoprotein recognized by the novel mAb 79, was found to be immunologically identical to the heat-stable antigen (HSA). It is a glycoprotein with a polypeptide core of only 30 amino acids and a very high carbohydrate content (Wenger, R. H., M. Ayane, R. Bose, G. Köhler, and P. J. Nielsen. 1991. Eur. J. Immunol. 21:1039-1046). Immunocytological studies using cultured splenic B-lymphocytes, neuroblastoma cells, and cerebellar cells indicated that nectadrin is preferentially expressed at sites of cell-cell contact. Purified nectadrin and monoclonal nectadrin antibody 79, but not other monoclonal nectadrin antibodies, inhibited the aggregation of B-lymphocytes by 70%, suggesting that nectadrin may act as a cell adhesion molecule. Nectadrin was purified from a mouse lymphoma cell line in two forms of 40-60 and 23-30 kD. The lower molecular weight form appears to be generated from the higher molecular weight form by degradative removal of saccharide residues characteristic of complex type oligosaccharide side chains. Latex beads coated with purified nectadrin aggregated and the rate of their aggregation depended on the molecular form of nectadrin, with the larger form being more potent than the smaller one in mediating bead aggregation. Nectadrin thus appears to be a self-binding cell adhesion molecule of a structurally novel type in that its extensive glycan structures may be implicated in mediating cell adhesion.

Animals

Failure of magnesium supplementation to influence marathon running performance or recovery in magnesium-replete subjects.

This study examined the effect of magnesium supplementation on muscle magnesium content, on running performance during a 42-km marathon footrace, and on muscle damage and the rate of recovery of muscle function following the race. Twenty athletes were divided equally into two matched groups and were studied for 4 weeks before and 6 weeks after a marathon in a double-blind trial; the experimental group received magnesium supplement (365 mg per day) and the control group, placebo. Magnesium supplementation did not increase either muscle or serum magnesium concentrations and had no measurable effect on 42-km marathon running performance. Extra magnesium ingestion also had no influence on the extent of muscle damage or the rate of recovery of muscle function. The latter was significantly reduced immediately after the marathon but returned to normal within 1 week. Thus, magnesium supplementation in magnesium-replete subjects did not enhance performance or increase resistance to muscle damage during the race, or the rate of recovery of muscle function following the race.

Adult

The octopaminergic system within the ventral nerve cord of the American cockroach.

Octopamine-immunoreactive neurons within the ventral nerve cord of the cockroach, Periplaneta americana, were mapped with a new anti-octopamine serum. The specificity of this antiserum was demonstrated by dot blot immunoassay and by comparing the immunocytochemical staining patterns obtained after incubation with anti-dopamine and anti-octopamine serum. Putative octopaminergic dorsal and ventral unpaired median (DUM resp. VUM) neurons showed octopamine-like immunoreactivity in all ventral ganglia. The numbers of DUM cells in the mesothoracic, metathoracic and terminal ganglia of females correspond to those previously characterized by retrograde staining 19, 33, 34. It could be shown that besides segmentally projecting there are also intersegmentally projecting DUM neurons within the thoracic ganglia. In addition various, previously unknown, paired octopamine-ir cells were revealed in all ventral ganglia except the abdominal ganglia 2-5.

Animals

Distribution of GABA-like immunoreactivity in myenteric plexus of carp, frog and chicken.

The distribution of GABA-like immunoreactivity was studied by means of indirect immunocytochemical methods in some lower vertebrate species (carp, frog, chicken). An immunoreactive network was revealed in the myenteric plexus of the alimentary canal of carp. GABA-positive nerve cells were attached closely to the fibres in the stomach. In other gut regions immunostained neurons were less frequent. Immunoreactive fibres often formed baskets on the surfaces of immunonegative neurons along the whole length of the alimentary canal. The number of immunopositive nerve fibres and pericellular baskets seemed to be lower in the mid- and hingut than in the foregut region. A similar distribution of GABA-immunoreactivity was revealed in the frog myenteric plexus. The ganglionated foregut region possessed a relatively dense GABAergic innervation. This part of the gut contained immunostained nerve cells and fibres, while the mid- and hindgut possessed only a scanty fibre system. Chicken exhibited an extensive immunoreactive plexus for GABA, although the GABA-stained perikarya were restricted mainly to the duodenum. Further regions of the small intestine were poor in immunoreactive cell bodies, which suggests a segmental origin and arrangement of GABAergic innervation within the plexus. In all three species studied, GABA-positive fibres run into the circular muscle layer. The varicosity suggests their influence on the movement of the smooth muscles through modifying the transmitter release of neighbouring terminals.

Animals

Demonstration of GABA-like immunoreactivity in myenteric plexus of frog stomach.

The GABAergic innervation of the frog stomach was studied by means of an indirect immunohistochemical method. Whole mount preparations were obtained from frog stomachs after the animals had been perfused with a mixture of picric acid, glutaraldehyde and glacial acetic acid. Samples were incubated with an antiserum specific for GABA coupled to BSA with glutaraldehyde. Anti-rabbit IgG-HRP was processed by the two step method (Eckert and Ude 1983). GABA-positive varicose fibers and also nerve cell bodies were revealed within the myenteric plexus. The density of GABA-immunoreactive neurons was not higher than 4-8 cell/cm2, which is approximately 1% of the total nerve cell number in the myenteric plexus.

Animals

Effects of alpha-interferon on theophylline pharmacokinetics and metabolism.

1. The influence of alpha-interferon (Roferon-A) on the pharmacokinetics and metabolism of theophylline was studied in healthy adults. Roferon-A was administered as an intra-muscular injection (3 x 10(6) iu) once-a-day over 3 days. One week prior to and immediately after this course a single 20 min aminophylline infusion (4 mg kg-1) was given. 2. Blood samples for theophylline analysis were taken over 48 h. Urine was collected up to 72 h and assayed for theophylline and its major metabolites 3-methylxanthine, 1,3-dimethyluric acid and 1-methyluric acid. 3. Pharmacokinetic parameters for theophylline in plasma were calculated. From urinary excretion data the overall metabolic clearance of theophylline and clearances for formation of the metabolites were calculated. 4. After interferon administration, there was a significant increase of approximately 15% in the mean values of the terminal elimination half-life, area under the curve and mean residence time of theophylline in association with a similar decrease in plasma clearance (P less than 0.05). Formation clearances of the metabolites tended to be smaller after treatment, but only the change in the overall clearance of theophylline was significantly different (P less than 0.05). There was no systematic shift in the metabolic pattern of theophylline. 5. Additional investigations of the influence of the duration of alpha-interferon treatment are necessary before definite conclusions can be drawn about the mechanism and the clinical relevance of the described interaction.

Adult

Single and multiple dose pharmacokinetics of tenoxicam in the elderly.

Fourteen elderly subjects (10 women, 4 men) with a mean age of 81 (SD 6.7) years and in need of anti-inflammatory drug treatment were given a single dose of 20 mg tenoxicam. After a drug-free interval of 5 weeks, multiple dose treatment with 20 mg tenoxicam once daily for 56 days was initiated. The single and multiple dose kinetics of tenoxicam were investigated after HPLC determination of tenoxicam in the plasma. The elimination half-life of tenoxicam ranged from 44 to 132 h (mean 71.9 h) with no significant difference between the single and multiple dosage regimens. Tenoxicam reached maximum plasma concentrations after 1.4 and 1.1 h, with values of 3.6 and 15.5 micrograms.ml-1, for the single and multiple dosage regimen respectively. The corresponding trough values (24-h values) were 1.8 and 11.7 micrograms.ml-1. A mean accumulation ratio of 5.1 was calculated. The mean increase in the area under the plasma concentration time curves at steady-state was 21% more than predicted from the initial single dose. This deviation from linearity was considered to be of minor clinical significance. The kinetics of tenoxicam in elderly were similar to that published for young healthy volunteers.

Aged

The influence of early odour experience on the neural response of the olfactory bulb in laboratory mice.

In mice (strain NMRI) the influence of olfactory rearing conditions on the ontogenetic development of the bulbar electroencephalogram (EEG) was investigated. The cages of control animals were perfused continually with filtered air, whereas in the three experimental groups geraniol was added to the atmosphere at different times (group G0-13, from birth till day 13; group G0-6, from birth till day 6; group G6-12, from day 6 till day 12). At various ages the EEG of the bulbus olfactorius was studied by means of permanently implanted tungsten electrodes, and the neural response to nest odour and geraniol (10(-2) vol. %) was recorded. No differences were found between the groups regarding the overall development of the bulbar EEG, nor did the raising conditions affect the neural response to nest odour. However, in groups G0-13 and G6-12 a marked response to the odour of geraniol was recorded, while in the controls and the individuals that had experienced geraniol only during their first week of life, the bulbar response to this odourant did not differ from that obtained following stimulation with clean air. In the animals of group G0-13, which were investigated as adults (day 70), the prominent geraniol response was still recordable 2 months after the last contact with the odour. These results indicate that odours experienced during a sensitive period in the nest evoke neuronal alterations in the olfactory system of the mouse that facilitate processing of a known odourant.

Aging

Simultaneous localization of a classical neurotransmitter (GABA) and a peptide transmitter candidate (proctolin) in the nervous system of the cockroach, Periplaneta americana.

The distribution of the neurotransmitter gamma-aminobutyric acid (GABA) in the 6th abdominal ganglion of the cockroach Periplaneta americana was investigated using an antiserum against GABA. The high number of GABA immunoreactive neurons refer to the important function of this transmitter substance. The relation between the GABAergic system and the proctolinergic system in the 6th abdominal ganglion was examined by means of an immunohistochemical double staining technique. The results show that probably GABA and proctolin do not coexist within one neuron.

Animals

A comparative study of the immunohistochemical localization of a presumptive proctolin-like peptide, thyrotropin-releasing hormone and 5-hydroxytryptamine in the rat central nervous system.

A proctolin (PROC)-like peptide was studied immunohistochemically in the hypothalamus, lower brainstem and spinal cord of the rat using an antiserum against PROC conjugated to thyroglobulin. Neuronal cell bodies containing PROC-like immunoreactivity (PROC-LI) were observed in the dorsomedial, paraventricular and supraoptic nuclei of the hypothalamus and in the nucleus raphe magnus, nucleus raphe pallidus, nucleus raphe obscurus and nucleus interfascicularis nervi hypoglossi in the medulla oblongata. Fibers containing PROC-LI were seen in the median eminence and in other hypothalamic nuclei, and in the lower brainstem in cranial motor nuclei including the dorsal motor nucleus of the vagus nerve, the motor trigeminal nucleus, the facial nucleus and nucleus ambiguous, and in lower numbers in the nucleus of the solitary tract and locus coeruleus. Fibers containing PROC-LI were also located in the spinal cord, in the intermediolateral cell column at thoracic levels and in the ventral horns at all levels of the spinal cord. After transection of the spinal cord, all PROC-immunoreactive fibers below the lesion disappeared. Following injection of Fast blue into the thoracic spinal cord, retrogradely labeled cells in the nuclei raphe pallidus, obscurus and magnus and nucleus interfasciculari nervi hypoglossi were seen to contain PROC-LI. PROC-LI had a similar distribution as thyrotropin-releasing hormone (TRH)-LI in the above-mentioned areas and coexistence of TRH-LI and PROC-LI was shown in cell bodies in the hypothalamus and medulla oblongata. PROC-LI could also be shown to coexist with 5-hydroxytryptamine (5-HT)-LI in neuronal cell bodies in the lower brainstem. The results demonstrate the occurrence of a PROC-like peptide in the mammalian nervous system, and these neurons seem to be at least largely identical to previously described TRH systems. A possible involvement of the PROC-like peptide in spinal motor control is discussed in relation to the well-established role of PROC in control of motor behavior in insects and invertebrates.

Animals

Comparative pharmacokinetics and cardiovascular effects of tiapamil in healthy volunteers and patients with hepatic cirrhosis.

Tiapamil 70 mg was administered i.v. to 8 healthy male volunteers and 8 patients (7 males, 1 female) with biopsy proven hepatic cirrhosis. Two of the patients also received 600 mg p.o. Serial plasma and urine samples were collected and the parent drug in plasma and urine and desmethyl-tiapamil in urine were assayed by a specific HPLC method. The plasma and urine data for the parent drug after i.v. and p.o. dosing were simultaneously fitted to linear p.o. and i.v. two compartment models with exit from and input into the central compartment. Absorption was assumed to be a first order process. In the volunteers the mean pharmacokinetic parameters were: 101 l for the steady-state volume of distribution 750 ml X min-1 for nonrenal clearance, 195 ml X min-1 for renal clearance and 1.7 h for the half-life of the terminal disposition phase. The urinary recoveries of the parent drug and desmethyltiapamil averaged 21.4 and 0.8% of the dose, respectively. In the patients the steady-state volume of distribution, the amount of unchanged drug in urine and the half-life of the terminal disposition phase were significantly increased (171 l, 29.0% of the dose, 3.5 h, respectively). Decreased plasma protein binding in the patients accounted for the larger steady-state volume of distribution. The nonrenal clearance of 519 ml X min-1, tended to be smaller in the patients than in the volunteers. Together with the increased urinary recovery of tiapamil in the patients this indicates a moderately impaired elimination capacity in the cirrhotics.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Proctolin immunoreactive neurons in the human brain stem.

Using the peroxidase-antiperoxidase (PAP) technique it could be established that a variety of nerve cells of human Pons and Medulla oblongata contain proctolin-like material. These neurons belong to the Nuc. olivaris caudalis, Nuc. originis n. hypoglossi, Nuc. raphes dorsalis and the Nuc. ambiguus. Furthermore, proctolin immunoreactive peptide was found to be contained in certain fiber systems (Lemniscus medialis and fiber tracts near the Raphe).

Aging