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Biomedical subjects

W Marquardt

Publications and source records attributed to W Marquardt.

11 recordsLinked to original sources

Lipoic acid in multiple sclerosis: a pilot study.

Lipoic acid (LA) is an antioxidant that suppresses and treats an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis. The purpose of this study was to determine the pharmacokinetics (PK), tolerability and effects on matrix metalloproteinase-9 (MMP-9) and soluble intercellular adhesion molecule-1 (sICAMP-1) of oral LA in patients with MS. Thirty-seven MS subjects were randomly assigned to one of four groups: placebo, LA 600 mg twice a day, LA 1200 mg once a day and LA 1200 mg twice a day. Subjects took study capsules for 14 days. We found that subjects taking 1200 mg LA had substantially higher peak serum LA levels than those taking 600 mg and that peak levels varied considerably among subjects. We also found a significant negative correlation between peak serum LA levels and mean changes in serum MMP-9 levels (T = -0.263, P =0.04). There was a significant dose response relationship between LA and mean change in serum sICAM-1 levels (P =0.03). We conclude that oral LA is generally well tolerated and appears capable of reducing serum MMP-9 and sICAM-1 levels. LA may prove useful in treating MS by inhibiting MMP-9 activity and interfering with T-cell migration into the CNS.

Adult↗

Preparation of hair for measurement of elements by inductively coupled plasma-mass spectrometry (ICP-MS).

The preparation of hair for the determination of elements is a critical component of the analysis procedure. Open-beaker, closed-vessel microwave, and flowthrough microwave digestion are methods that have been used for sample preparation and are discussed. A new digestion method for use with inductively coupled plasma-mass spectrometry (ICP-MS) has been developed. The method uses 0.2 g of hair and 3 mL of concentrated nitric acid in an atmospheric pressure-low-temperature microwave digestion (APLTMD) system. This preparation method is useful in handling a large numbers of samples per day and may be adapted to hair sample weights ranging from 0.08 to 0.3 g. After digestion, samples are analyzed by ICP-MS to determine the concentration of Li, Be, B, Na, Mg, Al, P, S, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ge, As, Se, Rb, Sr, Zr, Mo, Pd, Ag, Cd, Sn, Sb, I, Cs, Ba, Pt, Au, Hg, Tl, Pb, Bi, Th, and U. Benefits of the APLTMD include reduced contamination and sample handling, and increased precision, reliability, and sample throughput.

Hair↗

Determination of reference ranges for elements in human scalp hair.

Expected values, reference ranges, or reference limits are necessary to enable clinicians to apply analytical chemical data in the delivery of health care. Determination of references ranges is not straightforward in terms of either selecting a reference population or performing statistical analysis. In light of logistical, scientific, and economic obstacles, it is understandable that clinical laboratories often combine approaches in developing health associated reference values. A laboratory may choose to: 1. Validate either reference ranges of other laboratories or published data from clinical research or both, through comparison of patients test data. 2. Base the laboratory's reference values on statistical analysis of results from specimens assayed by the clinical reference laboratory itself. 3. Adopt standards or recommendations of regulatory agencies and governmental bodies. 4. Initiate population studies to validate transferred reference ranges or to determine them anew. Effects of external contamination and anecdotal information from clinicians may be considered. The clinical utility of hair analysis is well accepted for some elements. For others, it remains in the realm of clinical investigation. This article elucidates an approach for establishment of reference ranges for elements in human scalp hair. Observed levels of analytes from hair specimens from both our laboratory's total patient population and from a physician-defined healthy American population have been evaluated. Examination of levels of elements often associated with toxicity serves to exemplify the process of determining reference ranges in hair. In addition the approach serves as a model for setting reference ranges for analytes in a variety of matrices.

Adolescent↗

Interaction between glucocorticoids and cyclic AMP in the regulation of phosphoenolpyruvate carboxykinase (GTP) in the isolated perfused rat liver. Effects of cordycepin and cycloheximide.

The mechanism of the interaction between glucocorticoids and cyclic AMP in the regulation of phosphoenolpyruvate carboxykinase (GTP: oxalocetate carboxylase, transphosphorylating, EC 4.1.1.32) was investigated in the isolated perfused rat liver using inhibitors of transcription or translation. Dibutyryl cyclic AMP produced a rapid increase in P-enolpyruvate carboxykinase activity. The response of the enzyme to the cyclic nucleotide ceased however, at 4 h, but was restored by dexamethasone. The dibutyryl cyclic AMP-induced increase in P-enolpyruvate carboxykinase activity was completely blocked by cycloheximide, but not not by cordycepin. However, cordycepin totalaly suppressed the "permissive" effect of dexamethasone on the response of the enzyme to dibutyryl cyclic AMP. Preperfusion of the livers with dexamethasone and cycloheximide, following by perfusion without the steroid hormone and the inhibitor, resulted in a rapid rise in P-enolpyruvate carbosykinase activity, which was not affect by cordycepin. If livers were preperfused with cordycepin for different time-periods, followed by dibutyryl cyclic AMP stimulation of P-enolpyruvate carboxykinase synthesis, the response of the enzyme to the cyclic nucleotide was progressively reduced, achieving 50% inhibition after 1.5 h of preperfusion. These results suggest that the induction of hepatic P-enolpyruvate carboxykinase to maximum values, brought about by cyclic AMP at the level of translation, depends on the supply of newly synthetized mRNA provided by the transcriptional action of glucocorticoids.

Animals↗

[Karl Bragard].

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Germany, West↗