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J Martens

Publications and source records attributed to J Martens.

At least 19 recordsLinked to original sources

Direct resolution of (+/-)-ephedrine and atropine into their enantiomers by impregnated TLC.

Direct resolution of (+/-)-ephedrine and atropine into their enantiomers was achieved by normal-phase thin layer chromatography on silica gel plates impregnated with optically pure L-tartaric acid and L-histidine, respectively, as chiral selectors. The mobile phases enabling successful resolution were different combinations of acetonitrile-methanol-water. The spots were detected with iodine vapours and the detection limits were 2 and 6 microg, respectively, in terms of the racemate. The effects of concentration of the impregnating reagent, temperature and pH on resolution have been studied.

Acetonitriles↗

Separation of amino acids, their derivatives and enantiomers by impregnated TLC.

The present state of TLC with respect to separation of amino acids, their different derivatives and their enantiomers by the technique of impregnation is discussed. The main approaches to impregnation viz. mixing of a suitable reagent with the adsorbent prior to plate-making, immersion of the untreated plate in the solution of impregnating reagent prior to development, and modification of the adsorbent, have been identified and discussed for each class of these compounds. The role of impregnation in resolving enantiomers or in improving the separation of mixtures of amino acids or their derivatives in terms of ion pairing, complex formation, ligand exchange or other steric interactions has been elaborated in each category.

Adsorption↗

PD98059 attenuates hydrogen peroxide-induced cell death through inhibition of Jun N-Terminal Kinase in HT29 cells.

We have investigated the effects of hydrogen peroxide (H(2)O(2)), a potent naturally occurring oxidant on cell signaling and viability in the pluripotent HT29 intestinal cell line. There was a dose-dependent reduction in cell viability upon exposure to H(2)O(2) as measured by the XTT assay. Features of apoptosis were indicated by the findings of PARP and caspase 3 cleavage, as well as changes in cell morphology using phase contrast and nuclear fragmentation using fluorescence microscopy. There was a dose-dependent increase in the activation of p45-JNK, p42/p44-ERK, and p38-HOG. Surprisingly, oxidant-induced cell injury could be attenuated by preincubation with PD98059 to 50% of untreated control cells (P = 0.002). This and UO126, another MEK inhibitor were ably to reproducibly inhibit p45-JNK activation induced by hydrogen peroxide. Transfection with kinase-inactive constructs of JNK and ERK revealed that the improvement in cell viability was due to inhibition of JNK and not ERK. Transient transfections with AP-1 and NF-kappaB luciferase reporter constructs did not reveal any transcriptional activation due to hydrogen peroxide exposure however, in both cases the basal levels of transcriptional activity were suppressed in the presence of PD98059. It is concluded that JNK mediates H(2)O(2)-induced cellular injury in the HT29 cell line, and additionally, we report for the first time that JNK activation can be inhibited by both PD98059 and UO126 at conventional doses used to inhibit MEK.

Butadienes↗

Direct thin layer chromatography enantioresolution of some basic DL-amino acids using a pharmaceutical industry waste as chiral impregnating reagent.

Direct enantiomeric resolution of DL-arginine, DL-histidine, DL-lysine, DL-valine and DL-leucine into their enantiomers was achieved by thin layer chromatography (TLC) on silica gel plates impregnated with optically pure (1R, 3R, 5R)-2-azabicyclo[3,3,0]octan-3-carbo-xylic acid (0.011 M) as a chiral selector which is a waste of a pharmaceutical industry. Different combinations of acetonitrile-methanol-water were found to be successful in resolving the DL-amino acids. The spots were detected by ninhydrin (0.2% in acetone) and the detection limit was 0.66 microg.

Amino Acids↗

Multicomponent synthesis of novel amino acid-nucleobase chimeras: a versatile approach to PNA-monomers.

This paper describes a multicomponent approach to novel totally protected precursors of PNA-monomers via Ugi 4CC. The obtained bisamides are converted into several partially protected PNA-monomers or derivatives thereof using three different procedures. Methods for hydrolysis are shown to be dependent on the nature of the isocyano component required for Ugi 4CC. Several novel monomers suitable for oligomer synthesis are prepared demonstrating the high versatility of the reaction sequence.

Hydrolysis↗

Can keratin 8 and 17 immunohistochemistry be of diagnostic value in cervical cytology? A feasibility study.

BACKGROUND: Based on results from evaluation of tissue sections from premalignant lesions of the uterine cervix, the authors examined the hypothesis that immunostaining of Papanicolaou-stained cytologic smears with monoclonal antibodies to keratins 8 and 17 allows detection of cervical intraepithelial neoplasia (CIN) with progressive potential. They also investigated whether detection of these two keratin subtypes could be of help in the analysis of normal and/or poor quality cytology smears. METHODS: Sixty-one Papanicolaou-stained smears, representing 25 normal smears, 8 CIN 1, 7 CIN 2, 18 CIN 3, and 3 cervical carcinomas, were stained with CAM 5.2 and E3, which are capable of detecting keratin 8 and 17, respectively. The percentages of immunoreactive normal, metaplastic, dysplastic, and malignant epithelial cells were determined. RESULTS: In normal cervical smears, keratin 8 was detected in endocervical columnar cells and sporadically in immature squamous metaplastic cells. Keratin 17 was identified in reserve cells and frequently in immature squamous metaplasic cells. In CIN, the number of cases in which keratin 8 was present increased with the severity of the lesion. Keratin 17 was found in the majority of CIN lesions, irrespective of grade. Intensity of immunostaining and number of cells stained per lesion varied and were also not related to the severity of CIN. CONCLUSIONS: The use of the keratin 8 antibody in normal cervical smears enabled the detection of endocervical cells in cases where they were thought to be absent, particularly in cases with severe inflammation. Staining with keratin 17 enabled the identification of reserve cells or immature metaplastic cells, which were often misinterpreted as parabasal cells. The application of antibodies to these subtypes of keratins in cervical cytology can to a certain extent help in the identification of CIN and may in future be tested in automated screening.

Carcinoma, Squamous Cell↗

Pregnancy and dialysis.

The outcome of pregnancy in patients with end-stage renal failure has long been considered to be extremely poor, and the literature concerning pregnancy while on dialysis is rather scarce. We reviewed the records of five pregnancies in dialysis patients and performed a national survey on this topic. The dialysis technique and dialysis dose, the effects of erythropoietin (EPO), and the evolution of blood pressure levels in our patients are presented. The dose of EPO had to be increased to maintain the hemoglobin level at 10 to 11 g/dL. There was no case of EPO-related hypertension and no need for transfusion. The obstetric data of the national survey, including our own patients, were analyzed. The incidence of pregnancy going beyond the first trimester was 0.3 per 100 patient-years (15 cases in 1,472 females of childbearing age treated, for a total of 4,545 patient-years). In all but one patient initiating pregnancy while already on dialysis, the frequency and dose of dialysis were increased (to a weekly Kt/V of six to eight in our personal cases). The outcome was successful in 50% of pregnancies occurring in hemodialyzed patients and in 80% of patients who started dialysis after initiation of pregnancy. Polyhydramnios was found in eight of 13 cases and growth retardation in two of nine cases. The incidence of low birth weight and prematurity was 100%, and cesarean section was performed in 66% of successful pregnancies. In successful pregnancies, we found a correlation between birth weight and dose of dialysis. Our findings confirm the remarkable improvement in the prognosis of pregnancy in dialysis patients in recent years.

Adult↗

Solid-phase microextraction with capillary gas-liquid chromatography and nitrogen-phosphorus selective detection for the assay of antidepressant drugs in human plasma.

Solid-phase microextraction (SPME) was tested as a sample preparation for the simultaneous assay of ten antidepressant drugs and metabolites (TADs) in human plasma. Aqueous NaOH (0.5 ml, 1 M) and chloramitriptyline (50 microliters, 40 micrograms/ml) as internal standard (I.S.) were added to a 2-ml plasma sample. This mixture was extracted with a 100-micron polydimethylsiloxane SPME fiber (Supelco) for 10 min. After washing in water and methanol (50%) and subsequent drying at room temperature, desorption of the fiber was performed in the injection port of a gas chromatograph at 260 degrees C for 1 min (HP 5890, DB-17 30 m x 0.25 mm I.D., 0.25 micron capillary; 0.7 ml/min nitrogen; nitrogen-phosphorus selective detection). The recovery was found to be very low from plasma (0.3% to 0.8%) but considerably higher from water (about 15%). Therefore, the high protein binding of antidepressants appears to be the main limiting mechanism for a better extraction. However, the analytes were well separated and the calibrations were linear between 125 ng/ml and 2000 ng/ml. The limits of quantification were about 90 ng/ml for imipramine and desipramine, 125 ng/ml for amitriptyline, trimipramine, doxepine, nortriptyline and mianserine and about 200 ng/ml for maprotiline, clomipramine and desmethylclomipramine. The recovery was improved by increasing the extraction time. The influence of the concentrations of the sum of proteins and of alpha-acid glycoprotein on the peak-area ratios ATAD/A I.S. and on absolute peak areas was studied. Peak-area ratios increased with decreasing protein concentration but were found to be independent on alpha-acid glycoprotein. A simple model for the explanation of the effect is presented. Measures for the improvement of sensitivity are discussed. As presented in this paper, which first describes SPME for the analysis of drugs in plasma, SPME with a short extraction time can be of only very limited value for therapeutic drug monitoring. Lower concentrations than the limit of quantification are usually found at therapeutic doses. The method can be useful for toxicological analysis after the accidental or suicidal intake of higher doses. However, an about 10-fold improvement of the sensitivity of the method seems to be possible.

Antidepressive Agents↗

Simultaneous determination of midazolam and its metabolites 1-hydroxymidazolam and 4-hydroxymidazolam in human serum using gas chromatography-mass spectrometry.

A method for the quantitation of midazolam and its metabolites 1-hydroxymidazolam and 4-hydroxymidazolam from human serum capable of monitoring concentrations achieved under therapeutic conditions is presented. The substances were extracted under basic conditions with toluene and the hydroxy metabolites transformed to their tert-butyldimethylsilyl derivatives with N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide. The samples were measured by gas chromatography-mass spectrometry. The limits of detection are 0.2 ng ml(-1) for midazolam and 0.1 ng ml(-1) for 1-hydroxy- and 4-hydroxymidazolam. The coefficients of variation are 3.9% at 5 ng ml(-1) for midazolam, 6.7% at 2 ng ml(-1) for 1-hydroxymidazolam and 8.8% (22.2%) at 0.5 (0.2) ng ml(-1) for 4-hydroxymidazolam.

Anesthetics, Intravenous↗

Herpesvirus 6 variant A infection after heart transplantation with giant cell transformation in bile ductular and gastroduodenal epithelium.

Herpesvirus 6 (HHV-6) is a ubiquitous virus known to cause febrile syndromes and exanthema subitum in children. Less commonly, and particularly in organ transplant recipients, it may result in hepatitis, bone marrow suppression, interstitial pneunonitis, and meningoencephalitis. This report expands the spectrum of clinical disease associated with HHV-6 by documenting viral infection in a 44-year-old heart transplant recipient presenting with gastroduodenitis, pancreatitis, and hepatitis. On histopathologic examination, the gastric, duodenal, and bile ductular epithelium showed a multinucleate giant cell transformation similar to the cytopathic effect caused by the virus in human T-lymphocytes infected in vitro. Electron microscopy showed herpes particles with a thick tegument layer in the duodenum. Polymerase chain reaction amplified HHV-6 variant A sequences from multiple sites. Serology confirmed the presence of an acute HHV-6 infection. Thus, HHV-6 variant A can cause gastroduodenitis and pancreatitis in immunosuppressed individuals. Multinucleate giant cells and enveloped virions with a prominent tegument can be used as morphologic criteria to raise the possibility of HHV-6 infection in human biopsy tissue.

Adult↗

Determination of the terfenadine metabolite azacyclonol in human serum using gas chromatography-mass spectrometry.

In this work, a method for the determination of azacyclonol, a primary metabolite of terfenadine, in human serum is described. Sample preparation is carried out by liquid-liquid extraction under basic conditions. For an efficient clean up, the analytes are back-extracted into diluted hydrochloric acid and, after alkalinization, are once again extracted into the organic phase. No derivatisation step is performed. The samples are measured by gas chromatography-mass spectrometry with good selectivity. The limit of detection is 2 ng/ml. The coefficients of variation are 12.6% at 10 ng/ml and 6.44% at 200 ng/ml in the day-to-day control measurements.

Anti-Anxiety Agents↗

Determination of loratadine and pheniramine from human serum by gas chromatography-mass spectrometry.

In this work, a method for the determination of the antihistaminic drugs loratadine and pheniramine from human serum is presented. Serum samples are extracted under basic conditions with hexane-n-amyl alcohol (95:5, v/v), the analytes are reextracted into diluted hydrochloric acid and, after basification, are once again extracted into the organic phase. The samples are measured by GC-MS. The limits o detection of the assay are 0.5 ng/ml for loratadine and 2 ng/ml for pheniramine. The R.S.D.s in the day-to-day precision test for loratadine are 7.0% at 20 ng/ml and 12.4% at 2 ng/ml. for pheniramine, the R.S.D. are 6.4% at 300 ng/ml and 10.2% at 20 ng/ml.

Gas Chromatography-Mass Spectrometry↗

[Special qualification of a photometric procedure for determination of salicylic acid in therapeutic drug monitoring].

A procedure for the determination of salicylic acid from human serum is presented. It is based on an acidic extraction, a basic reextraction and the detection of salicylic acid as its iron-III-complex by photometry. The procedure is quantitative over a wide range of linearity, easy to carry out and is especially suitable for therapeutic drug monitoring in the treatment of juvenile rheumatoid arthritis.

Arthritis, Juvenile↗

Study on the bioequivalence of an oral nifedipine formulation and a sustained release reference preparation after single dose and repeated doses.

Pharmacokinetic parameters of an oral formulation of nifedipine (CAS 21829-25-4, Corinfar, test preparation T a dragee with 10 mg nifedipine) were compared with a reference preparation (R, a sustained release tablet with 20 mg nifedipine) in 16 healthy volunteers in a open two-way crossover study under the influence of ingestion of food. A GC/MS method was used to analyse the serum samples. The estimation of bioequivalence was based on a nonparametric statistical procedure of analysis of variance. Both, the test preparation T and the reference preparation R are bioequivalent at steady state. The main pharmacokinetic parameters (mean +/- standard deviation) used for the bioequivalence decision at steady state were AUC0- tau ss (T: 351.4 +/- 161.0 ng.ml-1.h; R: 345.5 +/- 146.8 ng.ml-1.h), Cmaxss (T: 67.3 +/- 29.5 ng.ml-1; 66.9 +/- 33.0 ng.ml-1) and HVDss (T: 3.8 +/- 1.3 h; R: 4.2 +/- 1.8 h). The bioequivalence of rate and extent of absorption was proved for both preparations at steady state by assessing mean serum level curves as well as by statistics (90% confidence intervals) using the main pharmacokinetic parameters AUC0 - tau ss (range: 0.84-1.02 point estimator: 0.92), Cmaxss (0.95-1.33; 1.15) HVDss (0.72-0.98; 0.82). The large interindividual variability of pharmacokinetics is typical of the drug and does not depend on the formulation used. No case of severe disturbance of circulatory function or other adverse events with the duty to treat occurred during the study. No volunteer dropped out.

Administration, Oral↗

Determination of nifedipine in human serum by gas chromatography-mass spectrometry: validation of the method and its use in bioavailability studies.

A procedure for the determination of nifedipine in human serum is described. The light-sensitive substance is isolated from serum by liquid-liquid extraction and analyzed using capillary gas chromatography with a mass-selective detector. The validation of the method shows that the extraction recovery is ca. 85%, the limit of detection is 2 ng/ml and the standard deviations of the intra-day precision test range from 5.8 to 7.4% with respect to the concentration. The procedure is highly selective and sensitive. It is especially suited for bioavailability studies because of its stability and high sampling rate.

Biological Availability↗

The cardiac effects of a novel A1-adenosine receptor agonist in guinea pig isolated heart.

Adenosine increases atrioventricular (AV) nodal conduction time and is used for termination of AV nodal re-entrant tachycardias, but it is rapidly metabolized. The purposes of the present study were to characterize the cardiac actions and effects of an orally active and stable adenosine analog, N6-cyclohexyl-2-O-methyladenosine (SDZ WAG-994) and to evaluate its potential as an antiarrhythmic agent. Guinea pig hearts were isolated and perfused with oxygenated Krebs-Henseleit solution. SDZ WAG-994 slowed the atrial rate and prolonged the AV nodal conduction time of spontaneously beating hearts in a concentration-dependent manner. The EC50 values for the negative chronotropic and dromotropic effects of SDZ WAG-994 were 0.69 +/- 0.04 and 1.49 +/- 0.54 microM, respectively. The A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.2 microM) significantly antagonized SDZ WAG-994-induced stimulus-to-His bundle (S-H) interval prolongation. The negative dromotropic effect of SDZ WAG-994 showed very strong frequency dependence. In hearts paced at an atrial cycle length of 300 msec (200 beats/min), the EC50 value of SDZ WAG-994 to prolong the S-H interval was 3.7-fold lower (0.40 +/- 0.02 microM) than in unpaced hearts, and at atrial pacing cycle lengths of 500 and 250 msec, 0.3 microM SDZ WAG-994 prolonged the S-H interval by 8 and 26 msec, respectively. SDZ WAG-994 also decreased coronary perfusion pressure (EC50 = 1.50 +/- 0.80 microM); this effect of SDZ WAG-994 was attenuated by adenosine deaminase and by 8-cyclopentyltheophylline (2 microM). Radioligand binding assays revealed that SDZ WAG-994 had a 280-fold greater affinity for A1- than for A2a receptors of the guinea pig brain. The marked frequency dependence of the negative dromotropic effect of SDZ WAG-994 suggests that this A1 agonist may be highly effective in the termination of AV nodal re-entrant tachycardias.

Adenosine↗

Validation of the analysis of carbamazepine and its 10,11-epoxide metabolite by high-performance liquid chromatography from plasma: comparison with gas chromatography and the enzyme-multiplied immunoassay technique.

An improved procedure for the determination of carbamazepine (CBZ) and its main active metabolite carbamazepine-10,11-epoxide (CBZ-e) in serum is described. The validation of this procedure shows that the limits of detection are lower than 80 ng/ml for CBZ and 7 ng/ml for CBZ-e. The relative standard deviation does not exceed 4.7% for both compounds in an inter-day precision test. In the intra-day precision test the relative standard deviations are 1.9% for CBZ-e and 1.1% for CBZ. A comparison of the described procedure with gas chromatography and the enzyme-multiplied immunoassay technique shows good agreement, but gas chromatography seems to have a relative poor reliability.

Carbamazepine↗