Studies on the Biotransformation of Veratric Acid, a Human Metabolite of Mebeverine, by Using the Incubated Hen's Egg.

Metabolism studies with selected test substances have shown that a model on the basis of the incubated hen's egg is suitable as a supplement to animal experimentation. Because of its 3,4-dimethoxyphenyl structure veratric acid (3,4-dimethoxybenzoic acid), a known human metabolite of mebeverine, was chosen as model substance for the present investigations and the parent compound as well as 4-hydroxy-3-methoxybenzoic acid were identified as main metabolites. The absence of 3-hydroxy-4-methoxybenzoic acid lets conclude that the O-demethylation takes place exclusively at the p-methoxyl function. In addition, 3,3',4,4'-tetramethoxy-l-ornithuric acid (2,5-bis-(3,4-dimethoxybenzoylamino)pentanoic acid) and its O-desmethyl derivative could be characterized as further metabolites. So far an amino acid conjugate has not been described after veratric acid administration in a vertebrate. There were no indications for the appearance of 3,4-dihydroxybenzoic acid in the veratric acid metabolism. This was confirmed by corresponding studies having the isomeric guaiacol acids as precursor. Furthermore, it could be proved that in ovo the O-methylation of 3,4-dihydroxybenzoic acid occurs regioselective at the m-hydroxyl group. The results which broaden the knowledge on the metabolic fate of veratric acid are discussed in comparison with those in mammals. The metabolites were identified by GC-MS, ESI-HRMS and LC/ESI-MS/MS. The structure of the synthesized reference substance was confirmed by MS, (1)H and (13)C NMR spectral data.

[Congenital syphilis despite prenatal screening? An evaluation of 14 cases]. / Konnatale Syphilis trotz Mutterschaftsvorsorge? Eine Evaluierung von 14 Fällen.

BACKGROUND: Congenital syphilis (CS) can be effectively avoided by adequate treatment of the mother during pregnancy. Nevertheless, in recent years, the Robert Koch Institute has reported 6-8 of CS cases per year. The aim of this study was to investigate cases of CS with regard to obstetrical history and results of maternal syphilis serology during pregnancy and postpartum. PATIENTS AND METHODS: Between 1997 and 2001, a total of 14 cases of CS were diagnosed after birth in the Stuttgart laboratory. Information on clinical and serological data obtained during prenatal care and at birth had been provided by the treating gynaecologists and paediatricians. Furthermore, serum samples from 11 of the 14 mothers were investigated at the Stuttgart laboratory after birth and also retrospectively at the Herford laboratory. RESULTS: All mothers presented without clinical signs of syphilis. Delayed prenatal care was observed in 6 out of 14 cases. Eleven of the 14 mothers had a positive treponemal screening test. Treatment was initiated only in two of them. During pregnancy treponemal IgM and cardiolipin antibodies were detected in none of 9 and in 5 of 8 sera of untreated mothers, respectively. In contrast, maternal serum samples investigated after birth were all positive for cardiolipin antibodies and 7 of 10 serum samples were positive for TP IgM antibodies. CONCLUSIONS: Delayed or absent prenatal care and misinterpretation of syphilis serology (or laboratory failures) in the presence of latent syphilis are mostly responsible for the inadequate management of syphilis during pregnancy and thus the occurrence of CS.

The addition of interscalene block to general anesthesia for patients undergoing open shoulder procedures.

Several studies have demonstrated that interscalene brachial plexus anesthesia alone decreases postoperative pain, nausea, vomiting, urinary retention, and unplanned hospital admissions compared with general anesthesia alone. Anecdotal evidence suggests that an interscalene block combined with general anesthesia decreases unwanted effects of general anesthesia following open shoulder surgery. We compared the effect of combined interscalene block and general anesthesia with general anesthesia alone on Aldrete scores, length of postanesthesia care unit (PACU) stay, verbal rating scale (VRS) pain scores, incidence of postoperative narcotic administration and nausea, and patient satisfaction in a convenience sample of 52 men and women, ASA physical status I, II, or III. Group 1 received standard general anesthesia alone. Group 2 received an interscalene block in combination with general anesthesia using a standard technique. Group 2 had significantly lower VRS scores than group 1 while in the PACU, on the day of surgery, and on postoperative days 1 and 2. Overall satisfaction with the anesthetic technique was higher in the group 2 than in group 1. Results suggest that adding an interscalene block to general anesthesia can be of value in today's outpatient-dominated surgery schedule.

Recombinant expression and isolation of human L-arginine:glycine amidinotransferase and identification of its active-site cysteine residue.

Creatine and its phosphorylated form play a central role in the energy metabolism of muscle and nerve tissues. l-Arginine:glycine amidinotransferase (AT) catalyses the committed step in the formation of creatine. The mitochondrial and cytosolic forms of the enzyme are believed to derive from the same gene by alternative splicing. We have expressed recombinant human AT in Escherichia coli with two different N-termini, resembling the longest two forms of the enzyme that we had isolated recently from porcine kidney mitochondria as a mixture. The enzymes were expressed with N-terminal histidine tags followed by factor Xa-cleavage sites. We established a new method for the removal of N-terminal fusion peptides by means of an immobilized snake venom prothrombin activator. We identified cysteine-407 as the active-site residue of AT by radioactive labelling and isolation of labelled peptides, and by site-directed mutagenesis of the protein.

Midgut nonrotation in adults. An aggressive approach.

Five adults with midgut nonrotation were treated at Tripler Army Medical Center between January 1, 1966 and January 1, 1974. These patients usually presented with vague epigastric or lower abdominal symptoms. Initial diagnosis was generally based on barium enema studies revealing an entirely left-sided colon. However, on upper gastrointestinal series the absence of a normal duodenal "c" loop with straightening is also seen. Duodenal obstructive bands are rarely documented radiographically. Surgical intervention is frequently delayed in these patients due to the "atypical" symptoms and lack of correlation of these symptoms with objective radiographic changes. The high incidence of associated duodenal ulcer disease, the frequent occurrence of bowel obstruction, the persistence of chronic abdominal pain in the untreated patients, and the resolution of symptoms after anatomic correction point to the need for an aggressive approach to treatment in those patients who have chronic recurrent symptoms secondary to midgut nonrotation.