Über die Verteilung von Radiostrontium in den Organen eines menschlichen Feten

Ohne Zusammenfassung     

In vivo measurement of intracellular pH in human brain during different tensions of carbon dioxide in arterial blood. A 31P-NMR study

The effect of changes in carbon dioxide tension in arterial blood upon intracellular pH in brain tissue was studied in seven healthy volunteers, aged 22-45 years. The pH changes were monitored by use of 31P nuclear magnetic resonance spectroscopy, performed on a whole-body 1.5 Tesla Siemens imaging system. The measurements were carried out during hyperventilation and with the subject breathing atmospheric air containing 5 vol. % and 7 vol. % carbon dioxide. Intracellular pH increased significantly during 15 min of hyper-ventilation and decreased significantly during 18 min respiration of air containing 7 vol. % carbon dioxide. The intracellular buffer capacity was estimated. These results suggest that the ventilation response to carbon dioxide is correlated to changes in intracellular fluid pH.     

EEG-Monitored ECT: A Comparison of Seizure Duration under Anesthesia with Etomidate and Thiopentone

Electroencephalogram-monitored electroconvulsive therapy (ECT) was carried out in 20 depressed inpatients. Before treatment, patients were randomly allocated to treatment using etomidate (Hypnomidat) (n = 10) or thiopentone (n = 10) for anesthesia. The groups were matched for sex, age, weight, and type and severity of depression. The seizure duration (seconds) was measured by electroencephalography (EEG), and the electrical energy (Joules, J) was determined for each treatment. A ratio of seizure duration:electrical energy (s/J) was computed. Both seizure duration and seizure duration:electrical energy were greater in the etomidate group than in the thiopentone group, whereas electrical energy did not differ significantly. The number of treatments in the etomidate group did not differ from that in the thiopentone group, as may be expected, perhaps because of the small size.     

Medical, social and occupational history as risk indicators for low-back trouble in a general population

Sixty-eight medical, social, and occupational history variables were analyzed in a general population of 442 men and 478 women, aged 30, 40, 50, and 60 years to identify possible indicators for first-time experience and recurrence or persistence of low-back trouble (LBT) during a 1-year follow-up. Variables that in univariate analyses showed statistically significant indications for future LBT were subjected to stepwise logistic regression analyses. The most important indicators for recurrence or persistence of LBT thus identified were, for men, intermittent claudication, restlessness, or other discomfort in the lower limbs, frequent headache, and living alone. For women, the corresponding indicators were rumbling of "the stomach" and feeling of fatigue. For first-time experience of LBT, the indicators identified by the regression analyses were frequent pain in the top of the stomach, previous hospitalizations and operations, daily smoking, and a long distance from home to work. The result suggests that the population likely to experience future LBT does not enjoy good general health even prior to its first LBT episode, and this, in turn, may be due to greater psychosocial pressure.     

CPCCOEt, a noncompetitive metabotropic glutamate receptor 1 antagonist, inhibits receptor signaling without affecting glutamate binding

Metabotropic glutamate receptors (mGluRs) are a family of G protein-coupled receptors characterized by a large, extracellular N-terminal domain comprising the glutamate-binding site. In the current study, we examined the pharmacological profile and site of action of the non-amino-acid antagonist 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt). CPCCOEt selectively inhibited glutamate-induced increases in intracellular calcium at human mGluR1b (hmGluR1b) with an apparent IC50 of 6.5 microM while having no agonist or antagonist activity at hmGluR2, -4a, -5a, -7b, and -8a up to 100 microM. Schild analysis indicated that CPCCOEt acts in a noncompetitive manner by decreasing the efficacy of glutamate-stimulated phosphoinositide hydrolysis without affecting the EC50 value or Hill coefficient of glutamate. Similarly, CPCCOEt did not displace [3H]glutamate binding to membranes prepared from mGluR1a-expressing cells. To elucidate the site of action, we systematically exchanged segments and single amino acids between hmGluR1b and the related subtype, hmGluR5a. Substitution of Thr815 and Ala818, located at the extracellular surface of transmembrane segment VII, with the homologous amino acids of hmGluR5a eliminated CPCCOEt inhibition of hmGluR1b. In contrast, introduction of Thr815 and Ala818 at the homologous positions of hmGluR5a conferred complete inhibition by CPCCOEt (IC50 = 6.6 microM), i.e., a gain of function. These data suggest that CPCCOEt represents a novel class of G protein-coupled receptor antagonists inhibiting receptor signaling without affecting ligand binding. We propose that the interaction of CPCCOEt with Thr815 and Ala818 of mGluR1 disrupts receptor activation by inhibiting an intramolecular interaction between the agonist-bound extracellular domain and the transmembrane domain.     

Pharmacokinetics of sulfadiazine and trimethoprim in man

Summary Sulfadiazine (SDZ) 800 mg and trimethoprim (TMP) 160 mg were given orally to 10 normal subjects and the concentration of SDZ and TMP in serum and urine was followed for 24 h. Both drugs showed a significant negative correlation between individual peak concentrations in serum and the body weight of the subject. Twelve hours after dosing the serum concentration was 12 to 25 µg/ml for SDZ and 0.3 to 1.1 µg/ml for TMP. Individual concentration ratios between SDZ and TMP in serum were 4.8 (1 h) – 145 (24 h), and in the urine the ratio was close to 6 throughout the 24 h collection period. The range of urinary concentrations was from 65 to 400 µg/ml for SDZ and from 13.8 to 93.4 µg/ml for TMP. The fraction acetylated SDZ/acetylated SDZ + SDZ was 21% during the 0–8 h period, 33% during the 8–15 h period and 41% during the 15–24 period. The average values for the notional volume of distribution, V_d, were 0.36±0.13 1/kg for SDZ and 1.39±0.25 1/kg for TMP. The average t_1/2 was 15.2±7.4 h for SDZ and 7.4±1.9 h for TMP. Individual subjects showed a significant correlation between the serum clearance of TMP and SDZ (p<0.01) and also between the renal clearance of the two drugs (p<0.05). The serum clearance was significantly correlated with the renal clearance for TMP but not for SDZ. For SDZ V_d was significantly negatively correlated with the elimination constant; for TMP no such correlation was found. The serum clearance of SDZ was significantly correlated with the percentage of SDZ which was excreted as the (presumably) acetylated compound. The renal clearance of SDZ was independent of the serum concentration of SDZ. There was a highly significant negative correlation between the renal clearance and serum concentration of TMP, as well as for acetylated SDZ. The renal clearance of acetylated SDZ averaged more than six times that of unconjugated SDZ. With increased urine flow the renal clearances of TMP and SDZ were significantly increased.