Die Anfänge der neuzeitlichen Chemie in der Pharmazie und Metallurgie. Zu E.F. Geoffroys tabelle stofflicher Beziehungen

E.F. Geoffroy's table of different relations (“rapports”) between different chemical substances is mainly based on empirical knowledge accumulated in 16th and 17th century metallurgy and pharmacy. The substances listed in the left half of the table were basic for the formation of salts which were produced for medical ends in the chemical-pharmaceutical practice of the 17th century. The right half of the table refers to substances and operations of metallurgy which had already been described in the metallurgical writings of the 16th century. Even Geoffroy's ordering of the substances within the columns of his table has its origin in metallurgical and pharmaceutical practice. The key concept of the conceptual framework underlying the table and its commentary is the concept of chemical compound which emerged at the end of the 17th century. Geoffroy extends the range of application of this concept, which was first limited to chemical artefacts, to include natural bodies. Eliminating the peripatetical distinction between natural bodies and chemical artefacts he formulates a new research program, consisting in the determination of the “laws” of the relations (“rapports”) between different chemical substances.     

Characterization of an ovarian cancer activating factor in ascites from ovarian cancer patients

Ascites from ovarian cancer patients contain potent growth-promoting activity toward human ovarian cancer cells both in vitro and in vivo. This activity is associated with rapid increases in cytosolic free calcium ([Ca2+]i) as a consequence of phosphoinositide hydrolysis. In this study, we describe the purification, characterization, and identification of an ovarian cancer activating factor (OCAF) from ascites of ovarian cancer patients. We have isolated OCAF by a combination of solvent extraction, silica gel chromatography, and TLC. Mass spectral analysis, phospholipase sensitivity, and gas chromatographic behavior of purified OCAF indicate that OCAF is composed of various species of lysophosphatidic acid (LPA), including LPAs with polyunsaturated fatty acyl chains (linoleic, arachidonic, and docosahexaenoic acids). However, OCAF is more potent than sn-1 palmitoyl, oleoyl, or stearoyl LPA in increasing [Ca2+]i in ovarian cancer cells. The ability of OCAF to alter [Ca2+]i is sensitive to the effects of lipoxidase, whereas the activity of sn-1 oleoyl, stearoyl, or palmitoyl LPA is not, suggesting that polyunsaturated bonds in the fatty acyl chain of OCAF may account for its increased ability to activate ovarian cancer cells. Furthermore, a sn-2 linoleoyl LPA generated by phospholipase A1 treatment of synthetic phosphatidic acid is much more active than are sn-1 palmitoyl, stearoyl, or oleoyl LPA in increasing [Ca2+]i in ovarian cancer cells. Taken together, these data suggest that the ability of OCAF to increase cellular calcium may reside in the structure and/or location of the fatty acyl chain of LPA. Purified OCAF, at concentrations similar to those present in ascites from ovarian cancer patients, was sufficient to induce proliferation of ovarian cancer cells, as indicated by thymidine incorporation, reduction of 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, or colony formation. However, even at optimal concentrations of OCAF, proliferation was lower than that induced by FCS or ascites from ovarian cancer patients, indicating that, although OCAF may be a major regulator of ovarian cancer cells in vivo, it is not the sole mediator present in ascites, and it likely functions in concert with other growth factor activities.     

Taking the challenge of multiple access for third-generationcellular mobile radio systems-a European view

In Europe, the challenge of the design of third-generation cellular mobile radio systems has been taken numerous research and development activities in this field have been started. The authors try to give an overview of the European activities in this field. The article is organized in two parts. In the first part, the requirements for third-generation cellular mobile radio systems such as Universal Mobile Telecommunications System (UMTS) and Future Public Land Mobile Telecommunications System (FPLMTS), which has been named International Mobile Telecommunications after the year 2000 (IMT-2000) are presented concisely. Also, the importance and challenge of the multiple access design for such third-generation cellular mobile radio systems is explained. In the second part, numerous European research activities with focus on the multiple access design for third-generation cellular mobile radio systems are reviewed     

The pharmacokinetics and pharmacodynamics of the oral iron chelator deferiprone (L1) in relation to hemoglobin levels

Recently, we demonstrated that administration of the orally active iron chelating agent deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one (L1)) at 6-hour intervals results in significantly greater urinary iron excretion than that induced during administration of the drug at 12-hour intervals. That study was conducted in thalassemia patients, all of whom had received a packed red cell transfusion of 15 cc/kg. 72 hours prior to evaluation of urinary iron excretion, at a time when endogenous erythropoiesis would be expected to be at its lowest. In clinical practice however, thalassemia patients, suppression of endogenous erythropoiesis is not sustained between transfusions. We set out to determine the influence that administration of deferiprone has on urinary iron excretion at lower hemoglobin concentrations, immediately prior to transfusion. We hypothesized that hemoglobin levels will affect the ability of deferiprone to chelate iron. Ten regularly transfused patients with homozygous beta-thalassemia (HBT) aged mean +/- SD, 20.9 +/- 4.7, range 13 - 27 years, receiving long-term therapy with deferiprone, were treated with deferiprone 75 mg/kg/day, administered every 6 hours (or every 12 hours) for 72 hours immediately prior to a blood transfusion in the first month. One month later each patient received the other of the 2 dosing regimens for 72 hours immediately prior to transfusion. The deferiprone-induced 24-hour urinary iron excretion was similar during both dosing regimens; 0.56 +/- 0.45 mg/kg when L1 was given every 6 hours and 0.48 +/- 0.52 mg/kg when L1 was administered every 12 hours (p = 0.79). However, the calculated 24-hour area under the plasma concentration-time curve (AUC0-24) of deferiprone was significantly lower when deferiprone was administered at 6-hour intervals (6,762.8 +/- 1,601.6 mg*min/l), than that observed when deferiprone was administered every 12 hours (8,250.1 +/- 1,235.7 mg*min/l) (p = 0.04). The pharmacokinetics of deferiprone when administered immediately prior to transfusions are different from those following transfusions. More studies assessing total body iron excretion are needed to determine the contribution of the fecal route in iron excretion.     

Flow reversal in the descending aorta: a guide to intraoperative assessment of aortic regurgitation with transesophageal echocardiography

This study assessed the value of biplane transesophageal echocardiographic assessment of diastolic flow reversal in the descending aorta as an alternative to Doppler color flow imaging in determining severity of aortic regurgitation. In 45 patients undergoing cardiac operations, the severity of aortic regurgitation was assessed by semiquantitative grading of the width of the Doppler color flow regurgitant jet relative to the left ventricular outflow tract, and the presence of diastolic flow reversal was assessed with pulsed-wave Doppler measurements at three sites in the descending aorta. In four patients, the diastolic flow reversal method was the only available form of assessment because of inadequate visualization of the left ventricular outflow tract beneath a mitral valve prosthesis. Diastolic flow reversal in the descending aorta was not observed in patients without aortic regurgitation and was always present in patients with severe aortic regurgitation. Aortic valve replacement successfully eliminated descending aortic flow reversal in all 19 patients in whom it was present before valve replacement. Identification of diastolic flow reversal at multiple sites in the descending aorta with biplane transesophageal echocardiography helps to confirm the presence of severe aortic regurgitation and can serve as an alternative method of assessment when visualization of the left ventricular outflow tract is impaired.     

Prostanoid biosynthesis by blood monocytes of children with hyperprostaglandin E syndrome

Hyperprostaglandin E syndrome (HPS), the prenatal variant of Bartter's syndrome, is characterized by a marked and selective stimulation of prostaglandin E (PGE2) synthesis. In the study group HPS patients showed increased urinary levels of PGE2, an index of renal, and of 11 alpha-hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostano ic acid (PGE-M), an index of systemic PGE2 synthesis of 470% and of 570%, respectively. In addition, plasma concentration of PGE-M was also elevated 6.3-fold when compared with a control group. The urinary levels of other prostanoids were unaltered. During indomethacin treatment in both groups prostanoid excretion rates were suppressed to similar levels. To investigate the origin of stimulated prostanoid biosynthesis in HPS patients CD14+ monocytes were isolated from plasma samples, and the prostanoid synthesis was analyzed. The pattern and amounts of metabolites synthesized from endogenous arachidonic acid pools did not vary significantly between monocytes of the HPS and the control group. Thromboxane A2 (TXA2) was formed as the major prostanoid product. Using PGH2 as an exogenous substrate, again no difference in PGE2 biosynthesis was observed, indicating no difference in PGE-synthetic activity between both groups. Additionally, mRNA expression analysis of CD14+ monocytes via RT-PCR delineated the constitutive expression of cyclooxygenase-1, cyclooxygenase-2, and thromboxane synthase mRNA in cells from HPS patients and controls without statistical differences between these two groups. In conclusion, our data show that monocytes are not the source for the increased PGE2 biosynthesis in children with HPS, and a genetic defect in PGE synthesis can be excluded as the primary event in the pathogenesis in HPS.