Biomedical subjects
Publications and source records attributed to C Brückner.
A series of new 2-pyrrolylthiones was synthesized and found to be good chelating agents for transition metals and technetium.
The rigid tris- and bis(catecholamide) ligands H(6)A, H(4)B and H(4)C form tetrahedral clusters of the type M(4)L(4) and M(4)L(6) through self-assembly reactions with tri- and tetravalent metal ions such as Ga(III), Fe(III), Ti(IV) and Sn(IV). General design principles for the synthesis of such clusters are presented with an emphasis on geometric requirements and kinetic and thermodynamic considerations. The solution and solid-state characterization of these complexes is presented, and their dynamic solution behavior is described. The tris-catecholamide H(6)A forms M(4)L(4) tetrahedra with Ga(III), Ti(IV), and Sn(IV); (Et(3)N)(8)[Ti(4)A(4)] crystallizes in R3(-)c (No. 167), with a = 22.6143(5) A, c = 106.038(2) A. The cluster is a racemic mixture of homoconfigurational tetrahedra (all Delta or all Lambda at the metal centers within a given cluster). Though the synthetic procedure for synthesis of the cluster is markedly metal-dependent, extensive electrospray mass spectrometry investigations show that the M(4)A(4) (M = Ga(III), Ti(IV), and Sn(IV)) clusters are remarkably stable once formed. Two approaches are presented for the formation of M(4)L(6) tetrahedral clusters. Of the bis(catecholamide) ligands, H(4)B forms an M(4)L(6) tetrahedron (M = Ga(III)) based on an "edge-on" design, while H(4)C forms an M(4)L(6) tetrahedron (M = Ga(III), Fe(III)) based on a "face-on" strategy. K(5)[Et(4)N](7)[Fe(4)C(6)] crystallizes in I43(-)d (No. 220) with a = 43.706(8) A. This M(4)L(6) tetrahedral cluster is also a racemic mixture of homoconfigurational tetrahedra and has a cavity large enough to encapsulate a molecule of Et(4)N(+). This host-guest interaction is maintained in solution as revealed by NMR investigations of the Ga(III) complex.
The metal-chelating ability of 2-pyrrolylthiones is described. The readily available ligands di-2-pyrrolyl thione (6), 2-thioacetylpyrrole (10), and 2-thiobenzoylpyrrole (11) constitute examples of monoanionic ligands with N,S-donor atom sets, although di-2-pyrrolyl thione (6) could theoretically also achieve chelation through an N,N-donor set. A square planar Ni(II) complex, 14, an octahedral Co(III) complex, 18, and a tetrahedral Hg(II) complex, 17, with the di-2-pyrrolyl thionato chelate have been prepared, and their structures have been characterized by 1H NMR, UV-vis, MS, IR, elemental analysis, and single-crystal X-ray diffraction. Crystal data for 14: C18H14N4NiS2.0.28H2O, trigonal, R3, a = 18.467(1) A, b = 18.467(1) A, c = 26.404(2) A, V = 7797(1) A3; Z = 18, R = 3.2%. Crystal data for 18-mer: C27H21CoN6S3.C3H6O (acetone), monoclinic, P21/n, a = 9.569(1) A, b = 23.152(1) A, c = 13.659(1) A, beta = 100.882(8) degrees, V = 2971.6(5) A3, Z = 4, R = 4.3%. Crystal data for 17: C18H14HgN4S2, triclinic, P1, a = 8.443(2), b = 14.278(1) A, c = 7.445(1) A, alpha = 90.561(9) degrees, beta = 97.64(1) degrees, gamma = 104.250(9) degrees, V = 861.3(2) A3, Z = 2, R = 4.2%. The bond lengths and angles of these metal complexes are comparable to those of known N,S-chelates. A comparison of the structural parameters of the ligand in the metal complexes with those for the free ligand 6 demonstrates the preorganization of the free ligand for complexation and demonstrates the spectator role of the noncoordinating pyrrolic unit. Chelation of Ni(II) by 2-thioacetylpyrrole (10) and 2-thiobenzoylpyrrole (11) to provide complexes 12 and 13 with structures analogous to complex 14 is also described.
Application of 4-aminopyridine (4-AP) has previously been reported to produce different patterns of epileptiform discharges in entorhinal cortex (EC)-hippocampal slices: recurrent short discharges (RSDs) in hippocampal area CA1, seizure-like events (SLEs) and negative-going potentials (NGPs) in the medial entorhinal cortex (mEC). Using recordings of field potentials, we investigated the pharmacological effects of the clinically employed standard anticonvulsant drugs phenytoin (PHT), carbamazepine (CBZ), valproic acid (VPA) and phenobarbital (PHB) and those of pentobarbital (PB) on 4-AP-induced epileptiform activity. The anticonvulsant drugs showed different effects: SLEs were completely blocked by all tested drugs. Valproic acid, which suppressed all epileptiform activities, seemed to have the most fundamental effect of all drugs on 4-AP induced activity, because under phenytoin and carbamazepine, some epileptiform activity was still observable. The RSDs in hippocampal area CA1 of the hippocampus did not respond to the different anticonvulsants. In contrast, PB decreased the frequency of the RSDs in CA1 and enhanced the frequency of the NGPs in the EC. We propose that the activities induced by 4-AP in the combined entorhinal cortex-hippocampal slices may provide an in vitro model for the development of new drugs against difficult-to-treat focal epilepsy.
Results regarding the anticonvulsant potency of bromide have been questioned, and the mechanisms of its action are unclear. Using combined rat hippocampus-entorhinal cortex slices we analyzed the effects of NaBr on four types of epileptiform discharges in two different models of epilepsy, the low-Ca2+ and the low-Mg2+ model. NaBr concentration-dependently reduced the frequency and finally blocked the low Ca2+-induced discharges. Low Mg2+-induced short recurrent discharges were also reduced in a concentration-dependent manner. In the entorhinal cortex the frequency of seizure-like events was reduced by 3 and 5 mM and the discharges were blocked by 7 mM NaBr. Also, the late recurrent discharges in the entorhinal cortex which do not respond to most clinically employed anticonvulsants were reduced by concentrations of 10 and 15 mM and completely blocked by 30 mM NaBr. Using pH-sensitive microelectrodes different effects of NaBr were seen than those of acetazolamide on extracellular pH under control conditions and after stimulation. Acetazolamide at 1 mM caused a reversible acidification of delta pH: 0.2+/-0.14 at rest whereas no change on extracellular pH was seen with 5 mM NaBr. Acetazolamide increased the transient alkalosis induced by repetitive stimulation of the stratum radiatum in area CA1 and reduced the subsequent acidosis. NaBr also increased the alkalosis but had no effect on the subsequent acidosis. A significant increase in paired-pulse inhibition was seen in a paired-pulse stimulation protocol used to monitor the efficacy of GABAergic inhibition at concentrations of 5 mM NaBr. This finding was confirmed in whole-cell patch clamp recordings from cultured hippocampal neurons showing an increase in inhibitory postsynaptic current amplitude. In summary, our results suggest a broad-spectrum anticonvulsant activity which is likely to be caused by its effects on membrane excitability, by an increase in GABAergic inhibition and is less likely caused by its effects on extracellular pH.
Application of 4-aminopyridine (4AP) has previously been reported to produce different patterns of epileptiform discharges in entorhinal cortex-hippocampal-slices. Here we describe that 4-AP induced epileptiform activity in the EC becomes insensitive to anticonvulsant drugs (phenytoin, carbamazepine, valproic acid, phenobarbital) when GABAergic transmission is blocked by bicuculline. We propose that the activities induced by 4-aminopyridine and bicuculline may provide an in vitro model for the development of new drugs against difficult-to-treat focal epilepsy.
The endoscopic release of the carpal ligament gives the opportunity to treat the carpal tunnel syndrome in a comfortable and minimal invasive way. Between 1 October 1994 and 7 May 1995, 46 patients who underwent endoscopic surgery on 55 hands were documented in a prospective study. The following results were taken from a questionnaire. There were not any complaints, or the complaints were so much diminished that complete division of the carpal ligament could be viewed as accomplished in 51 of 55 cases. There were continuing complaints in four cases, and after an additional check two patients were operated on again. The advantage of the endoscopic method is the inconspicuous scar and the reduced postoperative disablement. No complications have occurred.
Ring core-biotinylated testosterone tracers were synthesized with bridges of three different lengths connecting the biotin moiety to the steroid core (7 alpha-Cn-Bio-T, n = 3, 6, or 11). Together with a position 7-specific polyclonal anti-testosterone antibody, we used the 7 alpha-C11-Bio-T tracer to develop a novel, labeled-hapten competitive immunoassay for total testosterone in serum. (The C3 and C6 tracers proved to be not suitable for analogous immunoassays.) Enhanced chemiluminescence signal was generated by use of a second immobilized antibody and a streptavidin-horseradish peroxidase conjugate. The measuring range of the assay is 0.2-20.0 nmol/L, linearity of serial dilutions can be demonstrated, the lower detection limit is 0.125 nmol/L, and the interassay imprecisions are 13-16%. Accuracy determinations in mass spectrometry-controlled reference specimens showed a mean recovery of 95%. In addition, the assay shows low cross-reactivities, demonstrating the favorable specificity of the combination of a "nearly native" tracer with a position analog antibody. The optimized steric structure and the long spacer arm of the biotinylated testosterone tracer make this chemiluminescence assay well-suited for measuring total testosterone concentration in serum.
A unilateral written declaration in which someone expresses his or her will to die under certain circumstances is legally valid and binding on third persons who may have knowledge of this declaration, provided that the declaration contains only prohibitions and no orders to positive action, provided it has been written by an adult person not under the influence of error, fear or mental incapacity, provided also that the declaration is not in contradiction with the expression of actual desire to live, such as expression of hunger, thirst or fear of death, and provided finally that the declaration is not in contradiction with what has to be assumed as the future desire of the patient to live once he awakes from his present unconsciousness. Other instructions in the declaration, such as the desire to receive medicaments in lethal quantities, deprivation of artificial nutrition once the person no longer recognizes his relatives, or refusing of reanimation if future dependence on other people's help can be foreseen, are legally invalid.
Plant galactagogues can successfully help to stimulate lactation. A survey on the drugs most commonly used in Europe is presented, and their role in folk medicine as well as their efficiency in clinical tests are discussed. Recommendations for galactagogous teas to support breast-feeding are made.
We investigated a total of 537 patients (68 men, 469 women) working in the textile industry to ascertain their hearing level in the conventional hearing range as well as in the HF range. The persons tested work at 3 different noise levels (80-84, 85-89 and 90-94 dB [A] Leq). The differences in the hearing thresholds of the three sound level groups mentioned above were checked by means of discrimination analysis. The first hearing level changes noise levels below 90 dB develop mainly in the HF range; in the conventional hearing range, however, the hearing levels remain unchanged even during long exposure times. Hearing level impairment in the conventional range occurs only in the sound level group of 90-94 dB (A) Leq without attaining any social importance. The tests clearly show that if the noise level damage risk criterion of 85 dB (A) Leq at which hearing is impaired, is not exceeded any hearing lesions involving social hearing loss are definitely avoided.
In 59 workers between the ages of 22 and 66, who had been exposed to pesticides, and 31 healthy controls between the ages of 22 and 28, the hepatic demethylation capacity was studied using the aminophenazone breath test (ABT). The ABT was carried out in two versions (version A: 111 kBq 14C-aminophenazone per 630 mg, version B: 111 kBq 14C-aminophenazone per 3 mg). The amount of 14CO2 expired per mmol CO2 per 70 kg body weight (b.w.) detected 1 h after 14C-aminophenazone intake was used to determine the demethylation capacity of the liver. The amount of expired 14CO2 depended on the ingested dose (B greater than A). The 14CO2-values measured in 13 controls did not differ from those obtained in 37 subjects who had been exposed to pesticides for 650 h per year on the average [649 vs 726 DPM/mmol X 70 kg b.w. (A)]. The 14CO2-values obtained in 22 subjects exposed to pesticides for 990 h per year on the average (B) were lower than those obtained in 18 healthy controls (736 vs 1024 DPM/mmol CO2 X 70 kg; P less than 0.05). The 14CO2-values of ABT decreased with increasing length of exposure per year (B; r = -0.51, P less than 0.05).
The reactions of the human organism to noise are complicated and difficult to separate from other stressors, with the exception of hearing damage. After thorough experimental planning and a rigorous selection of sample persons, the reaction to noise of varying structures was studied by reactions of heart rate, blood pressure, reaction time, the temporary threshold shift (TTS) of hearing and the psychological parameters "Mood" (in German "Befinden"). We found a special kind of TTS dependent on the structure o noise and no effect of physiological parameters. The psychological parameter tended to have a significant influence on individual factors.
Explore the source record for details and available documents.
Four groups of 6-7-month-old Merino lambs were each dosed with 40 000 infective larvae of Trichostrongylus axei on 2 November 1976 and subsequently exposed to challenge with Haemonchus contortus on natural grazing at the University of Pretoria's Experimental Farm in the eastern suburbs of Pretoria. One of these groups and one group of controls were killed every 8 weeks from the end of December 1976-June 1977. Predosing with T. axei was greater than 50% effective against 5th stage and adult H. contortus in greater than 50% of sheep for 164 days (Class C), improving to greater than 60% in greater than 60% of sheep (Class B) 220 days after dosing T. axei. The numbers of retarded 4th stage larvae (L4) of H. contortus in the undosed controls as well as in the sheep predosed with T. axei rose from a low level in summer (December) to a peak in late Autumn (June).
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Two doses of infective larvae of 20 000 Trichostrongylus axei, dosed to Merino lambs at an interval of 14 days and subsequently challenged with Ostertagia circumcincta, caused a significant reduction (P less than 0.01) in the establishment of 5th and adult stages of the latter. T. axei was unable to protect Merino sheep against homologous challenge nor was Haemonchus contortus a successful vaccine against challenge with the same species. The vaccinated group showed a reduction (P less than 0,025) only in 5th and adult H. contortus, but not in the total worm burdens.