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Biomedical subjects

K Voigt

Publications and source records attributed to K Voigt.

At least 55 records · Page 3Linked to original sources

Inhibition of nitric oxide synthase results in a suppression of interleukin-1beta-induced fever in rats.

Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) induce nitric oxide synthase. The purpose of this study was to investigate the role of endogenous nitric oxide in IL-1beta-induced fever in rats. At a dose of 2.5 microg per animal intraperitoneal (i.p.) injections of rat recombinant IL-1beta evoked a febrile response with a duration of 8 hours. Simultaneous i.p. injection of 50 mg/kg N-nitro-L-arginine methyl ester hydrochloride (L-NAME) resulted in a complete suppression of IL-1beta-induced fever in rats. I.p. injection of 50 mg/kg L-NAME alone had no apparent influence on body core temperature. Endogenous formation of IL-6 in response to IL-1beta was not suppressed but rather enhanced by treatment with L-NAME during the early stage of IL-1beta-induced fever. This result indicates that activation of nitric oxide synthase and thereby endogenous NO-formation is essential for the generation of an IL-1beta-induced febrile response in rats and that the suppression of IL-1beta-induced fever by treatment with L-NAME seems not to be caused by an inhibition of IL-6 production.

Animals↗

Three-dimensional spiral CT angiography in the detection of cerebral aneurysm.

PURPOSE: The value of CT angiography in the detection and evaluation of aneurysms was compared to digital subtraction angiography (DSA). MATERIAL AND METHODS: Seventeen patients with acute subarachnoid hemorrhage (SAH) or with known or suspected aneurysm were investigated by means of spiral CT angiography, which included 3D reconstruction. These findings were compared with those at DSA. RESULTS: In 16 patients, 20 aneurysms were found; the remaining patient had an ectatic vessel that simulated an aneurysm. Seventeen of the angiographically proved aneurysms were detected at CT angiography (sensitivity 85%). One further aneurysm was identified retrospectively as the result of greater experience in the method. All the aneurysms that escaped detection at CT were 3 mm in size. All the vessels of the circle of Willis, except for the posterior communicating artery, were properly evaluated at CT angiography. Difficulties were encountered in assessing the posterior communicating artery and the extradural segment of the internal carotid artery owing to their close spatial relationship to the bony structures of the skull base and the cavernous sinus. CONCLUSION: CT angiography is a low-risk technique with a low level of invasiveness that is useful in following up known aneurysms. The 3D reconstruction yields further topographic information that helps in the planning of endovascular or surgical intervention. The facility for rotating the reconstructed vessels and displaying them from different angles is of particular value in cases difficult to assess at angiography.

Adult↗

Tumor-related venous obstruction and development of peritumoral brain edema in meningiomas.

OBJECTIVE: The exact pathogenesis of peritumoral brain edema (PTBE) in meningiomas is still unknown. A number of different pathophysiological hypotheses have been considered. A detrimental effect of tumor-related venous obstruction has been suggested as one pathogenetic mechanism. We sought to characterize the significance of venous stasis in the development of PTBE in meningiomas. METHODS: Angiograms for 134 patients with 136 intracranial meningiomas were analyzed. Pathological changes affecting cortical veins, sylvian veins, bridging veins, deep veins, transmedullary veins, and dural sinuses were evaluated. From preoperative computed tomographic scans, the total tumor volume, the tumor/PTBE volume ratio (edema index [EI]), and the location of the edema were determined. For statistical evaluation, meningiomas associated with pathological venous drainage were compared with size-matched controls. RESULTS: The edema incidence and the mean EI were not different for meningiomas with unselected signs of obstructed venous drainage, compared with controls. In particular, lesions with involvement of cortical veins, bridging veins, and dural sinuses showed no higher edema incidence. However, meningiomas associated with venous changes in sylvian veins (EI = 4.9 versus EI = 2.7; P < 0.004) and with dysplastic transmedullary veins (EI = 3.3 versus EI = 1.7; P < 0.04) showed significantly higher mean EI values, compared with meningiomas without involvement of these vessels. CONCLUSION: Our data suggest that tumor-related venous obstruction does not play an essential role in the development of PTBE for the majority of meningiomas. For a small subgroup of meningiomas with involvement of sylvian veins or development of dysplastic transmedullary veins, changes in venous drainage may aggravate preexisting PTBE.

Adult↗

Resting membrane properties of locust muscle and their modulation I. Actions of the neuropeptides YGGFMRFamide and proctolin.

The resting K+ conductance (GK,r) of locust jumping muscle and its modulation by two neuropeptides, proctolin (Arg-Tyr-Leu-Pro-Thr) and YGGFMRFamide (Tyr-Gly-Gly-Phe-Met-Arg-Phe-NH2), were investigated using the two-electrode voltage clamp. At a physiological [K+]o of 10 mM, GK,r accounts for approximately 90% of the membrane resting conductance, and the resting membrane potential differs by </=1 mV from EK (mean: -74 mV). There is a K+ conductance that slowly activates on hyperpolarization (GK,H) and that seems to be largely located in the transverse tubules. Steady-state activation of GK,H was analyzed by tail current measurements. GK,H is activated partially at EK but accounts for probably </=50% of total resting K+ conductance. Raising [K+]o caused a large increase in GK,r and in maximal steady state GK,H without shifting the voltage sensitivity of GK,H. YGGFMRFamide and proctolin reduce GK,H, mainly affecting the maximal steady-state conductance. The voltage-insensitive component of the resting K+ conductance is also reduced. The conductance suppressed by the peptides exhibited an outwardly rectifying instantaneous current/voltage-characteristic that is quite similar to that of GK,H. The actions of the two peptides appeared to be identical, but proctolin was by some two orders of magnitude more potent than YGGFMRFamide. The effects of both peptides are mediated by G proteins. They are mimicked by phorbol esters but do not seem to be initiated by either branch of the phospholipase C-dependent intracellular pathways. The properties of the resting K+ conductance in locust muscle and other invertebrate muscles are compared. The biological significance of peptide-induced reduction in resting K+ conductance is discussed in view of the known property of proctolin to support tonic force as opposed to FMRFamide-peptides that support quick leg movements.

Animals↗

Comparing motion- and imagery-related activation in the human cerebellum: a functional MRI study.

Cerebellar activation during execution and imagination of a finger movement was compared. Functional magnetic resonance imaging was used to detect cerebellar activation during execution and imagination of an untrained self-paced finger-to-thumb movement (left and right hand separately). The four fingers were opposed to the thumb in changing sequences freely chosen by the subjects. The activation maps of 10 right-handed healthy subjects were averaged after transformation into a common coordinate space. Averaged activation maps revealed strong motion-related bilateral activation in the anterior lobe of the cerebellum and in the paravermal regions of the posterior lobe. Ipsilateral activity predominated significantly. Compared to motion, imagination of the same task produced lower signal changes, and foci were more variable in position and strength. The averaged activation maps showed activity in the same regions as in motion. Activation in the posterior cerebellar lobe was more prominent extending into the lateral hemispheres. Ipsilateral dominance was significant for right-hand imagery. The left-hand task only showed marginally stronger ipsilateral activation. The activation pattern observed during execution of the finger-to-thumb movement is in agreement with theories of functional cerebellar topography. For imagery, activation at a comparable location may reflect common functionality, e.g., motor preparation and/or timing. Additional activation in the lateral hemispheres may be related to an imagery-specific function.

Adult↗

Peritumoural brain oedema in intracranial meningiomas: influence of tumour size, location and histology.

Peritumoural brain oedema was examined retrospectively in 175 patients with 179 intracranial meningiomas. The influence of tumour size, location and histology were investigated. Tumour volume and localization, and the presence of peritumoural brain oedema (PTBOe) were determined by computed tomography (CT). The oedema-tumour volume ratio was defined as Oedema Index (Oel). All patients underwent microsurgical removal of the tumour. Surgically resected meningiomas were classified histopathologically based on criteria of the new World Health Organization (WHO) classification. A close relationship was found between the tumour size and the incidence of peritumoural oedema: with increasing size of the tumour the incidence of oedema also rises, the oedema index, however decreases. Frontobasal and temporobasal meningiomas showed a significant increase in the oedema incidence and the mean oedema index. If major parts of the surface of meningiomas were adjacent to subarachnoid cisterns only a slight tendency for the development of oedema was observed. WHO-III-meningiomas showed a significantly higher oedema incidence (61.1% vs. 94.4%; p < 0.004) and mean oedema index (Oel = 2.7 vs. 3.7; p < 0.0009) than WHO-I-meningiomas. Brain tissue was affected in 59 cases. 19 meningiomas with infiltration into adjacent brain parenchyma revealed a statistically significant increase in oedema incidence (94.7% vs. 51.7%; p < 0.0003) and mean oedema index (Oel = 3.9 vs. Oel = 2.2; p < 0.0001) when compared to tumours without any brain tissue involvement in the histopathological specimens. Tumours with large volume, fronto-temporo-basal location and anaplastic histology were not only associated with the highest incidence of oedema formation but also presented with an overproportionate infiltrative growth. Thus, a disruption of the arachnoid or a true brain infiltration may be an essential factor for the development of a PTBOe.

Adult↗

Endoproteolysis of glucagon-like peptide (GLP)-1 (7-36) amide by ectopeptidases in RINm5F cells.

This study concerns whether the pancreatic beta cell expresses cell-surface ectopeptidases that are capable of proteolysis of peptide hormones and neuropeptides that modify glucose-dependent insulin release. These biochemical investigations of the RINm5F cell line found that these cells express ectopeptidases. We have characterized the limited endoproteolysis of GLP-1 (7-36) amide that occurs in the presence of RINm5F plasma membranes. The products and the sensitivity to specific peptidase inhibitors of the proteolysis is characteristic of neutral endopeptidase (NEP) 24.11. Vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating peptide (PACAP), amylin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), and exendin-4 also undergo proteolysis in the presence of RIN cell membranes. NEP 24.11-activity in RIN cell membranes was confirmed using a specific fluorogenic assay, by histochemistry, and by comparison with the recombinant enzyme with respect to the kinetics of proteolysis of GLP-1 (7-36) amide and of a fluorogenic substrate. Specific fluorogenic assays revealed the presence of aminopeptidase N and the absence of aminopeptidase A and of dipeptidylpeptidase IV.

Amino Acid Sequence↗

Action of FMRFamide-like peptides on porcine gastrointestinal motility in vitro.

Mechanical activity was recorded in circular and longitudinal smooth muscle preparations isolated from extensive regions of the porcine gastrointestinal tract in response to the FMRFamide-like neuropeptides F8Famide and A18Famide. In all preparations, the peptides were about equipotent in producing phasic contractions or enhancing spontaneous activity. The most prominent responses were observed in jejunal longitudinal strips which were on the average 91% (+/- 4% SEM, n = 15; 10(-6) M) of the histamine (10(-5) M) responses. The peptide-induced phasic activity was completely abolished by nifedipine but was unaffected by tetrodotoxin, atropine, phentolamine, yohimbine, phenoxybenzamine, propranolol, methysergide, cimetidine, indomethacin, levallorphane or naloxone. Both peptides enhanced acetylcholine-induced contractions. However, bovine ileum and guinea-pig taenia coli was not affected by these peptides. The results indicate that F8F- and A18F-amide contract porcine gastrointestinal smooth muscle by acting directly via non-opioid receptors on L-type calcium channels. In addition an increase of the sensitivity to cholinergic stimulation occurs.

Animals↗

Low-dimensional dynamics in sensory biology. 1: Thermally sensitive electroreceptors of the catfish.

We report the results of a search for evidence of periodic unstable orbits in the electroreceptors of the catfish. The function of these receptor organs is to sense weak external electric fields. In addition, they respond to the ambient temperature and to the ionic composition of the water. These quantities are encoded by receptors that make use of an internal oscillator operating at the level of the membrane potential. If such oscillators have three or more degrees of freedom, and at least one of which also exhibits a nonlinearity, they are potentially capable of chaotic dynamics. By detecting the existence of stable and unstable periodic orbits, we demonstrate bifurcations between noisy stable and chaotic behavior using the ambient temperature as a parameter. We suggest that the technique developed herein be regarded as an additional tool for the analysis of data in sensory biology and thus can be potentially useful in studies of functional responses to external stimuli. We speculate that the appearance of unstable orbits may be indicative of a state of heightened sensory awareness by the animal.

Animals↗

Five years of stereotactic radiosurgery at the University of Tübingen--a critical review of the method.

At the University of Tübingen a Linac based stereotactic system for radiosurgery has been used since 1991. The floorstand system (SRS 200, Phillips) developed at Gainsville is used in combination with a Cosman Roberts Weels system by Radionics. The floorstand enables the gantry to be rotated vertically and the table to be rotated in the horizontal plane. Additionally, patient's movements are reduced by the fixation of the stereotactic ring to the stereotactic floorstand. We report our experience with the first 50 patients treated between December 1991 and June 1995. The patients were treated with an interdisciplinary approach. This cooperation eases the transition from radiosurgery to other methods such as embolization, operation, and other radiooncologic treatment options.

Adult↗

The importance of pial blood supply to the development of peritumoral brain edema in meningiomas.

In a retrospective analysis, the authors studied the pial and dural blood supplies in 74 intracranial meningiomas and quantified their associated peritumoral brain edema (PTBE). The extent and localization of pial blush in relation to the total tumor volume were determined angiographically. The amount of edema and tumor size were calculated using computerized tomography. The edema-tumor volume ratio was defined as Edema Index (EI). There were 49 meningiomas with PTBE; of those tumors, 46 were supplied by pial vessels, and three were supplied exclusively by dural vessels. Tumors without PTBE showed no pial blush. The mean EI in meningiomas with pial blush was significantly larger (EI = 3) than in meningiomas without pial supply (EI = 1.1; p < 0.0001). Meningiomas with a smaller pial supply than dural supply had a significantly smaller mean EI than tumors with a pial supply equal to or greater than the dural supply (EI = 2.9 vs. EI = 3.7; p < 0.015). In 69.9% of cases with pial blood supply, major portions of the edema were located adjacent to the tumor region supplied by pial vessels. Edema index differences among tumors of different subgroups, as defined by size or histology, were significantly related to the pial supply in each subset. Thus, pial blood supply may be associated with the development of PTBE in meningiomas.

Adult↗

3D MR angiography with ramp-shaped flip-angle distribution.

This study addressed the use of 3D MR angiography with flip angles (FAs) linearly varying across the excitation volume in order to diminish spin saturation. The shape of the ramp profile was varied to optimize the method for different regions and pathological alterations. Radio frequency pulses with ramp-shaped excitation profiles were generated using Fourier transformation and integrated into a flow-compensated 3D-FISP sequence. With the use of ramp-shaped excitation profiles good results were obtained for intracranial arteries as well as for neck arteries (i.e. carotid and vertebral arteries) which were demonstrated in 6 healthy volunteers and in 5 patients with various stenoses and anomalies of the carotid and vertebral arteries. With this technique it was possible to use increased thicknesses of the excitation volume (slab) up to 256 mm. Ramp-shaped excitation pulses with linearly increasing FAs in main flow direction can provide improved contrast of the vessel parts located distally to the entry side of the slab. Although this method has no advantage concerning complex flow or other dephasing effects; its particular effectiveness lies in the reduction of spin saturation.

Aged↗

Three-dimensional chemical shift-selective MRI of a ruptured intracranial dermoid cyst.

We report a man with a ruptured intracranial dermoid cyst, suffering from headache, nausea, vomiting and a generalised seizure. MRI was performed before and 2 weeks after surgical resection. On T1-weighted images the tumour gave high signal, as did fatty material in the frontal and parietal brain sulci. Identification of this hyper-intense material as lipids was possible by chemical-shift-selective 3D gradient-echo imaging, which provided excellent contrast between the subarachnoid lipids and the adjacent normal brain, with a good spatial resolution. Possible complications of subarachnoid and intraventricular lipid particles after dermoid cyst rupture are discussed and the diagnostic value of 3 D chemical-shift-selective additional to conventional T-1-weighted spin-echo images in identification of even small amounts of fat is emphasised.

Adult↗

Pharmacological studies with cetrorelix (SB-75), a potent antagonist of luteinising hormone-releasing hormone.

The antitumour and hormone-suppressive effects of the luteinising hormone-releasing hormone LH-RH antagonist Cetrorelix (D-20761) and its pamoate salt (D-20762) were investigated in the model of the DMBA-induced mammary carcinoma of female rats and by testosterone determinations in normal male rats. Treatment with single high doses of D-20761 induced a rapid decrease of tumour weights with a dose-dependent duration of action. Strong antitumour effects were also observed by applying different multiple dose schedules, including a initial high dose (3.16 mg/kg, s.c.) followed by a low maintenance dose (31.6 micrograms/kg, s.c.). The stability of the molecule against degrading enzymes led to the idea of using the poorly soluble pamoate salt for facilitating a sustained release of active compound. This salt indeed induced a prolonged suppression of tumour growth and of testosterone levels. In conclusion, we found that Cetrorelix is a highly effective LH-RH antagonist which should be further developed for the treatment of hormone-dependent diseases.

Animals↗

Poor permeability of morphine 3-glucuronide and morphine 6-glucuronide through the blood-brain barrier in the rat.

To better understand the in vivo pharmacological effects of morphine 3-glucuronide (M3G, a weak opioid antagonist) and morphine 6-glucuronide (M6G, a potent opioid agonist), the permeability of the blood-brain barrier (BBB) for these metabolites was compared with morphine. Tracers were prepared by enzymatic glucuronidation of [N-methyl-3H]morphine. Brain uptake in rats was measured by the internal carotid perfusion technique and after intravenous bolus injections. In the perfusion experiments morphine showed a permeability-surface area product (PS) of 3.52 +/- 0.61 microliter min-1 g-1. Uptake seemed to be mediated by passive diffusion and was not saturable by 100 microM morphine in the perfusate. The BBB permeability of [3H]M3G and [3H]M6G was too low to be quantified after 5 min of perfusion. Brain uptake of [3H]M3G and [3H]M6G 60 min after i.v. bolus injection reached 0.0060 +/- 0.0003% and 0.0030 +/- 0.0005% injected dose per g, respectively. From these brain concentrations and the corresponding plasma concentration-time curves, BBB PS values of 0.14 +/- 0.02 microliter min-1 g-1 and 0.11 +/- 0.01 microliter min-1 g-1, respectively, were calculated. The ratio of BBB PS values is complementary to the analgesic potencies of morphine and M6G after different routes of administration. The low PS of M6G explains why it is approximately equipotent to morphine after systemic injection, although it is about 2 orders of magnitude more potent than morphine after administration directly into the central nervous system.

Animals↗