Biomedical subjects

G Adam

Publications and source records attributed to G Adam.

At least 37 records · Page 2Linked to original sources

PubMed2003

[MRI in the diagnosis of non-compacted ventricular myocardium (NCVM) compared to echocardiography].

PURPOSE: To report the detection of non-compacted ventricular myocardium (NCVM) with MRI compared to echocardiography in 8 patients. MATERIAL AND METHODS: Non-compaction of the ventricular myocardium is a congenital disorder characterized by an altered structure of the myocardial wall resulting from an intrauterine arrest in endomyocardial embryogenesis. The morphological findings consist of a prominent meshwork of multiple myocardial trabeculations and deep intertrabecular recesses, communicating with the left ventricular cavity. 8 consecutive patients (mean age 7.3 years) with clinical and echocardiographic signs of NCVM were examined by MRI (1.5 T, Vision, Siemens) in short axis and 2- and 4-chamber views, using T (1)-weighted TSE and Cine-GRE in 6 patients and true FISP sequences in 2 patients. MRI and echocardiography were evaluated for visibility, signs of NCVM and involvement of myocardial wall segments. Thickness was measured for non-compacted and compacted myocardium and the non-compacted to compacted (N/C) ratio calculated. RESULTS: MRI diagnosed 6 of 8 patients of having NCVM. Myocardial thickness as measured by echocardiography and MRI showed a good correlation in compacted myocardium (r = 8.82) and no correlation in non-compacted myocardium (r = 0.4). In 2 cases, non-compacted myocardium was detected but echocardiography did not reach the N/C ratio > 2 as required to diagnose NCVM in accordance with the criteria found in the literature. Both patients were also misdiagnosed by MRI performed with Cine-GRE. MRI reached a N/C ratio > 2 in only three patients. Newer TruFisp sequences showed no definite advantages. Extent of non-compaction could be visualized correctly with MRI. CONCLUSION: Echocardiography is the method of choice to detect NCVM. MRI can be an alternative in some cases. The diagnosis of NCVM should not be considered until N/C ratio is over 2.

Adolescent↗

PubMed2003

3D-imaging of the facial skeleton with an isocentric mobile C-arm system (Siremobil Iso-C3D).

OBJECTIVES: The purpose of this study was to compare three-dimensional (3D) imaging of the facial skeleton using an isocentric mobile C-arm system vs CT. METHODS: A dried human skull was scanned using a Siremobil Iso-C3D and a multi-detector CT (SOMATOM Volume Zoom; Siemens Medical Solutions, Erlangen, Germany) to compare reconstructed data sets. For each group of scans a standard protocol and a high resolution protocol were used. Image quality was analysed using six anatomical and six virtual structures in the primary reconstructed axial images of both data sets of the Siremobil Iso-C3D compared with CT. A receiver operating characteristic (ROC) study was performed with six examiners. RESULTS: The original categorical response data revealed no significant differences in sensitivity and specificity (P < 0.05). However, image quality of the reconstructed images of the Siremobil Iso-C3D was inferior to the CT images, with metal artefacts having a more prominent negative effect. CONCLUSIONS: The Siremobil Iso-C3D produces 3D images of the facial skeleton suitable for imaging osseous structures. No significant differences were found in sensitivity or specificity between the two methods. Metal objects degrade the image from the Iso-C method to a greater extent than those from CT.

Artifacts↗

PubMed2002

Aneurysmal bone cyst: value of MR imaging and conventional radiography.

Our objective was to investigate the accuracy and the diagnostic value of different imaging features of primary aneurysmal bone cysts (ABC) in conventional radiographs and MRI. Conventional radiographs and MR images of 34 patients with a suspected aneurysmal bone cyst were reevaluated by six independent radiologists in a blinded fashion. Morphological features, MR signal characteristics, and contrast enhancement patterns were assessed. Diagnoses were correlated with histology. Sensitivity and specificity of the different imaging findings for each imaging technique were calculated. In 24 patients ABC was histologically proven. In 10 cases diagnoses other than ABC were established. Conventional radiography and MRI each demonstrated a sensitivity of 76.4 and 77.8% with a specificity of 55.0 and 66.7%, respectively. With combined use of both imaging modalities sensitivity and specificity increased to 82.6 and 70%, respectively. The ABC was significantly more often seen as circumscribed lesion with bone expansion, lobulation, septa, and pathological cortical bone reaction than those cases with different diagnoses. Septal contrast enhancement proved to be a useful MR imaging finding in suspected ABC. The combined use of conventional radiographs and MRI revealed the highest sensitivity in the diagnosis of ABC in relation to histology. Magnetic resonance imaging provides improved diagnostic specificity and valuable information on soft tissue changes.

Adolescent↗

PubMed2002

Action of brassinosteroids in the cotton leafworm Spodoptera littoralis.

The two native plant hormones 24-epibrassinolide and 24-epicastasterone showed 50% competition for binding at IC(50) of 1-3.6 microM with [(3)H]ponasterone A using cultured imaginal wing discs from last-instar larvae of the cotton leafworm, Spodoptera littoralis (Boisduval) (Lepidoptera: Noctuidae). However, culture of imaginal wing discs in different concentrations of brassinosteroids, even up to 100 microM, demonstrated no induction of evagination. In contrast, 20E and the non-steroidal agonist RH-5992 competed respectively about 23- and 42-fold more effectively with labeled ponasterone A, and their ability (EC(50)) to induce disc evagination in vitro was 158 and 87 nM, respectively. Injection of 10 microg of brassinosteroids in newly-moulted last-instar larvae did not cause mortality above controls; higher mortalities were scored when brassinosteroids were injected late in the last instar.

Animals↗

PubMed2002

A combined pharmacological and genetic approach to investigate the role of orphanin FQ in learning and memory.

Using a combination of the selective opioid receptor-like1 (ORL1) receptor agonist, Ro 64-6198, and orphanin FQ/nociceptin (OFQ/N) peptide knockout (KO) mice, the influence of OFQ/N on cognition has been studied in the rodent. In wild type, C57BL/6J mice, Ro 64-6198 (0.3-1 mg/kg i.p.) impaired the acquisition of spatial learning in the Morris water maze, although a mild neurological impairment was evident which complicated precise interpretation. In Lister hooded rats, Ro 64-6198 (6 mg/kg i.p.) produced delay dependent impairments in rats performing either a delayed matching or a delayed nonmatching to position task with only a modest (< 20%) effect on omissions - an effect consistent with a short-term memory impairment. Electrophysiological studies demonstrated an inhibitory effect of OFQ/N on LTP recorded from the CA1 region of wild type mice, but not in ORL1 receptor knockout mice. In contrast to the ORL1 agonist, mice deficient in the OFQ/N peptide showed some evidence of improved spatial learning, fear conditioning and passive avoidance retention. However, CA1 LTP was similar between OFQ/N peptide KO mice and wild type controls. Subsequent receptor radioautography studies demonstrated the presence of ORL1 receptors within various regions of the medial temporal lobe system: i.e. CA1, dentate gyrus molecular layer, subiculum, perirhinal cortex. Taken together, these results suggest a bi-directional effect of OFQ/N containing systems on aspects of cognitive behaviour, particularly those elements associated with hippocampal function. This is consistent with a likely modulatory role of OFQ/N on hippocampal and associated cortical circuitry.

Animals↗

PubMed2002

[Value of triple phase helical CT for the detection of hepatocellular carcinoma in cirrhotic liver].

PURPOSE: Purpose of this study was to determine the value of the delayed-phase (DP) of helical CT in the detection of hepatocellular carcinoma (HCC) in cirrhotic liver in comparison to the arterial phase (AP) and the portal-venous phase (PP). MATERIAL AND METHODS: 51 patients with liver cirrhosis and suspected HCC were examined by triple-phase helical-CT (THCT). Images were standardized and obtained 20 seconds - AP, 60 - 70 seconds - PP, and 300 seconds - DP after injection of 140 ml of intravenous iodinated contrast material. Pictures were reviewed by two experienced radiologists for typical intrahepatic lesions. First, each single phase of contrast distribution were seen separately. Then all contrast phases were reviewed together. RESULTS: In 17 patients 49 typical lesions were found, histological work-up was performed, whereas in 34 patients clinical follow-up of at least 6 months was obtained. The arterial phase (AP) itself depicted 55 % of these lesions, whereas the portal-venous phase (PP) depicted 57 % and the delayed phase 78 %. DP showed a significantly higher detection rate in comparison to the PP (p = 0.008). By performing a biphasic helical CT 40 lesions would have been detected with AP and PP, whereas all 49 lesions would have been visualised by combining AP and DP. This means a significantly higher detection rate for AP/DP instead of using AP/PP (p = 0.031). CONCLUSION: Additionally to the AP and PP, a delayed phase should be performed when cirrhosis is present. Even though AP and DP depicted all HCC's in this study, the PP provides undispensable additional information, so that, in our opinion, a THCT should be given preference when HCC is suspected.

Adult↗

PubMed2002

Functional magnetic resonance imaging (fMRI) for fetal oxygenation during maternal hypoxia: initial results.

PURPOSE: To investigate the potential of fMRI to measure changes in fetal tissue oxygenation during acute maternal hypoxia in fetal lambs. MATERIAL AND METHODS: Two ewes carrying singleton fetuses (gestational age 125 and 131 days) underwent MR imaging under inhalation anesthesia. BOLD imaging of the fetal brain, liver and myocardium was performed during acute maternal hypoxia (oxygen replaced by N 2 O). Maternal oxygen saturation and heart rate were monitored by a pulse-oxymeter attached to the maternal tongue. RESULTS: Changes of fetal tissue oxygenation during maternal hypoxia were clearly visible with BOLD MRI. Signal intensity decreases were more distinct in liver and heart ( approximately 40 %) from control than in the fetal brain ( approximately 10 %). CONCLUSIONS: fMRI is a promising diagnostic tool to determine fetal tissue oxygenation and may open new opportunities in monitoring fetal well being in high risk pregnancies complicated by uteroplacentar insufficiency. Different signal changes in liver/heart and brain may reflect a centralization of the fetal blood flow.

Animals↗

PubMed2002

MR elastography of the breast:preliminary clinical results.

PURPOSE: Imaging of breast tumors and various breast tissues using magnetic resonance (MR) elastography (MRE) to explore the potential of elasticity as a new parameter for the diagnosis of breast lesions. METHODS: Low-frequency mechanical waves are transmitted into breast tissue by means of an oscillator. The local characteristics of the mechanical wave are determined by the underlying elastic properties of the tissue. Theses waves can be displayed by means of a motion-sensitive spin-echo MR sequence within the phase of the MR image. Elasticity reconstruction is performed on the basis of 8 "snapshots" of each wave within the three spatial directions. We performed in-vivo measurements in 15 female patients with malignant tumors of the breast, 5 patients with benign breast tumors, and 15 healthy volunteers. RESULTS: Malignant invasive breast tumors documented the highest values of elasticity with a median of 15.9 kPa and a wide range of stiffnesses between 8 and 28 kPa. In contrast, benign breast lesions represented low values of elasticity, which were significantly different from malignant breast tumors (median elasticity: 7.0 kPa; p = 0.0012). This was comparable to the stiffest tissue areas in healthy volunteers (median elasticity 7.0 kPa), whereas breast parenchyma (median: 2.5 kPa) and fatty breast tissue (median: 1.7 kPa) showed the lowest values of elasticity. Two invasive ductal carcinomas had elasticity values of 8 kPa and two stiff parenchyma areas in healthy volunteers had elasticities of 13 and 15 kPa. These lesions could not be differentiated by their elasticity. CONCLUSION: We conclude that MRE is a promising new imaging modality with the capability to assess the viscoelastic properties of breast tumors and the surrounding tissues. However, from our preliminary results in a small number of patients it is obvious that there is an overlap in the elasticity ranges of soft malignant tumors and stiff benign lesions.

Adult↗

PubMed2002

[Percutaneous core-needle biopsy of palpable breast tumors. Do we need ultrasound guidance?].

INTRODUCTION: Percutaneous core-needle biopsy is widely accepted for preoperative histologic assessment of suspicious breast lesions. The purpose of this study was to asses the impact of continuous sonographic guidance on diagnostic accuracy of large core needle biopsy of palpable breast lesions. METHOD: We analysed 170 breast lesions in a retrospective study. Percutaneous breast biopsies were performed by using a biopsy gun with 14-gauge needles. Eighty-eight biopsies were performed under continuous ultrasound guidance (group II) and 82 biopsies without ultrasound documentation of the procedure (group I). Core needle diagnoses were compared with the patients final tissue diagnosis as based on surgical excisional biopsy. RESULTS: In patient group I, 17 lesions were categorized as core breast biopsy cancer misses (sensitivity 79 %). The sensitivity in this group showed an obvious dependency on tumor size. Among the 17 false negative lesions, 13 lesions were 3 cm in mean diameter or smaller. Two false negative findings occurred in group II (sensitivity 98 %), with a tumor size of 0.5 and 1.0 cm. CONCLUSION: Sonographic guidance is indispensable to ensure adequate diagnostic accuracy for core-needle biopsy of palpable breast lesions.

Adult↗

PubMed2002

[MRI-based N-staging in esophageal cancer].

PURPOSE: For planning the therapeutic strategies and estimating the prognosis in esophageal cancer, N-staging is very important. To date, MRI still is of minor importance as imaging modality of the mediastinum despite promising developments in the past, like ECG-gating or "averaging" sequences, e. g., LOTA (Long-term averaging), which facilitate mediastinal and thoracic MR-imaging. In a prospective approach, the value of MRI based N-staging was examined with respect to LOTA-sequences. MATERIAL AND METHODS: Within four weeks prior to esophagectomy, standardized MRI of the esophagus was performed in 15 patients (10 squamous-cell-carcinomas and 5 adenocarcinomas) using a 1.5 T whole body scanner. Imaging quality was classified based on depiction of aortic wall or tracheal wall layers. Criteria for malignant infiltration were a diameter of more than 15 mm or a round appearance of a lymph node together with GD-DTPA enhancement. All data were blinded and separately read by two radiologists. The data of the study were compared with those from the pathological workup of the resected specimen. RESULTS: MRI had a sensitivity of 100 % and a specificity of 78 % for lymph node metastases. Due to incomplete depiction of the celiac trunk (M1), nodal metastasis in a non-enlarged node was missed. CONCLUSION: With modern MRI, N-staging is almost as accurate as the gold standard endoscopic ultrasound and should particularly be used in patients not suited for an endoscopic ultrasound examination.

Adenocarcinoma↗

PubMed2002

[Formation of portal venous collaterals after ligation of the portal vein for induction of liver regeneration].

PURPOSE: Unilateral occlusion of the portal vein induces contralateral lobar hypertrophy - in contrast to complete portal vein occlusion which will result in a cavernous transformation. The impact of the formation of collaterals in partial portal vein occlusion is not sufficiently known. The lobar-hypertrophy- phenomenon is in clinical use for several years to induce iatrogenic liver growth to enable extended resections. After portal vein ligation in patients prior to extended hepatic resections, we noticed a perfusion of the formerly occluded side on CT. Using the well-established mini pig model, we were interested whether portal collaterals are formed as cause of the reperfusion. Ex-situ angiograms of the liver were used for the depiction of collaterals. MATERIALS AND METHODS: Using a median laparotomy as access for preparation of the hepatoduodenal ligament, a proximal left portal vein ligation was performed in eight mini pigs under general anesthesia. The total arrest of the portal blood flow (except in segments VI and VII) was documented by duplex ultrasound. After 4 weeks, all pigs were sacrificed and the weight of the ligated liver segments and non-ligated liver segments was measured and compared to a sham group (n = 5). After insertion of a guiding sheath, an ex-situ DSA of the portal vein was acquired. RESULTS: Compared with the sham group, the liver weight increased by 60 % (23 - 99 %, std. dev. 30 %) in segments VI and VII. Atrophy of the ligated segments was signified by a weight loss of 10 % (standard deviation 15 %). The ex-situ angiograms revealed a uniform pattern of collaterals with subsequent complete total recanalization of the formerly occluded portal vein distal from the ligation. The collaterals reduced the portal venous flow rate. CONCLUSION: After portal vein ligation, uniform collateralization results in recanalization of the occluded portal vein. The extent of the collaterals exceeds the known cavernous transformation. The increase in liver volume is not restrained by the formation of collaterals.

Aged↗

PubMed2002

[The role of MRI for the evaluation of atrial septal defects before and after percutaneous occlusion with the amplatzer septal occluder(R)].

PURPOSE: Evaluation of morphologic and functional MRI of atrial septal defects (ASD) before and after percutaneous occlusion with the Amplatzer Septal Occluder (AOC). Comparison of MRI with transesophageal echocardiography (TEE), balloon measurement (IVBM) and cardiac catheterization with shunt quantification (CCSQ). MATERIALS AND METHODS: Twenty patients with ASD were examined before and three months after AOC implantation. ECG-triggered, breath-hold T1-weighted Turbo Spin Echo Segmented FLASH 2D and dynamic turbo-FLASH-GRE sequences after application of 0.2 mmol gadolinium DTPA per kg body weight were obtained in a 1.5 T MRI system. Defect size, and distance to coronal sinus (CS) and right upper pulmonary vein (RUPV) were determined for pre-interventional planning, and the AOC size was measured quantitatively for post-interventional follow-up. The shunts were evaluated qualitatively (occurrence of jets), semiquantitatively (jet length, turbulence square product) and quantitatively (flow measurement in the thoracic aorta and in the left and right pulmonary arteries). RESULTS: The average size of the ASD measured by MRI was 17.6 mm (11 - 24.8 mm) in the axial view, 15.9 mm (10.8 - 28.9 mm) in the sagittal view and 16.4 mm (12.1 - 24.8 mm) in the short axis view. In comparison, the average defect size was 15 mm (8 - 24 mm) by TEE and 20 mm (13 - 27 mm) by IVBM. The average distance to the RUPV was 17 mm (9.6 - 21.9 mm) and to the CS 11.2 mm (5 - 17 mm). The AOC was visualized with only minimal artifacts. Qualitative analysis of the MRI findings revealed an occurrence of jets in 17/20 patients. Semiquantitative analysis documented a high correlation for jet length and square product of the turbulence to defect size r = 0.81 resp. r = 0.82. Mean QP/QS-ratio measured by MR-volumetry was 1.6 +/- 0.29 and by MR-flow 1.6 +/- 0.26. The corresponding measurements were 1.7 +/- 0.3 for TEE and 1.5 +/- 0.5 for CCSQ. In comparison to TEE, the correlation coefficient was r = 0.96 for MR-volumetry and r = 0.85 for MR-flow measurement. CONCLUSION: MRI is found to be a valuable diagnostic method for pre-interventional planning and post-interventional follow-up of atrial septal defects occluded by the Amplatzer septal occluder.

Adult↗

PubMed2002

[Evaluation of TSE- and T1-3D-GRE-sequences for focal cartilage lesions in vitro in comparison to ultrahigh resolution multi-slice CT].

PURPOSE: Evaluation of TSE- and T 1 -3D-GRE-sequences for focal cartilage lesions in vitro in comparison to ultrahigh resolution multi-slice CT. MATERIALS AND METHODS: Forty artificial cartilage lesions in ten bovine patellae were immersed in a solution of iodinated contrast medium and assessed with ultrahigh resolution multi-slice CT. Fat-suppressed TSE images with intermediate- and T 2 -weighting at a slice thickness of 2, 3 and 4 mm as well as fat-suppressed T 1 -weighted 3D-FLASH images with an effective slice thickness of 1, 2 and 3 mm were acquired at 1.5 T. After adding Gd-DTPA to the saline solution containing the patellae, the T 1 -weighted 3D-FLASH imaging was repeated. RESULTS: All cartilage lesions were visualised and graded with ultrahigh resolution multi-slice CT. The TSE images had a higher sensitivity and a higher inter- and intraobserver kappa compared to the FLASH-sequences (TSE: 70 - 95 %; 0.82 - 0.83; 0.85 - 0.9; FLASH: 57.5 - 85 %; 0.53 - 0.72; 0.73 - 0.82, respectively). An increase in slice thickness decreased the sensitivity, whereby deep lesions were even reliably depicted on TSE images at a slice thickness of 3 and 4 mm. Adding Gd-DTPA to the saline solution increased the sensitivity by 10 % with no detectable advantage over the T 2 -weighted TSE images. CONCLUSION: TSE sequences and application of Gd-DTPA seemed to be superior to T 1 -weighted 3D-FLASH sequences without Gd-DTPA in the detection of focal cartilage lesions. The ultrahigh resolution multi-slice CT can serve as in vitro reference standard for focal cartilage lesions.

Animals↗

PubMed2002

[MRI in postoperative assessment of univentricular heart disease: correlation with echocardiography and angiography].

PURPOSE: To determine the value of MRI in the postoperative evaluation of a singular ventricle compared to echocardiography and cardiac catheterization. MATERIALS AND METHODS: Thirty-one patients (range: 6 months to 30 years) with a functional single ventricle following palliative corrective operations. Five patients had a Blalock-Taussig-Shunt, 8 patients a Glenn-Anastomosis and 18 a cavopulmonary shunt (6 with classic Fontan-Circulation, 12 with modified cavopulmonary anastomosis). The results in terms of postoperative morphologic changes were compared to percutaneous echocardiography (31/31) and cardiac catheterization (6/31). RESULTS: Echocardiography, which was performed on all patients, could not visualize the entire length of the tunnel, the Glenn-Anastomosis or the central pulmonary arteries in 70 % of the patients due to an inadequate acoustic window. MRI was able to show the entire tunnel in 11/12 patients and the central pulmonary arteries in 30/31 patients. The exact anatomy was seen in all 6 patients undergoing cardiac catheterization. CONCLUSION: MRI is useful in the postoperative evaluation of a functionally single ventricle. It is superior to echocardiography. Cardiac catheterization should be reserved for patients with inconclusive MRI findings.

Adolescent↗

PubMed2001

MR-guided percutaneous cryotherapy of the liver: in vivo evaluation with histologic correlation in an animal model.

The purpose of this study was to evaluate the feasibility of MR-guided percutaneous cryotherapy of the porcine liver and to correlate the resulting tissue necrosis with MR imaging and histology. Using an MR-compatible, argon-based cryotherapy system (CryoHit; Galil Medical Ltd., Israel) with 2- and 3-mm diameter tapered cryotherapy probes, MR-guided percutaneous cryotherapy was performed in seven pigs (mean body weight, 40 kg) under general anesthesia in a short-bore magnet (1.5 T ACS NT; Philips, The Netherlands) using an ultrafast T2-weighted single-shot LoLo TSE sequence and a T1-weighted gradient-echo sequence. The frozen liver tissue was depicted accurately on fast T2- and T1-weighted sequences, providing precise delineation of the ablated tissue volume. On follow-up postcontrast MR controls, the cryolesions appeared avascular. They decreased in size compared with the initially frozen volume down to 70% at a 2-week follow-up. Histologically, a coagulation necrosis with a close correlation to the MR follow-up examinations was objectified. No cryotherapy-related complications occurred. J. Magn. Reson. Imaging 2001;13:50-56.

Animals↗

PubMed2001

Comparison of aerosolized gadoteridol and gadopentetate dimeglumine for magnetic resonance ventilation imaging of the lung.

The purpose of this study was to compare aerosolized gadoteridol and gadopentetate dimeglumine in regard to homogeneity of aerosol distribution and relative pulmonary signal intensity (SI) changes after a 10-min mechanical ventilation period. Twenty experimental procedures were performed in 10 intubated domestic pigs that were mechanically aerosolized with the nebulized contrast medium. Images were obtained by using a respiratory-gated T(1)-weighted TSE sequence. Pulmonary SI increase for the right and left lung was 26% +/- 25% and 25% +/- 12%, respectively, for gadopentetate dimeglumine, and 45% +/- 12% and 43% +/- 10%, respectively, for gadoteridol. Aerosol distribution was rated homogeneous in all cases by two readers. It is concluded that both contrast agents in aerosolized form are capable of depicting pulmonary ventilation in healthy animals with lung capacities comparable to those of humans. SI differences between gadoteridol and gadopentetate dimeglumine are explained by their considerable difference in viscosity.

Aerosols↗

PubMed2001

Pharmacological properties of native metabotropic glutamate receptors in freshly dissociated Golgi cells of the rat cerebellum.

We have examined the pharmacological properties of native metabotropic glutamate (mGlu) receptors in freshly isolated rat cerebellar Golgi cells using the whole-cell configuration of the patch-clamp technique. Group II mGlu receptor agonists inhibited voltage-gated Ca(2+) channels (VGCC) currents in a reversible and concentration-dependent manner with a rank order of potency being LY354740> DCG-IV > L-CCG-I > glutamate >>1S,3R-ACPD > NAAG. The maximum degree of inhibition obtained was similar for all drugs tested, saturating at about 33-41%, except for NAAG that had a non saturating effect of 50% at 1mM. Two novel group II mGlu receptor antagonists, LY341495 and Ro 65-3479, reversed VGCC current inhibition by LY354740 with pK(B) values of 7.0 and 6.3, respectively. In a subpopulation of Golgi cells, the antagonistic effect of LY341495 was only partial, suggesting a remaining effect of group I mGlu receptors. This was confirmed by experiments with S-DHPG, a selective group I mGlu receptor agonist. These experiments suggest that Golgi cells of the cerebellum express group II mGlu receptors that couple to the inhibition of VGCCs. Therefore, inhibition of VGCCs in cerebellar Golgi cells is a useful model system to evaluate novel group II mGlu receptor ligands.

Animals↗

PubMed2001

Influence of the selective ORL1 receptor agonist, Ro64-6198, on rodent neurological function.

Identification of synthetic agonists and antagonists at orphan receptors represents an important step for understanding their physiological function and therapeutic potential. Accordingly, we have recently described a non-peptide agonist at the opioid receptor like (ORL1) receptor (1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one (Ro64-6198; Jenck et al., PNAS 94 (2000) 4938; Wichmann et al., Eur. J. Med. Chem. 35 (2000) 839). We have investigated the effects of this compound in various tests of rodent neurological function, utilising ORL1 knockout mice to examine the pharmacological specificity of Ro64-6198. In male C57BL/6J mice, effects on balance and motor co-ordination were detected following low doses (0.3-1mg/kg IP) of Ro64-6198. At higher doses (1-3mg/kg IP), effects on swim behaviour and hypothermia was observed. At 10mg/kg, each effect became more profound and a severe neurological disturbance appeared, including loss of righting reflex. These effects of Ro64-6198 (10mg/kg IP) were absent in ORL1 receptor knockout mice. In male, hooded Lister rats, Ro64-6198 (6-10mg/kg IP), produced some disturbance of neurological function, including hypoactivity, rotarod performance, grip strength and mild hypothermia. An impairment of food responding under a variable interval (VI) 20s schedule of reinforcement was noted at 3mg/kg. These results confirm Ro64-6198 to be a highly selective pharmacological tool to investigate ORL1 receptor function in vivo and, furthermore, that activation of this receptor is accompanied by a variety of effects on neurological function.

Animals↗