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PubMed2003

Orexin-A (hypocretin-1) impairs Morris water maze performance and CA1-Schaffer collateral long-term potentiation in rats.

Glucose-sensitive neurons in the lateral hypothalamic area produce orexin-A (hypocretin-1) and orexin-B (hypocretin-2) and send their axons to the hippocampus, which predominantly expresses orexin receptor 1 showing a higher sensitivity to orexin-A. The purpose of the present study was to assess the effects of orexin-A on the performance of Wistar rats during the Morris water maze test and then to determine the effects of orexin-A on both the long-term potentiation and long-term depression in Schaffer collateral/commissural-CA1 synapses in hippocampal slices. The results of the Morris water maze test show that 1.0 and 10 nmol of orexin-A, when administered intracerebroventricularly, retarded spatial learning. A probe test examined after training of water maze task also showed an impairment in spatial memory. The results of an electrophysiological study using hippocampal slices demonstrated that 1.0 to 30 nM of orexin-A applied to the perfusate produces a dose-dependent and time dependent suppression of the long-term potentiation. In addition, the long-term depression was not affected by orexin-A. The results of a paired-pulse facilitation experiment indicated that the effects of orexin-A were post-synaptic and not due to presynaptic transmitter release. These results show that orexin-A impairs spatial performance and these impairments can be attributed to a suppression of long-term potentiation in the Schaffer collateral-CA1 hippocampal synapses.

Animals↗
PubMed1986

Serotonin and the peripheral circulation.

A recent resurgence of interest into the role of platelets in the pathogenesis of ischaemic syndromes associated with atherosclerosis, and the development of new antagonists for major platelet products, has led to a broad range of studies into the mechanisms by which serotonin, and other factors released by platelets, may contribute to ischaemia. Serotonin influences large arteries in vivo to induce constriction through an action on the 5-HT2 serotonin receptor. Several studies now show, at least for the limb blood supply, that collateral arteries after major artery occlusion are extremely sensitive to serotonin acting on the 5-HT2 serotonin receptor. Preliminary studies on platelet activation secondary to endothelial damage induced by mechanical abrasion in the rabbit with collateral limb vessels indicate that vasoactive quantities of serotonin are, indeed, released and that the response of the collateral vessels is reversed, at least in part, by ketanserin. Preliminary evidence also indicates that simultaneous blockade of serotonin and thromboxane achieves a greater effect than blocking either alone, following platelet activation.

Animals↗
PubMed1994

Compressions of carotid and vertebral arteries in assessment of intracranial collateral flow: correlation between angiography and transcranial Doppler ultrasonography.

The authors examined 61 subjects with carotid angiography and 50 with vertebral angiography. Angiograms were evaluated for collateral flow through the ophthalmic, anterior communicating, and posterior communicating arteries. The authors evaluated the patency of collateral vessels directly using transcranial Doppler ultrasonography; they made indirect detection after the compression of carotid and vertebral arteries while monitoring flow velocities in the middle cerebral artery. They established criteria for the hemodynamic significance of tested collateral vessels. A combination of carotid compressions and transcranial Doppler ultrasonography detected the patency of the ophthalmic and anterior communicating arteries with a specificity and sensitivity of 1.00. Examination of the posterior communicating artery had a sensitivity of 0.97 and specificity of 0.98. Indirect evaluation of collateral vessels can not only detect their presence but also establish their hemodynamic significance with high accuracy.

Adult↗
PubMed2002

Nicorandil enhances myocardial tolerance to ischemia without progressive collateral recruitment during coronary angioplasty.

Nicorandil, a hybrid nitrate and ATP-sensitive potassium channel opener, has had a preconditioning effect in some coronary angioplasty studies. The present study investigated whether the cardioprotective effects of nicorandil involve coronary collateral function. Thirty-two patients with stable angina pectoris were randomized to receive a 1-min intravenous infusion of nicorandil (100 microg/kg) or normal saline. Five minutes later they underwent three 2-min balloon inflations 5-min apart. The maximum ST-segment elevation (deltaSTmax), the sum of ST-segment elevations in all leads (sigmaST), and the chest pain score were determined at the end of each balloon inflation. The collateral flow index (CFI) was derived from simultaneous measurement of the mean aortic pressure and the coronary wedge pressure obtained from a pressure guidewire during balloon inflation. The deltaSTmax, sigmaST, and chest pain score decreased progressively during the 3 sequential balloon inflations in both groups, and the deltaSTmax and sigmaST were less in the nicorandil group than in the control group during each inflation. The CFI did not change during the 3 inflations in either group and was similar in the 2 groups during each inflation. In conclusion, pretreatment with intravenous nicorandil enhances myocardial tolerance to ischemia without progressive collateral recruitment during coronary angioplasty.

Adult↗
PubMed1975

[Coronary collateral vessels after long-term treatment with fendiline hydrochloride in a double-blind study (author's transl)].

After long-therapy with 5 mg/kg body-weight of N-(2-benzhydryl-ethyl)-N-(1-phenyl-ethyl)amine hydrochloride (fendiline hydrochloride, Sensit) in dogs the development of functioning coronary collateral vessels can be proven by filling the vessel system with synthetic resin. From earlier studies, it is known that coronary collateral vessels can protect the heart from the consequences of stenoses and tissue damage due to hypoxia.

Animals↗
PubMed2005

Thermal optimisation of the Reimer-Tiemann reaction using thermochromic liquid crystals on a microfluidic reactor.

Microreactors incorporating thin film resistive heating elements for continuous flow organic synthesis are presented. Internal thermal conditions were monitored in real time using reflectance spectra of temperature sensitive thermochromic liquid crystals (TLC) in a collateral microfluidic network. To demonstrate the precise temperature control provided by this method, the thermal optimisation of the Reimer-Tiemann formylation of beta-naphthol was performed under hydrodynamic pumping regimes.

Crystallization↗
PubMed1991

Reactivity of canine isolated epicardial collateral coronary arteries. Relation to vessel structure.

To study the relation between structure and vascular reactivity in mature coronary collateral arteries, we prepared 17 dogs with a casein occluder near the origin of the circumflex coronary artery. At least 24 weeks later, we examined the reactivity of surface collateral arteries (approximately 500 micron i.d.) to a range of constrictor and dilator agents and compared them with normal left anterior descending coronary arteries of similar size branching away from the collateral zone. Pairs of normal and collateral arteries 2 mm long were mounted in a double-vessel myograph for isometric force recording. Arteries were contracted by K+ (124 mM) or by cumulative addition of endothelin-1 (1-100 nM) or U46619 (1-300 nM), a thromboxane A2 mimetic drug. In each case, the collateral vessels contracted to approximately half the force generated by the normal arteries. When partially contracted by K+ (25-30 mM), the collateral vessels had a greater range of relaxation and similar sensitivity to acetylcholine, sodium nitroprusside, and cromakalim compared with normal arteries. Morphological and morphometric analyses revealed that the collateral arteries had thickened adventitia, thinner media, ruptured internal elastic laminae, and a thick neointima lined by endothelium. Theoretical calculations of luminal area were made for isotonic conditions in response to constrictor stimuli. Despite the poor contractility of the collateral arteries, the neointimal luminal encroachment further reduced the lumen to zero, an exaggerated response compared with normal arteries. Coronary collateral arteries are thus compromised flow conduits that may play a role in vasospastic angina.

Animals↗
PubMed1997

Fas ligand-mediated bystander lysis of syngeneic cells in response to an allogeneic stimulus.

Using a mouse allospecific lymph node (LN) CTL (H-2b) response to transplanted cells (H-2k), effector cells were shown to lyse C3H/HeJ or L929-Fas (H-2k) target cells in either a perforin-dependent or a Fas ligand (FasL)-dependent manner. C3H/HeJ.lpr targets or L929 targets lacking Fas were not sensitive to these effectors generated in perforin-deficient (Po) mice. By contrast, C3H/HeJ.lpr target cells and L929 were as responsive as C3H/HeJ and L929-Fas targets to the effectors generated in perforin wild-type (P+/+) mice. To measure potential bystander lysis in allogeneic responses, these same effector LN from either C57BL/6 P+/+ or P(o) mice were examined for lysis of C3H/HeJ (or C3H/HeJ.lpr) or L929-Fas (or L929) cocultured with 51Cr-labeled C57BL/6 (H-2b) target cells. Bystander lysis of C57BL/6 targets was observed only in those allogeneic responses where FasL was the defined mechanism of lysis. By contrast, perforin-mediated lysis was restricted by allo-recognition. Syngeneic (H-2b) targets that were not sensitive to Fas-mediated lysis were not lysed in a bystander fashion. Depletion of subsets of LN Po effectors (b anti-k) demonstrated that CD4+ T cells were primarily responsible for FasL-mediated direct and bystander lysis. FasL-mediated bystander lysis was also observed in H-2k anti-b reactions, except when the effectors were FasL mutant (gld). These data suggest that CTL responses to foreign Ag may evoke a certain amount of collateral damage to local host Fas-sensitive cells.

Animals↗
PubMed2004

MDCT evaluation of thoracic aortic anomalies in pediatric patients and young adults: comparison of axial, multiplanar, and 3D images.

OBJECTIVE: The objective of our study was to compare accuracies of axial, multiplanar, and 3D volume-rendered images in the diagnosis of thoracic aortic anomalies in pediatric patients and young adults. MATERIALS AND METHODS: Fourteen patients, 17 days to 20 years old, with thoracic aortic anomalies underwent MDCT using axial, multiplanar, and 3D volume-rendering imaging. All images were reviewed by three radiologists for position of the aortic arch, coarctation, vascular compression of the airway, collateral vessel formation, and aortopulmonary shunts (patent ductus arteriosus). Final diagnosis was determined by echocardiography, conventional angiography, bronchoscopy, or surgery. Diagnostic accuracy, sensitivity, and interobserver agreement were evaluated. RESULTS: Average accuracies (average of the three observers for a correct diagnosis) were greater than or equal to 96% for diagnoses of aortic position and airway narrowing on all image types. For the diagnosis of coarctation, average sensitivities (average of the three observers for a true diagnosis) were 73% for axial, 100% for multiplanar, and 100% for 3D volume-rendered images. For the diagnosis of patent ductus arteriosus, average sensitivities were 78% for axial, 94% for multiplanar, and 89% for 3D volume-rendered images. No patients in this study had collateral vessel formation. For the diagnosis of absence of collateral vessel formation, average sensitivities were 100% for axial, 100% for multiplanar, and 100% for 3D volume-rendered images. There were no significant statistical differences in diagnostic performances, agreement with truth, or confidence scores among observers or imaging formats (p > 0.05). CONCLUSION: Axial, multiplanar, and 3D volume-rendered images serve equally well as methods for assessing the side of the aorta to diagnose anomalies. For evaluation of coarctation and patent ductus arteriosus, multiplanar and 3D volume-rendered images perform slightly better than axial images.

Adolescent↗
PubMed1996

Assessment of deep venous thrombosis in the lower limbs and pelvis: MR venography versus duplex Doppler sonography.

OBJECTIVE: This study was designed to compare the diagnostic value of MR venography and color Doppler sonography in the assessment of deep venous thrombosis. SUBJECTS AND METHODS: MR venograms and color Doppler examinations were obtained in 37 patients either with suspected deep venous thrombosis of the lower limbs or pelvis or with pulmonary embolism. Two-dimensional time-of-flight venography was used for all studies. MR and color Doppler data were collected prospectively and analyzed in a blinded manner. In a subset of 21 patients, MR venography and color Doppler sonography were prospectively compared with contrast-enhanced venography. RESULTS: When compared with contrast-enhanced venography, MR venography was 100% sensitive and 100% specific in the diagnosis of deep venous thrombosis above the knee. Color Doppler imaging depicted 13 of 15 cases of deep venous thrombosis and 5 of 6 venous examinations that had normal results, yielding a sensitivity and a specificity of 87% and 83%, respectively. The differences in sensitivity and specificity between MR venography and color Doppler sonography were not statistically significant. MR venography was 95% sensitive and 99% specific in detecting the extension of deep venous thrombosis, compared with the 46% sensitivity and 100% specificity of color Doppler sonography (differences in sensitivity, p < .01). MR images showed 29 collateral vessels, whereas only 21 were detected by contrast-enhanced venography (p < .04). CONCLUSION: MR venography seems to be more accurate than color Doppler sonography in detecting the extension of deep venous thrombosis. The positive diagnosis and extent of deep venous thrombosis can be easily detected and monitored by a noninvasive technique such as MR venography.

Adult↗
PubMed1995

Inhibition of O6-alkylguanine-DNA alkyltransferase in animal and human ovarian tumor cell lines by O6-benzylguanine and sensitization to BCNU.

O6-Alkylguanine-DNA alkyltransferase (O6-AGT) activity in rat ovarian tumor lines O-342 and O 342/DDP was 103.4 +/- 18.4 and 240.9 +/- 40.2 fmol/mg protein, respectively; thus, cisplatin (DDP) resistance was paralleled by an increase in O6-AGT activity by a factor of approximately 2.3. The DDP-resistant line expressed a collateral resistance to BCNU. Both lines could be sensitized to BCNU by O6-BG, with sensitization factors of 6.0 and 2.1, respectively. In neither line did depletion of O6-AGT have any sensitizing effect towards DDP. In the human ovarian cancer lines SK-OV-3 and OAW 42, O6-AGT activity was 337.6 +/- 18.2 and 180.0 +/- 39.9 fmol/mg protein, respectively; in these lines depletion of O6-AGT activity by O6-BG treatment resulted in sensitization factors of 3.0 and 4.1, respectively. The increase in sensitivity of ovarian tumor cell lines against a chloroethylating agent by O6-AGT depletion and possible pharmacological advantages of regional (i.p.) administration of this combination might be beneficial in advanced ovarian cancer.

Animals↗
PubMed2004

Monitoring of motor evoked potentials compared with somatosensory evoked potentials and microvascular Doppler ultrasonography in cerebral aneurysm surgery.

OBJECT: The aims of this study were to compare the efficiency of motor evoked potentials (MEPs), somatosensory evoked potentials (SSEPs), and microvascular Doppler ultrasonography (MDU) in the detection of impending motor impairment from subcortical ischemia in aneurysm surgery; to determine their sensitivity for specific intraoperative events; and to compare their impact on the surgical strategy used. METHODS: Motor evoked potentials, SSEPs, and MDU were monitored during 100 operations for 129 aneurysms in 95 patients. Intraoperative events, monitoring results, and clinical outcome were correlated in a prospective observational design. Motor evoked potentials indicated inadequate temporary clipping, inadvertent occlusion, inadequate retraction, vasospasm, or compromise to perforating vessels in 21 of 33 instances and deteriorated despite stable SSEPs in 18 cases. Microvascular Doppler ultrasonography revealed inadvertent vessel occlusion in eight of 10 cases and insufficient clipping in four of four cases. Stable evoked potentials (EPs) allowed safe, permanent vessel occlusion or narrowing despite reduced flow on MDU in five cases. Two patients sustained permanent and 10 showed transient new weakness, which had been detected by SSEPs in two of 12 patients and MEPs in 10 of 11 monitored cases. The surgical strategy was directly altered in 33 instances: by MEPs in 16, SSEPs in four, and MDU in 13. CONCLUSIONS: Monitoring of MEPs is superior to SSEP monitoring and MDU in detecting motor impairment, particularly that from subcortical ischemia. Microvascular Doppler ultrasonography is superior to EP monitoring in detecting inadvertent vessel occlusion, but cannot assess remote collateral flow. Motor evoked potentials are most sensitive to all other intraoperative conditions and have a direct influence on the course of surgery in the majority of events. A controlled study design is required to confirm the positive effect of monitoring on clinical outcome in aneurysm surgery.

Adult↗
PubMedDate not supplied

Prolonged administration of imipramine and (+)-oxaprotiline, but not citalopram, results in sensitization of the rat hippocampal CA1 neurons to serotonin ex vivo.

Prolonged (14 days, twice daily), but not acute, application of imipramine and (+)-oxaprotiline (10 mg/kg) induced sensitization of hippocampal CA1 neurons to the inhibitory effect of 5-hydroxytryptamine (5-HT), as studied ex vivo in the rat hippocampal slice preparation. Attenuation of the population spike, recorded in the CA1 pyramidal cell layer in response to stimulation of the Schaffer collateral-commisural pathway, was used to asses the sensitivity of neurons to 5-HT. Prolonged and acute administration of the selective 5-HT reuptake blocker citalopram did not change the responsiveness of hippocampal neurons to 5-HT. Since imipramine and (+)-oxaprotiline share the inhibitory effect on the norepinephrine reuptake, our results may indicate that long-term alterations in the noradrenergic system lead to modifications in postsynaptic serotonergic receptors.

Animals↗
PubMed1993

The differential induction of collateral resistance to 62.5 MeV (p-->Be+) neutrons and 4 MeV photons by exposure to cis-platinum.

PURPOSE: To determine the relative sensitivity to cis-platinum, 4 MeV photons and 62.5 MeV (p-->Be+) neutrons in five human tumor cell lines, and their cis-platinum resistant variants. METHODS AND MATERIALS: The degree of cross-resistance of five human in-vitro cell lines to photons or fast neutrons was analysed for both cisplatinum-sensitive and resistant variants. RESULTS: The development of acquired cis-platinum resistance conferred collateral resistance to 62.5 MeV (p--Be+) neutrons in all five cell lines, but did not consistently decrease the photon sensitivity of these same cells. CONCLUSION: The reduction in photon and neutron sensitivity following the development of acquired cis-platinum resistance may possibly be regulated by different mechanisms. The reduction in neutron sensitivity was primarily due to a 1.3-1.7 fold reduction in the magnitude of the initial slope (alpha), which was independent of the degree of platinum resistance induced, suggesting a non-stochiometric relationship between the mechanisms responsible for acquired cis-platinum, and 62.5 MeV (p-->Be+) neutron resistance.

Cell Survival↗
PubMed2004

Quantitative microcomputed tomography analysis of collateral vessel development after ischemic injury.

Transgenic mouse models are increasingly being used to investigate the functions of specific growth factors or matrix proteins to design therapeutic strategies for controlling blood vessel growth. However, the available methodologies for evaluating angiogenesis and arteriogenesis in these models are limited by animal size, user subjectivity, the power to visualize the three-dimensional vessel networks, or the capability to employ a vigorous quantitative analysis. In this study, we employed contrast-enhanced microcomputed tomography imaging to assess collateral development after induction of hindlimb ischemia in the mouse. The morphological parameters vessel volume, connectivity, number, thickness, thickness distribution, separation, and degree of anisotropy were evaluated in control and surgery limbs 0, 3, and 14 days postsurgery. Results indicate that the vascular volume of the surgically manipulated limb was reconstituted as early as 3 days after femoral artery excision through development of a series of highly connected, small caliber, closely spaced, and isotropically oriented collateral vessels. Parametric analyses were completed to assess the sensitivity of the calculated morphological parameters to variations in image binarization threshold and voxel size. Images taken at the 36-microm voxel size were found to be optimal for evaluating collateral vessel formation, whereas 8- to 16-microm voxel sizes were needed to resolve smaller vascular structures. This study demonstrates the utility of microcomputed tomography as a robust method for quantitative, three-dimensional analysis of blood vessel networks. Whereas these initial efforts focused on the mouse hindlimb ischemia model, the developed techniques may be applied to a variety of model systems to investigate mechanisms of angiogenesis and arteriogenesis.

Animals↗
PubMed2003

Assessment of the collateral function of the circle of Willis: three-dimensional time-of-flight MR angiography compared with transcranial color-coded duplex sonography.

BACKGROUND AND PURPOSE: Identification of the intracranial collaterals assists in identifying patients with severe occlusive disease of the internal carotid arteries who are at lower risk of transient ischemic attacks (TIAs) and stroke. We investigated the usefulness of MR angiography in identifying functional collaterals of the circle of Willis. METHODS: MR angiography of the circle of Willis was performed in 50 healthy volunteers. Visibility was used as the criterion to define the intracranial collaterals as being functional. Two observers independently assessed the MR angiograms. Results were compared with those of transcranial color duplex sonography (TCCD), and results of carotid compression tests were the standard of reference for the identification of functional intracranial collaterals. RESULTS: With MR angiograms, reviewer 1 achieved a sensitivity of 85%, a specificity of 81%, a positive predictive value of 95%, and a negative predictive value of 55%. Reviewer 2 achieved a sensitivity of 87%, a specificity of 67%, a positive predictive value of 92%, and a negative predictive value of 53%. Interobserver agreement on MR angiograms was moderate (kappa = 0.57, 95% confidence interval: 0.42, 0.72). CONCLUSION: Visible collaterals of the circle of Willis on MR angiograms are able to supply collateral flow in the presence of carotid artery obstruction. However, the low negative predictive value of MR angiography indicates that, if collaterals are not visible, supplementary TCCD investigation is required.

Adult↗
PubMed1988

Quantitation of nerve terminal populations: synaptic vesicle-associated proteins as markers for synaptic density in the rat neostriatum.

This study has assessed the contributions of the corticostriatal fibers, the ascending striatopetal fibers, and the intrinsic neostriatal neurons to the nerve terminal population found in the rat neostriatum (caudatoputamen). For this purpose, we have analysed the levels of two different synaptic vesicle-associated proteins, synapsin I and protein p38 (also called synaptophysin), in the neostriatum after specific lesions. Our results indicate that 45-50% of the synaptic vesicle proteins in the rat neostriatum derive from the corticostriatal fibers, that approximately 25-30% of the synaptic vesicle proteins are present in kainic acid-sensitive structures, presumably intrinsic terminals and local collaterals, and that ascending fibers contain 20-25% of the vesicle-associated proteins in the neostriatum. These three neuronal populations therefore comprise 95-100% of the synaptic vesicle-associated proteins in the rat neostriatum, and thus make up most of the nerve terminals in this brain region. The results, which are in general agreement with previous morphometric studies on the rat basal ganglia, therefore indicate that nerve terminals in the central nervous system can be quantitated by use of these biochemical nerve terminal markers. The results also indicate that a somewhat higher percentage of neostriatal nerve terminals belongs to the corticostriatal fibers that previously believed.

Animals↗
PubMed2004

Magnetic resonance imaging of the elbow. Part II: Abnormalities of the ligaments, tendons, and nerves.

Part II of this comprehensive review on magnetic resonance imaging of the elbow discusses the role of magnetic resonance imaging in evaluating patients with abnormalities of the ligaments, tendons, and nerves of the elbow. Magnetic resonance imaging can yield high-quality multiplanar images which are useful in evaluating the soft tissue structures of the elbow. Magnetic resonance imaging can detect tears of the ulnar collateral ligament and lateral collateral ligament of the elbow with high sensitivity and specificity. Magnetic resonance imaging can determine the extent of tendon pathology in patients with medial epicondylitis and lateral epicondylitis. Magnetic resonance imaging can detect tears of the biceps tendon and triceps tendon and can distinguishing between partial and complete tendon rupture. Magnetic resonance imaging is also helpful in evaluating patients with nerve disorders at the elbow.

Carpal Tunnel Syndrome↗