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1.
Oper Dent ; 46(5): E199-E223, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-35486507

ABSTRACT

OBJECTIVES: A systematic review and network meta-analysis were performed to answer the following research question: Are there differences in the risk and the intensity of tooth sensitivity (TS) among eight light activation systems for in-office bleaching in adults? METHODS: Randomized controlled trials (RCTs) that compared at least two different in-office bleaching light activations were included. The risk of bias (RoB) was evaluated with the RoB tool version 1.0 from the Cochrane Collaboration tool. A random-effects Bayesian mixed treatment comparison (MTC) model was used independently for high- and low-concentration hydrogen peroxide. The certainty of the evidence was evaluated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. A comprehensive search was performed in PubMed, Bridge Base Online (BBO), Latin American and Caribbean Health Sciences Literature database (LILACS), Cochrane Library, Scopus, Web of Science, and grey literature without date and language restrictions on April 23, 2017 (updated on September 26, 2019). Dissertations and theses, unpublished and ongoing trials registries, and IADR (International Association for Dental Research) abstracts (2001-2019) were also searched. RESULTS: After title and abstract screening and the removal of duplicates, 32 studies remained. Six were considered to be at low RoB, three had high RoB, and the remaining had an unclear RoB. The MTC analysis showed no significant differences among the treatments in each network. In general, the certainty of the evidence was graded as low due to unclear RoB and imprecision. CONCLUSION: There is no evidence that the risk and intensity of TS are affected by light activation during in-office bleaching.


Subject(s)
Dentin Sensitivity , Tooth Bleaching Agents , Tooth Bleaching , Humans , Hydrogen Peroxide/therapeutic use , Network Meta-Analysis , Tooth Bleaching Agents/therapeutic use
2.
Oper Dent ; 42(2): E44-E54, 2017.
Article in English | MEDLINE | ID: mdl-27892835

ABSTRACT

This study aimed to quantify the concentration of hydrogen peroxide into the pulp chamber in the presence or absence of adhesive enamel restorations and to analyze the resin-dentin interface of bleached groups. Bovine incisors (120) were randomly divided into three groups according to enamel treatment (n=40 each): (1) enamel without restoration (control); (2) enamel cavities (3 mm diameter × 1.5 mm depth) restored with a silorane-based (SB) system; or (3) enamel cavities (3 mm diameter × 1.5 mm depth) restored with a dimethacrylate-based (DB) system. Restorations were thermocycled, and all groups were submitted to one application of 35% hydrogen peroxide (HP) agent for 45 minutes and subjected to four light activation methods (n=10 each): without light, light-emitting diode (LED), LED/diode laser, or halogen light. Acetate buffer solution was placed into the pulp chamber before bleaching, and this solution was collected to spectrophotometrically determine the concentration of HP that reached the pulp chamber after bleaching. Rhodamine B was added to the HP agent and applied on additional enamel samples of each group for 24 hours. Samples were sectioned mesiodistally, and the bleaching agent was traced using confocal microscopy. According to two-way analysis of variance and Tukey test (α=0.05), the HP concentration in the pulp chamber of the control group was significantly lower than that of the SB group (p<0.05), regardless of light activation. No differences were observed between DB and SB groups and between control and DB groups, except for the DB halogen light activated group, which exhibited higher HP intrapulpal concentration (p<0.05). Confocal microscopy exhibited HP diffusion through the interface of the SB and DB restored groups as well as enamel prisms in the control group. The SB restorative system increased the HP diffusion into the pulp chamber, but HP was able to diffuse even in the absence of enamel restorations.


Subject(s)
Composite Resins/pharmacology , Dental Enamel Permeability , Dental Pulp Cavity/drug effects , Hydrogen Peroxide/pharmacology , Resin Cements/pharmacology , Silorane Resins/pharmacology , Animals , Cattle , Dental Restoration, Permanent , In Vitro Techniques , Materials Testing , Microscopy, Confocal , Rhodamines , Tooth Bleaching
3.
5.
Cell Death Discov ; 1: 15009, 2015.
Article in English | MEDLINE | ID: mdl-27551444

ABSTRACT

Necroptosis and signaling regulated by RIP1 kinase activity is emerging as a key driver of inflammation in a variety of disease settings. A significant amount has been learned about how RIP1 regulates necrotic cell death through the use of the RIP1 kinase inhibitor Necrostatin-1 (Nec-1). Nec-1 has been a transformational tool for exploring the function of RIP1 kinase activity; however, its utility is somewhat limited by moderate potency, off-target activity against indoleamine-2,3-dioxygenase (IDO), and poor pharmacokinetic properties. These limitations of Nec-1 have driven an effort to identify next-generation tools to study RIP1 function, and have led to the identification of 7-Cl-O-Nec-1 (Nec-1s), which has improved pharmacokinetic properties and lacks IDO inhibitory activity. Here we describe the characterization of GSK'963, a chiral small-molecule inhibitor of RIP1 kinase that is chemically distinct from both Nec-1 and Nec-1s. GSK'963 is significantly more potent than Nec-1 in both biochemical and cellular assays, inhibiting RIP1-dependent cell death with an IC50 of between 1 and 4 nM in human and murine cells. GSK'963 is >10 000-fold selective for RIP1 over 339 other kinases, lacks measurable activity against IDO and has an inactive enantiomer, GSK'962, which can be used to confirm on-target effects. The increased in vitro potency of GSK'963 also translates in vivo, where GSK'963 provides much greater protection from hypothermia at matched doses to Nec-1, in a model of TNF-induced sterile shock. Together, we believe GSK'963 represents a next-generation tool for examining the function of RIP1 in vitro and in vivo, and should help to clarify our current understanding of the role of RIP1 in contributing to disease pathogenesis.

6.
Oper Dent ; 40(2): E76-82, 2015.
Article in English | MEDLINE | ID: mdl-25535786

ABSTRACT

UNLABELLED: In tooth whitening, the hydrogen peroxide (HP) diffuses in the enamel and dentin, reaching the pulp. This in vitro study aimed to quantify the penetration of HP in the pulp chamber in teeth submitted to bleaching agents of different concentrations of HP without calcium (HP 20% [20CF], HP 35% [35CF]) and with calcium (HP 20% [20CC], HP 35% [35CC]). METHOD: Fifty human premolars were sectioned 3 mm from the cemento-enamel junction and the pulp tissue was removed. The teeth were divided into five groups according to treatment and with a control group (n=10). An acetate buffer solution was placed in the pulp chamber of all teeth. The control group was exposed only to distilled water, while the other groups were treated with a bleaching procedure, according to the manufacturer's recommendations. After treatment, the acetate buffer solution was transferred to a glass tube in which leuco-crystal violet and peroxidase solutions were added, resulting in a blue solution. The optical density of this blue solution was determined spectrophotometrically and converted into micrograms equivalent to the HP. Data were analyzed using analysis of variance and Tukey tests (α=0.05). RESULTS: The HP concentration did not affect the HP inside the pulp chamber, but the presence of calcium significantly reduced it (p<0.0001). CONCLUSION: The amount of HP that reaches the pulp chamber depends on the bleaching protocol and the product employed, and it seems to be less affected by HP concentration.


Subject(s)
Dental Pulp Cavity/metabolism , Hydrogen Peroxide/pharmacokinetics , Tooth Bleaching Agents/pharmacokinetics , Bicuspid/metabolism , Dose-Response Relationship, Drug , Humans , Hydrogen Peroxide/administration & dosage , Tooth Bleaching/methods , Tooth Bleaching Agents/administration & dosage
7.
Minerva Stomatol ; 62(6): 199-205, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23828257

ABSTRACT

AIM: This study evaluated the cytotoxicity of a dental bonding model resin (DBMR) submitted to different photo-activation distances. METHODS: A monomer mixture based on Bis-GMA and HEMA was used to assess the cytotoxicity in a mouse fibroblast-cell line. To promote different photo-activation distances glass slides were interposed between DBMR surface and halogen light curing unit (LCU) tip. Afterwards, the specimens were immersed in RPMI culture medium for 24 h to obtain extracts. The extracts were incubated in contact with the cells for 24 h. Finally, an MTT colorimetric assay was used to assess the cytotoxicity. The cell viability data (absorbance) were analyzed by one way ANOVA followed by Tukey's test (P<0.05). RESULTS: The light output decreased according to the increase in the number of glass slides between the halogen LCU tip and DBMR surface. Yet, the distance between the tip of the curing light system and the specimens had significant influence on the cytotoxicity. All extracts produced by groups submitted to different photo-activation distances showed cytotoxic effect after 24h of incubation. CONCLUSION: The photo-activation distance and the interposition of glass slides between LCU tip and DBMR was shown to play an important role in the cytotoxic effect.


Subject(s)
Bisphenol A-Glycidyl Methacrylate/toxicity , Curing Lights, Dental , Light-Curing of Dental Adhesives/methods , Methacrylates/toxicity , NIH 3T3 Cells/drug effects , Resins, Synthetic/toxicity , Animals , Bisphenol A-Glycidyl Methacrylate/radiation effects , Camphor/analogs & derivatives , Camphor/pharmacology , Cell Survival , Halogens , Hydrophobic and Hydrophilic Interactions , Materials Testing , Methacrylates/radiation effects , Mice , Photochemistry , Photoinitiators, Dental/pharmacology , Resins, Synthetic/radiation effects , para-Aminobenzoates/pharmacology
8.
Oper Dent ; 37(5): 518-25, 2012.
Article in English | MEDLINE | ID: mdl-22433029

ABSTRACT

This study evaluated the microhardness and histomorphology of bovine enamel when 35% hydrogen peroxide is used. A total of 44 specimens were adapted to removable devices used by 11 individuals subjected to dental caries challenge. A decrease in microhardness was observed for all groups after the cariogenic challenge. Microscopic analysis revealed that fragments subjected to cariogenic challenge associated with bleaching had more intense superficial histologic changes, but the depth of the lesions remained unchanged. It was concluded that 35% hydrogen peroxide enhanced the reduction in hardness and histomorphologic changes in the enamel surface exposed to cariogenic challenge.


Subject(s)
Dental Enamel/drug effects , Hydrogen Peroxide/pharmacology , Tooth Bleaching Agents/pharmacology , Tooth Demineralization/physiopathology , Adult , Animals , Biofilms , Cariogenic Agents/pharmacology , Cattle , Dental Caries/pathology , Dental Caries/physiopathology , Dental Enamel/pathology , Hardness , Humans , Microscopy, Electron, Scanning , Microscopy, Polarization , Sucrose/pharmacology , Tooth Demineralization/pathology , Young Adult
9.
Minerva Stomatol ; 60(10): 501-8, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22082855

ABSTRACT

AIM: This study evaluated the temperature change into the pulp chamber during the light curing of composite resin by direct (bovine tooth) and indirect (matrix) methods. METHODS: Direct method: fifty standardized cavities (2x2x2 mm) were prepared in bovine incisors, which were randomly assigned to evaluation of the temperature changes in the pulp chamber. Indirect method: temperature changes were evaluated through a dentine slice of 1.0 mm thickness in a elastomer cubic mold (2x2x2 mm). Filtek Z250 composite resin (3M/ESPE) was photo-activated using three light curing units: quartz-tungsten-halogen (QTH) by continuous, soft-start or intermittent light modulations; light emitting diode (LED); and plasma arc-curing (PAC). Ten groups (N.=10) were established according to technique evaluation and photo-activation methods. All experiments were carried out in a controlled environment (37 °C and 50 ± 10% relative humidity). The temperature changes were recorded using a digital thermometer attached to a type-K thermocouple in contact with the dentin slice (indirect method) or in contact with the axial wall (dentin) of pulp chamber (direct method). The results were submitted to ANOVA and Tukey's test (α=0.05). RESULTS: Temperature changes were statistically higher for the matrix indirect method (2.56 ºC) than bovine teeth direct method (1.17ºC). The change temperature was statistically higher for the PAC (1.77 ºC) when compared to other photo-activation modes in bovine teeth direct method. CONCLUSION: The two methods of temperature evaluation were different, however indirect method detected the higher temperature increase. Higher energy density arising from the light curing units and polymerization techniques promoted higher temperature increase.


Subject(s)
Curing Lights, Dental , Polymerization , Temperature , Animals , Camphor/analogs & derivatives , Camphor/radiation effects , Composite Resins , Curing Lights, Dental/classification , Dentin , Humidity , In Vitro Techniques , Materials Testing , Photochemistry , Photoinitiators, Dental/radiation effects , Polymerization/radiation effects , Thermometers
10.
AJR Am J Roentgenol ; 170(4): 1085-91, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9530065

ABSTRACT

OBJECTIVE: Before the development of dental CT reformatting software, much of the radiographic assessment of the mandible and maxilla was performed in the dentist's office using plain radiographs. The widespread use of dental reformatting software, however, has caused the radiologist to take a more active role in evaluating the jaw. Unfortunately, most radiologists have had little experience in this area, and many of the CT findings are undescribed. Our objective, therefore, was to determine the CT appearance of dental-related inflammatory disease of the jaw and to discuss the mechanisms causing such disease. MATERIALS AND METHODS: Reformatted CT scans of 400 patients referred for dental implant assessment were evaluated for abnormalities related to infection of dental origin, inflammation of dental origin, or both. The diagnosis was confirmed by surgery, clinical presentation, classic plain film appearance, or a combination of the three. RESULTS: The following disease processes were identified and described: periodontal lesions, periapical lesions, condensing osteitis, disuse bone atrophy associated with edentia, and maxillary sinus abnormalities associated with dental disease. CONCLUSION: Inflammatory diseases of the jaw and their sequelae are frequently seen on CT scans of patients referred for examination before dental implantation. Because radiologists now take an active role in evaluating the jaw, they need to become familiar with these findings.


Subject(s)
Image Processing, Computer-Assisted , Jaw Diseases/diagnostic imaging , Tomography, X-Ray Computed , Adult , Atrophy , Female , Humans , Inflammation/diagnostic imaging , Jaw/diagnostic imaging , Jaw/pathology , Male , Middle Aged , Osteitis/diagnostic imaging , Periapical Diseases/diagnostic imaging , Periodontal Diseases/diagnostic imaging
11.
Stereotact Funct Neurosurg ; 71(2): 62-75, 1998.
Article in English | MEDLINE | ID: mdl-10087470

ABSTRACT

OBJECTIVE: Since a simple, rapid and accurate stereotactic system allowing CT monitoring would offer the neurosurgeon several advantages, the feasibility and application accuracy of frameless laser-guided freehand point stereotaxis for neurosurgical interventions was studied. METHODS: A Cartesian coordinate grid mounted upon the far wall of a CT scan room defined a plane. The scanner isocenter defined the origin of a three-dimensional coordinate system. Phantom entry point and target point coordinates were determined by the positional CT cursor. These coordinates were entered into a computer which determined the coordinates of the grid intersection point with a line passing through the entry and target points. A tripod-mounted laser assembly comprising two encased lasers oriented retrograde and antegrade along opposite vectors, was positioned near the grid. The retrograde laser was positioned to illuminate the marked grid intersection point while the antegrade laser simultaneously illuminated the entry point; the beams were thereby aligned along the line of trajectory. The tip of a probe was placed on the entry point; the hub was then moved into the path of the antegrade laser, thereby aligning the probe with the line of trajectory. The probe was then inserted to the target at a trigonometrically calculated distance. RESULTS: Ten consecutive phantom tests averaged 17.5 min. Phantom test application accuracy averaged +/-2 mm at an average insertion distance of 7.1 cm. CONCLUSION: Phantom tests indicate that simple, rapid and accurate CT-monitored frameless laser-guided freehand point stereotaxis is feasible. Clinical investigation is warranted.


Subject(s)
Laser Therapy , Monitoring, Intraoperative/methods , Phantoms, Imaging , Stereotaxic Techniques , Tomography, X-Ray Computed , Humans , Image Processing, Computer-Assisted , Reproducibility of Results
12.
Interv Neuroradiol ; 4(2): 143-50, 1998 Jun 30.
Article in English | MEDLINE | ID: mdl-20673402

ABSTRACT

SUMMARY: While receiving optimal antibiotic therapy for subacute bacterial endocarditis (SBE), a teenage girl with mild congenital mitral insufficiency presented with two separate episodes of subarachnoid haemorrhage from two rapidly evolving metachronous mycotic aneurysms within the vertebrobasilar circulation. Both aneurysms were successfully treated by endovascular coil embolisation with the GDC system. This permitted at the minimum, successful amelioration of the short term risk of rerupture of the aneurysms, and facilitated operative management of the patient's infected mitral valve. The case further illustrates the utility and effectiveness of endovascular therapy for managing not only the neurovascular sequelae of SBE, but also perhaps the enhanced ability to optimally manage the source of mycotic aneurysms. In addition, the potential limitations and risks of this therapeutic strategy are assessed.

13.
AJNR Am J Neuroradiol ; 17(7): 1384-7, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8871729

ABSTRACT

We describe an adult patient with recurrent juvenile angiofibroma, which presented as a rapidly enlarging, hypervascular mass in the anterior part of the cheek. The case is unusual because of the extreme delay (greater than 30 years) and the anatomic location of the recurrence.


Subject(s)
Angiofibroma/blood supply , Angiofibroma/diagnosis , Cheek , Soft Tissue Neoplasms/blood supply , Soft Tissue Neoplasms/diagnosis , Adult , Angiofibroma/pathology , Angiography , Carotid Artery, External/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Neoplasm Recurrence, Local , Soft Tissue Neoplasms/pathology , Tomography, X-Ray Computed
15.
AJR Am J Roentgenol ; 166(3): 505-10, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8623616

ABSTRACT

With the advent of high-speed, high-resolution digital imaging and network transmission, teleradiology promises to dramatically change the mechanism for interpreting radiologic images and the traditional relationships between radiologists and patients and referring physicians. We discuss the current status of medical-legal issues pertaining to privacy, licensing, credentialing, liability, and fraud for teleradiology. Special emphasis is placed on the technical factors that may result in differences in image properties, consequently affect radiologic diagnosis, and bring the potential for liability.


Subject(s)
Malpractice/legislation & jurisprudence , Teleradiology/legislation & jurisprudence , Confidentiality/legislation & jurisprudence , Credentialing/legislation & jurisprudence , Diagnostic Errors , Fraud , Humans , Licensure, Medical/legislation & jurisprudence , United States
16.
AJR Am J Roentgenol ; 165(5): 1273-6, 1995 Nov.
Article in English | MEDLINE | ID: mdl-7572517

ABSTRACT

OBJECTIVE: Oroantral fistula, an abnormal communication between the oral cavity and the maxillary sinus, is infrequently diagnosed radiologically. The purpose of this study was to describe the CT findings and clinical features of oroantral fistula and to show that dental CT multiplanar reformatting programs can be instrumental in diagnosing this condition. SUBJECTS AND METHODS: The study included eight patients with clinically confirmed oroantral fistula or with radiologic evidence of oroantral fistula. Fistula size, degree of alveolar atrophy, nature of maxillary sinus disease, and related dental disease were assessed along with the clinical presentations. RESULTS: The most frequent CT findings were bony discontinuity of the maxillary sinus floor, communication between the oral cavity and the sinus, soft-tissue opacification of the ipsilateral maxillary sinus, focal areas of alveolar atrophy, and associated periodontal disease. In 6 of 8 patients there was 100% opacification of the ipsilateral maxillary sinus, and in 5 of 8 patients the contralateral sinus appeared completely normal. The fistula size ranged from 13.5 mm2 to 189 mm2. CONCLUSION: The appearance of oroantral fistula on multiplanar CT imaging is disruption of the bony floor of the maxillary sinus with soft-tissue opacification of the ipsilateral sinus. Dental reformatted CT can be useful for evaluating patients suspected of having oroantral fistula, and this condition may be found incidentally in patients referred for evaluation for osseointegrated root-form dental implants.


Subject(s)
Oroantral Fistula/diagnostic imaging , Tomography, X-Ray Computed , Adult , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Radiography, Panoramic
17.
Comput Methods Programs Biomed ; 46(2): 113-9, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7796580

ABSTRACT

We designed and implemented algorithms for three-dimensional (3-D) reconstruction of brain images from serial sections using two important supercomputer architectures, vector and parallel. These architectures were represented by the Cray YMP and Connection Machine CM-2, respectively. The programs operated on linear octree representations of the brain data sets, and achieved 500-800 times acceleration when compared with a conventional laboratory workstation. As the need for higher resolution data sets increases, supercomputer algorithms may offer a means of performing 3-D reconstruction well above current experimental limits.


Subject(s)
Algorithms , Brain/anatomy & histology , Computer Systems , Diagnostic Imaging , Image Processing, Computer-Assisted , Animals , Image Enhancement , Information Systems , Male , Models, Structural , Neural Networks, Computer , Radiographic Image Enhancement , Signal Processing, Computer-Assisted , Software Validation , Time Factors , Tomography, X-Ray Computed
18.
Obstet Gynecol ; 84(4 Pt 2): 701-3, 1994 Oct.
Article in English | MEDLINE | ID: mdl-9205455

ABSTRACT

BACKGROUND: Müllerian anomalies are associated with several gynecologic complications including endometriosis, infertility, and pelvic pain. CASE: A woman with duplicate cervix and a non-communicating longitudinal vaginal septum, but no other uterine anomalies, presented with pelvic pain, secondary infertility, and a long history of endometriosis. She was treated with operative laparoscopy and excision of the vaginal septum. CONCLUSION: A thorough evaluation, including history, physical examination, and appropriate imaging techniques (hysterosalpingography and magnetic resonance imaging) facilitates accurate diagnosis of anatomical defects and any associated disease in cases of unusual müllerian anomalies. An accurate preoperative diagnosis allows a planned, efficient surgical approach.


Subject(s)
Abnormalities, Multiple , Cervix Uteri/abnormalities , Endometriosis/complications , Infertility, Female/complications , Pelvic Pain/complications , Uterine Neoplasms/complications , Vagina/abnormalities , Adult , Chronic Disease , Female , Humans
19.
J Cereb Blood Flow Metab ; 12(5): 717-26, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1380515

ABSTRACT

We investigated whether inhibition of nitric oxide (NO) biosynthesis with N-omega-nitro-L-arginine (NNA), a competitive inhibitor of NO synthase (NOS), would modify the volume of the focal ischemic infarction produced by occlusion of the middle cerebral artery (MCA) in spontaneously hypertensive rats. NNA was infused for 1 h (2.4 mg/kg/h) immediately following occlusion of the MCA. NNA increased lesion volume 24 h later by 32% over controls (150.8 +/- 16.6 to 199.2 +/- 17.4 mm3; p less than 0.001, n = 6). This effect was antagonized by co-infusion of L- but not D-arginine. The antihypertensive rilmenidine (0.75 mg/kg) reduced the lesion by 27% (p less than 0.05, n = 4). Changes in lesion size were confined to the penumbra. NNA increased arterial pressure (AP) (118 +/- 8.9 to 149 +/- 16.0 mm Hg; p less than 0.01, n = 3) but did not change regional CBF. However, elevation of AP did not change the lesion volume or distribution. We conclude that inhibition of the constitutive form of NOS in vivo increases the volume of focal ischemic infarction as a consequence of reduced NO biosynthesis. The absence of NO availability may extend lesion formation by inhibition of reactive hyperemia, platelet disaggregation, and/or release of neuroprotective neuromodulators in the penumbra, which may counteract and override any of its neurotoxic actions.


Subject(s)
Cerebral Infarction/metabolism , Ischemic Attack, Transient/metabolism , Nitric Oxide/metabolism , Amino Acid Oxidoreductases/antagonists & inhibitors , Analysis of Variance , Animals , Antihypertensive Agents/pharmacology , Arginine/analogs & derivatives , Arginine/pharmacology , Male , Nitric Oxide Synthase , Nitroarginine , Oxazoles/pharmacology , Phenylephrine/pharmacology , Rats , Rats, Inbred WKY , Rilmenidine
20.
J Cereb Blood Flow Metab ; 12(1): 53-63, 1992 Jan.
Article in English | MEDLINE | ID: mdl-1345758

ABSTRACT

Treatment with the alpha 2-adrenergic antagonist idazoxan (IDA) can provide protection from global cerebral ischemia. However, IDA also recognizes another class of receptors, termed imidazole (IM) receptors, which differ from alpha 2-adrenergic receptors and are responsible for the hypotensive actions of some centrally acting agents such as the oxazole rilmenidine (RIL). We therefore sought to determine whether RIL, an agent highly selective for IM receptors, offered protection from focal cerebral ischemia elicited in rat by ligation of the middle cerebral artery (MCA). We compared the effects of RIL with the effects of IDA and the selective non-IM alpha 2-antagonist SKF 86466 (SKF). In addition, we examined whether the neuroprotective effects of RIL and IDA could be attributed to changes in local CBF (LCBF). The MCA was occluded and animals either received immediate administration of drug while arterial pressure was maintained for 1 h or had local CBF increased to 200% of control for 1 h by hypercapnia or hypertension. RIL elicited a significant dose-dependent preservation of tissue to 33% of control at optimal dose (0.75 mg/kg). IDA (3 mg/kg) significantly reduced the size of ischemic infarction by 22%. In contrast, SKF (15 mg/kg) as well as doubling of LCBF did not preserve ischemic tissue. We conclude that both RIL and IDA can reduce focal ischemic infarction but that the mechanism does not appear secondary to antagonism of alpha 2-adrenergic receptors or elevation of LCBF. Occupation of IM receptors, either in the ischemic zone or at remote brain sites, may be responsible for neuroprotection of RIL and IDA.


Subject(s)
Adrenergic alpha-Agonists/therapeutic use , Brain/drug effects , Ischemic Attack, Transient/drug therapy , Oxazoles/therapeutic use , Adrenergic alpha-Agonists/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Animals , Benzazepines/pharmacology , Benzazepines/therapeutic use , Brain/metabolism , Brain/pathology , Dioxanes/pharmacology , Dioxanes/therapeutic use , Dose-Response Relationship, Drug , Idazoxan , Imidazoles/metabolism , Ischemic Attack, Transient/metabolism , Ischemic Attack, Transient/pathology , Male , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Oxazoles/pharmacology , Rats , Rats, Inbred SHR , Receptors, Drug/metabolism , Rilmenidine
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