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21.
Evidence that [3H]forskolin binding in the substantia nigra is intrinsic to a striatal-nigral projection: an autoradiographic study of rat brain 总被引:1,自引:0,他引:1
D R Gehlert T M Dawson F M Filloux E Sanna I Hanbauer J K Wamsley 《Neuroscience letters》1987,73(2):114-118
The neuronal localization of binding sites for the diterpene activator of adenylate cyclase, forskolin, has been determined. Kainic or ibotenic acid lesions were administered into the caudate-putamen or substantia nigra of Sprague-Dawley rats. The binding of 20 nM [3H]forskolin was examined autoradiographically and quantitated using computerized densitometry with tritium standards. Neurochemical lesions placed in the caudate-putamen markedly reduced [3H]forskolin binding in this structure and distal to the site of injection in the substantia nigra. Ibotenic acid lesions placed in the substantia nigra did not appreciably alter binding in the substantia nigra, caudate-putamen, nucleus accumbens or olfactory tubercle. These results indicate that 'forskolin-identified' adenylate cyclase in the substantia nigra is located in nerve terminals from the caudate-putamen. In addition, these sites are presumably located on cell bodies or interneurons in the caudate-putamen. 相似文献
22.
Semiquantitative detection by real-time PCR of Aspergillus fumigatus in bronchoalveolar lavage fluids and tissue biopsy specimens from patients with invasive aspergillosis
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Rantakokko-Jalava K Laaksonen S Issakainen J Vauras J Nikoskelainen J Viljanen MK Salonen J 《Journal of clinical microbiology》2003,41(9):4304-4311
A real-time PCR method was developed and used to detect Aspergillus fumigatus mitochondrial DNA (mtDNA) in bronchoalveolar lavage (BAL) fluids and tissue biopsy specimens. The analytical sensitivity of the assay was one A. fumigatus conidium per reaction, and the assay was linear at least over 4 orders of magnitude above the detection limit. BAL fluids from 66 immunocompromised patients at risk of invasive pulmonary aspergillosis (IPA) and 33 immunocompetent controls and tissue biopsy specimens from 10 immunocompromised patients were analyzed. The results were related to the clinical diagnosis established according to recently published consensus criteria. A. fumigatus mtDNA positivity was encountered in 16 of 81 (20%) BAL fluid specimens from patients at risk and 1 of 33 (3%) specimens from immunocompetent controls. PCRs were positive in six of seven, two of four, and four of five of the patients with proven, probable, and possible IPA, respectively, as well as in four patients at risk but without any other evidence of IPA. With qualitative detection, the diagnostic sensitivity of PCR was 73%, specificity was 93%, and predictive values of positive (PPV) and negative (NPV) results were 73 and 95%, respectively. Using a threshold cycle of <35 as a limit for positive PCR, the specificity and PPV of PCR in the diagnosis of invasive aspergillosis were 100%, but its sensitivity was only 45% and NPV was 92%. PCR was positive in tissue biopsy specimens from all patients with invasive aspergillosis caused by A. fumigatus. Semiquantitative detection of A. fumigatus mtDNA in BAL fluid may be helpful in the diagnosis of IPA. PCR is well suited for the verification of the presence of A. fumigatus in tissue biopsy specimens. 相似文献
23.
Herkama Sanna Kontio Mari Sainio Miia Turunen Tiina Poskiparta Elisa Salmivalli Christina 《Prevention science》2022,23(6):954-968
Prevention Science - The long-term sustainment of bullying prevention programs has rarely been investigated. This study addresses this gap by identifying facilitators and barriers to the systematic... 相似文献
24.
Sanna E Pau D Tuveri F Massa F Maciocco E Acquas C Floris C Fontana SN Maira G Biggio G 《Arzneimittel-Forschung》1999,49(2):88-95
The thienobenzodiazepine derivative etizolam (CAS 40054-69-1, 6-(o-chlorophenyl)-8-ethyl-1-methyl-4H-s-triazolo-(3,4-c)thienol(1 ,4) diazepine) is a potent anxiolytic with a pharmacological profile similar to that of classical benzodiazepines. In order to rationalize the therapeutic use of etizolam, its pharmacodynamics properties on GABAA receptors were investigated by a comparative study with other ligands on human recombinant GABAA as well as rat brain native receptors. Etizolam inhibited in a concentration-dependent manner [3H]flunitrazepam (CAS 1622-62-4) binding to rat cortical membranes, with an affinity of 4.5 nmol/l greater than that of alprazolam (CAS 28981-97-7) (7.9 nmol/l). Ethizolam enhanced GABA-induced Cl- currents in oocytes expressing human cloned GABAA receptors. With alpha 1 beta 2 gamma 2S subunit combination, etizolam produced a 73% increase in GABA-induced currents with an EC50 of 92 nmol/l. At the same receptor type, alprazolam showed a higher degree of potentiation and potency (98%, EC50 56 nmol/l). At alpha 2 beta 2 gamma 2S or alpha 3 beta 2 gamma 2S subunit constructs, the effects of etizolam were similar to those of alprazolam. Flumazenil (CAS 78755-81-4) completely blocked both etizolam and alprazolam effects on GABA-induced currents. Etizolam, administered i.p., was uneffective in changing ex vivo t-[35S]butylbicyclophosphorothionate ([35S]-TBPS) binding to rat cerebral cortex, whereas alprazolam and abecarnil (CAS 111841-85-1) significantly reduced this parameter. However, etizolam similarly to abecarnil and alprazolam, antagonized isoniazid-induced increase (61%) in [35S]-TBPS binding to rat cortical membranes. Further, etizolam inhibited in a dose-dependent manner basal acetylcholine release from both hippocampus and prefrontal cortex, and reversed foot-shock-induced increase of basal acetylcholine release to a control level. Altogether, these results suggest that etizolam may have a reduced intrinsic activity, at least at specific subpopulations of GABAA receptors. This property, together with the pharmacokinetic indication of a short-acting drug, may characterize etizolam as a ligand endowed with less side-effects typical of full agonits such as diazepam (CAS 439-14-5) and alprazolam. Finally, given its marked efficacy under conditions of GABAergic deficit, etizolam may represent a possible drug of choice with reduced liability to produce tolerance and dependence after long-term treatment of anxiety and stress syndromes. 相似文献
25.
M Serra P Madau M F Chessa M Caddeo E Sanna G Trapani M Franco G Liso R H Purdy M L Barbaccia G Biggio 《British journal of pharmacology》1999,127(1):177-187
Selective activation of peripheral benzodiazepine receptors (PBRs) in adrenal cells and brain oligodendrocytes promotes steroidogenesis. Three 2-phenyl-imidazo[1,2-a]pyridine derivatives (CB 34, CB 50 and CB 54) have now been investigated with regard to their selectivity for PBRs and their ability to stimulate central and peripheral steroidogenesis in rats. The three CB compounds (10(-10)-10(-4) M) potently inhibited the binding of the PBR ligand [3H]-PK 11195 to brain and ovary membranes in vitro, without substantially affecting [3H]-flunitrazepam binding to central benzodiazepine receptors. These compounds (10(-7)-10(-4) M) also had little or no marked effects on GABA-evoked Cl- currents in voltage-clamped Xenopus oocytes expressing human alpha1beta2gamma2S GABA(A) receptors. In addition, they failed to affect ligands binding to GABA(B), D1/D2 dopamine, muscarinic acetylcholine, N-methyl-D-aspartic acid and opiate receptors. Intraperitoneal administration of CB compounds (3-50 mg kg(-1)) induced a dose-dependent increase in the concentrations of neuroactive steroids in plasma and brain. The brain concentrations of pregnenolone, progesterone, allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC) showed maximal increases in 96+/-3, 126+/-14, 110+/-12 and 70+/-13% above control, respectively, 30 to 60 min after injection of CB 34 (25 mg kg(-1)). CB 34 also increased the brain concentrations of neuroactive steroids in adrenalectomized-orchiectomized rats, although to a lesser extent than in sham-operated animals, suggesting that CB compounds stimulate brain steroidogenesis independently of their effects on peripheral tissues. The increase in brain and plasma neurosteroid content induced by CB 34 was associated with a marked anticonflict effect in the Vogel test. Our results indicate that the three CB compounds tested are specific and potent agonists at peripheral benzodiazepine receptors, and that they stimulate steroidogenesis in both the brain and periphery. 相似文献
26.
The microvascular response to two polycationic proteins, poly-l-lysine (mol wt 104,000) and leukocyte elastase, was studied in the hamster cheek pouch microcirculation model. A 2-min topical application of polylysine (100g/ml) induced vigorous macromolecular leakage from venules only that declined within 30 min. A second application induced significantly less leakage. The leakage was inhibited by admixing polylysine with dextran sulfate prior to application or by giving hamsters an intravenous injection of dextran sulfate. The histamine antagonist pyrilamine did not interfere with the leakage, and only a few degranulated mast cells were found after polylysine application. No intravascular adhesion of leukocytes could be detected. Elastase (100g/ml) was deposited adjacent to venules with micropipets. The resulting leakage response was not inhibited by L658,758, an inhibitor of elastase enzymatic activity, but by dextran sulfate. These results may prove significant in light of the numerous polycationic proteins present within neutrophil granules.The material presented in this report is original and has not been submitted for publication elsewhere.This investigation complies with NIH guidelines for the care and use of laboratory animals. 相似文献
27.
Giovanni Biggio Laura Dazzi Francesca Biggio Luisa Mancuso Giuseppe Talani Fabio Busonero Maria Cristina Mostallino Enrico Sanna Paolo Follesa 《European neuropsychopharmacology》2003,13(6):411
Here, we summarize recent data pertaining to the effects of GABAA receptor modulators on the receptor gene expression in order to elucidate the molecular mechanisms behind tolerance and dependence induced by these drugs. Drug selectivity and intrinsic activity seems to be important to evidence at the molecular level the GABAA receptor tolerance. On the contrary, we suggested that all drug tested are equally potentially prone to induce dependence. Our results demonstrate that long-lasting exposure of GABAA receptors to endogenous steroids, benzodiazepines and ethanol, as well as their withdrawal, induce marked effects on receptor structure and function. These results suggest the possible synergic action between endogenous steroids and these drugs in modulating the functional activity of specific neuronal populations. We report here that endogenous steroids may play a crucial role in the action of ethanol on dopaminergic neurons. 相似文献
28.
Mario Sanna Abdelkader Taibah Alessandra Russo Maurizio Falcioni Manoj Agarwal 《Otology & neurotology》2004,25(3):379-386
OBJECTIVE: Retrospective study and review of the complications other than those related to the facial nerve and hearing, encountered in acoustic neuroma surgery. Also, an evaluation of hospital stay and its relation with various factors. STUDY DESIGN: Retrospective case review. SETTING: Tertiary neurotologic and skull base referral center. PATIENTS: A series of 707 patients who underwent surgical removal of acoustic neuroma from April 1987 to December 2001. INTERVENTIONS: The surgical approaches used were the enlarged translabyrinthine approach, the enlarged middle fossa approach, and the retrosigmoid approach. In a small number of cases, the operations were performed through other approaches. MAIN OUTCOME MEASURES: The duration of hospital stay and appearance of complications in the perioperative period along with their management. Results related to the facial nerve and hearing were not considered in this study. RESULTS: The most frequent complication was abdominal subcutaneous hematoma (site of fat harvest), which occurred in 23 patients (3.2%). Cerebrospinal fluid leak was present in 20 patients (2.8%), 15 of whom needed revision surgery. Other complications included VIth cranial nerve dysfunction in 12 cases (1.68%), subdural hematoma in 3 cases (0.4%), cerebellopontine angle hematoma in 4 cases (0.6%), cerebellar edema in 2 cases (0.28%), brainstem hematoma in 1 case (0.14%), transitory aphasia in 1 case (0.14%), and lower cranial nerve dysfunction in 1 case (0.14%). Mortality occurred in only one case (0.14%). Medical complications seldom occurred. The postoperative hospital stay ranged from 2 to 36 days, with an average of 6.4 days. The overall hospital stay diminished over time from 10.2 days in 1987 to 1990, to 4.9 days in 2001. There was a significant relation between hospital stay and tumor size, approach used, and presence/absence of complications. CONCLUSIONS: Perioperative complications in acoustic neuroma surgery do exist, but this study demonstrated how low the incidence is. The authors believe that the low percentage of complications is mainly attributable to the majority of operations being carried out in specialized clinics, where they are considered routine operations. They believe that following individualized approaches, depending on tumor size and on the preoperative function of the cranial nerves, is the proper way to reach a significant reduction in complications while maintaining a high percentage of total tumor removal. The results of this study, considered as a basis of comparison with other studies, will certainly be useful in preoperative patient counseling. 相似文献
29.
Mario Sanna Yogesh Jain Giuseppe De Donato Lorenzo RohitLauda Abdelkader Taibah 《Otology & neurotology》2004,25(5):797-804
OBJECTIVE: The objective of this study was to review the outcome of surgical management in patients of jugular paragangliomas. STUDY DESIGN: We conducted a retrospective case review. SETTING: Tertiary care otology and skull base center. MATERIALS AND METHODS: Fifty-five patients with the diagnosis of a jugular paraganglioma (Fisch Class C and D Glomus Jugulare) were managed over a period of 15 years. All patients with adequate follow up and complete records (53 cases) were reviewed with emphasis on the results of surgical management and the factors influencing them. INTERVENTION: All 53 patients were managed with a view to surgically extirpate the tumor. The primary approach was the infratemporal fossa approach-Type A used in the majority of the patients. In eight cases, the procedure was staged owing to the presence of large intracranial extension. Three patients required additional procedures to ameliorate the after-effects of lower cranial nerve resection. RESULTS: Gross total tumor removal was achieved in 49 patients. There were five cases of recurrence. Coupled with the residual tumors in five patients, the surgical control achieved was 83%. There was no perioperative mortality. There were two cases of postoperative cerebrospinal fluid leak, both of which required surgical exploration and closure. The facial nerve was resected in seven patients. The overall preservation rate of clinically uninvolved lower cranial nerves was 75%. CONCLUSIONS: The low level of complications along with a high surgical control achieved makes surgery the primary mode of treatment in the vast majority of these tumors, regardless of the size and location. 相似文献
30.
Mario Sanna Paolo Piazza Giuseppe Ditrapani Manoj Agarwal 《Otology & neurotology》2004,25(6):998-1005
OBJECTIVE: To present our experience with permanent preoperative balloon occlusion of the internal carotid artery while dealing with different abnormalities of the lateral skull base and a comparison with the results mentioned in the literature. STUDY DESIGN: Retrospective case review. SETTING: Private neurotologic and skull base tertiary referral center. PATIENTS: Fifteen patients who underwent preoperative balloon occlusion of the internal carotid artery and surgery subsequently for various abnormalities of the lateral skull base between 1989 and 2002. INTERVENTIONS: Each patient was subjected to four-vessel angiography along with the manual cross-compression test and balloon test occlusion to assess the efficacy of the collateral circulation. After angiography, each patient underwent a preoperative balloon occlusion, after which a lateral skull base procedure was performed for removal of the abnormality. MAIN OUTCOME MEASURES: Only those patients showing evidence of adequate collateral cerebral circulation and a less than 1-second delay between the angiographic phases of the two cerebral hemispheres on angiography were considered fit for preoperative balloon occlusion. While under going the preoperative balloon occlusion, the patients were clinically assessed for the development of any neurologic symptoms and signs. Long-term follow-up after surgery was also based on the development of symptoms and signs of neurovascular compromise. RESULTS: A major complication in the form of long-lasting hemiplegia occurred in one patient (6.7%). This complication was the result of technical factors rather than an effect of cerebral ischemia, because it was caused by an intimal dissection produced by the catheter. A defect in the visual field occurred in one patient (6.7%) that resolved partially after antiplatelet therapy. There was no mortality in our series related to preoperative balloon occlusion of the internal carotid artery. CONCLUSION: Preoperative balloon occlusion of the internal carotid artery can still be considered a viable option for the management of the internal carotid artery during lateral skull base surgery. Proper preoperative evaluation of the adequacy and efficacy of the collateral cerebral circulation reduces the chances of postoperative neurovascular complications. 相似文献