The effect of inflammatory stimuli on NMDA-related activation of glutamine synthase in human cultured astroglial cells

Removal of glutamate from the synaptic cleft by astroglial glutamine synthase (GS) is a crucial step in the regulation of glutamate turnover and metabolism, thus participating in endogenous neuroprotective processes occurring within brain tissues. Here we investigated on the effect of inflammatory cytokines on GS activity in astroglial cells undergoing NMDA receptors stimulation. Incubation of human cultured astroglial cells with NMDA (100 microM) enhanced GS expression, an effect driven by the generation of nitric oxide (NO) since l-NAME (500 microM), an inhibitor of NO synthase, reversed this effect. NMDA-related increase of GS activity and glutamine concentration was antagonised by previous incubation of astroglial cells with a mixture of LPS plus gammaIFN, an effect counteracted by dexamethasone, the latter effect being accompanied by inhibition of inducible NO synthase. These results show that LPS plus gammaIFN inhibit elevation of GS activity subsequent to NMDA receptor stimulation in astroglial cells via enhancement of inducible NO synthase, and this may represent the site of interaction between pro-inflammatory and excitotoxic stimuli in the brain.     

Estradiol reduces cytochrome c translocation and minimizes hippocampal damage caused by transient global ischemia in rat

It is well-established that 17beta-estradiol (17beta-E(2)) confers neuroprotection to male and female rats exposed to focal cerebral ischemia, while less is known about the effects of the hormone under conditions of transient global ischemia. Since translocation of cytochrome c from the mitochondria to the cytosol is a critical step in apoptotic cell death after cerebral ischemia, we have investigated whether 17beta-E(2) interferes with such mechanism to exert neuroprotection. Global ischemia, induced in male Wistar rats by 5-min 4 vessel occlusion (4VO), resulted in a significant increase of cytosolic cytochrome c (cyt-c) levels as detected by Western blotting at 6h after reperfusion. 17beta-E(2) (0.2mg/kg, i.p.) given 1h before ischemia minimized cytochrome c translocation and the latter effect was partially reversed by tamoxifen (0.25mg/kg, i.p.). Bilateral cell counting revealed that delayed hippocampal damage typically caused by 4VO was abolished by 17beta-E(2) and this was partially reversed by tamoxifen in the CA3 subregion, but not in CA1/CA2 or CA4. These findings provide the original observation that 17beta-E(2) reduces delayed hippocampal damage caused by 4VO in male rats and blocks cytochrome c translocation during the early stages of neuronal death, thus providing an important mechanism involved in estrogen-mediated neuroprotection.     

Intimate behavior and allergy: a narrative review.

OBJECTIVE: To determine how sex and intimate contacts can represent a risk factor for allergic reactions, because they may favor direct contact with sensitizing substances. DATA SOURCES: We collected in this review the available literature on this subject. The MEDLINE database was searched by a combination of keywords: sex OR sexual intercourse OR kiss OR seminal plasma OR condom AND allergy OR allergic reaction. STUDY SELECTION: The studies retrieved were independently evaluated by the authors and included in this review based on their clinical pertinence (i.e., dealing with clinical presentation, diagnosis, or treatment). RESULTS: Sex and intimate behavior seem to be increasingly described as triggers of allergic reactions, although the pertaining literature is represented mostly by case reports. Kissing has been described as a risk factor for food- and drug-induced severe reactions. Seminal plasma allergy has been repeatedly described and investigated. In this case, practical diagnostic algorithms have been proposed, and desensitization protocols are available. Similarly, there are numerous case reports of allergic reaction due to latex condoms, for which the diagnostic procedure is standardized. CONCLUSIONS: The available literature on intimate behavior, and sex in general, as a trigger of allergic reactions is not abundant. This is probably because of the particular nature of the problem, which concerns intimacy. Nevertheless, reliable diagnostic procedures are available in some specific cases. The possible link between sex and allergy should become part of the personal culture of allergists to extend and improve the diagnosis of unusual or unexplained conditions.     

Evaluating hospital appropriateness with different tools: administrative data versus analytic review

PRUO, a modified version of AEP, is a widely used clinical-based tool to evaluate hospital appropriateness in Italy. We developed the APPRO method for assessing organizational appropriateness using administrative data. APPRO estimates the amount of inappropriate hospitalisation, giving consideration to severity of illness through APR-DRG classification system. The aims of the study were to: measure the agreement between evaluators using PRUO; investigate the relation between APR-DRG severity subgroups and PRUO assessment; asses the validity of APPRO method comparing its performance to PRUO results. We selected 361 hospital episodes assigned to DRG 39 ("lens procedures with or without vitrectomy") and 242 hospital episodes assigned to DRG 183 ("miscellaneous of digestive disorders, age > 17") from three hospitals in 2000. Clinical records were independently evaluated by two pairs of physicians using PRUO. Proportions of inappropriate episodes by hospital and DRG were also estimated through APPRO using data from Lazio regional hospital information system. The agreement between the two pairs of evaluators was high (k=0.93; p<0.0001). We observed no statistically significant association between APR-DRG severity subgroups and inappropriate hospitalisation found by PRUO. APPRO underestimates rates of inappropriate hospitalisation compared to PRUO. It depends on the different characteristics of the tools and particularly on the caution of APPRO in performing the evaluation using routine data.     

Estimates of pleural mesothelioma incidence in the Lazio region (Italy), 1997-2000

BACKGROUND: Malignant mesothelioma is indicative of past exposure to asbestos. In recent years an increase of incidence and mortality from malignant mesothelioma has been observed. Recent legislation in Italy requires nation-wide registration of asbestos-related pathologies. We conducted a preparatory study for systematic recording of cases of malignant pleural mesothelioma in the Lazio region. OBJECTIVES: To register new diagnoses of malignant mesothelioma, to estimate the incidence in the Lazio region, and to evaluate possible survey instruments. METHODS: We conducted a systematic study of hospital admissions in the region with diagnosis of cancer of the pleura (ICD-IX 163) in the period 1997-2000. Clinical information and results of diagnostic tests were requested for 530 patients from the hospitals involved. Using the capture-recapture method, it was possible to estimate the accuracy of the data we compiled using hospital admissions as the data source (76.8%, 95% C.I.=76.4-77.3). RESULTS: After careful review of clinical documentation, the diagnosis of malignant mesothelioma of the pleura was confirmed in 31.6% of cases (156 cases diagnosed). The percentage of confirmed cases has risen over the years (from 21% in 1997 to 45.1% in 2000) and it was higher in large public hospitals than in other types of health care facilities. On the basis of 156 confirmed cases of mesothelioma (116 males and 40 females), we estimated the annual incidence of the disease in the Lazio region as 1.73 new cases per 100,000 inhabitants among men and 0.47 new cases per 100,000 inhabitants among women. CONCLUSIONS: The results show that the incidence of mesothelioma in the region is consistent with national data, falling in the middle of the range for all Italian regions. However, some areas emerge (for example, Colleferro, Civitavecchia, Tarquinia, Ferentino, Gaeta, Aprilia, Pomezia) that have particularly high rates, probably in relation to past occupational asbestos exposure. The role of diffuse environmental exposure in Rome may warrant further investigation.     

Epileptogenic effects of skin extracts from the Australian frog Pseudophryne coriacea after intracerebral microinfusion in rats.

The behavioural and electrocortical (ECoG) effects induced by a methanol extract of the skin of the Australian frog Pseudophryne coriacea, directly microinjected into several areas of the brain, were studied in freely moving rats. Administration of the P. coriacea extract (5, 10, 15 and 20 micrograms) into the dorsal hippocampus produced a dose-dependent and reversible behavioural stimulation and ECoG spikes lasting 20-140 min. Similar but less intense effects were elicited in rats receiving injections into the III cerebral ventricle, amygdala and caudate nucleus. In conclusion, the present experiments show that the skin extract of P. coriacea produces behavioural stimulation and ECoG spikes when injected into the rat brain, the most sensitive area being the hippocampus.     

Choline pivaloyl ester strengthened the benefit effects of Tacrine and Galantamine on electroencephalographic and cognitive performances in nucleus basalis magnocellularis-lesioned and aged rats

The aim of the present work was the assessment of the effects produced on the electroencephalographic (EEG) activity and the cognitive and memory performances of nucleus basalis magnocellularis (NBM)-lesioned or aged rats by the combined treatment with [2-(2,2-dimethylpropionyloxy)ethyl]trimethylammonium 2,2-dimethylpropionate (choline pivaloyl ester) (CPE) and the Cholinesterase inhibitors (ChEIs) Tacrine (THA) and Galantamine (GAL). Intraperitoneal administration of CPE combined with THA or GAL to both NBM-lesioned or aged rats, produced EEG desynchronisation, and a significant decrease in the energy of the total EEG spectrum and the lower frequency bands (delta 0.25-3 and theta 4-7 Hz) lasting many minutes. Furthermore, drug associations reversed in aged rats the scopolamine (0.2 mg/kg, i.p.)-induced increase in EEG power, slow waves and high-voltage spindle (HVS). Furthermore, the combined administration of CPE and Cholinesterase inhibitors in both NBM-lesioned or aged animals, improved performances in all behavioural tasks, enhancing object discrimination, increasing locomotory activity and alternation choice in T-maze, ameliorating retention in passive avoidance and decreasing escape latency in Morris water maze. In all test, AChEIs and CPE combinations proved to be more effective than CPE, THA or GAL given alone. In conclusion, the present work shows the ability of choline pivaloyl ester in strengthening the positive cerebral activity of THA and GAL.     

Tissue plasminogen activator is required for striatal post-ischemic synaptic potentiation

Recent experimental observations indicate that tPA plays a key role in the development of neuronal damage that follows cerebral ischemia and excitotoxicity. In an attempt to clarify how tPA favors ischemia-induced neuronal damage, we performed in vitro electrophysiological experiments in striatal slices by using mice selectively lacking this serine protease.We found that tPA ablation did not affect the membrane depolarization of striatal neurons exposed to combined oxygen and glucose deprivation but fully prevented the induction of NMDA-dependent post-ischemic long-term synaptic potentiation. The absence of striatal post-ischemic pote ntiat ion observed in tPA-lacking mice may account for the significant neuroprotection observed in these animals after the occlusion of middle cerebral artery.     

Enhanced behavioural,electrocortical and hyperthermic effects of serotonin-like agents after impairment of serotonin transmission in fowl brain

Summary In adult fowls and in young chicks (Gallus domesticus) the effects were studies on body temperture, behaviour and electrocortical activity of 5-HT and other direct or indirect serotonin agonists given into the III cerebral ventricle in conditions of prolonged impairment of serotoninergic transmission.In chicks pretreated with 5,6-dihydroxytryptamine the subsequent intraventricular injection of 5-HT produced more intense and longer-lasting hyperthermic response and behavioural and electrocortical sleep. On the other hand fenfluramine given intraventricularly in fowls pretreated with 5,6-DHT did not produce significant body temperature and behavioural changes.After 14 and 21 day treatment with methysergide the subsequent administration of 5-HT, fenfluramine and quipazine produced in fowls an hyperthermic response and behavioural sleep more marked and longer-lasting than in control animals.The present experiment show that in conditions of chronic impairment of 5-HT function there is an enhanced behavioural and body temperature response to 5-HT and drugs acting by releasing endogenous 5-HT or as 5-HT agonists.     

Behavioural, electrocortical and body temperature effects after intracerebral infusion of TRH in fowls.

In fowls TRH given into the III cerebral ventricle (0.25–5 μg) produced intense behavioural stimulation, electrocortical desynchronization and a slight increase in body temperature. In particular, an intense pattern of stereotyped head-neck movements, increase in locomotor activity, repeated and preening, vocalization, erection of the tail feathers and occasionally ‘escape responses’ were observed. This picture lasted for about 30 min and was followed by slight behavioural sedation during which stereotypies continued to occur but to a lesser extent. Similar increases in locomotor activity and stereotypies were evoked by infusing TRH into the hypothalamus whereas the unilateral microinfusion into the n. basalis or the n. mesencephalicus profundus, homologous to the mammalian striatum and s. nigra respectively, produced very intense stereotyped head-neck movements, wet-dog syndrome and vocalization. TRH given into the other areas of the brain (e.g. hyperstriatum, neostriatum, olfactory ventricle, eminentia basalis and lateral part of the mesencephalon) lacked effects on behaviour and body temperature. The effects of intraventricular infusion of TRH were antagonized by prior administration of haloperidol and spiperone whereas antagonists at α and β-adrenoceptors and at 5-HT receptors were ineffective. In addition, TRH reversed sedation induced by intraventricular α-methyl-p-tyrosine. Behavioural and body temperature effects of TRH were independent of its endocrine properties since these were not observed after systemic or intracerebroventricular injection of thyrotropin, triidothyronine and thyroxine. The increase in body temperature evoked by intracerebroventricular injection of TRH was due to activation of heat production and decrease in thermodispersive mechanisms.