Safe resumption of driving after a severe acquired brain injury (sABI) is a strongly felt need because driving is related to recovery of independence and social-occupational re-integration. The aim ...of this prospective observational cohort study was to determine whether epilepsy secondary to sABI is a significant factor for being declared fit to drive by the relevant government authorities in Italy. In the period 2006-2015 we recruited 187 patients with sABI, 30 of whom (16.4%) developed secondary epilepsy. The interval between the acute event and the first seizure varied widely (6-96 months), confirming the need for prolonged follow-up. With regard to the aetiology, traumatic brain injury (TBI) was associated with the highest risk of epilepsy: 66.7% of the 30 patients with epilepsy had TBI, as opposed to cerebrovascular disease or anoxic brain damage (33.3%). The percentage of patients who resumed driving was about the same in the epilepsy (80%) and non-epilepsy (81%) groups.
In order to evaluate the reliability of the masseteric inhibitory reflex (MIR) as a screening method in the diagnosis of multiple sclerosis (MS), a series of 41 consecutive patients affected by ...clinically defined, long-duration forms (mean duration 10.9 years) of the disease was examined. In all cases magnetic resonance imaging and CSF isoelectrofocusing confirmed the diagnosis. Sensitivity of MIR, Blink Reflex and BAEPs were compared. Statistical analysis of data suggested the following considerations: 1) a significant concordance was found between MIR and the other neurophysiological tests performed (MIR vs. BAEPs in 78.4% of cases, p < 0.001; MIR vs. blink reflex in 68.3%, p < 0.02). 2) The S1 early component of MIR is a more reliable indicator than S2 late component. 3) In detecting brainstem lesions the sensitivity of MIR equaled that of the other neurophysiological tests. 4) Poor localizing concordance between neurophysiological tests and neuroimaging was found in our series. A possible utilization of MIR, as a part of a multimodal neurophysiological approach, even in patients affected by possible or probable MS is suggested.
We observed transient parkinsonism in 2 young epileptic patients with valproate (VPA) therapy. Complete recovery from extrapyramidal disorder occurred spontaneously in a few weeks. The lack of ...apparent susceptibility related to age and to VPA dosage, the rapid recovery from the extrapyramidal reaction, and the prevalence of negative signs such as bradykinesia and bradyphrenia can be considered the main clinical findings of this disease process. Pathophysiologic mechanisms of this rare "toxic" reaction remain unknown, although a transient imbalance between functionally reciprocal subgroups of GABA pathways leading to remediable dopamine inhibition might be hypothesized.
Acute disseminated encephalomyelitis (ADEM) is a well known complication of measles infection. Electroencephalographic abnormalities may occur frequently, in the form of moderate to severe diffuse ...high voltage theta-delta activity. We report a case of measles encephalitis with rapid benign outcome, that showed peculiar EEG features both of a "spindle coma" pattern and of an "alternating pattern." Possible physiological explanations of the EEG findings are discussed.
A reassessment of how the legacy of ancient philosophy functioned in early modern Europe In his Nicomachean Ethics, Aristotle affirms that despite his friendship with Plato, he was a better friend of ...the truth. With this statement, he rejected his teacher's authority, implying that the pursuit of philosophy does not entail any such obedience. Yet over the centuries Aristotle himself became the authority par excellence in the Western world, and even notorious anti-Aristotelians such as Galileo Galilei preferred to keep him as a friend rather than to contradict him openly. In Early Modern Aristotle, Eva Del Soldato contends that because the authority of Aristotle—like that of any other ancient, including Plato—was a construct, it could be tailored and customized to serve agendas that were often in direct contrast to one another, at times even in open conflict with the very tenets of Peripatetic philosophy.Arguing that recourse to the principle of authority was not merely an instrument for inculcating minds with an immutable body of knowledge, Del Soldato investigates the ways in which the authority of Aristotle was exploited in a variety of contexts. The stories the five chapters tell often develop along the same chronological lines, and reveal consistent diachronic and synchronic patterns. Each focuses on strategies of negotiation, integration and rejection of Aristotle, considering both macro- phenomena, such as the philosophical genre of the comparatio (that is, a comparison of Aristotle and Plato's lives and doctrines), and smaller-scale receptions, such as the circulation of legends, anecdotes, fictions, and rhetorical tropes ("if Aristotle were alive..."), all featuring Aristotle as their protagonist. Through the analysis of surprisingly neglected episodes in intellectual history, Early Modern Aristotle traces how the authority of the ancient philosopher—constantly manipulated and negotiated—shaped philosophical and scientific debate in Europe from the fifteenth century until the dawn of the Enlightenment.
The natural alkaloid camptothecin is the lead compound of a new class of antitumor agents with a unique mechanism of action (i.e. inhibition of DNA topoisomerase I). The pharmacological interest of ...these agents has generated a large number of derivatives and analogues endowed with potent cytotoxic activity, two of them being in clinical use as antitumor drugs. We have synthesized a new series of camptothecins substituted in position 7 with an alkyl or alkenyl chain bearing cyano and/or carbethoxy groups. These compounds showed potent cytotoxic activity in vitro against the human non-small-cell lung carcinoma H460 cell line, most of them exhibiting IC50 values in the 0.05−1 μM range, more active than topotecan used as a reference compound. In particular 7-cyano-20S-camptothecin (5a) showed high in vitro cytotoxicity against a topotecan-resistant H460 cell subline (H460/TPT) and a cisplatin-resistant ovarian carcinoma subline (IGROV-1/Pt 1). In an in vivo evaluation of the antitumor activity, 5a appeared significantly more effective than topotecan in the H460 tumor model and comparable with topotecan in a small-cell lung carcinoma model and a colon carcinoma model. The efficacy and good tolerability of this compound increase interest for further preclinical development.
In this article, the Ostpolitik of European transnational parties is examined as a "process within the process" of the eastward enlargement of the European Union. First, the Eastern politics of major ...European transnational parties is analyzed within the framework of their development and institutionalization processes. Then, the European transnational party-level dimension is examined as part of the development of party systems and party politics in the postcommunist candidate countries, with specific references to the EU enlargement policy and a focus on Central Europe. /// L'auteure examine l'évolution de la politique d'ouverture "Ostpolitik" des partis européens transnationaux en tant que processus sous jacent à l'élargissement de l'Union vers l'est. Elle met en rapport la politique des principaux partis européens transnationaux et leur propre développement et institutionnalisation. Une attention spéciale est portée à l'élargissement vers l'Europe centrale.
Background: A novel class of nitric oxide‐releasing nonsteroidal anti‐inflammatory drug (NO‐NSAID) derivatives has recently been described which exert anti‐inflammatory activities but produce ...significantly less gastrointestinal injury than the parent NSAID from which they are derived. The present studies were performed to determine if a nitroxybutylester derivative of naproxen was less ulcerogenic to the gastrointestinal tract than its parent NSAID, and if it exerted comparable analgesic and anti‐inflammatory properties to the parent NSAID.
Methods: The two drugs were compared in an acute gastric injury model, an antral ulcer model and after twice‐daily administration for 18 days (small intestinal damage model). Anti‐inflammatory activity was examined in the carrageenan‐induced paw oedema model, while analgesia was examined in the acetic acid‐induced writhing model. The pharmacokinetic profiles of naproxen vs. NO‐naproxen were compared by HPLC analysis.
Results: NO‐naproxen was found to produce significantly less gastric damage despite inducing similar increases in plasma TNFα to naproxen. With chronic administration, small intestinal damage was markedly less with NO‐naproxen than with the parent NSAID. However, NO‐naproxen exerted superior analgesic and comparable anti‐inflammatory effects to naproxen. NO‐naproxen was not completely converted to naproxen, but the reduced plasma levels of the latter was not the underlying reason for reduced gastrointestinal toxicity of NO‐naproxen.
Conclusion: NO‐naproxen represents a novel, gastrointestinal‐sparing NSAID derivative with superior analgesic and comparable anti‐inflammatory properties to naproxen.
Effects of a nitroxybutylester derivative of aspirin (NCX 4215) on platelet aggregation and prostanoid synthesis were compared to the effects of aspirin. NCX 4215 was approximately seven times more ...potent than aspirin as an inhibitor of thrombin-induced human platelet aggregation in vitro, but did not inhibit platelet thromboxane synthesis or gastric prostaglandin synthesis. NCX 4215 released nitric oxide when incubated in the presence of platelets and increased platelet levels of cGMP within 10 min of exposure, while aspirin did not. The anti-aggregatory effects of NCX 4215 in vitro were significantly attenuated by 10 microM hemoglobin. In ex vivo studies of ADP- or collagen- or thrombin-induced rat platelet aggregation, aspirin and NCX 4215 had comparable inhibitory effects 3 h after administration. Aspirin (10-120 mg/kg) caused extensive hemorrhagic erosion formation in the stomach of the rat within 3 h of oral administration, while NCX 4215 did not produce significant damage at doses of up to 300 mg/kg, nor when given daily for two weeks at 166 mg/kg. NCX 4215 did not alter systemic arterial blood pressure when administered intravenously to the rat. These studies demonstrate that NCX 4215 has comparable or enhanced anti-thrombotic activity to that of aspirin, but does not cause gastric damage or alter systemic blood pressure. The anti-thrombotic actions of NCX 4215 are, at least in part, due to generation of nitric oxide.
Objective
Nitric oxide–donating nonsteroidal anti‐inflammatory drugs (NO‐NSAIDs) are a new class of cyclooxygenase (COX) inhibitors. To investigate whether these drugs actually release nitric oxide ...(NO), we labeled the nitroxy group of nitroflurbiprofen with nitrogen 15 to determine the metabolic fate of this compound in humans.
Method
Six healthy volunteers who fasted were given an oral dose of 15N‐nitroflurbiprofen (100 mg). Samples of blood, urine, and gastric headspace gas were taken over a 24‐hour period to determine the levels of nitroflurbiprofen, flurbiprofen, total nitrate/nitrite, 15N‐nitrate/nitrite, COX activity, and gastric NO. In a crossover study (1 week apart), a further 6 healthy volunteers who fasted were given an oral dose of nitroflurbiprofen (100 mg) or flurbiprofen (65 mg) and levels of gastric NO were determined.
Results
Nitroflurbiprofen was undetectable in the systemic circulation. Levels of 15N‐nitrate/nitrite (5.2% ± 1.5% enrichment) and flurbiprofen (2.4 ± 0.7 μg/mL) peaked at 4 hours in the plasma and gradually decreased thereafter. In unstimulated blood, the plasma levels of thromboxane B2 (COX‐1 activity) were 2 to 3 ng/mL, and after calcium ionophore stimulation, large amounts of thromboxane B2 were produced (112 ± 31 ng/mL). Prostaglandin E2 was undetectable in unstimulated blood. After lipopolysaccharide stimulation, the plasma levels of prostaglandin E2 increased to 15 ± 4 ng/mL. The metabolite flurbiprofen inhibited plasma COX‐1 activity for the duration of the study period (maximum inhibition at 4 hours), whereas COX‐2 activity recovered after 6 hours. In the crossover study, levels of gastric NO were higher in subjects given nitroflurbiprofen, when compared with those given flurbiprofen. (The area under the curve for gastric NO was 435 ± 107 ppm · h versus 305 ± 94 ppm · h 95% confidence interval of the difference, 89–172 ppm · h; P < .001).
Conclusion
Nitroflurbiprofen was undetectable in the systemic circulation, suggesting metabolism to 15N‐nitrate/nitrite and flurbiprofen in the presystemic circulation. Levels of gastric NO were significantly higher after ingestion of nitroflurbiprofen than flurbiprofen.
Clinical Pharmacology & Therapeutics (2004) 76, 350–358; doi:10.1016/j.clpt.2004.05.008
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