פרסומים

The 37-kDa protein annexin 1 (Anx-1; lipocortin 1) has been implicated in the regulation of phagocytosis, cell signaling, and proliferation and is postulated to be a mediator of glucocorticoid action in inflammation and in the control of anterior pituitary hormone release. Here, we report that mice lacking the Anx-1 gene exhibit a complex phenotype that includes an altered expression of other annexins as well as of COX-2 and cPLA2. In carrageenin- or zymosan-induced inflammation, Anx-1-/- mice exhibit an exaggerated response to the stimuli characterized by an increase in leukocyte emigration and IL-1beta generation and a partial or complete resistance to the antiinflammatory effects of glucocorticoids. Anx-1-/- polymorphonuclear leucocytes exhibited increased spontaneous migratory behavior in vivo whereas in vitro, leukocytes from Anx-1-/- mice had reduced cell surface CD 11b (MAC-1) but enhanced CD62L (L-selectin) expression and Anx-1-/- macrophages exhibited anomalies in phagocytosis. There are also gender differences in activated leukocyte behavior in the Anx-1-/- mice that are not seen in the wild-type animals, suggesting an interaction between sex hormones and inflammation in Anx-1-/- animals.

The information used in reaching a decision between alternatives is often gleaned through samples drawn from the distributions of their outcomes. Since in most cases it is the direction of the difference in value, rather than its magnitude, that is of primary interest, the decision maker may benefit from sampling data in a way that will accentuate, rather than accurately estimate, the magnitude of that difference, as it helps to reach a decision swiftly and confidently. A reanalysis of performance in a study by Fiedler, Brinkmann, Betsch, and Wild (Journal of Experimental Psychology: General, 2000, 129, 399-418), in which participants had the freedom to sample data any way they wished, demonstrates that their apparently poor performance as estimators of conditional probability may actually reflect sophisticated sampling, which resulted in accentuating the sample value of the degree of contingency in the data. Thus, participants might be characterized as "sensitive research designers", intent on increasing the chances of detecting an effect (if one existed).

This study examined whether negative group stereotypes similarly affect adolescents' reasoning about peer and spousal retribution in interpersonal situations. Findings from cognitive domain theory, school violence, family violence, and group stereotyping and prejudice literatures were used to examine this. The sample of adolescents was drawn from northern and central Israel and consisted of 1,168 Arab and Jewish students (grades 7-11). A quasi-experimental between-subject design was used, in which the students in each grade were randomly assigned to one of two peer retribution scenarios and one of two spousal retribution scenarios. In each scenario, only the ethnicity of the peers and married couples depicted in the story was systematically altered. The study was a 2 (Arab/Jewish respondent) × 2 (peer retribution scenarios) × 2 (spousal retribution scenarios) factorial design. The findings provide evidence that Arab and Jewish students have negative stereotypes about one another; however, these group stereotypes did not affect their judgments and justifications about peer and spousal retribution. Jewish and Arab students judged peer retribution similarly, but differed in their judgments of spousal retribution. However, altering the ethnic background of the individuals in the scenarios did not affect respondents' judgments. This suggests that respondents in both groups did not base their judgments on negative stereotypes about the out-group, but instead were focusing on the behavioural act itself. Overall, the vast majority of respondents condemned retribution based on moral, social conventional and personal reasons. This inquiry provides evidence that it was the number of justifications endorsed within a specific domain that distinguished Arab and Jewish respondents. Theoretical and practical implications are discussed.

Semitic templates systematically encode two dimensions of verb meaning: (a) agency, the thematic role of the verb's external argument, and (b) voice. The assumption that this form-meaning correspondence is mediated by syntax allows the parallel compositional construction of the form and the meaning of a verb from the forms and the meanings of its root and template. The root and its arguments are optionally embedded under a light verb v which introduces the agent (Hale and Keyser 1993; Kratzer 1994). But this is only the unmarked case, which, in Semitic, is encoded by the simple templates. Two dimensions of markedness are introduced by two additional types of syntactic heads: (a) agency heads, which modify agency and are morphologically realized as the intensive and causative templates, and (b) voice heads, which modify voice and are morphologically realized as the passive and middle templates. Causative and middle morphemes are thus accounted for within a unified system, which, first, explains their affinity in language in general (both are found crosslinguistically as markers of transitivity alternations), and which, moreover, sheds new light on problems in the interface of semantics and morphology. One problem is the impossibility, mostly ignored in linguistic theory, of deriving the semantics of middle verbs from that of the corresponding transitive verbs. The second is explaining the identity found crosslinguistically between middle and reflexive morphology. The third is determining the grammatical function of the causee in causative constructions.

A novel liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for quantification of topiramate (TPM) and its metabolites 10-hydroxy topiramate (10-OH-TPM), 9-hydroxy topiramate (9-OH-TPM), and 4,5-O-desisopropylidene topiramate (4,5-diol-TPM) in plasma and urine. The method uses 0.5 mL of plasma or 1 mL of urine that is extracted with diethyl ether and analyzed by LC-MS. Positive ion mode detection enables tandem mass spectrometric (MS/MS) identification of the aforementioned four compounds. Calibration curves of TPM, 4,5-diol-TPM, 9-OH-TPM, and 10-OH-TPM in plasma and urine were prepared and validated over the concentration range of 0.625 to 40 microg/mL using TPM-d(12) as an internal standard. Calibration curves were linear over this concentration range for TPM and its metabolites. Accuracy and precision ranged in urine from 83% to 114% and 4% to 13% (%CV), respectively, and in plasma from 82% to 108% and 6% to 13%, respectively. The applicability of the assay was evaluated by analyzing plasma samples from a healthy subject who received a single oral dose of TPM (200 mg) and urine samples from 11 patients with epilepsy treated with TPM (daily dose between 100 to 600 mg) alone or with other antiepileptic drugs. Only TPM was detected and quantified in the plasma samples, and its concentration ranged between 0.7 and 4.3 microg/mL. The concentrations of TPM and 10-OH TPM were quantifiable in all urine samples and ranged from 20 to 300 microg/mL for TPM and from 1 to 50 microg/mL for 10-OH-TPM. The metabolites 4,5-diol-TPM and 9-OH-TPM were also detected in all urine samples, but their concentrations were quantifiable only in 4 patients. An unidentified peak in the chromatograms obtained from patients' urine was attributed to 2,3-O-desisopropylidene topiramate (2,3-diol-TPM). Due to a lack of reference material of 2,3-diol TPM and the similar MS/MS spectrum with 4,5-diol-TPM, the calibration curves of 4,5-diol-TPM were used for the quantification of its isomer 2,3-diol-TPM. Based on these determinations, the apparent 2,3-diol-TPM-to-TPM concentration ratio in patients' urine ranged from 0.05 to 0.51 and the 10-OH-TPM-to-TPM ratio ranged from 0.02 to 0.17. In conclusion, a novel LC-MS method for the assay of TPM and four of its metabolites in plasma and urine was developed. Its utilization for analysis of urine samples from patients with epilepsy showed that the method was suitable for analysis of TPM and its metabolites in clinical samples. Two quantitatively significant TPM metabolites (10-OH-TPM and 2,3-diol-TPM) and two quantitatively minor metabolites (9-OH-TPM and 4,5-diol-TPM) were detected and quantified in urine samples from patients with epilepsy.

PURPOSE: The objective of this study was to synthesize anhydride prodrugs for prolong action to shield the carboxylic acid group from irritative effects and to temporary hydrophobize the drug so that it becomes accessible to aqueous media when the anhydride residue is hydrolyzed. METHODS: Ibuprofen, a nonsteroidal anti-inflammatory agent, was used as a representative drug for anhydride derivatization. Mixed anhydrides of ibuprofen with fatty acids of different chain length were prepared by reacting acid chloride derivatives with the corresponding acid in the presence of acid acceptor and two-phase reaction. Mixed anhydrides were also prepared by dehydration reaction using acetic anhydride and anhydride interchange of symmetric anhydrides. The analgesic effects of mixed anhydride prodrugs were tested using nonsteroidal anti-inflammatory drug rat paw edema model. In vitro degradation of mixed anhydrides and drug release were monitored by high-performance liquid chromatography. RESULTS: Ibuprofen was bound to aliphatic and aromatic acids via an anhydride bond in high reaction yields (>85%) with high mixed anhydride content (>80%). The mix anhydride was purified by chromatography and stored at 4 degrees C to minimize conversion into the symmetric anhydride. These anhydride derivatives hydrolyzed at different time intervals depending on the hydrophobicity of conjugated acid. In vivo testing of the ibuprofen anhydride derivatives for analgesic effect indicated an extended action of the drug for over 24 h as a function of the fatty acid chain length. CONCLUSION: This study demonstrates the promise of anhydride prodrugs for extending drug action and shielding the carboxylic acid group.

The biologically active compounds, antioxidant activities, and free radical scavenging effects of black mussel dry matter (Mytilus galloprovincialis)–(BMDM) were investigated. The extract from BMDM with absolute methanol (BMDMAMet) showed the strongest inhibition of lipid peroxidation as a function of its concentration, and was comparable to the antioxidant activity of butylated hydroxyanisole, at the same concentration of 0.2 mg/ml. The extract with 50%methanol/water (BMDM50%Met) had the weakest antioxidant activity, whereas other extracts such as 1.2 M HCl in 50%methanol/water (BMDM50%Met/HCl) exhibited an average inhibition of lipid peroxidation. BMDMAMet extract showed marked activities in free radical scavenging determined by beta-carotene bleaching (beta-carotene), nitric oxide (NO*) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical cation (ABTS*+ methods. The antioxidant activities of BMDMAMet extract determined beta-carotene, NO* and ABTS*+ methods showed the highest correlation coefficients (R2) such as 0.998, 0.9976 and 0.6103, respectively, with the presence of total polyphenols. BMDM50%Met had lower antioxidant ability than BMDM50%Met/HCl in different scavenging methods, indicating that the major antioxidant components in these extracts must be derived from the polyphenols. Correlation between proteins and antioxidants was very low (0.0318 and 0.0433). The mussel extracts from polluted areas have shown by all using methods higher antioxidant activity than from the clean ones. The results presented in this report indicate that the antioxidant activities of mussel extracts could possibly be an additional index of pollution characterization.

Behavior in dynamic competitive situations requires decision makers to evaluate their own as well as their competitors positions. This paper uses data from a realistic competitive risk taking setting, Jeopardy s Tournament of Champions, to test whether individual players choose the strategic best response in making their betting decisions. The analyses show that the percentage of players choosing the strategic best response is very low, a rather surprising finding because the Tournament of Champions is contested by the very best and most experienced players of the Jeopardy game. We conjecture that performance aspiration and survival targets guide risk-taking behavior in competitive situations. Furthermore, in situations where decisions are made under pressure, contestants tend to focus on one target while ignoring alternative targets and the choices that are available to their competitors. This may lead them to select inferior competitive strategies.

The asymptotic value, introduced by Kannai in 1966, is an asymptotic approach to the notion of the Shapley value for games with infinitely many players. A vector measure game is a game v where the worth v(S) of a coalition S is a function f of ¼(S) where ¼ is a vector measure. Special classes of vector measure games are the weighted majority games and the two-house weighted majority games where a two-house weighted majority game is a game in which a coalition is winning if and only if it is winning in two given weighted majority games. All weighted majority games have an asymptotic value. However, not all two-house weighted majority games have an asymptotic value. In this paper we prove that the existence of infinitely many atoms with sufficient variety suffice for the existence of the asymptotic value in a general class of nonsmooth vector measure games that includes in particular two-house weighted majority games.

It has been argued that in the presence of an Atmosphere Externality and competitive behavior by households, a uniform commodity tax on the externality - generating good attains the first best. It is demonstrated, however, that if income redistribution is desirable then personalized taxes are required for a second-best optimum. Each of these taxes is the sum of a uniform (across households) tax and a component, positive or negative, which depends on the household s income and demand elasticities. Second-best optimal indirect taxes and rules for investment in externality - reducing measures are also considered.