Biomedical subjects

M Wierzbicki

Publications and source records attributed to M Wierzbicki.

At least 19 recordsLinked to original sources

PubMed2001

S17834, a new inhibitor of cell adhesion and atherosclerosis that targets nadph oxidase.

microdant stress is involved in the events that accompany endothelial cell expression of adhesion molecules and leukocyte adherence in many disease states, including atherosclerosis. A recently discovered benzo(b)pyran-4-one derivative, S17834 (10 to 50 micromol/L), reduced tumor necrosis factor-stimulated vascular cell adhesion molecule-1 (VCAM) mRNA accumulation and protein expression in human umbilical vein endothelial cells. Intercellular cell adhesion molecule-1 and E-selectin were also inhibited by S17834, but platelet endothelial cell adhesion molecule-1 was not. Adherence of U937 monocytic cells to the endothelial cells as well as to plastic plates coated with soluble VCAM, intercellular cell adhesion molecule-1, P-selectin, and E-selectin was also decreased. Consistent with an antioxidant mechanism of action, S17834 (10 to 50 micromol/L) inhibited tumor necrosis factor-stimulated release of superoxide from endothelial cells measured by cytochrome c reduction. S17834 had no effect on superoxide produced by xanthine oxidase, indicating that rather than by acting as a scavenger of superoxide anion, the drug acts by inhibiting the production of free radicals. Indeed, S17834 inhibited NADPH oxidase activity of endothelial cell membranes. The ability to inhibit superoxide anion production appears to be key in the effect of S17834 on superoxide anion production and VCAM expression, because these actions were mimicked by adenovirus-mediated overexpression of superoxide dismutase. Furthermore, these actions may be relevant in vivo, because S17834 reduced aortic superoxide anion levels by 40% and aortic atherosclerotic lesions by 60% in apolipoprotein E-deficient mice. These results indicate that S17834 inhibits adhesion molecule expression and adherence of leukocytes to endothelial cells as well as aortic atherogenesis and that perhaps these effects can be explained by its ability to inhibit endogenous superoxide anion production.

Animals↗

PubMed2000

Preparation and pharmacological profile of 2-trifluoromethyl-benzo(8,9)-1,3-diaza-spiro (4,6)-undeca-2,8-diene and its enantiomers as new anti-obesity agents.

Obesity affects a large population of industrialised countries in which occurrence may reach 20%. The multifactorial aspect of the pathology prompted us to develop new entities associating favourable effects on both eating behaviour and metabolic parameters. The 2-trifluoromethyl-benzocyloheptene moiety has been combined with an imidazoline ring for synthesising a new anti-obesity agent. Preparation of the already known 2-trifluoromethyl-5-H-6,7,8,9-tetrahydro-benzocyclohepten-7-one as a key intermediate has been significantly improved, and an enantioselective procedure has been developed for imidazoline construction. The syntheses and pharmacological profiles of the compounds are presented here, particularly the effects on eating behaviour and body weight, and the putative involvement of the L-enantiomer in the treatment of metabolic diseases.

Animals↗

PubMed1998

Cognitive and behavioral correlates of depression in learning-disabled and nonlearning-disabled adult students.

Cognitive and behavioral correlates of depression were examined in 33 learning-disabled (LD) and 99 nonlearning-disabled (NLD) adult students. Self-reported depressive symptomatology was significantly correlated with dysfunctional cognitions and reinforcement level in LD students. LD students reported engaging in significantly more unpleasant activities and experiencing significantly less pleasure than NLD students. There was a nonsignificant trend for LD students to report more depression than NLD students. These results are discussed in the context of cognitive and behavioral theories of depression.

Adolescent↗

PubMed1998

General pharmacology of S 15261, a new concept for treatment of diabetes.

The new compound S 15261 (CAS 159978-02-6) is the I-isomer of 3-[2-[2-[4-[2-(alpha-Fluorenylacetylamino)ethyl]benzoyloxy]ethylam ino]-1- methoxyethyl]trifluoromethylbenzene. The general synthetic pathway used for the preparation of S 15261 and related esters is given in this paper. This compound was selected for its promising therapeutical action on blood glucose, insulin resistance and associated risk factors present in patients with non-insulin-dependent Diabetes mellitus (NIDDM). The general pharmacological profile of S 15261 was investigated. The data given in this paper show that S 15261 has presented a very low acute toxicity (lethal dose in mice greater than 1600 mg/kg orally) and did not induce significant behavioural changes in rats. A poor anorectic effects was observed after acute administration in rats. In guinea pigs S 15261 acutely induced a significant and dose-dependent hypoglycaemic effect (ED25 = 40 mg/kg orally). Biogenic amines and their metabolites in different structures of the brain were only slightly affected after acute administration of S 15261. Chronic administration of this compound (2.5 mg/kg bid for 14 days p.o.) did not cause significant alterations in the brain amines content, with the exception of an increase of serotonin (19%) in the striatum, a result not confirmed by the dose-effect study (from 1 mg/kg to 12.5 mg/kg bid for 14 days p.o.). In vitro binding assays with 31 different receptors did not show significant affinity of S 15261 for any of them. The rat arterial blood pressure was decreased (12 mmHg) after acute (25 mg/kg i.v.) or repeated administration (2.5 mg/kg bid for 14 days p.o.) without any dose-dependent effect. We therefore conclude that S 15261 may not have significant adverse effect even at doses higher than the pharmacological effective range of doses. Although the mechanism of action of this new class of compounds was not fully understood, other pharmacological data suggest that S 15261 acts at both the liver (intraportal infusion) and skeletal muscle (microdialysis studies) at least in part to enhance insulin sensitivity. For all these activities S 15261 may be useful to treat patients with NIDDM or insulin resistance known to be the major risk for onset of NIDDM.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1998

Amino derivatives of phenyl alkyl thiophene as inhibitors of bone resorption. Structure-activity relationship.

Metabolism of arachidonic acid through the 5-lipoxygenase (LO) pathway generates compounds that stimulate osteoclastic bone resorption; since LO metabolites might play a role in bone loss due to excessive resorption it was tried to develop a series of antiresorptive agents starting from an already known LO inhibitor. Of the 35 compounds synthesized, 11 strongly inhibited (10 mumol/l) retinoic acid-induced bone resorption in cultured mouse calvariae; they were also tested for their effect on LO activity using rat peritoneal neutrophils, but no correlation could be drawn between inhibition of LO and bone resorption. Other pathways, still to be identified, must therefore be targeted by these compounds even though LO inhibition might contribute to their effects on bone. Two compounds selected for further studies were found active on parathyroid hormone-induced osteolysis, while they had no effect on basal resorption; they must, therefore, act at some key point in the process of activation of osteoclastic resorption. This series of compounds may represent a new way for the treatment of bone loss due to excessive resorption.

Animals↗

PubMed1997

Use of subtle and obvious scales to detect faking on the MCMI-II.

Subtle and obvious MCMI-II items were identified using ratings of item subtlety by 103 college students. Another group of 304 students completed the MCMI-II under instructions to answer honestly or to fake their appearance. An index of differential endorsement of subtle and obvious items (S-O) was significantly correlated with the Desirability and Debasement validity scales. S-O was about as successful as the three MCMI-II validity scales in discriminating between subjects who answer honestly and who fake their appearance. Although S-O is related to the MCMI-II validity scales, it appears to add to the ability of these scales to identify subjects who attempt to fake their profile.

Alcoholism↗

PubMed1995

Correspondence between students' scores on the Millon Clinical Multiaxial Inventory-II and Personality Diagnostic Questionnaire-Revised.

The relation between two measures of personality disorders was examined in a nonclinical sample of 113 college students (86 women, 27 men) who completed the Millon Clinical Multiaxial Inventory-II and the Personality Diagnostic Questionnaire-Revised. Raw scores for 10 of 11 corresponding scales on the two instruments were significantly correlated (median r = .49). Compared to Millon's inventory, the Personality Diagnostic Questionnaire-Revised designated more subjects as having eccentric personality disorders but fewer as having anxious personality disorders. The significant association between scores on the inventories suggests that they assess personality traits that vary continuously in nonclinical samples. However, the finding that they differ significantly in their assignment of clinical labels shows that they should not be used to diagnose personality disorders in nonclinical populations.

Adult↗

PubMed1994

S15261, a new compound for the treatment of the insulin resistance syndrome.

A new oral agent, S15261 (the L-isomer of 3-[2-[2-[4-[2-[alpha-fluorenyl acetyl amino ethyl] benzoyloxy] ethyl amino] 1-methoxy ethyl] trifluoromethyl-benzene), has been developed for the treatment of the so-called "insulin resistance syndrome". In obese, insulin-resistant ageing Sprague-Dawley rats, chronic treatment with S15261 (0.5-2.5 mg.kg-1.day-1 twice per day, for 14 days) resulted in dose-dependent decreases in plasma insulin (43%), and triglyceride levels (36%), and in an increase of the glucose disposal rate during an intravenous glucose tolerance test (IVGTT) (48.5%). An increase in peripheral insulin sensitivity produced by S15261 was revealed by the glucose clamp technique. Thus, the glucose infusion rate was increased by 20% whilst steady-state insulin levels decreased by 15%. At the higher doses S15261 led to a decrease in body weight (3%), plasma glucose (13%) and blood pressure (8 mm Hg) in mildly hypertensive animals. At the doses used to achieve these results, the compound has no hypoglycaemic activity in normoglycaemic animals. Acute administration of S15261 directly into the portal vein provoked a marked increase in glucose disappearance rate during an intravenous glucose tolerance test (60%) and also in the pancreatic response to the glucose challenge. Thus, acute administration of the compound has a direct effect on glucose metabolism. These data suggest that S15261 could be a useful agent for the treatment of the insulin resistance syndrome.

Animals↗

PubMed1994

A comparison of cognitive and behavioral inductions of negative mood.

Sixty undergraduate subjects were exposed to one of three depressive mood inductions: cognitive, behavioral, or control. Subjects in the cognitive induction group read negative self-statements consistent with Beck's (1974) cognitive theory of depression. Subjects in the behavioral induction group were exposed to insoluble discrimination problems consistent with Lewinsohn's (1974) behavioral theory that lack of reinforcement produces depression. The control group read a neutral passage. Following the mood induction, subjects rated their current moods using the Multiple Affect Adjective Checklist (MAACL; Zuckerman & Lubin, 1965). The cognitive and behavioral inductions produced significantly higher MAACL total and subscale scores than did the control condition; however, the cognitive and behavioral inductions did not differ from one another. Because the cognitive and behavioral mood inductions appear equally powerful, they may be used by researchers who are attempting to identify variables that are related to subjects' differing responses to behavioral and cognitive influences on depression.

Cognition↗

PubMed1993

The differential responding of college students to subtle and obvious MCMI subscales.

This study investigated the differential responding of 49 male and 92 female college students to subtle and obvious MCMI scale items. It had been predicted that item subtlety would be correlated positively with item endorsement. This prediction was supported across all 175 MCMI items (r = .34). In addition, subjects endorsed a greater percentage of subtle than obvious subscale items for eight Basic Personality scales and two of three Pathological Personality scales. However, this pattern was not consistent for the nine Symptom Disorder scales. It also had been predicted that gender would moderate subjects' differential responding to subtle and obvious items, whereby males would show a greater tendency than females to endorse relatively more subtle than obvious items. This prediction was not supported.

Adolescent↗

PubMed1993

Use of MCMI subtle and obvious subscales to detect faking.

College students (N = 241) completed the MCMI under different instructional sets. An index of differential endorsement of subtle and obvious MCMI items was found to discriminate more strongly than the MCMI Validity Scale between subjects instructed to answer honestly and subjects instructed to fake good, fake bad, or portray specific forms of psychopathology. In addition, differential endorsement of subtle and obvious items on MCMI subscales tended to discriminate more strongly than the MCMI Validity Scale between subjects instructed to answer honestly and subjects instructed to portray the forms of psychopathology assessed by the subscales. The use of the subtle-obvious distinction to assess the validity of the MCMI is discussed.

Adult↗

PubMed1993

The relationship between MCMI subtlety and severity.

Wierzbicki (Wierzbicki & Daleiden, 1993; Wierzbicki & Howard, 1992) has suggested that the Subtle-Obvious distinction may be useful for detecting faking on the Millon Clinical Multiaxial Inventory (MCMI; Millon, 1983). This study examined Schretlen's (1990) criticism that, on the MMPI, subtlety is confounded with severity. Nine clinical psychology graduate students rated MCMI items for severity. Severity was significantly correlated (r = -.48) with item subtlety. However, this association was lower than that reported by Schretlen on the MMPI.

Comment↗

PubMed1993

Sex-typing of the Millon Clinical Multiaxial Inventory.

College students (27 men, 47 women) rated Millon Clinical Multiaxial Inventory items for sex-typedness. Men and women did not differ in their perceptions of the sex-typing of the test, either for individual items or for 11 personality disorder scales; however, subjects perceived items in general as slightly more likely to be endorsed by women than men. In addition, 10 of the 11 scales were perceived as significantly more likely to be endorsed by one sex or the other. These sex differences were generally consistent with reports of actual sex differences in the frequencies of diagnosis of Axis II conditions. Several inconsistencies between actual sex differences and the sex-typedness of Millon scales were identified and discussed.

Adult↗

PubMed1992

The differential responding of male prisoners to subtle and obvious MCMI subscales.

We investigated the differential responding of 100 male inmates to subtle and obvious MCMI scale items; subtlety was determined by judgments by college students. It has been predicted that item subtlety would be positively correlated with item endorsement. This prediction was supported across all 175 MCMI items, as well as across items on 7 of 8 personality and 8 of 12 clinical scales. It had also been predicted that education and intelligence would moderate the relationship between subtlety and endorsement, with inmates higher in education and intelligence demonstrating a greater tendency than other inmates to avoid obvious items. Modest support was obtained for this prediction, with statistically significant results found for 4 personality and 5 clinical scales. The significance of the subtle-obvious distinction is discussed, especially when employing the MCMI with an inmate population.

Adult↗

PubMed1991

Depression and engagement in pleasant and unpleasant activities in normal children.

This study investigated Lewinsohn's reinforcement model of depression by examining the relationship between depressive symptomatology and mood-related activities in normal children. Subjects were 138 children aged 8 to 14 years. Children and their parents rated the children's depression and engagement in pleasant and unpleasant activities. It was found that children's depression was correlated positively with increased engagement in unpleasant activities. However, the predicted negative correlation between children's depression and engagement in pleasant activities was supported only when children's mood was assessed by parental report, and not by children's self-report.

Adaptation, Psychological↗

PubMed1990

Anchoring errors in clinical-like judgments.

Anchoring errors occur when the final judgment in a series is biased in the direction of the initial judgment. Subjects (142 undergraduates) made sequential judgments about each of four cases (Alcohol Abuse, Anxiety, Depression, Antisocial Behavior). After each of five segments of case material, subjects rated the case's severity and prognosis and their own confidence in these judgments. It was found that initial judgments significantly predicted most of the later judgments, which demonstrated the anchoring effect. The anchoring effect occurred most strongly for the Antisocial and Anxiety cases, moderately for the Alcohol case, and only modestly for the Depression case. Contrary to expectation, confidence was related negatively to the occurrence of the anchoring effect; that is, anchoring was highest when confidence was low. Implications of this study are discussed.

Alcoholism↗

PubMed1989

Cognitive and behavioral correlates of depression in clinical and nonclinical populations.

The relationships among depression, depressogenic cognitions, and mood-related activities were examined in clinic and nonclinic populations. Fifty-seven participants in a treatment program for depression and 143 undergraduate subjects were administered a questionnaire battery that included the Beck Depression Inventory (BDI), Automatic Thoughts Questionnaire (ATQ), Dysfunctional Attitude Scale (DAS), and the mood-related items of both the Pleasant Events Schedule (PES) and Unpleasant Events Schedule (UES). Depressogenic cognitions and mood-related activities were correlated with one another and with depression in both populations: As depression increased, depressogenic cognitions and unpleasant activities increased while pleasant activities decreased. In addition, partial correlational analyses demonstrated that both depressogenic cognitions and mood-related activities, independent of one another, were correlated significantly with depression. This demonstrates that cognitive and behavioral variables, while related to one another, contribute independent information concerning depression.

Adaptation, Psychological↗

PubMed1989

Twins' responses to pleasant, unpleasant, and life events.

Pairs of monozygotic (n = 41) and same-sex dizygotic (n = 29) twins were administered the Pleasant Events Schedule, the Unpleasant Events Schedule (Lewinsohn & Amenson, 1978), and the Life Experiences Survey (Sarason, Johnson, & Siegel, 1978). These provided indices of both the frequency of and the emotional response to mood-related events. Monozygotic twins resembled one another more than dizygotic twins on all subscales of these measures, and the greater similarity was statistically significant for most of the subscales. This suggests that there may be a genetic influence on affect, which is expressed through both the frequency of engagement in and the emotional response to mood-related events. The results are discussed in the context of studies of genetic influences on subclinical levels of depression and other emotions.

Adaptation, Psychological↗