The role of quinone reductase (NQO1) and quinone chemistry in quercetin cytotoxicity.

The effects of quercetin on viability and proliferation of Chinese Hamster Ovary (CHO) cells and CHO cells overexpressing human quinone reductase (CHO+NQO1) were studied to investigate the involvement of the pro-oxidant quinone chemistry of quercetin. The toxicity of menadione was significantly reduced in CHO+NQO1 cells compared to wild-type CHO cells, validating the NQO1-overexpression in the CHO+NQO1 transfectant. Quercetin inhibited the proliferation of wild-type CHO and CHO+NQO1 cells to a similar extent without affecting cell viability, indicating that NQO1 enrichment of CHO cells did not provide increased protection. On the other hand, inhibition of NQO1 in both types of cells by dicoumarol significantly potentiated the inhibitory effect of quercetin on cell proliferation, revealing the role of NQO1 in cellular protection against quercetin. Altogether, these results can be explained by the hypothesis that both wild-type CHO and CHO+NQO1 cells contain sufficient NQO1 activity for optimal protection against the pro-oxidant effect of quercetin on cell proliferation. The results also point at a cellular NQO1 threshold for optimal protection against quercetin. This NQO1 threshold seems to be in the range of NQO1 activities already present in various tissues.     

Development of the Home Care Client Satisfaction Instrument

Abstract Client (patient) satisfaction has been studied extensively in the health care sector, yet those receiving home health care services have been the focus of few studies. The purpose of this study was to test the reliability and validity of the Home Care Client Satisfaction Instrument (HCCSI). A total of 400 clients, randomly selected from 20 randomly chosen home care agencies in one state, completed the HCCSI and demographic form. Most respondents were older adults with multiple health problems and their families or informal support systems. Since data were skewed, item analysis was used. The revised instrument (HCCSI-R) is unidimensional and includes 12 items rated on a 5-point Likert scale measuring specific aspects of care. In addition, there are three global measures of satisfaction rated on a 10-point scale. All items except one had significant item-total correlations greater than .59. The total score correlates with likeliness to recommend the agency to others (.37, p = .0001), showing some evidence for criterion-related validity.     

Use of current situational information and causal inference: Do dysphoric individuals make “unwarranted” causal inferences?

According to Beck's original theory, depressives make unwarranted negatively biased personal inferences. Specifically, Beck suggested that depressives ignore current positive situational information and are unduly influenced by current negative situational information in making inferences. To test Beck's theory, we used Kelley's normative model of causal inference to examine the utilization of causally relevant situational information by dysphoric, nondepressed, and very nondepressed subjects in making causal attributions for personal success and failure. We used Stevens and Jones' classic method from social psychology and embedded the relevant causal information in the natural flow of events. Results showed that dysphoric, nondepressed, and very nondepressed subjects did, to an equal degree, use such information to make causal attributions. Although dysphoric and both groups of nondepressed subjects used current situational information consistently with Kelley's model, clear-cut baseline differences in the content of their causal attributions existed. Thus, the results supported the reformulations of Beck's theory that emphasize content, rather than process, differences between depressive and nondepressive cognition for dysphoria.Preparation of this article was supported by a Vilas Award, a University of Wisconsin Graduate School Grant, a Romnes Fellowship, a Biomedical Grant, and NIMH Grant R01MH43866 to Lyn Y. Abramson.     

KY-62, a Polyene Analog of Amphotericin B, for Treatment of Murine Candidiasis

KY-62 is a water-soluble analog of amphotericin B. In vitro testing of five clinical isolates of Candida albicans showed KY-62 to have potency similar to that of amphotericin B. KY-62 was administered to mice infected intravenously with C. albicans. In vivo, KY-62 was effective in immunocompetent mice, with potency similar to that of amphotericin B. KY-62 was well tolerated up to 30 mg/kg of body weight per dose, an amount that would be lethal with amphotericin B. KY-62 was less effective in mice rendered neutropenic with 5-fluorouracil. The addition of flucytosine had little effect. KY-62 may have potential for clinical development.     

Profile of Cytokines in Synovial Fluid Specimens from Patients with Arthritis. Interleukin 8 (IL-8) and IL-6 Correlate with Inflammatory Arthritides

The synovial fluid aspirated from patients with symptomatic arthritis was analyzed for the presence of tumor necrosis factor (TNF), interleukin 6 (IL-6) and interleukin 8 (IL-8). All three cytokines were found in both inflammatory and non-inflammatory arthritides: IL-8 levels ranged from less than 20 to 38,990 pg/ml, IL-6 from less than 10 to 72,300 pg/ml and TNF from less than 4 to 61 pg/ml. No inhibitors of cytokine activity were found. IL-8 and IL-6 were present in significantly higher levels in patients with inflammatory arthritis compared to patients with osteoarthritis, and there was significant correlation between the IL-6 and IL-8 levels. These findings document the presence of multiple cytokines in the synovial fluid specimens of patients with arthritis, and demonstrate that higher cytokine levels accompany inflammatory arthritis.     

Combined tool approach is 100% successful for emergency football face mask removal.

OBJECTIVE: To compare effectiveness of two techniques for removing football face masks: cutting loop straps [cutting tool: FMXtractor (FMX)] or removing screws with a cordless screwdriver and using the FMXtractor as needed for failed removals [combined tool (CT)]. Null hypotheses: no differences in face mask removal success, removal time or difficulty between techniques or helmet characteristics. DESIGN: Retrospective, cross-sectional. SETTING: NOCSAE-certified helmet reconditioning plants. PARTICIPANTS: 600 used high school helmets. INTERVENTIONS: Face mask removal attempted with two techniques. MAIN OUTCOME MEASUREMENTS: Success, removal time, rating of perceived exertion (RPE). RESULTS: Both techniques were effective [CT 100% (300/300); FMX 99.4% (298/300)]. Use of the backup FMXtractor in CT trials was required in 19% of trials. There was significantly (P<0.001) less call for the backup tool in helmets with silver screws (6%) than in helmets with other screws (31%). Mean removal time was 44.51+/-18.79s (CT: 37.84+/-15.37s, FMX: 51.21+/-19.54s; P<0.001). RPE was different between techniques (CT: 1.83+/-1.20, FMX: 3.11+/-1.27; P<0.001). Removal from helmets with silver screws was faster (Silver=33.38+/-11.03, Others=42.18+/-17.64; P<0.001) and easier (Silver=1.42+/-0.89, Other=2.23+/-1.33; P<0.001). CONCLUSIONS: CT was faster and easier than FMX. Most CT trials were completed with the screwdriver alone; helmets with silver screws had 94% screwdriver success. Clinically, these findings are important because this and other research shows that compared to removal with cutting tools, screwdriver removal decreases time, difficulty and helmet movement (reducing potential for iatrogenic injury). The combined-tool approach captures benefits of the screwdriver while offering a contingency for screw removal failure. Teams should use degradation-resistant screws. CLINICAL RELEVANCE: Sports medicine professionals must be prepared with appropriate tools and techniques to efficiently remove the face mask from an injured football player's helmet.     

Bilateral complete discoid medial meniscus combined with posterior cyst formation

Bilateral discoid medial menisci is an extremely rare condition of the knee and it can be associated to other pathological findings, including anterior portion cyst formation. We report on the clinical features, radiographic findings, treatment and results of one patient who presented a bilateral medial discoid meniscus combined with posterior portion cyst of the left knee. To the best of the author’s knowledge, this is the first case of bilateral medial discoid meniscus associated with posterior portion cyst formation.     

Antisense knockdown of the Shaker-like Kv1.1 gene abolishes the central stimulatory effects of amphetamines in mice and rats.

Amphetamine (AMPH) is an indirect sympathomimetic compound classified as a substrate-type releaser that distinguishes it from other stimulants that act as uptake 1 blockers, such as cocaine (COC). In mammals, AMPH elicits central stimulation, hypermotility, anorexia, analgesia and analeptic activity, mainly through the increase of extracellular brain dopamine (DA). The inversion of vesicular transporters and/or intravesicular alkalinization is assumed to have a role in AMPH-induced exocytosis. However, the action mechanism of this compound has not yet been completely clarified. Recent evidence on the action of AMPHs indicates potassium channel-blocking properties in peripheral tissues. We investigated the possible involvement of a Shaker-like Kv1.1 channel subtype in the central effects of AMPH, using an antisense oligodeoxyribonucleotide (aODN) that specifically and reversibly inhibits the expression of these channels in the brain. The effect of aODN pretreatments was studied by evaluating the modification of behavioral effects induced in mice through the intracerebroventricular administration of AMPH, COC, or other compounds. The aODN in mice almost completely blocked the stimulatory effects of AMPH and other releasers but was ineffective in reducing the central activity of COC. In aODN-pretreated rats a strong reduction of the AMPH, but not of the COC-stimulated DA efflux from nucleus accumbens was observed. Our results suggest that the stimulant effects of AMPH and chemically related compounds, but not COC, require the presence of functionally active Kv1.1 channels in the brain.