Activity of Quinolones Against Gram-Positive Cocci: Mechanisms of Drug Action and Bacterial Resistance

The quinolones are a potent class of antimicrobial agents that target two essential enzymes of bacterial cells: DNA gyrase and topoisomerase IV. Resistance is mediated chiefly through stepwise mutations in the genes that encode these enzymes, leading to alterations of the target site. These mutations occur in an area called the "quinolone resistance determining region". In gram-positive organisms, mutations occur more often in topoisomerase IV than in DNA gyrase. This target preference appears to depend upon two factors: the species of organism and the selecting drug. Resistance can be enhanced by a decrease in intracellular drug concentration, which is mediated through efflux pumps. The newer generation of fluoroquinolones and non-fluorinated quinolones exhibits enhanced activity against gram-positive organisms compared to the older members of this drug class, although development of resistance to these drugs has been demonstrated in vitro. This review gives a chronological perspective of the literature on the action of DNA gyrase and topoisomerase IV and the mechanisms of resistance to quinolones in staphylococci, streptococci and enterococci. Electronic Publication     

Antiseptics for treating infected wounds: Efficacy on biofilms and effect of pH

Abstract

Biofilm recalcitrance is a persistent problem when managing difficult to heal and infected chronic wounds. The wound biofilm is a fundamental factor in the re-occurrence and delayed healing commonly observed in non-healing and infected chronic wounds. However, there is presently no single antimicrobial agent that is completely efficacious against both the planktonic and sessile polymicrobial communities evident in at risk or infected wounds. We will review currently available antimicrobials, with particular emphasis on silver and iodine, employed to help suppress biofilms in wounds. In addition, we will also review the effect of pH on antimicrobial efficacy. Available evidence suggests that it is best to take a multifactorial approach towards controlling biofilm in chronic, “at risk” and infected wounds. This highlights the growing importance of avoiding indiscriminate or inappropriate use of antimicrobials in the treatment of chronic wounds.     

卟啉及其衍生物抗癌活性机理研究进展

综述卟啉类抗癌活性化合物在肿瘤细胞中的优先聚集机理及抗癌活性机理,为进一步研发卟啉类抗癌新药提供参考。     

Voluntary Facial Action Generates Emotion-Specific Autonomic Nervous System Activity

Four experiments were conducted to determine whether voluntarily produced emotional facial configurations are associated with differentiated patterns of autonomic activity, and if so, how this might be mediated. Subjects received muscle-by-muscle instructions and coaching to produce facial configurations for anger, disgust, fear, happiness, sadness, and surprise while heart rate, skin conductance, finger temperature, and somatic activity were monitored. Results indicated that voluntary facial activity produced significant levels of subjective experience of the associated emotion, and that autonomic distinctions among emotions: (a) were found both between negative and positive emotions and among negative emotions, (b) were consistent between group and individual subjects' data, (c) were found in both male and female subjects, (d) were found in both specialized (actors, scientists) and nonspecialized populations, (e) were stronger when the voluntary facial configurations most closely resembled actual emotional expressions, and (f) were stronger when experience of the associated emotion was reported. The capacity of voluntary facial activity to generate emotion-specific autonomic activity: (a) did not require subjects to see facial expressions (either in a mirror or on an experimenter's face), and (b) could not be explained by differences in the difficulty of making the expressions or by differences in concomitant somatic activity.     

Relationship Between beta-Lactamase Activity and Resistance of Enterobacter to Cephalothin

The relationship between cephalosporin β-lactamase activity and resistance to cephalothin was investigated in strains of Enterobacter cloacae and E. aerogenes. β-Lactamase activity was detected in all strains, but a quantitative correlation between amount of β-lactamase activity and level of resistance to cephalothin was not observed. Permeability barriers to cephalothin were observed and varied from strain to strain. β-Lactamase activity was increased by growing organisms in the presence of penicillin G. These enzymes hydrolyzed cephalosporins more rapidly than penicillins. Penicillinase-resistant penicillins, especially those of the isoxazolyl series, effectively inhibited Enterobacter β-lactamase. A synergistic antibacterial effect was observed when organisms were exposed to cephalothin and oxacillin in combination, and the resistance of even very small inocula to cephalothin was reduced by addition of oxacillin. Oxacillin probably exerts its effect by inhibiting β-lactamase at an intracellular site. Intracellular β-lactamase may make an important contribution to the resistance of even small inocula of gram-negative bacilli to cephalosporin and penicillin antibiotics. Although β-lactamase plays a significant role in the resistance of Enterobacter to cephalothin, other factors, such as permeability barriers, also participate in determining the level of resistance.     

Specific and Nonspecific Immune Resistance Enhancing Activity of Staphage Lysate

The immunopotentiating activity of staphage lysage (SPL) was evaluated in terms of its imune protection against lethal bacterial infection and its antitumor activity. Mice were pretreated weekly with 108 viable, Staphylococcus aureus?, strain 18Z for 3 weeks (Induction), followed by intraperitoneal SPL injections (Elicitation) at various times in relation to infectious challenge or tumor implantation. Induction without elicitation, or elicitation alone failed to provide protection against Klebsiella pneumoniae? infection and resulted in only 30-40% survival against homologous infection with pathogenic S. aureus? type III, whereas combined induction and elicitation produced enhanced resistance to infection and reduced mortality. Survival following combined induction and elicitation regimens resulted in 50% and 80-100% survival in mice inoculated with K. pneumoniae and S. aureus, respectively. SPL had no antitumor effect in mice implanted with Sarcoma-180. However, there was a significant prolongation of median survival time resulting from induction and elicitation in animals implanted which Ehrlich's ascites. This enhancement of immune resistance may possibly be related to activation of thymus-modulated lymphocytes and macrophages by SPL.     

Inmjnostimjlant Activity of A Novel Lipopeptide and Its Protective Action Against Leishmnia Donovani

Novel lipopeptides 84/201 and 86/450 synthesized in this laboratory stimulated antibody and delayed type hypersensitivity (DTH) response to ovalbumin in guinea pigs. Lipopeptide 86/450 also stimulated antibody and DTH responses in albino mice and enhanced nonspecifically macrophage migration index (fvMI), phagocytic activity and incorporation of [¹⁴C] glucosamine in peritoneal macrophages of the treated animals. Proliferative response of splenocytes from lipopeptide 86/450 treated animals was significantly higher than that from untreated controls. Peritoneal macrophages from lipopeptide 86/450 treated mice were less susceptible to Leishmania donovani promastigote invasion when co-cultured in vitro. the treated animals on challenge with L. donovani promastigote/amastigote showed 80 to 90% lower intake of infection than the control animals.     

Inmjnostimjlant Activity of A Novel Lipopeptide and Its Protective Action Against Leishmnia Donovani

Abstract

Novel lipopeptides 84/201 and 86/450 synthesized in this laboratory stimulated antibody and delayed type hypersensitivity (DTH) response to ovalbumin in guinea pigs. Lipopeptide 86/450 also stimulated antibody and DTH responses in albino mice and enhanced nonspecifically macrophage migration index (fvMI), phagocytic activity and incorporation of [¹⁴C] glucosamine in peritoneal macrophages of the treated animals. Proliferative response of splenocytes from lipopeptide 86/450 treated animals was significantly higher than that from untreated controls. Peritoneal macrophages from lipopeptide 86/450 treated mice were less susceptible to Leishmania donovani promastigote invasion when co-cultured in vitro. the treated animals on challenge with L. donovani promastigote/amastigote showed 80 to 90% lower intake of infection than the control animals.     

Physical Activity and Quality of Life: Assessing the Influence of Activity Frequency,Intensity, Volume,and Motives

In the present study, the authors investigated the impact of exercise frequency, intensity, and volume along with exercise motives on quality of life (QOL) reports. The authors assessed exercise habits with the Godin Leisure Time Activity Scale and measured exercise motives with the Reasons for Exercise Inventory. The Quality of Life Inventory assessed satisfaction in 16 domains including health, work, and recreation. High-frequency exercisers reported significantly higher health, helping, and community-related QOL than those who exercised less frequently. The authors noted significantly higher healthrelated QOL in the heavy volume group compared with the other volume groups. Multiple regression tests revealed that activity intensity and exercise motives significantly predicted QOL reports. The strongest bivariate correlations with QOL existed for mild activity and exercising for fitness and health reasons. Thus, high-frequency activity of mild intensity that produces high kcal utilization and is performed to improve health and fitness has the strongest influence on QOL reports.     

Understanding the Effects of Message Framing on Physical Activity Action Planning: the Role of Risk Perception and Elaboration

Purpose

This study aimed to determine the effects of action planning, risk perception, and message elaboration on the creation and quality of physical activity action plans. Risk perception was hypothesized as a potential moderator and elaboration as a potential mediator of the message framing-action planning relationship.

Method

Inactive adults (N?=?180; 44% women; M_age =?29.7, SD?=?9.92) were randomized to one of two framed action planning messages and responded to an online questionnaire pre- and post-message. Participants were asked about two types of risk perception towards action planning: emotional and plan creation risk perception. Post-message participants were asked about their elaboration regarding the message and presented with the opportunity to create action plans, which were scored for quality. A moderation model and a moderated mediation model were tested.

Results

Emotional risk perception moderated the message framing-action plan creation relationship. Individuals with increased emotional risk perception, as opposed to increased plan creation risk perception, were more likely to create an action plan when given a gain-framed message, as opposed to a loss-framed message. The moderated mediation model was not significant, but message elaboration predicted action plan creation. Individuals with greater message elaboration were more likely to create an action plan, regardless of the message frame.

Conclusion

Gain-framed messages may be more effective than loss-framed messages at promoting action plan creation in individuals with greater emotional risk perception. One’s elaboration of an action planning message may increase their likelihood of creating a physical activity action plan.

     

Psychodynamic Psychotherapy,Insight, and Therapeutic Action

It has often been observed that, in general, different psychotherapies do equally well. Some have taken this as good evidence that therapeutic action in psychotherapy rests not on the factors specific to individual therapies, but on common factors. I argue against this view in favor of a theory of therapeutic action deriving from psychodynamic psychotherapy. This identifies the therapeutic relationship (and with it, many so‐called common factors) and “psychodynamic insight” as therapeutic factors. I review the evidence from outcome studies and from studies into two concepts related to insight, specifically reflection function and psychological defense. I argue that the best interpretation of the evidence supports the claim that insight, in interrelation with the therapeutic relationship, contributes to therapeutic action.     

Helping Middle-Aged Women Translate Physical Activity Intentions Into Action: Combining the Theory of Planned Behavior and Implementation Intentions

The current experiment examined whether women with implementation intentions show greater correspondence between their exercise intentions and behaviors, exercise more frequently, and show changes over time in measures of theory of planned behavior (TPB) constructs and scheduling self-efficacy relative to a control group. Participants were 47 women randomly allocated to an implementation intentions or control condition. Measures of TPB constructs and scheduling self-efficacy were assessed at baseline and 8 weeks later. Regression analyses showed that intentions were a significant predictor of behavior for women in the experimental condition (p .01). A significant Condition * Time interaction was found for scheduling efficacy (p .03) and a nonsignificant interaction was found for perceived behavioral control (p = .06), indicating that only the experimental group increased scheduling self-efficacy and perceived behavioral control. No significant group differences were found for the other TPB constructs or self-reported exercise.     

Human nasal mucosal carboxypeptidase: Activity, location, and release

Background: Carboxypeptidases (CPs), such as carboxypeptidase N (CPN) (kininase I, E.C.3.4.17.3), may regulate peptide-mediated vasodilation and vascular permeability in respiratory mucosa by degrading proinflammatory peptides such as bradykinin, anaphylatoxins, and neuropeptides during allergic and nonallergic inflammation. The sources of CP activity in human nasal secretions were investigated. Methods: Well-characterized human nasal provocation and secretion analysis methods were used. Potential sources of CPN in human nasal mucosa were identified by immunohistochemistry. CP activity was defined as DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid inhibitable Bz-Gly-Lys degradation. CP activity was measured in nasal mucosal homogenates and nasal lavage fluids induced by methacholine, histamine, and allergen nasal provocation. Results: CPN-immunoreactive material was localized to the glycocalyx of the epithelium, some vessels, and gland ducts near the epithelial basement membrane but not to submucosal gland cells. CP activity in human nasal lavage fluid after saline nasal provocation was 0.10 ± 0.04 U/L. Histamine provoked secretion of significantly more CP activity (3.84 ± 0.99 U/L; p < 0.01 vs saline). Methacholine did not significantly increase secretion (0.54 ± 0.22 U/L). After nasal allergen challenge, CP activity was at a maximum between 11 and 20 minutes, and CP activity correlated with IgG concentration (r = 0.91, p < 0.01), a marker for proteins of plasma origin, suggesting that CP activity originated in plasma. Conclusions: These data suggest that plasma is the predominant source of CP activity secreted from human nasal mucosa and that plasma extravasation and interstitial fluid exudation across the epithelium are the primary processes regulating its appearance in nasal secretions. (J ALLERGY CLIN IMMUNOL 1995;96:924-31.)     

Correlation of Increased Metabolic Activity, Resistance to Infection, Enhanced Phagocytosis, and Inhibition of Bacterial Growth by Macrophages from Listeria- and BCG-Infected Mice

Macrophages from mice infected with facultative intracellular organisms such as Listeria monocytogenes and BCG have been shown to resist infection by antigenically unrelated intracellular bacterial parasites. This study compares phagocytosis, bacterial growth inhibition, and oxidation of glucose by macrophages from normal mice, mice infected with listeria or BCG, or mice immunized with killed listeria in incomplete Freund's adjuvant. Macrophages from listeria- and BCG-infected mice ingested more listeria; 67 and 57%, respectively, had three or more cell-associated bacteria versus 22% of controls (P < 0.001). Peritoneal macrophages from listeria- and BCG-infected animals significantly (P < 0.001 covariance analysis) inhibited growth of listeria in suspension, whereas control macrophages had no such inhibitory effect. The rate of oxidation of glucose-1-(14)C was higher in macrophages from listeria- and BCG-infected mice than from either uninfected animals or those immunized with killed listeria. During phagocytosis of killed or live bacteria, or latex particles, the rate of glucose oxidation was increased (P < 0.01). These data suggest that the cellular immunity after infection by an intracellular organism is associated with an increase in metabolic activity of macrophages, namely, an increase in the rate of glucose oxidation resulting in enhancement of phagocytosis and killing.     

Resistance training: cortical, spinal, and motor unit adaptations.

During the first few weeks of isometric resistance training there is an increase in maximal muscle force output that cannot be accounted for by muscle hypertrophy. Early on, researchers postulated the existence of neural adaptations to training primarily through the use of surface electromyographic recordings. More recent evidence also suggests that increased excitation may occur at the cortical levels following short-term resistance training. Alterations in synergistic activation and reductions in antagonist activation are neural factors that have been identified as changing during the early stages of resistance training which could contribute to maximal force generation. Neural adaptations that occur during the ramp-up phase of isometric contraction include decreases in motor unit recruitment thresholds, increased motor unit discharge rates, and increases in double discharges. An increase in the maximal rate of force development also occurs during the early stages of resistance training, but whether the neural mechanisms associated with the increase in the rate of rise are also associated with the increase in maximal force has not been elucidated. More work is needed to examine the integration of changes in cortical and spinal excitability with single motor unit firing patterns during this simple form of exercise before we can extend our understanding to different types of training.