Ischemic Stroke Predictors in Patients Presenting with Dizziness,Imbalance, and Vertigo

Objects

To identify predictors of acute ischemic stroke (AIS) among patients presenting to the Emergency Department (ED) with dizziness, imbalance, or vertigo (DIV) based on demographic and clinical characteristics.

Enhanced intestinal motor response to cholecystokinin in post-Nippostrongylus brasiliensis-infected rats: modulation by CCK receptors and the vagus nerve

The jejunal inflammation induced in rats by the nematode Nippostrongylus brasiliensis is followed by intestinal neuroimmune alterations including mast cell hyperplasia and nerve remodelling. On the other hand, cholecystokinin (CCK) plays a pivotal role in the regulation of intestinal motility. The aim of this study was to determine whether the intestinal motor response to CCK is altered 30 days after infection by N. brasiliensis. Thus, CCK-8 (50 microg kg(-1) intraperitoneally) disrupted the pattern of jejunal migrating myoelectric complexes for a longer time in postinfected rats (95.5 +/- 3.5 min) than in controls (48.1 +/- 5.1 min). This enhanced jejunal response was also found after oral administration of the potent releaser of endogenous CCK, soybean trypsin inhibitor. In contrast, no alteration of the inhibition of colonic motility by CCK administration was observed. The increased responsiveness of jejunal motility to CCK persisted after mast cell stabilisation or depletion but was prevented by atropine, devazepide and L-365260 (CCK-A and CCK-B receptor antagonists, respectively) and vagotomy. These results indicate that neuroimmune alterations after N. brasiliensis infection lead to an increased intestinal motility response to CCK that involves a cholinergic mediation, a vagal pathway and alterations in intestinal CCK-A and CCK-B receptors.     

Effects of home-based exercise on fatigue in postpartum depressed women: Who is more likely to benefit and why?

Objectives

(1) To explore moderators of the effects of home-based exercise on reductions in physical and mental fatigue scores in postpartum depressed women and (2) to explore mediators of the intervention on changes in physical fatigue.

Method

Eighty-eight women in the postpartum period (4-38 weeks) obtaining a score ≥10 on the Edinburgh Postnatal Depression Scale were randomly assigned to a 12-week individualized home-based exercise intervention (n=46) or a no-treatment control group (n=42). The present analyses include the 35 women who adhered to the intervention and the no-treatment control group. Participants completed a cardiovascular fitness test, and a battery of questionnaires assessing the outcomes (Physical and Mental Fatigue) as well as potential moderators and mediators at baseline and posttreatment.

Results

Hierarchical linear regressions evaluating moderators of changes in mental fatigue with exercise showed that the intervention was effective for women entering the study later in the postpartum period (P=.001) and women with higher depression scores (P=.014). Reductions in physical fatigue with exercise were partially mediated by reductions in perceived stress and increased exercise-related energy expenditure.

Conclusion

Identification of moderators allows for the tailoring of exercise interventions to particular subgroups of women that are most likely to benefit. The identified mediators may be enhanced and directly tested in future trials.     

In vitro and in vivo synergistic activities of linezolid combined with subinhibitory concentrations of imipenem against methicillin-resistant Staphylococcus aureus

Indifference or moderate antagonism of linezolid combined with other antibiotics in vitro and in vivo have mainly been reported in the literature. We have assessed the in vitro activities of linezolid, alone or in combination with imipenem, against methicillin-resistant Staphylococcus aureus (MRSA) strains using the dynamic checkerboard and time-kill curve methods. Linezolid and low concentrations of imipenem had a synergistic effect, leading us to evaluate the in vivo antibacterial activity of the combination using the rabbit endocarditis experimental model. Two MRSA strains were used for in vivo experiments: one was a heterogeneous glycopeptide-intermediate clinical S. aureus strain isolated from blood cultures, and the other was the S. aureus COL reference strain. Animals infected with one of two MRSA strains were randomly assigned to one of the following treatments: no treatment (controls), linezolid (simulating a dose in humans of 10 mg/kg of body weight every 12 h), a constant intravenous infusion of imipenem (which allowed the steady-state concentration of about 1/32 the MIC of imipenem for each strain to be reached in serum), or the combination of both treatments. Linezolid and imipenem as monotherapies exhibited no bactericidal activity against either strain. The combination of linezolid plus imipenem showed in vivo bactericidal activity that corresponded to a decrease of at least 4.5 log CFU/g of vegetation compared to the counts for the controls. In conclusion, the combination exhibited synergistic and bactericidal activities against two MRSA strains after 5 days of treatment. The combination of linezolid plus imipenem appears to be promising for the treatment of severe MRSA infections and merits further investigations to explore the mechanism underlying the synergy between the two drugs.     

Enhanced membrane disruption and antibiotic action against pathogenic bacteria by designed histidine-rich peptides at acidic pH

The histidine-rich amphipathic cationic peptide LAH4 has antibiotic and DNA delivery capabilities. Here, we explore the interaction of peptides from this family with model membranes as monitored by solid-state (2)H nuclear magnetic resonance and their antibiotic activities against a range of bacteria. At neutral pH, the membrane disruption is weak, but at acidic pH, the peptides strongly disturb the anionic lipid component of bacterial membranes and cause bacterial lysis. The peptides are effective antibiotics at both pH 7.2 and pH 5.5, although the antibacterial activity is strongly affected by the change in pH. At neutral pH, the LAH peptides were active against both methicillin-resistant and -sensitive Staphylococcus aureus strains but ineffective against Pseudomonas aeruginosa. In contrast, the LAH peptides were highly active against P. aeruginosa in an acidic environment, as is found in the epithelial-lining fluid of cystic fibrosis patients. Our results show that modest antibiotic activity of histidine-rich peptides can be dramatically enhanced by inducing membrane disruption, in this case by lowering the pH, and that histidine-rich peptides have potential as future antibiotic agents.