Influence of cyclooxygenase inhibitors on gut immune cell distribution and apoptosis rate in experimental sepsis

The aim of this study was to determine if cyclooxygenase (COX) inhibitors influence immune cell distribution in the small intestinal mucosa and mesenteric lymph nodes (MLNs), the grade of mucosal damage, and the rate of apoptosis in septic rats. The effects induced by a selective COX-2 inhibitor (SC-236) were compared with those of a nonselective COX-1 and -2 inhibitor (indomethacin). Cecal ligation and puncture (CLP), CLP + SC-236 p.o, and CLP + indomethacin p.o, were evaluated. Animals were harvested 6 and 24 h after CLP, respectively. The concentration of proinflammatory cytokines was higher in ascitic fluid than in blood. CLP + SC-236 attenuated IL-6 in plasma and in ascitic fluid and CLP + indomethacin augmented TNF-alpha in ascitic fluid compared with CLP at 6 h. CLP + SC-236 gave a lesser degree of mucosal damage compared with CLP alone or with indomethacin at 6 and 24 h (P < 0.05). Untreated CLP had significant reductions in the number of T lymphocytes in the villi and increases of macrophages in the mucosa and MLNs compared with controls (P < 0.05). CLP + indomethacin decreased T lymphocytes in the villi and MLNs. CLP caused an enhanced apoptosis in the mucosa compared with controls (P < 0.05), pretreatment with COX inhibitors did not significantly change this. Both COX inhibitors enhanced apoptosis in MLNs and attenuated the increase of macrophages in mucosa and MLNs (P < 0.05). It is proposed that the increased apoptosis and the decrease in T cells in the mucosa may be causally related. Apoptosis of lymphocytes may impair the immunologic defense in sepsis. Furthermore, loss of intestinal epithelial cells may compromise bowel wall integrity and facilitate translocation.     

The effect of open lung ventilation on right ventricular and left ventricular function in lung-lavaged pigs

Introduction  

Ventilation according to the open lung concept (OLC) consists of recruitment maneuvers, followed by low tidal volume and high positive end-expiratory pressure, aiming at minimizing atelectasis. The minimization of atelectasis reduces the right ventricular (RV) afterload, but the increased intrathoracic pressures used by OLC ventilation could increase the RV afterload. We hypothesize that when atelectasis is minimized by OLC ventilation, cardiac function is not affected despite the higher mean airway pressure.     

Hormone-replacement therapy influences gene expression profiles and is associated with breast-cancer prognosis: a cohort study

Background

The aim of the current study was to assess the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort) extract WS^® 5570 at doses of 600 mg/day in a single dose and 1200 mg/day in two doses.

Methods

The participants in this double-blind, randomized, placebo-controlled, multi-center clinical trial were male and female adult out-patients with an episode of mild or moderate major depressive episode (single or recurrent episode, DSM-IV criteria). As specified by the relevant guideline, the study was preceded by a medication-free run-in phase. For the 6-week treatment, 332 patients were randomized: 123 to WS^® 5570 600 mg/day, 127 to WS^® 5570 1200 mg/day, and 82 to placebo. The primary outcome measure was the change in total score on the Hamilton Rating Scale for Depression (HAM-D, 17-item version) between baseline and endpoint. Additional measures included the number of responders, the number of patients in remission, and several other standard rating scales. Efficacy and safety were assessed after 2 and 6 weeks. The design included an interim analysis performed after randomization with the option of early termination.

Results

After 6 weeks of treatment, mean ± standard deviation decreases in HAM-D total scores of 11.6 ± 6.4, 10.8 ± 7.3, and 6.0 ± 8.1 points were observed for the WS^® 5570 600 mg/day, 1200 mg/day and placebo groups, respectively (endpoint analysis). Secondary measures of treatment efficacy also showed that both WS^® 5570 groups were statistically superior to placebo. Significantly more patients in the WS^® 5570 treatment groups than in the placebo group showed treatment response and remission. WS^® 5570 was consistently more effective than placebo in patients with either less severe or more severe baseline impairment. The number of patients who experienced remission was higher in the WS^® 5570 1200 mg/day group than the WS^® 5570 600 mg/day group. The incidence of adverse events was low in all groups. The adverse event profile was consistent with the known profile for Hypericum extract preparations.

Conclusion

Hypericum perforatum extract WS^® 5570 at doses of 600 mg/day (once daily) and 1200 mg/day (600 mg twice daily) were found to be safe and more effective than placebo, with comparable efficacy of the WS^® 5570 groups for the treatment of mild to moderate major depression.     

Assessment of PINK1 (PARK6) polymorphisms in Finnish PD

Recent data has demonstrated that mutations in PINK1, encoding PTEN-induced kinase 1, are a cause of early onset recessive parkinsonism (PARK6 locus). Common variability in genes implicated in hereditary forms of parkinsonism may be a predisposing factor in sporadic Parkinson's disease (PD). We analyzed whether six different genetic variants within and surrounding PINK1 contribute to the risk of sporadic PD in a Finnish case-control series. Our results indicate that this gene does not play a major role in the genetic predisposition to PD in this population.     

Selective attention for negative information and depression in schizophrenia

OBJECTIVES: Depression is a frequent feature of schizophrenia but the cognitive processes involved in its development and maintenance are unclear. Recent studies have shown that clinical depression is associated with faulty inhibitory mechanisms of selective attention for negative information. The current study examined whether patients with schizophrenia also have an attentional bias towards negative stimuli. The inhibitory processes of interference control and task-shifting abilities were also examined to assess whether patients would show a selective impairment. METHOD: Forty-three patients with schizophrenia and 24 healthy controls completed the Affective Shifting Task. RESULTS: As a group, schizophrenia patients did not show an attentional bias for negative material. However, those patients with high levels of depression demonstrated faster latencies when negative words were the targets, and higher depression scores were found to be associated with an increasing number of false alarms for negative words when they were not the targets. The results also showed that patients had impaired interference control but intact task-shifting abilities.CONCLUSIONS: Faulty inhibitory mechanisms of selective attention for negative information are not a general feature of schizophrenia but appear to be selective to those with a depressed mood. The results highlight the need for further studies examining the exact nature of the affective dysfunction in schizophrenia and the cognitive processes supporting negative emotions.     

IgAs against acetaldehyde-modified red cell protein as a marker of ethanol consumption in male alcoholic subjects, moderate drinkers, and abstainers

BACKGROUND: Alcohol abuse has been shown to result in the production of antibodies against acetaldehyde-modified epitopes in proteins. However, as yet, only limited information has been available on the clinical usefulness of such responses as markers of hazardous drinking. METHODS: We developed an ELISA to measure specific IgAs against acetaldehyde-protein adducts. This method was evaluated in cross-sectional and follow-up studies on male heavy drinkers with a current ethanol consumption of 40 to 540 g/d (n=40), moderate drinkers consuming 1 to 40 g/d (n=25), and abstainers (n=16). The clinical assessments included detailed interviews on the amounts and patterns of ethanol consumption and various biochemical markers of alcohol abuse and liver function. RESULTS: The mean antiadduct IgAs (198+/-28 U/L) in the alcohol abusers were significantly higher than those in the moderate drinkers (58+/-11 U/L, p<0.001) or abstainers (28+/-8 U/L, p<0.001). The values of moderate drinkers were also higher than those in abstainers (p<0.05). The amount of ethanol consumed during the period of 1 month preceding blood sampling correlated strongly with antiadduct IgAs (r=0.67, p<0.001). The sensitivity (73%) and specificity (94%) of this marker were found to exceed those of the conventional laboratory markers of alcohol abuse in comparisons contrasting heavy drinkers with abstainers although not in comparisons contrasting heavy drinkers with moderate drinkers. During abstinence, antiadduct IgAs disappeared with a mean rate of 3% per day. In additional analyses of possible marker combinations, antiadduct IgAs, together with CDT, were found to provide the highest sensitivity and specificity. CONCLUSIONS: Measurements of antiadduct IgAs may provide a new clinically useful marker of alcohol abuse, providing a close relationship between marker levels and the actual amounts of recent ethanol ingestion.     

Determination of toxic perilla ketone,secondary plant metabolites and antioxidative capacity in five Perilla frutescens L. varieties

Perilla frutescens L. is a traditional Asian crop with multiple uses. Several varieties exist but only little data is available about the content of the toxic perilla ketone and secondary plant metabolites of those genotypes. To estimate the nutritional value of this new vegetable more information about those components is necessary.