Comparison of intranasal and transcutaneous immunization for induction of protective immunity against chlamydia muridarum respiratory tract infection

Chlamydia pneumoniae causes a range of respiratory infections including bronchitis, pharyngitis and pneumonia. Infection has also been implicated in exacerbation/initiation of asthma and chronic obstructive pulmonary disease (COPD) and may play a role in atherosclerosis and Alzheimer's disease. We have used a mouse model of Chlamydia respiratory infection to determine the effectiveness of intranasal (IN) and transcutaneous immunization (TCI) to prevent Chlamydia lung infection. Female BALB/c mice were immunized with chlamydial major outer membrane protein (MOMP) mixed with cholera toxin and CpG oligodeoxynucleotide adjuvants by either the IN or TCI routes. Serum and bronchoalveolar lavage (BAL) were collected for antibody analysis. Mononuclear cells from lung-draining lymph nodes were stimulated in vitro with MOMP and cytokine mRNA production determined by real time PCR. Animals were challenged with live Chlamydia and weighed daily following challenge. At day 10 (the peak of infection) animals were sacrificed and the numbers of recoverable Chlamydia in lungs determined by real time PCR. MOMP-specific antibody-secreting cells in lung tissues were also determined at day 10 post-infection. Both IN and TCI protected animals against weight loss compared to non-immunized controls with both immunized groups gaining weight by day 10-post challenge while controls had lost 6% of body weight. Both immunization protocols induced MOMP-specific IgG in serum and BAL while only IN immunization induced MOMP-specific IgA in BAL. Both immunization routes resulted in high numbers of MOMP-specific antibody-secreting cells in lung tissues (IN > TCI). Following in vitro re-stimulation of lung-draining lymph node cells with MOMP; IFNγ mRNA increased 20-fold in cells from IN immunized animals (compared to non-immunized controls) while IFNγ levels increased 6- to 7-fold in TCI animals. Ten days post challenge non-immunized animals had >7000 IFU in their lungs, IN immunized animals <50 IFU and TCI immunized animals <1500 IFU. Thus, both intranasal and transcutaneous immunization protected mice against respiratory challenge with Chlamydia. The best protection was obtained following IN immunization and correlated with IFNγ production by mononuclear cells in lung-draining LN and MOMP-specific IgA in BAL.

Inhibition of orexin-1/hypocretin-1 receptors inhibits yohimbine-induced reinstatement of ethanol and sucrose seeking in Long-Evans rats

Abstract RATIONALE: Previous studies have shown that orexin-1/hypocretin-1 receptors play a role in self-administration and cue-induced reinstatement of food, drug, and ethanol seeking. In the current study, we examined the role of orexin-1/hypocretin-1 receptors in operant self-administration of ethanol and sucrose and in yohimbine-induced reinstatement of ethanol and sucrose seeking. MATERIALS AND METHODS: Rats were trained to self-administer either 10% ethanol or 5% sucrose (30 min/day). The orexin-1 receptor antagonist SB334867 (0, 5, 10, 15, 20 mg/kg, i.p.) was administered 30 min before the operant self-administration sessions. After these experiments, the operant self-administration behaviors were extinguished in both the ethanol and sucrose-trained rats. Upon reaching extinction criteria, SB334867 (0, 5, 10 mg/kg, i.p.) was administered 30 min before yohimbine (0 or 2 mg/kg, i.p.). In a separate experiment, the effect of SB334867 (0, 15, or 20 mg/kg, i.p.) on general locomotor activity was determined using the open-field test. RESULTS: The orexin-1 receptor antagonist, SB334867 (10, 15 and 20 mg/kg) decreased operant self-administration of 10% ethanol but not 5% sucrose self-administration. Furthermore, SB334867 (5 and 10 mg/kg) significantly decreased yohimbine-induced reinstatement of both ethanol and sucrose seeking. SB334867 did not significantly affect locomotor activity measured using the open-field test. CONCLUSIONS: The results suggest that inhibition of OX-1/Hcrt-1 receptors modulates operant ethanol self-administration and also plays a significant role in yohimbine-induced reinstatement of both ethanol and sucrose seeking in rats.

Physical activity, sitting and depression during pregnancy

Aims The aim of this cross sectional study is to explore levels of physical activity and sitting behaviour amongst a sample of pregnant Australian women (n = 81), and investigate whether reported levels of physical activity and/or time spent sitting were associated with depressive symptom scores after controlling for potential covariates. Methods Study participants were women who attended the antenatal clinic of a large Brisbane maternity hospital between October and November 2006. Data relating to participants. current levels of physical activity, sitting behaviour, depressive symptoms, demographic characteristics and exposure to known risk factors for depression during pregnancy were collected; via on-site survey, follow-up telephone interview (approximately one week later) and post delivery access to participant hospital records. Results Participants were aged 29.5 (¡¾ 5.6) years and mostly partnered (86.4%) with a gross household income above $26,000 per annum (88.9%). Levels of physical activity were generally low, with only 28.4 % of participants reporting sufficient total activity and 16% of participants reporting sufficient planned (leisure-time) activity. The sample mean for depressive symptom scores measured by the Hospital Anxiety and Depression Scale (HADS-D) was 6.38 (¡¾ 2.55). The mean depressive symptom scores for participants who reported total moderate-to-vigorous activity levels of sufficient, insufficient, and none, were 5.43 (¡¾ 1.56), 5.82 (¡¾ 1.77) and 7.63 (¡¾ 3.25), respectively. Hierarchical multivariable linear regression modelling indicated that after controlling for covariates, a statistically significant difference of 1.09 points was observed between mean depressive symptom scores of participants who reported sufficient total physical activity, compared with participants who reported they were engaging in no moderate-to-vigorous activity in a typical week (p = 0.05) but this did not reach the criteria for a clinically meaningful difference. Total physical activity was contributed 2.2% to the total 30.3% of explained variance within this model. The other main contributors to explained variance in multivariable regression models were anxiety symptom scores and the number of existing children. Further, a trend was observed between higher levels of planned sitting behaviour and higher depressive symptom scores (p = 0.06); this correlation was not clinically meaningful. Planned sitting contributed 3.2% to the total 31.3 % of explained variance. The number of regression covariates and limited sample size led to a less than ideal ratio of covariates to participants, probably attenuating this relationship. Specific information about the sitting-based activities in which participants engaged may have provided greater insight about the relationship between planned sitting and depressive symptoms, but these data were not captured by the present study. Conclusions The finding that higher levels of physical activity were associated with lower levels of depressive symptoms is consistent with the current body of existing literature in pregnant women, and with a larger body of evidence based in general population samples. Although this result was not considered clinically meaningful, the criterion for a clinically meaningful result was an a priori decision based on quality of life literature in non-pregnant populations and may not truly reflect a difference in symptoms that is meaningful to pregnant women. Further investigation to establish clinically meaningful criteria for continuous depressive symptom data in pregnant women is required. This result may have implications relating to prevention and management options for depression during pregnancy. The observed trend between planned sitting and depressive symptom scores is consistent with literature based on leisure-time sitting behaviour in general population samples, and suggests that further research in this area, with larger samples of pregnant women and more specific sitting data is required to explore potential associations between activities such as television viewing and depressive symptoms, as this may be an area of behaviour that is amenable to modification.

The influence of sensitivity to reward and punishment, propensity for sensation seeking, depression, and anxiety on the risky behaviour of novice drivers : a path model

Young novice drivers are significantly more likely to be killed or injured in car crashes than older, experienced drivers. Graduated driver licensing (GDL), which allows the novice to gain driving experience under less-risky circumstances, has resulted in reduced crash incidence; however, the driver's psychological traits are ignored. This paper explores the relationships between gender, age, anxiety, depression, sensitivity to reward and punishment, sensation-seeking propensity, and risky driving. Participants were 761 young drivers aged 17–24 (M= 19.00, SD= 1.56) with a Provisional (intermediate) driver's licence who completed an online survey comprising socio-demographic questions, the Impulsive Sensation Seeking Scale, Kessler's Psychological Distress Scale, the Sensitivity to Punishment and Sensitivity to Reward Questionnaire, and the Behaviour of Young Novice Drivers Scale. Path analysis revealed depression, reward sensitivity, and sensation-seeking propensity predicted the self-reported risky behaviour of the young novice drivers. Gender was a moderator; and the anxiety level of female drivers also influenced their risky driving. Interventions do not directly consider the role of rewards and sensation seeking, or the young person's mental health. An approach that does take these variables into account may contribute to improved road safety outcomes for both young and older road users.

The relationship of meta-worry and intolerance of uncertainty with pathological worry, anxiety, and depression

This study explored how meta-worry and intolerance of uncertainty relate to pathological worry, generalised anxiety, obsessive compulsive disorder, social phobia, and depression. University students (n = 253) completed a questionnaire battery. A series of regression analyses were conducted. The results indicated that meta-worry was associated with GAD, social phobia, obsessive compulsive, and depressive symptoms. Intolerance of uncertainty was related to GAD, social phobia, and obsessive compulsive symptoms, but not depressive symptoms. The importance of meta-worry and intolerance of uncertainty as predictors of pathological worry, GAD, social phobia, obsessive compulsive and depressive symptoms was also examined. Even though both factors significantly predicted the aforementioned symptoms, meta-worry emerged as a stronger predictor of GAD and obsessive compulsive symptoms than did intolerance of uncertainty. Intolerance of uncertainty, compared with meta-worry, appeared as a stronger predictor of social phobia symptoms. Findings emphasise the importance of addressing meta-worry and/or intolerance of uncertainty not only for the assessment and treatment of generalised anxiety disorder (GAD), but also obsessive compulsive disorder, social phobia, and depression.

Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients

Background: High-flow nasal cannulae (HFNC) create positive oropharyngeal airway pressure but it is unclear how their use affects lung volume. Electrical impedance tomography (EIT) allows assessment of changes in lung volume by measuring changes in lung impedance. Primary objectives were to investigate the effects of HFNC on airway pressure (Paw) and end-expiratory lung volume (EELV), and to identify any correlation between the two. Secondary objectives were to investigate the effects of HFNC on respiratory rate (RR), dyspnoea, tidal volume and oxygenation; and the interaction between body mass index (BMI) and EELV. Methods: Twenty patients prescribed HFNC post-cardiac surgery were investigated. Impedance measures, Paw, PaO2/FiO2 ratio, RR and modified Borg scores were recorded first on low flow oxygen (nasal cannula or Hudson face mask) and then on HFNC. Results: A strong and significant correlation existed between Paw and end-expiratory lung impedance (EELI) (r=0.7, p<0.001). Compared with low flow oxygen, HFNC significantly increased EELI by 25.6% (95% CI 24.3, 26.9) and Paw by 3.0 cmH2O (95% CI 2.4, 3.7). RR reduced by 3.4 breaths per minute (95% CI 1.7, 5.2) with HFNC use, tidal impedance variation increased by 10.5% (95% CI 6.1, 18.3) and PaO2/FiO2 ratio improved by 30.6 mmHg (95% CI 17.9, 43.3). HFNC improved subjective dyspnoea scoring (p=0.023). Increases in EELI were significantly influenced by BMI, with larger increases associated with higher BMIs (p<0.001). Conclusions: This study suggests that HFNC improve dyspnoea and oxygenation by increasing both EELV and tidal volume, and are most beneficial in patients with higher BMIs.