Selective inhibition of the a form of monoamine oxidase by 4-dimethylamino-α-methylphenylalkylamine derivatives in the rat

The inhibitory effects on monoamine oxidase (MAO) of some dimethylamino-α-phenylalkylamine derivatives were examined in a rat brain mitochondrial preparation in vitro and in rat brain slices following oral administration. In the in vitro assay the compounds were shown to be selective inhibitors of the A form of MAO, being 100–600 limes more potent in inhibiting the deamination of [¹⁴C]5-hydroxytryptamine than that of [¹⁴C]phenetylamine. Using an ex vivo brain slice technique it was found that the new compounds were reversible and very selective inhibitors of type A MAO in the rat brain and the most potent compounds (FLA 405, 314, 336 and 558) were equipotent with clorgyline. The compounds increased the monoamine concentrations in whole rat brain, particularly that of 5-hydroxytryptamine, in the same dose range which produced MAO inhibition. Some of the new compounds, e.g. FLA 336 and FLA 717, caused only weak potentiation of the vaso-pressor effect of orally administered tyramine.     

Three-dimensional computed tomography imaging in an animal model of emphysema.

Emphysema is a major health problem and novel drugs are needed. Animal disease models are pivotal in their development, but the validity and sensitivity of current tools for the evaluation of drug efficacy is limited. The usefulness of micro computed tomography (CT) as an innovative tool to assess emphysema in a mouse model was investigated. Serial CT scans were performed in bi-weekly intervals in Smad3 knockout (KO) mice, which spontaneously develop airspace enlargement. Lung density was quantified in two- and three-dimensional images and correlated to mean linear intercept and lung compliance. CT scans of Smad3 KO lungs revealed a significant decrease in lung density at age 8 weeks and a further progression at age 14 weeks with respect to age-matched wild-type (WT) animals. Emphysema could be reliably assessed with both the two- and three-dimensional approach, but the three-dimensional approach was superior, due to normalisation to lung volumes and less variability. Lung compliance by week 14 was 0.053+/-0.005 and 0.034+/-0.002% of maximum volume.cmH(2)O(-1) for KO and WT mice, respectively, reflecting significant physiologically relevant emphysema. Small animal computed tomography imaging and density quantification in a reconstructed three-dimensional image is a useful tool for quantifying emphysematous changes in an animal disease model. It adds significant information to conventional assessment.     

VEGF ameliorates pulmonary hypertension through inhibition of endothelial apoptosis in experimental lung fibrosis in rats

Idiopathic pulmonary fibrosis (IPF) can lead to the development of secondary pulmonary hypertension (PH) and ultimately death. Despite this known association, the precise mechanism of disease remains unknown. Using a rat model of IPF, we explored the role of the proangiogenic and antiapoptotic growth factor VEGF in the vascular remodeling that underlies PH. In this model, adenoviral delivery of active TGF-β1 induces pulmonary arterial remodeling, loss of the microvasculature in fibrotic areas, and increased pulmonary arterial pressure (PAP). Immunohistochemistry and mRNA analysis revealed decreased levels of VEGF and its receptor, which were inversely correlated with PAP and endothelial cell apoptosis in both the micro- and macrovasculature. Treatment of IPF rats with adenoviral delivery of VEGF resulted in reduced endothelial apoptosis, increased vascularization, and improved PAP due to reduced remodeling but worsened PF. These data show that experimental pulmonary fibrosis (PF) leads to loss of the microvasculature through increased apoptosis and to remodeling of the pulmonary arteries, with both processes resulting in PH. As administration of VEGF ameliorated the PH in this model but concomitantly aggravated the fibrogenic process, VEGF-based therapies should be used with caution.     

Psychological adjustment one year after the diagnosis of breast cancer: a prototype study of delayed post-traumatic stress disorder

OBJECTIVE. The utilization of a post-traumatic stress disorder (PTSD) diagnostic framework for categorizing the psychological adjustment of breast cancer (BC) patients has been debated. We wanted to study the prevalence of PTSD and predictors for PTSD. DESIGN. The current study is a one-year follow-up of 64 early BC patients. METHODS. PTSD, subclinical PTSD, delayed onset PTSD and several theory-driven predictive variables were examined. RESULTS. Thirteen per cent of the patients showed full symptoms of disease-related PTSD compared with 7% at the initial study (6 weeks after diagnosis). Considerable changes were observed in all PTSD clusters (intrusion, avoidance, and arousal), in most cases representing a decrease in symptom level. Immature defence style, emotional coping, avoidant behaviour, and negative affectivity were all implicated as predicting variables in a hierarchical multiple regression analysis which explained 65% of the variability of PTSD severity one year after diagnosis. CONCLUSIONS. This study highlights the PTSD diagnosis as being highly relevant in oncology settings. Early screening for the above-mentioned four variables may help early identification of the patients most at risk of developing PTSD.     

Variation in post-traumatic response: the role of trauma type in predicting ICD-11 PTSD and CPTSD symptoms

Purpose

The World Health Organization’s 11th revision to the International Classification of Diseases manual (ICD-11) will differentiate between two stress-related disorders: PTSD and Complex PTSD (CPTSD). ICD-11 proposals suggest that trauma exposure which is prolonged and/or repeated, or consists of multiple forms, that also occurs under circumstances where escape from the trauma is difficult or impossible (e.g., childhood abuse) will confer greater risk for CPTSD as compared to PTSD. The primary objective of the current study was to provide an empirical assessment of this proposal.

Methods

A stratified, random probability sample of a Danish birth cohort (aged 24) was interviewed by the Danish National Centre for Social Research (N?=?2980) in 2008–2009. Data from this interview were used to generate an ICD-11 symptom-based classification of PTSD and CPTSD.

Results

The majority of the sample (87.1%) experienced at least one of eight traumatic events spanning childhood and early adulthood. There was some indication that being female increased the risk for both PTSD and CPTSD classification. Multinomial logistic regression results found that childhood sexual abuse (OR?=?4.98) and unemployment status (OR?=?4.20) significantly increased risk of CPTSD classification as compared to PTSD. A dose–response relationship was observed between exposure to multiple forms of childhood interpersonal trauma and risk of CPTSD classification, as compared to PTSD.

Conclusions

Results provide empirical support for the ICD-11 proposals that childhood interpersonal traumatic exposure increases risk of CPTSD symptom development.

     

Youth Responses to School Shootings: a Review

Purpose of Review

This paper aims to synthesize research relating to youth responses to school shootings between 2014 and 2017. The main questions it addresses are how such events impact young people psychologically, and what risk or protective factors may contribute to different trajectories of recovery?

Recent Findings

Recent research suggests that most young people exposed to school shootings demonstrate resilience, exhibiting no long-term dysfunction. However, a minority will experience severe and chronic symptoms. The likelihood of experiencing clinically significant reactions is influenced by pre-trauma functioning as well as peri-traumatic and post-traumatic factors. These include proximity to the trauma, peri-traumatic dissociation, post-traumatic emotional regulation difficulties, social support, and flexibility of coping styles.

Summary

Research that separates the distinguishing features of young people with differing recovery styles is vital to tailor intervention. But methodological and design issues associated with such research necessitates caution in drawing conclusions. Variation in definitions and measures and the self-report nature of many of the studies are potential sources of bias. Greater uniformity across designs would enhance confidence and allow for improved evidence-based intervention.

     

Inotropic and chronotropic effects of isoprenaline in rats exposed to 30 bar

Inotropic and chronotropic responses to the beta-agonist, isoprenaline (ISO) were studied with a transducer located in the left ventricle and a catheter placed in the left femoral artery in anesthetized rats at 1 and 30 bar. The hemodynamic control values were equal in both series. During ISO infusion the chronotropy increased equally (34%) at 1 and 30 bar. The inotropy increased by 38% during ISO infusion at 1 bar (Series 1). Increased inotropy (44%), and unchanged chronotropy were found during compression to 30 bar (Series 2). The ISO evoked inotropic responses in absolute values were greater at 30 bar than at 1 bar. Nevertheless, an equal relative (%) increase in inotropy was found during ISO infusion at 30 bar compared to 1 bar. The cardiac oxygen consumption was estimated to be 65% higher at 30 bar during ISO infusion compared to that at 1 bar.     

Pressure/flow studies in elderly men without voiding problems: Estimation of the urethral pressure/flow relation and urethral elasticity

The flow in the urethra is controlled by an elastic constriction, the flow-controlling zone. The distensibility of this zone is described by the pressure/area relation, which gives the static pressure as a function of the cross-sectional area at the flow-controlling zone. The pressure/area relation can be calculated from the pressure/flow relation, which is estimated from the pressure/flow plot obtained at a urodynamic examination. In this study the urethral pressure/flow and pressure/area relations were estimated for 21 randomly selected men (62–75 years old) without voiding problems. Nineteen of 21 persons in this group had pressure/flow relations with a low slope. This corresponds to a low slope in the pressure/area relation indicating high distensibility of the flow-controlling zone, which for 18 persons was estimated to be distended to areas larger than 10 mm² during micturition. Twenty persons had a minimal urethral opening pressure below 55 cm H₂O. The estimated pressure/area relation was linear in 59% of the micturitions, indicating that the flow-controlling zone could have been distended to a larger cross-sectional area, if the bladder had achieved a higher pressure. The 10th–90th percentiles for maximum flow and detrusor pressure at maximum flow were 7.2–24.3 ml/s and 24–76 cm H₂O, respectively. Four persons had low flow and low pressure, indicating diminished detrusor contractility with age. Twenty-four percent of the persons had unstable bladder contractions with a pressure rise < 15cm H₂O and 19% with a pressure rise < 15cm H₂O.     

Comparison of HPV detection in parallel biopsies and cervical scrapes by PCR.

PCR was used to detect HPV DNA in cervical scrapes of 23 women with cervical cancer. Compared with PCR-assisted HPV DNA detection in parallel biopsies, the sensitivity was 81% and the specificity 100%. We conclude that cervical scrapes can be used for detection of HPV DNA in women with cervical cancer.