The Anti-Inflammatory and Antibacterial Basis of Human Omental Defense: Selective Expression of Cytokines and Antimicrobial Peptides

BACKGROUND: The wound healing properties of the human omentum are well known and have extensively been exploited clinically. However, the underlying mechanisms of these effects are not well understood. We hypothesize that the omentum tissue promotes wound healing via modulation of anti-inflammatory pathways, and because the omentum is rich in adipocytes, the adipocytes may modulate the anti-inflammatory response. Factors released by human omentum may affect healing, inflammation and immune defense. METHODOLOGY: Six human omentum tissues (non obese, free from malignancy, and any other systemic disorder) were obtained during diagnostic laparoscopies having a negative outcome. Healthy oral mucosa (obtained from routine oral biopsies) was used as control. Cultured adipocytes derived from human omentum were exposed to lipopolysaccharide (LPS) (1-50 ng/mL) for 12-72 hours to identify the non-cytotoxic doses. Levels of expression (mRNA and protein) were carried out for genes associated with pro- and anti-inflammatory cytokine responses and antibacterial/antimicrobial activity using qRT-PCR, western blotting, and cell-based ELISA assays. RESULTS: The study shows significant higher levels of expression (mRNA and protein) of several specific cytokines, and antibacterial peptides in the omentum tissues when compared to oral sub-mucosal tissues. In the validation studies, primary cultures of adipocytes, derived from human omentum were exposed to LPS (5 and 10 ng/mL) for 24 and 48 h. The altered expressions were more pronounced in cultured adipocytes cells when exposed to LPS as compared to the omentum tissue. CONCLUSIONS/SIGNIFICANCE: Perhaps, this is the first report that provides evidence of expressional changes in pro- and anti-inflammatory cytokines and antibacterial peptides in the normal human omentum tissue as well as adipocytes cultured from this tissue. The study provides new insights on the molecular and cellular mechanisms of healing and defense by the omentum, and suggests the potential applicability of cultured adipocytes derived from the omentum for future therapeutic applications

A Glial Variant of the Vesicular Monoamine Transporter Is Required To Store Histamine in the Drosophila Visual System

Unlike other monoamine neurotransmitters, the mechanism by which the brain's histamine content is regulated remains unclear. In mammals, vesicular monoamine transporters (VMATs) are expressed exclusively in neurons and mediate the storage of histamine and other monoamines. We have studied the visual system of Drosophila melanogaster in which histamine is the primary neurotransmitter released from photoreceptor cells. We report here that a novel mRNA splice variant of Drosophila VMAT (DVMAT-B) is expressed not in neurons but rather in a small subset of glia in the lamina of the fly's optic lobe. Histamine contents are reduced by mutation of dVMAT, but can be partially restored by specifically expressing DVMAT-B in glia. Our results suggest a novel role for a monoamine transporter in glia that may be relevant to histamine homeostasis in other systems

Additive Effects of Threat-of-Shock and Picture Valence on Startle Reflex Modulation

The present study examined the effects of sustained anticipatory anxiety on the affective modulation of the eyeblink startle reflex. Towards this end, pleasant, neutral and unpleasant pictures were presented as a continuous stream during alternating threat-of-shock and safety periods, which were cued by colored picture frames. Orbicularis-EMG to auditory startle probes and electrodermal activity were recorded. Previous findings regarding affective picture valence and threat-of-shock modulation were replicated. Of main interest, anticipating aversive events and viewing affective pictures additively modulated defensive activation. Specifically, despite overall potentiated startle blink magnitude in threat-of-shock conditions, the startle reflex remained sensitive to hedonic picture valence. Finally, skin conductance level revealed sustained sympathetic activation throughout the entire experiment during threat- compared to safety-periods. Overall, defensive activation by physical threat appears to operate independently from reflex modulation by picture media. The present data confirms the importance of simultaneously manipulating phasic-fear and sustained-anxiety in studying both normal and abnormal anxiety.This work was supported in part by scholarships awarded to F. B. by the German Academic Exchange Service (DAAD) and by the State Ministry for Education and Cultural Affairs of Baden-Wuerttemberg (LGFG); a DFG grant Schu 1074/11-2; and the research group: Junta de Andalucía, group: HUM-388

Mechanism of Action in CBT (MAC): Methods of a multi-center randomized controlled trial in 369 patients with Panic Disorder and Agoraphobia

Cognitive behavioral therapy (CBT) is efficacious for panic disorder with agoraphobia (PD/A). Nevertheless, the active ingredients of treatment and the mechanisms through which CBT achieves its effects remain largely unknown. The mechanisms of action in CBT (MAC) study was established to investigate these questions in 369 patients diagnosed with PD/A. The MAC study utilized a multi-center, randomized controlled design, with two active treatment conditions in which the administration of exposure was varied, and a wait-list control group. The special feature of MAC is the way in which imbedded experimental, psychophysiological, and neurobiological paradigms were included to elucidate therapeutic and psychopathological processes. This paper describes the aims and goals of the MAC study and the methods utilized to achieve them. All aspects of the research design (e.g., assessments, treatment, experimental procedures) were implemented so as to facilitate the detection of active therapeutic components, and the mediators and moderators of therapeutic change. To this end, clinical, behavioral, physiological, experimental, and genetic data were collected and will be integrated

Low vagal tone is associated with impaired post stress recovery of cardiovascular, endocrine, and immune markers

Reduced heart rate variability (HRV) and delayed blood pressure recovery are associated with increased cardiovascular risk. Besides this evident link, the vagus is thought to play an inhibitory role in the regulation of other allostatic systems, including inflammation and the hypothalamic-pituitary-adrenal (HPA) axis. However, human evidence is scarce. To further explore these associations and with special regard to the postulated mediating role of the vagus, we hypothesised that subjects with low vagal tone as indexed by reduced resting HRV would show impaired post-stress recovery of cardiovascular, endocrine and immune system markers involved in cardiovascular pathology. 44 healthy men underwent a standardised mental stress test. Besides continuous measurement of systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), and HRV serum cortisol, tumour necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured before, after, 20, and 60 min after stress. Low versus high HRV groups was defined by median split on resting HRV (RMSSD). The task elicited significant time effects for SBP, DBP, HR, HRV, cortisol, and TNF-alpha. Subjects with low baseline HRV showed almost no modulation of HRV coupled with overall reduced HRV levels, and impaired recovery of DBP, cortisol, and TNF-alpha. Confirming our hypothesis, low vagal tone was associated with impaired recovery of cardiovascular, endocrine, and immune markers in healthy males. The data support an inhibitory role of the vagus in the regulation of allostatic systems as described in the neurovisceral integration model. We posit reduced resting HRV as a risk marker for future cardiovascular and other stress-related disease