Effect of blockade of mGluR5 on stress hormone release and its gene expression in the adrenal gland.

The aim of this study was to verify the presence of metabotropic glutamate receptor subtype 5 (mGluR5) in the adrenal gland of male rats of 2 different strains, and to test the hypothesis that treatment with mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) affects hormone release and adrenal gene expression of mGluR5 under conditions of stress. The results clearly show the gene expression of mGluR5 in the adrenal gland in both the adrenal cortex and medulla. Treatment with the glutamate release inhibitor riluzole (4 mg·(kg body mass)(-1)·day(-1) for 2 weeks) failed to modify mRNA levels of either the mGluR5 or NR1 subunit of the NMDA receptor in the adrenal glands, as measured by real-time PCR. Blockade of mGluR5 with MPEP (1 mg·kg(-1) for 4 days) increased corticosterone but not catecholamine release during restraint stress (20 min). Treatment with MPEP had no effect on mRNA levels coding for steroidogenic factors StAR and SF-1, and decreased mGluR5 gene expression in the adrenal gland. In conclusion, mGluR5 is not likely to play a significant role in stress-induced catecholamine release. Pharmacological blockade of mGluR5 has a modest influence on the hypothalamic-pituitary-adrenocortical axis, as reflected in adrenal hypertrophy and increased corticosterone concentrations.

The effectiveness of otis urethrotomy combined with six weeks urethral dilations until 40 Fr in the treatment of bladder outlet obstruction in women: a prospective study.

PURPOSE: To evaluate the effectiveness of Otis urethrotomy combined with six weekly urethral dilations until 40 French (Fr) in the treatment of women with urodynamic diagnosis of bladder outlet obstruction (BOO). MATERIALS AND METHODS: Women diagnosed with lower urinary tract symptoms underwent urodynamic evaluation. Severity of symptoms and quality of life were assessed with international prostate symptom score (IPSS) and quality of life (QoL) questionnaires. Bladder outlet obstruction was defined as the presence of two or more of the following: maximum flow rate (Qmax) < 12 mL/s, detrusor pressure at maximum flow (PdetQmax) > 50 cmH2O and urethral resistance factor (URF) greater than 0.2. Ten out of 25 women diagnosed with BOO met the criteria. All women underwent Otis urethrotomy to 40 F and six-week urethral dilations until 40 F. After six months all patients underwent free uroflowmetry. Moreover post voiding residual (PVR), IPSS-QoL were recorded. RESULTS: Six months post-operatively there was a significant improvement in all parameters: IPSS = 13.5 vs. 22.5 (P = .001), QoL = 3 vs. 5 (P = .001), voided volume = 312 mL vs. 216 mL (P = .055), Qmax = 27.5 mL/s vs. 12 mL/s (P = .001), and PVR = 27.5 mL vs. 170 mL (P = .005). Five women had close follow up during an average of 82 months. They maintained improved QoL (P < .005) and low PVR (P < .002). All other parameters lost their statistical significance. CONCLUSION: The described therapeutical modality seems to improve all clinical and urodynamic parameters in women with evidence of BOO not related to detrusor sphincter dyssynergia or obvious functional and anatomical pathology.

Increased anxiety induced by listening to unpleasant music during stress exposure is associated with reduced blood pressure and ACTH responses in healthy men.

The relationship between anxiety and the neuroendocrine response to stress stimuli is still not fully understood. The aim of this study was to evaluate the contribution of an acute increase in state anxiety to neuroendocrine activation under stress conditions. To do so, it was necessary to find a stress condition of the same character and intensity with and without a rise in state anxiety. We decided to examine the effects of listening to music on anxiety and to apply a new methodological approach. A group of 14 healthy volunteers participated in a counterbalanced crossover design study. The stress procedure consisted of mental (Stroop test, mental arithmetic) and physical (handgrip exercise) tasks combined with listening to music played forward (pleasant) or backwards (unpleasant). The results confirmed our hypothesis, namely the condition with listening to unpleasant music was anxiogenic, while the other was not. In case of increased state anxiety, the rise in ACTH concentrations in response to mental challenge and the increase in systolic blood pressure induced by handgrip exercise was reduced compared to the situation with unchanged anxiety. Concentrations of testosterone, oxytocin, vasopressin and aldosterone were slightly increased in response to the stress paradigm accompanied with increased anxiety. In conclusion, the present data demonstrate that an acute increase in state anxiety contributes to neuroendocrine activation under stress conditions. Moreover, the results show that listening to music may both positively and negatively influence the perception of stress and the level of anxiety, which might have functional consequences.

Hematuria secondary to an internal iliac artery aneurysm.

We report a case of macroscopic hematuria secondary to an aneurysm of the internal iliac artery. An 84-year-old male presented to our department with a 12-hour history of painless gross hematuria. Cystoscopy showed decreased expansion suggesting compression from outside the bladder. At the point of compression, increased vascularization was noted in the bladder mucosa without evidence of active bleeding. No trace of blood was identified coming from the ureteric orifices, the bladder neck, or the prostate. There was no evidence of intra-vesicular masses or other inflammatory changes. The abdominal computed tomography scan revealed left-sided hydronephrosis and an abdominal aortic aneurysm involving the aortic bifurcation and both internal iliac arteries. There was no evidence of rupture. An aneurysm of the internal iliac artery is a rare cause of macroscopic hematuria that can be fatal. Awareness of this as a possible cause of hematuria may assist in immediate diagnosis and appropriate treatment.

Altered coordination of the neuroendocrine response during psychosocial stress in subjects with high trait anxiety.

Contradicting data are available on stress responsiveness in subjects with high anxiety. In the present study we tested the hypothesis that high trait anxiety is associated with impaired coordination of the stress response, rather than global hypo- or hyper-responsiveness. The sample consisted of subjects with high (n=15) and with low (n=12) trait anxiety. Subjects with middle-range levels of anxiety were excluded from the study. After psychological characterization, the volunteers were exposed to a public speech procedure. A spectrum of neuroendocrine parameters was measured before, during and after the procedure and the results were analyzed by exploratory statistics. Psychological characterization of subjects revealed a lower preference for task-oriented but a higher one for emotion-oriented coping strategies as well as lower scores on hardiness in subjects with high trait anxiety. After the speech procedure, differences in selected mood and personality characteristics were observed, with the anxious group scoring significantly higher in scales for stress, tiredness, arousal, anxiety and depression. Factor analysis revealed that one common factor grouped blood pressure, catecholamine concentrations in blood and heart rate in non-anxious subjects, while three distinct factors separated these parameters in anxious subjects. Correlation analysis in anxious subjects showed that lower adrenocorticotropin (ACTH) and cortisol responses during stress were associated with exaggerated perception of stress and worse mental performance. Our findings indicate that subjects with high anxiety have different relationships between specific neuroendocrine parameters, subjective perception of stress and Stroop test performance.

Subchronic treatment with amino acid mixture of L-lysine and L-arginine modifies neuroendocrine activation during psychosocial stress in subjects with high trait anxiety.

The aim of the present study was to evaluate possible modulatory effect of the treatment with L-lysine and L-arginine on neuroendocrine activation during psychosocial stress in healthy subjects with relatively high trait anxiety in a randomized, double blind placebo controlled trial. In 29 healthy subjects at the upper limit of the normal range of a trait anxiety scale, a mixture of L-lysine and L-arginine (3 g each/day) was administered for 10 days followed by exposure to a psychosocial stress procedure based on public speech. Hormone levels, cardiovascular activation and skin conductance were measured. Amino acid treatment resulted in enhanced adrenocorticotropic hormone, cortisol, adrenaline and noradrenaline levels and galvanic skin responses during stress compared to those in placebo-treated group. Increases in the heart rate and blood pressure in response to public speaking task were not influenced by amino acid treatment. Results of the present study support the hypothesis that L-lysine in combination with L-arginine, which may induce anxiolytic effects, modify hormonal responses during psychosocial stress in humans. Such action may represent a normalization of hormone levels to the pattern observed previously in subjects with low trait anxiety.

High trait anxiety in healthy subjects is associated with low neuroendocrine activity during psychosocial stress.

Altered stress responsiveness has been repeatedly related to mood and anxiety disorders. In a traditional view, a reduction of the stress response has been thought favorable. The goal of the present study was to verify the hypothesis that high anxiety is accompanied by enhanced hormone release during stress. Healthy subjects at the upper (anxious, n = 15) and lower (non-anxious, n = 12) limits of the normal range of a trait anxiety scale (State trait anxiety inventory) were exposed to psychosocial stress procedure based on public speech. Hormone levels, cardiovascular activation and skin conductance were measured. Exposure to psychosocial stress was associated with significant increases of all parameters measured. During the stress procedure, subjects with high trait anxiety exhibited lower levels of hormones of the hypothalamo-pituitary-adrenocortical axis, namely ACTH and cortisol in plasma, as well as cortisol in saliva. Similarly, the stress-induced activation of epinephrine, norepinephrine and prolactin secretion was significantly lower in anxious subjects in comparison with that in non-anxious subjects. Thus, in contrast to the traditional view, high anxiousness was not associated with exaggerated stress response. Our findings suggest that high trait anxiety may be associated with an inability to respond with adequate hormone release to acute stress stimuli.

Prenatal immune challenge affects growth, behavior, and brain dopamine in offspring.

It is known that the development and plasticity of the neuroendocrine system can be affected by many factors, and that adverse events during the prenatal period can result in long-lasting changes in adulthood. This study was aimed at evaluating the possible consequences for offspring from chronic inflammation during pregnancy. Chronic inflammation was simulated by treatment with increasing doses of lipopolysaccharide (LPS) to dams on days 15 through 19 of pregnancy. Attempts were made to prevent possible negative alterations by keeping animals in an enriched environment (EE). Maternal exposure to LPS resulted in a significant reduction of body weight of male offspring during the weaning period. This difference remained until the age of 63 days in controls (C), but not in animals reared in EE. The content of dopamine in the nucleus accumbens was found to be lower in prenatally stressed (PS) adult males. Furthermore, prenatal exposure to maternal immune challenge was associated with lower locomotor activity in elevated plus maze and increased number of skips in the beam-walking test, as observed in female offspring. No differences in ACTH and corticosterone concentrations with regard to prenatal treatment were found; however, both groups kept in EE showed increased levels of corticosterone as well as enlarged adrenal glands. Thus, immune activation during pregnancy may induce long-term changes in brain catecholamines and behavior, but it is not harmful to basal hormone secretion in the offspring.

Modulation of neuroendocrine response and non-verbal behavior during psychosocial stress in healthy volunteers by the glutamate release-inhibiting drug lamotrigine.

The present work was aimed at verifying the following hypotheses: (a) lamotrigine, a drug used to treat mood disorders, affects regulation of stress hormone release in humans, and (b) non-verbal behavior during mental stress situations (public speech) is related to hormonal responses. To achieve these aims, we performed a controlled, double-blind study investigating hormonal responses and non-verbal behavior during public speech in healthy subjects with placebo or lamotrigine (300 mg per os) pretreatment. The stress procedure was performed in 19 young healthy males 5 h following drug or placebo administration. Data were obtained from cardiovascular monitoring, blood and saliva samples, as well as the video-recorded speech. Pre-stress hormone levels were not affected by lamotrigine treatment. Lamotrigine significantly inhibited diastolic blood pressure, growth hormone and cortisol increases during psychosocial stress. In contrast, it potentiated plasma renin activity and aldosterone responses. Non-verbal behavior analysis revealed a correlation between catecholamines and submissive or flight behavior in controls, while between catecholamines and displacement behavior following lamotrigine administration. In conclusion, effects of lamotrigine on hormone release might be of value for its mood-stabilizing action used in the treatment of bipolar disorder. The data are in support of a stimulatory role of glutamate in the control of cortisol and growth hormone release during psychosocial stress in humans; however, further studies using more selective drugs are needed to prove this suggestion. The effects on plasma renin activity and aldosterone release observed seem to be related to other actions of lamotrigine.