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ObjectivesExperiments using P2X3 knock-out mice or more general P2X receptor antagonists suggest that P2X3 receptors contribute to visceral hypersensitivity. We aimed to investigate the effect of the selective P2X3 antagonist A-317491 on visceral sensitivity under physiological conditions, during acute colitis and in the post-inflammatory phase of colitis.MethodsTrinitrobenzene sulphonic-acid colitis was monitored by colonoscopy: on day 3 to confirm the presence of colitis and then every 4 days, starting from day 10, to monitor convalescence and determine the exact timepoint of endoscopic healing in each rat. Visceral sensitivity was assessed by quantifying visceromotor responses to colorectal distension in controls, rats with acute colitis and post-colitis rats. A-317491 was administered 30 min prior to visceral sensitivity testing. Expression of P2X3 receptors (RT-PCR and immunohistochemistry) and the intracellular signalling molecules cdk5, csk and CASK (RT-PCR) were quantified in colonic tissue and dorsal root ganglia. ATP release in response to colorectal distension was measured by luminiscence.ResultsRats with acute TNBS-colitis displayed significant visceral hypersensitivity that was dose-dependently, but not fully, reversed by A-317491. Hypersenstivity was accompanied by an increased colonic release of ATP. Post-colitis rats also displayed visceral hypersensitivity that was dose-dependently reduced and fully normalized by A-317491 without increased release of ATP. A-317491 did not modify visceral sensitivity in controls. P2X3 mRNA and protein expression in the colon and dorsal root ganglia were similar in control, acute colitis and post-colitis groups, while colonic mRNA expression of cdk5, csk and CASK was increased in the post-colitis group only.ConclusionsThese findings indicate that P2X3 receptors are not involved in sensory signaling under physiological conditions whereas they modulate visceral hypersensitivity during acute TNBS-colitis and even more so in the post-inflammatory phase, albeit via different mechanisms of sensitization, validating P2X3 receptors as potential new targets in the treatment of abdominal pain syndromes.

To investigate the influence of the hormonal status on skin vascular reactivity, 18 males, 18 women using oral contraceptives (oc), 17 premenopausal, and 18 postmenopausal women were studied. Finger skin temperature (FST, in degrees C) and laser Doppler flux (LDF, in perfusion units) were measured during heating (45 degrees C water bath) and cooling (15 degrees C) followed by a subsequent recovery period. Maximal heat-induced vasodilation was significantly higher in women using oc and in premenopausal women when compared with males. During cooling, FST and LDF were significantly higher in males compared with women using oc and premenopausal women, respectively. FST was also higher in postmenopausal women than in women using oc. During recovery, FST and LDF were significantly higher in males than in women using oc, and LDF was also higher in males than in premenopausal women. These findings are consistent with a less pronounced and less prolonged cold-induced vasoconstriction in males. Other hemodynamic (blood pressure or heart rate) or biological factors (age, amount of subcutaneous fat, hand volume, or body mass index) that possibly influence peripheral blood flow were found not to influence the results. The observed differences in vascular reactivity toward temperature changes between subjects with a different hormonal status suggest that sex hormones influence finger skin perfusion.

Context Women are at increased risk for depressive symptoms during the menopause transition. Changes in estradiol secretion and presence of vasomotor symptoms (VMS) contribute to perimenopausal depressive symptoms, but links with progesterone have not been investigated. Objective To determine whether estradiol variability, ovulatory levels of progesterone, and VMS burden are independently associated with perimenopausal depressive symptomatology. Design and Intervention Depressive symptoms, serum levels of estradiol and progesterone, and VMS frequency were assessed weekly in an 8-week observational study. Association of mood with estradiol variability, ovulatory levels of progesterone, and VMS frequency were estimated using generalized estimating equation models. Setting Academic medical center. Patients Fifty unmedicated perimenopausal women with mild-to-moderate depressive symptoms (mean Montgomery-Åsberg Depression Rating Scale [MADRS] score 15.5 ± 5.3). Main Outcome Measure Depressive symptoms (MADRS score). Results During the study, 90.0% of participants had varying estradiol levels, 51.1% had ovulatory progesterone levels, and 90% had VMS. Greater estradiol variability and absence of progesterone levels consistent with ovulation, but not VMS frequency, are associated with higher levels of depressive symptoms (β = 0.11 [95% confidence interval (95% CI), 0.04 to 0.18; P = 0.001]; β = −2.62 [95% CI, −4.52 to −0.71; P = 0.007], respectively), after accounting for higher body mass index, lifetime history of depression, and stressful life events. Conclusions Increasing dysregulation of ovarian hormones, but not VMS, associates with more depressive symptom burden during perimenopause. These results suggest that perimenopausal mood instability is driven by the underlying hormonal dysregulation of the menopause transition involving changes in both estradiol and progesterone.

The aim of the study was to assess the impact of a vestibular-stimulating exercise regime on postural stability in individuals with visual impairment. The study group consisted of 70 people, including 28 persons (15 female and 13 male) with visual impairment and 42 (21 female and 21 male) without visual impairment. Each individual in the group with visual impairment was medically qualified for a 3-month training program. The research methodology included medical examination, anthropometric tests, and stabilometry tests on a Biodex Balance System SD (BBS). The tests were conducted twice: once before the start of training and again after 3 months of rehabilitation. The group with visual impairment showed significantly worse postural stability results than the control group for most of the stability parameters evaluated (OSI, APSI, and MLSI). Differences were noted between the groups with and without visual impairment for dynamic tests in women and for static tests in men. After training, the two groups showed roughly similar results for the stabilometry test with eyes closed. We conclude that exercises stimulating the vestibular system with head and body movements should be recommended for individuals with visual impairments to achieve better balance retention.

Various training devices have been developed to facilitate 'plyometric' training, one such device being the 'pendulum swing'. To assess the effectiveness of the pendulum swing, the results of a 3 week training programme using a combination of pendulum swing and weight-training exercises were compared to those of a weight-training programme. Subjects were assigned to one of two groups (n = 9) for weight-training only or for combined pendulum and weight-training. Both groups performed the same number of exercise repetitions. Measurements of isometric knee and hip extension-flexion, 1-RM squat weight, maximum jump height and power for a counter-movement jump were taken pre-training, 2 days after the end of the programme and 2 weeks after the end of the programme. The data were analysed using two-way MANOVA and MANCOVA techniques. Both methods showed significant (P < 0.05) increases in knee and hip extension strength. Hip and knee flexion strength increased only for the weight-trained group. Counter-movement jump height increased for both groups (weight-trained, P < 0.05; combined, P < 0.01). Maximum power increased only for the combined group (P < 0.05). When the pre-training scores were used as a covariate, the weight-trained group showed a greater increase in hip flexion and extension strength and knee flexion strength than the combined training group (P < 0.05). The combined group showed the greatest increase in knee extensor strength. It is concluded that the pendulum system induces a training effect which could be used to supplement weight-training for improving vertical jump performance.

Exercises stimulating the vestibular organ, such as those described herein, should be a part of efforts to improve balance in older people.