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Accumulating data point to K+ channels as relevant players in controlling cell cycle progression and proliferation of human cancer cells, including prostate cancer (PCa) cells. However, the mechanism(s) by which K+ channels control PCa cell proliferation remain illusive. In this study, using the techniques of molecular biology, biochemistry, electrophysiology and calcium imaging, we studied the expression and functionality of intermediate-conductance calcium-activated potassium channels (IKCa1) in human PCa as well as their involvement in cell proliferation. We showed that IKCa1 mRNA and protein were preferentially expressed in human PCa tissues, and inhibition of the IKCa1 potassium channel suppressed PCa cell proliferation. The activation of IKCa1 hyperpolarizes membrane potential and, by promoting the driving force for calcium, induces calcium entry through TRPV6, a cation channel of the TRP (Transient Receptor Potential) family. Thus, the overexpression of the IKCa1 channel is likely to promote carcinogenesis in human prostate tissue.Oncogene (2009) 28, 1792–1806; doi:10.1038/onc.2009.25; published online 9 March 2009 [ABSTRACT FROM AUTHOR]

Neuroendocrine (NE) differentiation is a hallmark of advanced, androgen-independent prostate cancer, for which there is no successful therapy. NE tumor cells are nonproliferating and escape apoptotic cell death; therefore, an understanding of the apoptotic status of the NE phenotype is imperative for the development of new therapies for prostate cancer. Here, we report for the first time on alterations in intracellular Ca2+ homeostasis, which is a key factor in apoptosis, caused by NE differentiation of androgen-dependent prostate cancer epithelial cells. NE-differentiating regimens, either cAMP elevation or androgen deprivation, resulted in a reduced endoplasmic reticulum Ca2+-store content due to both SERCA 2b Ca2+ ATPase and luminal Ca2+ binding/storage chaperone calreticulin underexpression, and to a downregulated store-operated Ca2+ current. NE-differentiated cells showed enhanced resistance to thapsigargin- and TNF-a-induced apoptosis, unrelated to antiapoptotic Bcl-2 protein overexpression. Our results suggest that targeting the key players determining Ca2+ homeostasis in an attempt to enhance the proapoptotic potential of malignant cells may prove to be a useful strategy in the treatment of advanced prostate cancer.Cell Death and Differentiation (2004) 11, 321-330. doi:10.1038/sj.cdd.4401375 Published online 19 December 2003 [ABSTRACT FROM AUTHOR]

Background: Video-feedback observational therapy (VOT) is an intensive rehabilitation technique based on movement repetition and visualization that has shown benefits for motor rehabilitation of the upper and lower limbs. Despite an increase in recent literature on the neurophysiological effects of VOT in the upper limb, there is little knowledge about the cortical effects of visual feedback therapies when applied to the lower limbs. The aim of our study was to better understand the neurophysiological effects of VOT. Thus, we identified and compared the EEG biomarkers of healthy subjects undergoing lower limb VOT during three tasks: passive observation, observation and motor imagery, observation and motor execution., Methods: We recruited 38 healthy volunteers and monitored their EEG activity while they performed a right ankle dorsiflexion task in the VOT. Three graded motor tasks associated with action observation were tested: action observation alone (O), motor imagery with action observation (OI), and motor execution synchronized with action observation (OM). The alpha and beta event-related desynchronization (ERD) and event-related synchronization (or beta rebound, ERS) rhythms were used as biomarkers of cortical activation and compared between conditions with a permutation test. Changes in connectivity during the task were computed with phase locking value (PLV)., Results: During the task, in the alpha band, the ERD was comparable between O and OI activities across the precentral, central and parietal electrodes. OM involved the same regions but had greater ERD over the central electrodes. In the beta band, there was a gradation of ERD intensity in O, OI and OM over central electrodes. After the task, the ERS changes were weak during the O task but were strong during the OI and OM (Cz) tasks, with no differences between OI and OM., Conclusion: Alpha band ERD results demonstrated the recruitment of mirror neurons during lower limb VOT due to visual feedback. Beta band ERD reflects strong recruitment of the sensorimotor cortex evoked by motor imagery and action execution. These results also emphasize the need for an active motor task, either motor imagery or motor execution task during VOT, to elicit a post-task ERS, which is absent during passive observation. Trial Registration NCT05743647., (© 2024. The Author(s).)

Background: Mirror therapy (MT) has been shown to be effective for motor recovery of the upper limb after a stroke. The cerebral mechanisms of mirror therapy involve the precuneus, premotor cortex and primary motor cortex. Activation of the precuneus could be a marker of this effectiveness. MT has some limitations and video therapy (VT) tools are being developed to optimise MT. While the clinical superiority of these new tools remains to be demonstrated, comparing the cerebral mechanisms of these different modalities will provide a better understanding of the related neuroplasticity mechanisms., Methods: Thirty-three right-handed healthy individuals were included in this study. Participants were equipped with a near-infrared spectroscopy headset covering the precuneus, the premotor cortex and the primary motor cortex of each hemisphere. Each participant performed 3 tasks: a MT task (right hand movement and left visual feedback), a VT task (left visual feedback only) and a control task (right hand movement only). Perception of illusion was rated for MT and VT by asking participants to rate the intensity using a visual analogue scale. The aim of this study was to compare brain activation during MT and VT. We also evaluated the correlation between the precuneus activation and the illusion quality of the visual mirrored feedback., Results: We found a greater activation of the precuneus contralateral to the visual feedback during VT than during MT. We also showed that activation of primary motor cortex and premotor cortex contralateral to visual feedback was more extensive in VT than in MT. Illusion perception was not correlated with precuneus activation., Conclusion: VT led to greater activation of a parieto-frontal network than MT. This could result from a greater focus on visual feedback and a reduction in interhemispheric inhibition in VT because of the absence of an associated motor task. These results suggest that VT could promote neuroplasticity mechanisms in people with brain lesions more efficiently than MT., Clinical Trial Registration: NCT04738851., (© 2024. The Author(s).)

Characterization of cortical activation patterns during movements in healthy adults may help our understanding of how the injured brain works. Upper limb motor tasks are commonly used to assess impaired motor function and to predict recovery in individuals with neurological disorders such as stroke. This study aimed to explore cortical activation patterns associated with movements of the hand and shoulder using functional near-infrared spectroscopy (fNIRS) and to demonstrate the potential of this technology to distinguish cerebral activation between distal and proximal movements. Twenty healthy, right-handed participants were recruited. Two 10-s motor tasks (right-hand opening-closing and right shoulder abduction-adduction) were performed in a sitting position at a rate of 0.5 Hz in a block paradigm. We measured the variations in oxyhemoglobin (HbO 2 ) and deoxyhemoglobin (HbR) concentrations. fNIRS was performed with a 24-channel system (Brite 24®; Artinis) that covered most motor control brain regions bilaterally. Activation was mostly contralateral for both hand and shoulder movements. Activation was more lateral for hand movements and more medial for shoulder movements, as predicted by the classical homunculus representation. Both HbO 2 and HbR concentrations varied with the activity. Our results showed that fNIRS can distinguish patterns of cortical activity in upper limb movements under ecological conditions. These results suggest that fNIRS can be used to measure spontaneous motor recovery and rehabilitation-induced recovery after brain injury. The trial was restropectively registered on January 20, 2023: NCT05691777 (clinicaltrial.gov)., (© 2023. The Author(s).)

Force and effort are important components of a motor task that can impact rehabilitation effectiveness. However, few studies have evaluated the impact of these factors on cortical activation during gait. The purpose of the study was to investigate the relation between cortical activation and effort required during exoskeleton-mediated gait at different levels of physical assistance in healthy individuals. Twenty-four healthy participants walked 10 m with an exoskeleton that provided four levels of assistance: 100%, 50%, 0%, and 25% resistance. Functional near-infrared spectroscopy (fNIRS) was used to measure cerebral flow dynamics with a 20-channel (plus two reference channels) device that covered most cortical motor regions bilaterally. We measured changes in oxyhemoglobin (HbO 2 ) and deoxyhemoglobin (HbR). According to HbO 2 levels, cortical activation only differed slightly between the assisted conditions and rest. In contrast, bilateral and widespread cortical activation occurred during the two unassisted conditions (somatosensory, somatosensory association, primary motor, premotor, and supplementary motor cortices). A similar pattern was seen for HbR levels, with a smaller number of significant channels than for HbO 2 . These results confirmed the hypothesis that there is a relation between cortical activation and level of effort during gait. This finding should help to optimize neurological rehabilitation strategies to drive neuroplasticity.

The present study aimed to examine the impact of the level of physical activity on prefrontal cortex activation in older adults during single- and dual-task walking. Thirty physically inactive and 36 active older adults (60-85 years old) performed six 2-min tasks on a treadmill: two static cognitive tasks, two single-task walking tests, and two dual-task walking tests. Hemodynamics at the level of the prefrontal cortex were measured continuously using functional near-infrared spectroscopy to evaluate cortical activation. The perceived difficulty of the task, cognitive performance, and gait parameters were also measured. During the walking tasks, the level of prefrontal cortex activation, the perceived difficulty of the task, cognitive performance, and motor parameters were not significantly different between active and inactive older adults. This unchanged activation with physical activity was likely the consequence of a similar motor and cognitive load and cardiorespiratory fitness in both active and inactive older adults.

We report a case of acute icteric hepatitis attributed to goserelin acetate, occurred during prostate cancer treatment. Gosereline acetate could induce acute hepatitis, which characteristics are close to autoimmune hepatitis type I and may require hepatic monitoring., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

During the EAU and AUA congress in 2009, major work about the urothelial carcinoma was interested in the classification T1a / b and its therapeutic consequences, the last results of BCG therapy and photodynamic diagnosis. At ASCO congress, the main studies presented focused on the systemic treatment, in adjuvant situation, in first line treatment of metastatic bladder cancer, particularly with the addition of anti-angiogenic to chemotherapy, and in conservative treatment in association with radiotherapy.

TRPM8 (melastatine-related transient receptor potential member 8), a member of the transient receptor potential (TRP) superfamily of cation channels, has been shown to be a calcium-channel protein. TRPM8 mRNA has also been shown to be overexpressed in prostate cancer and is considered to play an important role in prostate physiology. This study was designed to determine the androgen-regulation mechanisms for TRPM8 mRNA expression and to identify the phenotype of TRPM8-expressing cells in the human prostate. Our findings show that trpm8 gene expression requires a functional androgen receptor. Furthermore, this article argues strongly in favour of the fact that the trpm8 gene is a primary androgen-responsive gene. Single-cell reverse transcriptase PCR and immunohistochemical experiments also showed that the trpm8 gene was mainly expressed in the apical secretory epithelial cells of the human prostate and trpm8 down-regulation occurred during the loss of the apical differentiated phenotype of the primary cultured human prostate epithelial cells. The androgen-regulated trpm8 expression mechanisms are important in understanding the progression of prostate cancer to androgen-independence. These findings may contribute to design a strategy to predict prostate cancer status from the TRPM8 mRNA level. Furthermore, as the TRPM8 channel is localized in human prostate cells, it will be interesting to understand its physiological function in the normal prostate and its potential role in prostate cancer development.

Neuroendocrine (NE) differentiation is a hallmark of advanced, androgen-independent prostate cancer, for which there is no successful therapy. NE tumor cells are nonproliferating and escape apoptotic cell death; therefore, an understanding of the apoptotic status of the NE phenotype is imperative for the development of new therapies for prostate cancer. Here, we report for the first time on alterations in intracellular Ca(2+) homeostasis, which is a key factor in apoptosis, caused by NE differentiation of androgen-dependent prostate cancer epithelial cells. NE-differentiating regimens, either cAMP elevation or androgen deprivation, resulted in a reduced endoplasmic reticulum Ca(2+)-store content due to both SERCA 2b Ca(2+) ATPase and luminal Ca(2+) binding/storage chaperone calreticulin underexpression, and to a downregulated store-operated Ca(2+) current. NE-differentiated cells showed enhanced resistance to thapsigargin- and TNF-alpha-induced apoptosis, unrelated to antiapoptotic Bcl-2 protein overexpression. Our results suggest that targeting the key players determining Ca(2+) homeostasis in an attempt to enhance the proapoptotic potential of malignant cells may prove to be a useful strategy in the treatment of advanced prostate cancer.

Clean intermittent catheterization has become a usual procedure in urologic practice. Self lubrificated catheters are nowadays accepted as the most efficient. This randomised and prospective study compared tolerance and efficiency in a group of 27 patients of three well known catheters (12 charriere, straight): Flocath (Ruschcare), Lofric (Astratech) and Easycath (Coloplast). The systematic comparison of this three catheters did not allow to put in a prominent position one of these. The three catheters are extremely close in terms of tolerance and performance.

Peristomal varices can occur in patients with gastrointestinal or urinary diversions associated with portal hypertension. It is now no longer rare to propose radical surgery for invasive bladder tumours in patients also suffering from hepatic cirrhosis, responsible for specific subsequent complications. Less than ten cases of varicose haemorrhages have been described on ileal bladders. The authors report the case of a patient with cirrhosis (Child B) treated surgically (radical cystoprostatectomy and Bricker transileal cutaneous diversion) for invasive bladder tumour. Episodes of bleeding varices occurred two months after surgery. Repeated and abundant haemorrhage led to the placement of an intrahepatic shunt (TIPS) allowing reduction of the portal hypertension and the severity of the bleeding. When local control of the bleeding is no longer possible, reduction of the portosystemic pressure gradient is required. TIPS is an effective alternative to surgical shunts, responsible for high morbidity and mortality in these debilitated patients.

Objective: To study the late results of interferential current stimulation in the treatment of detrusor instability., Material and Methods: 62 patients with detrusor instability refractory to medical treatment by anticholinergic drugs were treated by interferential current stimulation. This technique combines the advantages of retraining stimulation with external application. This retrospective study was based on 62 patients (43 children, 11 men and 8 women) presenting with detrusor instability between January 1990 and December 1997. All patients were assessed clinically and by a radiological, bacteriological and urodynamic work-up prior to treatment. The mean follow-up was 5 years (range: 18 months to 10 years)., Results: The results of this technique were excellent, with 80.9% of cures at one year, but they tended to fade over time to 40% of cures at 5 years. However, results which deteriorate after one year can generally be maintained by performing 5 maintenance sessions every 12 or 18 months., Conclusion: Treatment of detrusor instability by interferential current is a reliable technique which constitutes an alternative to the other methods of retraining stimulation and can be performed in cases of instability refractory to anticholinergic drugs, before considering neuromodulation or surgery. Five to 10 maintenance sessions every 12 or 18 months ensure stable long-term results in the majority of cases.

Objectives: Preliminary clinical studies of the combination of hyperthermia and intravesical chemotherapy indicated very encouraging results in favour of multidisciplinary treatment of recurrent superficial bladder tumours. The authors studied the in vitro and early in vivo effects of this treatment., Material and Methods: An intravesical catheter equipped with a microwave antenna was used for hyperthermia in vivo in dogs. The temperature was controlled by two intravesical thermocouples and 4 transducers on the bladder wall. 0, 40 or 80 mg of mitomycin were instilled in 60 ml of physiological saline. Dogs were sacrificed after each one-hour session, and histological intravesical lesions were defined as grade 0, 1 or 2 corresponding to absence of lesions, or the presence of inflammatory lesions or urothelial lesions, respectively. In vitro, the first step consisted of creation of an immortalized tumour cell line from a grade II bladder papilloma. This HVT 196 cell line was incubated between 37 degrees C and 44 degrees C with increasing mitomycin concentrations of 0 to 10 micrograms per ml. The cytotoxicity was measured by the MTT quantitative colorimetric method., Results: In vivo, in 8 dogs, histological analysis of the comparative cytotoxicity of the various treatments confirmed the synergistic effect of heat and mitomycin C. In dogs treated at 45 degrees C, marked urothelial lesions were observed, regardless of the mitomycin C concentration. The in vitro comparative toxicity study on our cell line showed a much more intense cytotoxic effect with combined treatment than with cytostatic treatment alone. Expressed as the percentage of cytotoxicity compared to a control cell pool for a concentration of 1 microgram per ml. the temperature rise of the medium between 37 degrees C and 44 degrees C was accompanied by a cytotoxic effect of 8.4% and 98.41% respectively., Conclusion: A possible clinical application is potentiation of the action of mitomycin C by hyperthermia in the prevention of recurrent superficial bladder tumours, achieving increased efficacy and/or a decreased number of instillations.

Heart rate variability is a sign of sympathetic activity. The authors compared two study populations of young males aged 19 to 30 years: population T comprised 15 healthy volunteers who had two negative tilt tests, one under basal conditions and the other after a bolus of isoproterenol; population S comprised 12 patients without cardiac or other disease, who were followed up for malaise and in whom the basal tilt test was positive, confirming the vagal origin of syncope. Temporal and spectral (total power, low frequency 0.04-0.15 Hz, hight frequency 0.16-0.40 Hz) data was obtained concerning heart rate variability from 24 hour Holter monitoring. The main difference between the two study populations was in the temporal data over 24 hours especially with respect to the heart rate (T = 73.5 +/- 6.9; S = 65.4 +/- 6.2/min; p = 0.004) and the percentage of successive R-R intervals varying by more than 50 ms (PNN 50) (T = 20.2 +/- 8.3%; S = 30.7 +/- 10.2%; p = 0.024). At night, the lowest SDANN/5 (standard deviation of RR intervals over periods of 5 minutes) were observed in group S (67.2 +/- 16.7 ms vs 87.3 +/- 24.4 ms; p = 0.026). No statistically significant differences between the two groups was observed in the spectral data. The temporal data of heart rate variability on Holter ECG monitoring over 24 hours could therefore have a good predictive value of the vagal origin of syncope in young adults.

Considerable progress has been made in the treatment of female urinary incontinence over the last 20 years, affecting both surgical treatment, by the introduction, apart from reference techniques, of so-called "minimal" techniques, which allow an extension of the indications to elderly patients, and medical treatment, but also due to the introduction of increasingly better defined retraining techniques. A better understanding of the pathophysiology of incontinence and the growth of urodynamic techniques allow a better analysis of the mechanisms responsible for incontinence, which is often multifactorial. The prevalence of female urinary incontinence also gives this disease a considerable economic significance. Surgery is therefore no longer currently the only treatment that can be proposed to the patient. The respective indications for retraining and surgery need to be discussed, bearing in mind that, schematically, the 2-year results of surgery achieve 80 to 85% of cure with a more marked erosion over time when the initial repair was less solid, and retraining cures approximately 30% of women and improves another 30%.

In cervical dysplasia and neoplasia, recent studies have reported the unreliability of the pap smear. We have used a new screening technique, cervicography and have compared it to cervix cytology. We have performed biopsies under colposcopy as reference and quality control. On a series of 65 selected patients with pap smear screening program which were sent to the colposcopic triage, the cervicography is more sensitive (83%) than the pap smear (sensitivity: 42%). However, those two tests are from a specificity point of view, comparable (cervicography: 95% versus pap smear: 98%). The association of these two techniques has detected all the lesions: they seem to be complementary. In the Bordet Institute we decided to systematically perform both pap smear and cervicography for cervix screening.

The management of 21 parasagittal meningiomas is described; three were located in the anterior third of the sinus, 14 in the middle third, and four in the posterior third. Of these, four meningiomas were attached only to the lateral wall, two invaded the external layer of only one sinus wall, two involved the lateral recess of the sinus, and seven invaded one or two sinus walls. The remaining six tumors invaded the three walls of the sinus, which was completely blocked. There was bilateral meningiomas in four cases. Complete excision of the meningioma with preservation of the venous flow in the sinus and its collateral veins was attempted in each case. In the first eight cases it was possible to preserve the patency of the sinus without graft. In six of the next seven cases the removal of the two invaded walls permitted preservation of the third healthy wall and entailed the repair of the two involved walls by a partial graft, either dural graft (three cases) or venous graft (three cases). In one of the last six cases, a total vein graft was performed after complete excision of the invaded sinus. Two cortical veins were sutured to a collateral branch of the autogenous vein graft. The surgical technique of the partial and the total vein graft is described and clinical results and angiographic controls are discussed.