Peptide receptor radionuclide therapy with [177Lu]Lu-DOTA-TATE.

This continuing education aims to present in a clear and easy-to-understand way, the biology of neuroendocrine tumors (NETs), the characteristics of somatostatin receptors, the selection of patients for radiolabelled peptide therapy (PRRT), the inclusion criteria to benefit from treatment with the minimum possible adverse effects, the administration protocol, follow-up and response evaluation. The functional imaging studies necessary to explore the biology of the tumor and to individualize the treatment are also carried out, and constitute the cornerstone for the development of teragnosis. Clinical trials are being developed to better define the position of PRRT within the broad therapeutic options, and among the future perspectives, there are several lines of research to improve the objective response rate and survival with PRRT, focused on the development of new agonists and somatostatin receptor antagonists, new radionuclides and radiosensitizing combination therapies. In conclusion, PRRT is a great therapeutic, well-tolerated and safe tool with generally mild and self-limited acute side effects, that must be sequenced at the best moment of the evolution of the disease of patients with NET. Candidate patients for PRRT should always be evaluated by a multidisciplinary clinical committee.

LPA1 receptor and chronic stress: Effects on behaviour and the genes involved in the hippocampal excitatory/inhibitory balance.

The LPA1 receptor, one of the six characterized G protein-coupled receptors (LPA1-6) through which lysophosphatidic acid acts, is likely involved in promoting normal emotional behaviours. Current data suggest that the LPA-LPA1-receptor pathway may be involved in mediating the negative consequences of stress on hippocampal function. However, to date, there is no available information regarding the mechanisms whereby the LPA1 receptor mediates this adaptation. To gain further insight into how the LPA-LPA1 pathway may prevent the negative consequences of chronic stress, we assessed the effects of the continuous delivery of LPA on depressive-like behaviours induced by a chronic restraint stress protocol. Because a proper excitatory/inhibitory balance seems to be key for controlling the stress response system, the gene expression of molecular markers of excitatory and inhibitory neurotransmission was also determined. In addition, the hippocampal expression of mineralocorticoid receptor genes and glucocorticoid receptor genes and proteins as well as plasma corticosterone levels were determined. Contrary to our expectations, the continuous delivery of LPA in chronically stressed animals potentiated rather than inhibited some (e.g., anhedonia, reduced latency to the first immobility period), though not all, behavioural effects of stress. Furthermore, this treatment led to an alteration in the genes coding for proteins involved in the excitatory/inhibitory balance in the ventral hippocampus and to changes in corticosterone levels. In conclusion, the results of this study reinforce the assumption that LPA is involved in emotional regulation, mainly through the LPA1 receptor, and regulates the effects of stress on hippocampal gene expression and hippocampus-dependent behaviour.

Geographic Tongue: What a Dermatologist Should Know. / Lengua geográfica: ¿qué es lo que un dermatólogo debería saber?

Geographic tongue, also known as benign migratory glossitis, is a benign chronic inflammatory condition of the tongue. It is characterized by erythematous lesions with filiform papillae atrophy, surrounded by white limited areas in the dorsal and lateral aspects of the tongue, producing a map-like aspect. This lesions change in size and shape with time, and are characterized by periods of exacerbation and remission without scaring. The cause is unknown, but multiple associations have been described, which will be discussed below.

Comparative analysis and characterization of soluble factors and exosomes from cultured adipose tissue and bone marrow mesenchymal stem cells in canine species.

The two main sources of mesenchymal stem cell (MSCs) in the canine species are bone marrow (cBM-MSCs) and adipose tissue (cAd-MSCs). The secretion of multitude bioactive molecules, included under the concept of secretome and found in the cultured medium, play a predominant role in the mechanism of action of these cells on tissue regeneration. Although certain features of its characterization are well documented, their secretory profiles remain unknown. We described and compared, for the first time, the secretory profile and exosomes characterization in standard monolayer culture of MSCs from both sources of the same donor as well as its immunomodulatory potential. We found that despite the similarity in surface immunophenotyping and trilineage differentiation, there are several differences in terms of proliferation rate and secretory profile. cAd-MSCs have advantages in proliferative capacity, whereas cBM-MSCs showed a significantly higher secretory production of some soluble factors (IL-10, IL-2, IL-6, IL-8, IL-12p40, IFN-γ, VEGF-A, NGF-ß, TGF-ß, NO and PGE2) and exosomes under the same standard culture conditions. Proteomics analysis confirm that cBM-MSCs exosomes have a greater number of characterized proteins involved in metabolic processes and in the regulation of biological processes compared to cAd-MSCs. On the other hand, secretome from both sources demonstrate similar immunomodulatory capacity when tested in mitogen stimulated lymphocyte reaction, but not in their exosomes at the dose used. Considering that the use of secretome open as a new therapeutic strategy for different diseases, without the need to implant cells, those biological differences should be considered, when choosing the MSCs source, for either cellular implantation or direct use of secretome for a specific clinical application.

Brain Glucose-Sensing Mechanism and Energy Homeostasis.

The metabolic and energy state of the organism depends largely on the availability of substrates, such as glucose for ATP production, necessary for maintaining physiological functions. Deregulation in glucose levels leads to the appearance of pathological signs that result in failures in the cardiovascular system and various diseases, such as diabetes, obesity, nephropathy, and neuropathy. Particularly, the brain relies on glucose as fuel for the normal development of neuronal activity. Regions adjacent to the cerebral ventricles, such as the hypothalamus and brainstem, exercise central control in energy homeostasis. These centers house nuclei of neurons whose excitatory activity is sensitive to changes in glucose levels. Determining the different detection mechanisms, the phenotype of neurosecretion, and neural connections involving glucose-sensitive neurons is essential to understanding the response to hypoglycemia through modulation of food intake, thermogenesis, and activation of sympathetic and parasympathetic branches, inducing glucagon and epinephrine secretion and other hypothalamic-pituitary axis-dependent counterregulatory hormones, such as glucocorticoids and growth hormone. The aim of this review focuses on integrating the current understanding of various glucose-sensing mechanisms described in the brain, thereby establishing a relationship between neuroanatomy and control of physiological processes involved in both metabolic and energy balance. This will advance the understanding of increasingly prevalent diseases in the modern world, especially diabetes, and emphasize patterns that regulate and stimulate intake, thermogenesis, and the overall synergistic effect of the neuroendocrine system.

Pilocarpine and artificial saliva for the treatment of xerostomia and xerophthalmia in Sjögren syndrome: a double-blind randomized controlled trial.

BACKGROUND: Sjögren syndrome (SS) is associated with xerostomia and xerophthalmia. Pilocarpine has been shown to stimulate the secretion of saliva. OBJECTIVES: To investigate and compare the efficacy of pilocarpine and artificial saliva as symptomatic treatments for xerostomia and xerophthalmia in patients with SS. METHODS: A double-blind randomized controlled study was performed. A total of 72 patients with SS were assigned randomly to receive 10 drops of pilocarpine (5 mg) or 10 drops of artificial saliva orally, three times daily for 12 weeks. Whole saliva and tear flow were evaluated at baseline and periodically throughout the study to provide a global assessment of dryness and to report any adverse effects. RESULTS: Patients receiving pilocarpine had a statistically significant improvement in their salivary flow (P < 0·001), lacrimal flow (P < 0·001) and their subjective global assessment (P < 0·001), compared with patients who received artificial saliva. The most common side-effects were sialorrhoea and nausea. CONCLUSIONS: Pilocarpine is more effective than artificial saliva for enhancing salivary and lacrimal secretion in patients with SS. This is the first study to compare the efficacy of pilocarpine and artificial saliva for the treatment of xerostomia and xerophthalmia in SS.

Expression of a Novel Ciliary Protein, IIIG9, During the Differentiation and Maturation of Ependymal Cells.

IIIG9 is the regulatory subunit 32 of protein phosphatase 1 (PPP1R32), a key phosphatase in the regulation of ciliary movement. IIIG9 localization is restricted to cilia in the trachea, fallopian tube, and testicle, suggesting its involvement in the polarization of ciliary epithelium. In the adult brain, IIIG9 mRNA has only been detected in ciliated ependymal cells that cover the ventricular walls. In this work, we prepared a polyclonal antibody against rat IIIG9 and used this antibody to show for the first time the ciliary localization of this protein in adult ependymal cells. We demonstrated IIIG9 localization at the apical border of the ventricular wall of 17-day-old embryonic (E17) and 1-day-old postnatal (PN1) brains and at the level of ependymal cilia at 10- and 20-day-old postnatal (PN10-20) using temporospatial distribution analysis and comparing the localization with a ciliary marker. Spectral confocal and super-resolution Structured Illumination Microscopy (SIM) analysis allowed us to demonstrate that IIIG9 shows a punctate pattern that is preferentially located at the borders of ependymal cilia in situ and in cultures of ependymocytes obtained from adult rat brains. Finally, by immunogold ultrastructural analysis, we showed that IIIG9 is preferentially located between the axoneme and the ciliary membrane. Taken together, our data allow us to conclude that IIIG9 is localized in the cilia of adult ependymal cells and that its expression is correlated with the process of ependymal differentiation and with the maturation of radial glia. Similarly, its particular localization within ependymal cilia suggests a role of this protein in the regulation of ciliary movement.

Etapa de diagnóstico del Cáncer de Próstata ¿Estamos llegando a tiempo? / Prostate cancer stage at diagnosis. Are we running late?

INTRODUCCIÓN: El cáncer de próstata es el segundo cáncer más diagnosticado en hombres en Chile y el mundo. El tamizaje modificó la etapa de diagnóstico, siendo actualmente en EE.UU. un 80 por cinto localizada, 12 por cinto compromiso regional y 4 por ciento metastásico. Tamizaje con APE no está considerado dentro de un programa nacional en Chile. El objetivo de este estudio es caracterizar a la población diagnosticada de cáncer de próstata en un Hospital público en Chile. MATERIALES Y MÉTODO: Estudio descriptivo, retrospectivo. Se revisaron todas las fichas de los pacientes ingresados al GES por Cáncer de Próstata en el Hospital Carlos Van Buren de Valparaíso desde el año 2014 a 2016. RESULTADOS: Se revisaron 259 fichas y se analizaron 226. Edad promedio fue 70,5 años. 46 por ciento presentó APE sobre 20 ng/dL. 31 por ciento presentó metástasis. 42 por ciento recibió tratamiento paliativo. 57 por ciento se realizó tratamiento curativo, con edad promedio 67,4 años. De estos, 31,8 por ciento a cirugía, 68 por ciento índice Gleason <6 y 90 por ciento APE <20. 68 por ciento a RDT con o sin HT, 44 por ciento índice Gleason <6, 75 por ciento APE <20. DISCUSIÓN: El tamizaje del cáncer de próstata es un tema en discusión. En Chile no hay un programa nacional para realizar APE. Centros de atención primaria con acceso a APE tienen mayor tasa de tamizaje. La etapa al diagnóstico en nuestro centro difiere a las series de países desarrollados, siendo considerablemente superior la etapa metastásica. Esto podría deberse a la poca cobertura para detección temprana. Parece ser necesario implementar un programa nacional con cobertura de tamizaje para cáncer de próstata.(AU)

INTRODUCTION: Prostate cancer is the second most diagnosed cáncer in Chile and the world. Screening modified the stage at diagnosis, beeing now in the US 80 pertcent localized, 12 pertcent with regional compromised and 4 pertcent metastatic. Screening with PSA isn't considerd within a national program in Chile. The objetive of this study is to caracterize men diagnosed with prostate cancer at a public hospital in Chile. MATERIALS AND METHODS: Retrospective and descriptive study. Every patient who entered GES because of prostate cancer at the Carlos Van Buren Hospital from Valparaiso between 2014 and 2016 was review. RESULTS: 259 clinical records were review and 226 analized. Mean age was 70,5 years. 46 pertcent had PSA above 20 ng/dL. 31 % had metástasis. 42 % received paliative treatment. 57 % had curative treatment with a mean age of 67,4 years.From this group 31,8 pertcent surgery with a Gleason index <6 and 90 pertcent PSA <20. 68 pertcent had EBRT with or without HT, 44 pertcent of this group had Gleason index <6 and 75 pertcent PSA <20. DISCUSSION: Prostate cancer screening it's a debated topic. In Chile there's no national program to do a PSA. Primary care centers with acces to PSA have more rate of screening. Stage at diagnosis in our center difers from developed countries series, beeing metastatic stage considerably superior. This could be because of the low screening rate for early diagnosis. It seems necesary to implement a national program for prostate cancer screening.(AU)

[Ergotism due to simultaneous use of ergot alkaloids and high activity antiretroviral therapy]. / Ergotismo por uso simultáneo de ergotamínico y terapia antirretroviral: Report of one case.

High activity antiretroviral therapy may exacerbate the activity of ergot alkaloids due to an inhibition of cytochrome P450. We report a 57 years old female with AIDS treated with lamivudine, zidovudine, atazanavir, ritonavir and cotrimoxazole presenting with ischemic signs in the four limbs. There was acrocyanosis and weak radial and ulnar pulses. A family member referred that the patient used ergot alkaloids for headaches. An ergotism due to the simultaneous use of ergot alkaloids and antiretroviral therapy was suspected. The latter was discontinued and intravenous nitroglycerin, nifedipine and pentoxifyline were started with good results.

Ergotismo por uso simultáneo de ergotamínico y terapia antirretroviral: Report of one case / Ergotism due to simultaneous use of ergot alkaloids and high activity antiretroviral therapy

High activity antiretroviral therapy may exacerbate the activity of ergot alkaloids due to an inhibition of cytochrome P450. We report a 57 years old female with AIDS treated with lamivudine, zidovudine, atazanavir, ritonavir and cotrimoxazole presenting with ischemic signs in the four limbs. There was acrocyanosis and weak radial and ulnar pulses. A family member referred that the patient used ergot alkaloids for headaches. An ergotism due to the simultaneous use of ergot alkaloids and antiretroviral therapy was suspected. The latter was discontinued and intravenous nitroglycerin, nifedipine and pentoxifyline were started with good results.

Mente Activa® Improves Impaired Spatial Memory in Aging Rats.

OBJECTIVES: Aging is accompanied by a decline in several aspects of the cognitive function, having negative personal and socioeconomic impacts. Dietary supplements could be beneficial for preventing age-related cognitive decline. In this context, we examined whether the nutritional supplement Mente Activa® has beneficial effects on aging-related cognitive deficits without inducing side effects. METHODS: Mente Activa® was administered to old rats (n= 30 treated rats and n= 30 control rats) during 5 months, and the Morris water maze was used to test the learning capacities of the animals. The first assessment was conducted before the nutritional intervention (age of 18-19 months), to determine the baseline of the performance of animals on this test, and the second assessment was performed at the end of the treatment (23-24 moths). In order to examine possible secondary effects of this nutritional supplement, plasma, heart anatomy and liver parameters were evaluated. RESULTS: Our data indicate that supplemented rats showed less escape latency, distance swum, higher use of spatial search strategies, and crossed the former platform location with higher frequency than control rats. These effects were specific of the treatment, indicating that this nutritional supplement has a beneficial effect on spatial memory. On the other hand, the regular intake of Mente Activa® did not induce any negative effects in plasma parameters and heart size. CONCLUSIONS: Aged rats under a sustained dietary intake of the nutritional supplement Mente Activa® displayed improved learning and memory abilities compared to the non-treated rats. These results suggest the therapeutic potential and safety of use of Mente Activa® for age-related cognitive deficits, particularly, in the onset of the first cognitive dysfunction symptoms.

Selective inactivation of NADPH oxidase 2 causes regression of vascularization and the size and stability of atherosclerotic plaques.

BACKGROUND: A variety of NADPH oxidase (Nox) isoforms including Noxs 1, 2, 4 and 5 catalyze the formation of reactive oxygen species (ROS) in the vascular wall. The Nox2 isoform complex has arguably received the greatest attention in the progression of atherogenesis in animal models. Thus, in the current study we postulated that specific Nox2 oxidase inhibition could reverse or attenuate atherosclerosis in mice fed a high-fat diet. METHODS: We evaluated the effect of isoform-selective Nox2 assembly inhibitor on the progression and vascularization of atheromatous plaques. Apolipoprotein E-deficient mice (ApoE-/-) were fed a high fat diet for two months and treated over 15 days with Nox2ds-tat or control sequence (scrambled); 10 mg/kg/day, i.p. Mice were sacrificed and superoxide production in arterial tissue was detected by cytochrome C reduction assay and dihydroethidium staining. Plaque development was evaluated and the angiogenic markers VEGF, HIF1-α and visfatin were quantified by real time qRT-PCR. MMP-9 protein release and gelatinolytic activity was determined as a marker for vascularization. RESULTS: Nox2ds-tat inhibited Nox-derived superoxide determined by cytochrome C in carotid arteries (2.3 ± 0.1 vs 1.7 ± 0.1 O2(•-) nmol/min*mg protein; P < 0.01) and caused a significant regression in atherosclerotic plaques in aorta (66 ± 6 µm(2) vs 37 ± 1 µm(2); scrmb vs. Nox2ds-tat; P < 0.001). Increased VEGF, HIF-1α, MMP-9 and visfatin expression in arterial tissue in response to high-fat diet were significantly attenuated by Nox2ds-tat which in turn impaired both MMP-9 protein expression and activity. CONCLUSION: Given these results, it is quite evident that selective Nox inhibitors can reverse vascular pathology arising with atherosclerosis.

Job strain and cognitive decline: a prospective study of the framingham offspring cohort.

BACKGROUND: Workplace stress is known to be related with many behavioral and disease outcomes. However, little is known about its prospective relationship with measures of cognitive decline. OBJECTIVE: To investigate the association of job strain, psychological demands and job control on cognitive decline. METHODS: Participants from Framingham Offspring cohort (n=1429), were assessed on job strain, and received neuropsychological assessment approximately 15 years and 21 years afterwards. RESULTS: High job strain and low control were associated with decline in verbal learning and memory. Job strain was associated with decline in word recognition skills. Active job and passive job predicted decline in verbal learning and memory relative to low strain jobs in the younger subgroup. Active job and demands were positively associated with abstract reasoning skills. CONCLUSIONS: Job strain and job control may influence decline in cognitive performance.

Large electric-field-induced strain in centrosymmetric crystals of a dipolar ruthenium alkynyl complex.

Dipolar molecular crystals present different physical properties from traditionally strongly correlated ionic solid-state inorganic crystals due to the weak intermolecular bonding. Herein, centrosymmetric dipolar molecular crystals of the organoruthenium complex trans-[Ru(C≡CC6H4-4-NO2)(C≡CPh)(dppe)2] [dppe = 1,2-bis(diphenylphosphino)ethane] display a large electric-field-induced strain behaving differently from conventional piezoelectric materials that must, structurally, be noncentrosymmetric. Further studies of related systematically varied crystalline organoruthenium complexes reveal that the strong electromechanical coupling effect is not from classical ferroelectricity, electrostriction, flexoelectricity or electrochemical strain. It is, instead, attributed to the disorder in the molecular packing, which facilitates reorientation of the molecular dipoles under the action of an applied electric field. This provides a fresh insight into the design and development of new functional materials and a promising source of electromechanical coupling in organometallic, and more generally dipolar molecular, crystals.

Rehabilitación de piso pélvico en el tratamiento del síndrome de vejiga hiperactiva / Pelvic Floor Rehabilitation in the treatment of overactive bladder syndrome

El objetivo de este trabajo es dar a conocer los resultados, a mediano plazo, de una cohorte de mujeres con Síndrome de Vejiga Hiperactiva (SVH) tratadas mediante un protocolo de rehabilitación de piso pélvico en una consulta kinésica particular. Se intervino una cohorte de 20 mujeres derivadas a la Unidad de Piso Pélvico del Centro Médico IDG por diagnóstico de SVH entre marzo de 2010 y marzo de 2012. La evaluaciones se realizaron al momento del enrolamiento, al finalizar la intervención y luego de 5 a 12 meses de concluida la intervención. Las variables evaluadas fueron: frecuencia miccional diurna y nocturna, urgencia miccional, fuerza muscular de piso pélvico y calidad de vida. La intervención consistió en 10 sesiones de 45 minutos, 2 veces por semana. Se aplicó un protocolo que comprende: entrena- miento muscular de piso pélvico y biofeedback, neuromodulación tibial posterior y reeducación vesical mediante calendario miccional y láminas educativas. La mediana de edad de las pacientes fue 54.5 años y la media de seguimiento fue 11.77 meses. Completaron las 10 sesiones programadas el 80 por ciento de las pacientes. Existió una mejoría significativa entre el basal y el control inmediato a la intervención en las siguientes variables: incontinencia de esfuerzo, score de urgencia, frecuencia miccional diurna y nocturna, fuerza muscular y calidad de vida. Esta tendencia se mantiene al final del seguimiento para las variables frecuencia miccional diurna, frecuencia miccional nocturna y la calidad de vida. El único parámetro que mantuvo su significancia estadística en el seguimiento a mediano plazo fue la frecuencia miccional diurna. Esto no ocurrió con los parámetros frecuencia miccional nocturna y calidad de vida. La rehabilitación integral del piso pélvico es una herramienta eficiente en el tratamiento del SVH, mejorando significativamente parámetros como urgencia, frecuencia miccional diurna y nocturna, fuerza de los músculos elevadores del ano.

The aim of this paper is to present medium term results of a cohort of women with overactive bladder syndrome (SVH) treated with a protocol of pelvic floor rehabilitation in a private Kinesiology office. A cohort of 20 women referred to the Pelvic Floor unit of IDG Medical Center due to diagnosis of SVH between March 2010 and March 2012 was evaluated. The evaluations were performed at enrollment, at the end of intervention and 5-12 months after having completed the intervention. Evaluated variables were: daytime and nighttime urinary frequency, urinary urgency, pelvic floor muscle strength and quality of life. The intervention consisted of 10 sessions of 45 minutes, 2 times a week. Using muscular workout, pelvic floor biofeedback, posterior tibial neuromodulation and bladder voiding re-education through educational micturition calendar. The median age of patients was 54.5 years and the mean follow-up was 11.77 months. 80 percent of patients completed the 10 sessions as scheduled. There was a significant improvement between baseline and immediate intervention in the following control variables: stress incontinence, urgency score, daytime and nighttime urinary frequency, muscle strength and quality of life. This trend is maintained at follow-up variables for daytime frequency, nighttime frequency and quality of life. The only parameter that maintained its statistical significance in the midterm follow-up was daytime voiding frequency. This did not happen with the parameters nocturnal voiding frequency and quality of life. The comprehensive rehabilitation of the pelvic floor is an efficient tool in the treatment of SVH, significantly improving parameters such as urgency, daytime and nighttime urinary frequency, strength of the levator any muscles and quality of life.

Resultados de la rehabilitación kinésica de piso pélvico en un grupo de mujeres con incontinencia de orina / Results of pelvic floor kinesiologic rehabilitation in a group of women with urinary incontinence

Según la ICS, la primera línea de tratamiento para Incontinencia de Orina debería ser la rehabilitación kinésica de piso pélvico ya que se produce una mejoría de los síntomas hasta en un 85 por ciento de los casos. El objetivo de este trabajo fue describir los resultados de una cohorte de mujeres incontinentes tratadas con un protocolo de rehabilitación, comparando la técnica biofeedback manual versus biofeedback electromiográfico. Se analizó un total de 68 mujeres de 30 a 80 años de edad con diagnóstico médico de IU, derivadas a Rehabilitación kinésica de piso pélvico entre marzo de 2011 y marzo de 2012. Se generaron 2 grupos de intervención mediante muestreo dirigido. En el grupo 1 (G1) constó de 48 mujeres que recibieron el siguiente protocolo: biofeedback manual (BM), pauta de ejercicios en domicilio y neuro modulación de tibial posterior. El grupo 2 (G2) constó de 20 mujeres que fueron tratadas con biofeedback electromiográfico (BEM) y la misma pauta de ejercicios en domicilio y protocolo de neuro modulación de tibial posterior. Al evaluar los datos obtenidos no se objetivaron diferencias signi-ficativas entre ambos grupos previo a la intervención. En todos los casos y con ambas técnicas se objetivan mejorías significativas en cuanto a frecuencia miccional diurna / nocturna, numero de apósitos diurno / nocturno, cuantía de la fuga, fuerza muscular y calidad de vida. Sin embargo, se objetivo menor frecuencia de micción diurna al final del seguimiento con técnica BEM (mediana de 5, IC 95 por ciento 1.12 – 7) respecto al BM (mediana de 7, IC 95 por ciento 6-7) p= 0.0208. Conclusión: Ambas protocolos de rehabilitación kinésica del piso pélvico mostraron mejoría significativa en la calidad de vida y fuerza perineal, evidenciando una disminución en los episodios de incontinencia, urgencia y uso de apósitos. Por otra parte, la única diferencia significativa entre el protocolo de biofeedback electromiográfico y manual, fue que el primero mostró menor...

According to the ICS, the first line of treatment for urinary incontinence should be pelvic floor rehabilitation, as it shows an improvement of symptoms in 85 percent of cases. The aim of this study was to describe the results of a cohort of incontinent women treated with a rehabilitation protocol, comparing the techniques: Manual versus Electromyographic biofeedback. Material and methods: We analyzed a total of 68 women, 30- 80 years of age, with medical diagnosis of urinary incontinente referred to Pelvic Floor Rehabilitation between March 2011 and March 2012. 2 groups were generated by targeted intervention. Group 1 (G1) consisted of 48 women who received the following protocol: Manual biofeedback (BM), exercise regimen at home and posterior tibial neuromodulation. Group 2 (G2) consisted of 20 women who were treated with Electromyographic biofeedback (BEM) and the same pattern of exercise protocol and posterior tibial neuromodulation. The data obtained showed no signi¬ficant differences between the two groups before the intervention. In all cases and with both techniques are we objectified significant improvements in terms of urinary frequency day / night, number of pads day / night, amount of leakage, muscle strength and quality of life. However, we observed less daytime micturition frequency at follow- up with BEM technique (median 5, 95 percent CI 1.12 - 7) compared to BM (median of 7, 95 percent CI 6- 7) p = 0.0208. Both pelvic floor reahabilitation protocols showed significant improvement in quality of life and perineal strength, showing a decrease in incontinence episodes, urgency and use of pads. Moreover, the only signi¬ficant difference between electromyographic biofeedback protocol and manual biofeedback protocol, was that the daytime voiding frequency was lower in the ¬ first Group compared to the second.

A local paracrine and endocrine network involving TGFß, Cox-2, ROS, and estrogen receptor ß influences reactive stromal cell regulation of prostate cancer cell motility.

The tumor microenvironment plays a critical role in supporting cancer cells particularly as they disengage from limitations on their growth and motility imposed by surrounding nonreactive stromal cells. We show here that stromal-derived androgenic precursors are metabolized by DU145 human prostate cancer (PCa) cells to generate ligands for estrogen receptor-ß, which act to limit their motility through transcriptional regulation of E-cadherin. Although primary human PCa-associated fibroblasts and the human WPMY-1-reactive prostate stromal cell line maintain this inherent estrogen receptor (ER)ß-dependent motility inhibitor activity, they are subverted by TGF-ß1 pro-oxidant signals derived from cocultured DU145 PCa cells. Specifically, stromal-produced H(2)O(2), which requires Cox-2, acts as a second paracrine factor to inhibit ERß activity in adjacent DU145 cells. Chromatin immunoprecipitation analysis reveals that ERß recruitment to the E-cadherin promoter is inhibited when H(2)O(2) is present. Both neutralization of H(2)O(2) with catalase and prevention of its production by silencing Cox-2 expression in stromal cells restore the motility-suppression activity of stromal-derived ERß ligand precursors. These data suggest that reactive stromal cells may still have a capacity to limit cancer cell motility through a local endocrine network but must be protected from pro-oxidant signals triggered by cancer cell-derived TGF-ß1 to exhibit this cancer-suppressive function.

A comparative analysis of intraperitoneal versus intracerebroventricular administration of bromodeoxyuridine for the study of cell proliferation in the adult rat brain.

Bromodeoxyuridine (BrdU) is the most widely used marker to detect proliferative cells in the adult brain. Here we analyse whether the route of administration of the tracer influences the number of labelled cells. For the intraperitoneal (ip) administration of BrdU, we performed two daily injections during 7 days, and for an intracerebroventricular (icv) delivery, it was continuously infused into one lateral ventricle for a 7 days period as well. After ip administration, cells labelled with BrdU were seen in the subventricular zone of the striatal wall of the lateral ventricle, the hippocampus and the neurohemal circumventricular organs. Also, the habenula and large myelinated tracts, such as the fornix and the corpus callosum, showed many BrdU-positive nuclei. Labelled nuclei were scarce in the parenchymal regions of the rest of the brain. In contrast, a significant increase in the number of BrdU-positive nuclei was observed in the parenchyma of the periventricular zones after icv administration of the marker, thus showing a greater availability of the tracer when it was administered directly into the ventricular cerebrospinal fluid. We suggest that the availability of BrdU in the vicinity of proliferating cells may depend on the permeability of the brain vessels to nucleosides in each location. By using double immunocytochemistry we found that neurons, astrocytes, oligodendrocytes, tanycytes and microglia had incorporated the tracer, demonstrating their proliferation capacity.