[Impact of pelvic floor educational sessions on teenage girls]. / Impact de sessions d'éducation périnéale chez des adolescentes.

INTRODUCTION: Our objective was to evaluate the impact of pelvic floor educational sessions on teenage girls about their general knowledge of pelvic floor disorders (PFD) and the anatomy of the pelvic floor. MATERIAL: Educational sessions were offered to teenage girls from middle and high schools in the city of Caen. Each session included pelvic floor anatomy, urinary and digestive physiology as well as situations that favor PFD. At the beginning and end of the session, the participants received a questionnaire on their knowledge and questions concerning their satisfaction were asked at the end of the session. A questionnaire was sent at 2 months to assess the changes in their urinary and digestive habits as well as the dissemination of information to those around them. RESULTS: One hundred and five teenage girls, average age 15, participated in these sessions; 61% responded at 2 months. The educational sessions have significantly improved knowledge about the pelvic floor. After the sessions, 92% and 52% reported having changed their urinary and defecatory habits. Participants found the sessions very useful and all participants recommended these sessions to a friend. CONCLUSION: Pelvic floor educational sessions improve the knowledge of teenage girls and limit behaviors that favor PFD. Teenage satisfaction is important and the dissemination of information is high. A pelvic floor educational program in schools could help limit risky behaviors for the pelvic floor.

[Pelvic floor disorders: What do adolescents and young women know? A literature review]. / Troubles pelvi-périnéaux : quelles connaissances en ont les adolescentes et les jeunes femmes ? Une revue de la littérature.

AIM: To assess the knowledge of adolescent girls and young women on pelvic-perineal disorders (PPD). METHOD: We searched on PubMed, Cochrane Library, Kinédoc and Semantic Scholar databases using the MeSH keywords: "knowledge" "awareness" "surveys" "young women" "pelvic floor" "adolescent" "teenager" "athletic injury" "urinary incontinence". The articles had to have been published within the last 15 years, written in French or English, and deal with the state of knowledge of adolescents and young women concerning the perineal sphere using questionnaires. RESULTS: A total of 8 studies were included in the review, 5 cross-sectional studies and 3 intervention studies. The knowledge of adolescent girls and young women interviewed about the anatomy of the pelvic floor, its function, and risk factors for PPD was low. The majority of the participants wanted more information about the pelvic floor. Two studies that conducted an educational intervention showed a significant improvement in knowledge. CONCLUSION: Knowledge of pelvic-perineal disorders and pelvic floor function is poor in adolescent girls and young women. To better assess them, it would be necessary to validate a questionnaire containing all the items about knowledge.

[Benefits of group pelvic floor education sessions: satisfaction and improvement of women's knowledge]. / Intérêt de sessions d'éducation périnéale en groupe : satisfaction et amélioration des connaissances des femmes.

INTRODUCTION: Pelvic floor dysfunctions are an important health-care issue however there are no primary prevention programs for perineal health. This study aims to evaluate the impact of perineal education group sessions on women's urinary and digestive behaviors and their satisfaction with these sessions. MATERIAL: Perineal education sessions were proposed to women working in a gynecology department. Each session covered perineal physiology and anatomy, urinary and digestive physiology as well as risk situations for the pelvic floor. At the beginning and end of the sessions, participants completed a questionnaire on their knowledge about the pelvic floor and questions concerning their satisfaction were asked at the end of the session. A 2-month questionnaire assessed changes in urinary and digestive habits as well as the dissemination of information. RESULTS: One hundred and sixty-three women, average age 38, participated in these sessions; 107 responded at 2 months. The education sessions significantly improved pelvic floor fonctions knowledge. After the sessions, 81.3% of women reported changing their urinary habits and 60.7% their defecatory habits. Participants found the sessions very useful (rating 9.7/10), all participants recommended these sessions to a friend and the dissemination of the information was important. CONCLUSION: Perineal education sessions improve women's knowledge and limit risky behaviors for the pelvic floor. The satisfaction of women who received information is important and the dissemination of information strong. LEVEL OF EVIDENCE: 4.

[Benefits of pelvic floor education in perineal re-education in women]. / Intérêt de l'éducation périnéale en rééducation périnéale chez la femme.

AIM: Evaluate the impact of pelvic floor education on the symptoms of female patients referred for pelvic floor muscle training (PFMT). METHODS: Forty female patients suffering from pelvic floor disorders and referred to independent practice for PFME between February and May 2019 answered a survey on symptoms and quality of life before PFME, after four sessions of pelvic floor education and at the end of PFME. The ICIQ-SF, USP, Contilife, PDFI 20, Kess, and Wexner scores were used to evaluate the results. The protocol consisted in four initial sessions of pelvic floor education including information on each field of perineology ; the fifth session was dedicated to visual feedback using a mirror ; the following five sessions were tailored according to the care objectives established based on the initial assessment. RESULTS: The scores were significantly improved after the four initial sessions of pelvic floor education. The improvement was significant at the end of the re-education program. The PFDI-20 score dropped from 66,9 to 20,9 (P=0,002), the ICIQ-SF score from 8,4 to 1,5 (P<10-3), the Wexner score from 7,4 to 5,1 (P<10-3) and the Kess score from 14,2 to 8,7 (P=0,05). CONCLUSION: The results showed that female patients undergoing perineal re-education including pelvic floor education sessions show a significant improvement in their symptoms already immediately after the pelvic floor education sessions.

Filariasis asymptomatically infected donors have lower levels of disialylated IgG compared to endemic normals.

Helminths induce strong regulatory and T helper 2-type responses, whereby antibody-derived host protection and regulation are essential components. Lymphatic filariasis is an immune-mediated spectral disease that manifests as two main clinical outcomes: chronic pathology or asymptomatic infection. These outcomes depend on a multitude of factors, including parasite-induced immunoregulation and host genetic background; antibody responses contribute to this outcome. N-glycosylation of the Fc region of antibodies is a post-translational modification required for the structure and molecular function, influencing host inflammatory and regulatory responses. Altered IgG glycosylation correlates with disease, whereby decreased galactosylation is associated with inflammation while increased sialylation is associated with anti-inflammatory responses. We purified N-linked glycans from the Fc region of total IgG from Wuchereria bancrofti-infected patients characterizing the two clinical manifestations (chronic pathology and asymptomatic infection) and compared them to infection-free endemic normals. Using capillary electrophoresis, we found that there was no difference in galactosylation of total IgG between the three groups; however, asymptomatically infected patients had significantly lower levels of disialylated IgG compared to endemic normals and patients with pathology. These data suggest that while galactosylation does not contribute to disease outcome, sialylation may be involved in asymptomatic infection.

Alzheimer pathology disorganizes cortico-cortical circuitry: direct evidence from a transgenic animal model.

It has been proposed that Alzheimer disease (AD) is associated with a "disconnection syndrome" due to the gradual loss of morphological and functional integrity of cortico-cortical pathways. This hypothesis derives from indirect neuropathological observations, but definitive evidence that AD primarily targets cortico-cortical networks is still lacking. By means of neuroanatomical anterograde tracing methods, we have investigated, in a murine transgenic model of AD, the impact of the amyloid burden on axonal terminals in different neural systems. Axonal tracings revealed, in accordance with the "disconnection syndrome" hypothesis, that cortico-cortical fibers are significantly disorganized. Terminal fields in local and distant cortical areas contained numerous swollen dystrophic neurites often grouped in grape-like clusters at the plaque periphery. In contrary to fibers of cortical origin, those originating from subcortical brain structures only showed limited signs of degeneration upon reaching their cortical targets. These observations suggest a selective disruption of cortico-cortical connections induced by AD brain pathology.

Increased tau phosphorylation but absence of formation of neurofibrillary tangles in mice double transgenic for human tau and Alzheimer mutant (M146L) presenilin-1.

Neurofibrillary tangles, composed of tau proteins, are a key lesion observed in sporadic forms of Alzheimer's disease and in familial forms associated with mutations of presenilin-1 (PS1). We have generated a double transgenic mouse line expressing a human tau isoform and a mutated form of PS1 (M146L) in neurons. Increased expression of the PS1 holoprotein was observed in the tau/PS1 transgenic mice and the proteolytic fragments of PS1 did not appear to be modified. A somatodendritic accumulation of the transgenic tau and an increase in tau phosphorylation were observed in both tau- and tau/PS1 transgenic mice. Neurofibrillary tangles were not observed in animals analyzed up to 17 months. Immunoprecipitation of tau from brain homogenates demonstrated its binding with active glycogen synthase kinase-3beta in control, tau- and tau/PS1 transgenic lines. These results suggest that overexpression of this Alzheimer mutant PS1 in vivo is not by itself sufficient to induce the formation of neurofibrillary tangles, even in neurons co-expressing and accumulating a human tau isoform.

Reelin in plaques of beta-amyloid precursor protein and presenilin-1 double-transgenic mice.

There is circumstantial evidence that the reelin signaling pathway may contribute to neurodegeneration in the adult brain and could be linked to Alzheimer's disease (AD). In the present immunohistochemical report we studied the reelin expression profile in double-transgenic mice that express both human mutant beta-amyloid precursor protein (APP) and human mutant presenilin-1. We were able to demonstrate that reelin immunostaining was found together with human APP in the neuritic component of many AD-typical plaques in both hippocampus and neocortex. This observation gives the first evidence for the association of reelin with amyloid deposits.

Intraneuronal Abeta accumulation precedes plaque formation in beta-amyloid precursor protein and presenilin-1 double-transgenic mice.

beta-Amyloid peptides are key molecules that are involved in the pathology of Alzheimer's disease (AD). The source and place of the neurotoxic action of Abeta, however, is still a matter of controversial debates. In the present report, we studied the neuropathological events in a transgenic mouse model expressing human mutant beta-amyloid precursor protein and human mutant presenilin-1 in neurons. Western blot and immunohistochemical analysis revealed that intracellular Abeta staining preceded plaque deposition, which started in the hippocampal formation. At later stages, many neuritic Abeta positive plaques were found in all cortical, hippocampal and many other brain areas. Interestingly, intraneuronal Abeta staining was no longer detected in the brain of aged double-transgenic mice, which correlates with the typical neuropathology in the brain of chronic AD patients.

Parkin immunoreactivity in the brain of human and non-human primates: an immunohistochemical analysis in normal conditions and in Parkinsonian syndromes.

The etiology of Parkinson's disease is unknown, but the gene involved in an autosomic recessive form of the disease with early onset has recently been identified. It codes for a protein with an unknown function called parkin. In the present study we produced a specific polyclonal antiserum against human parkin. Immunohistochemical analysis showed that parkin is expressed in neuronal perikarya and processes but also in glial and blood vessels in the primate brain (human and monkey). Electron microscopy indicated that parkin immunoreactivity is mostly located in large cytoplasmic vesicles and at the level of the endoplasmic reticulum. Parkin was expressed heterogeneously in various structures of the brain. It was detectable in the dopaminergic systems at the level of the perikarya in the mesencephalon but also in the striatum. However, parkin was also expressed by numerous nondopaminergic neurons. The staining intensity of parkin was particularly high in the hippocampal formation, the pallidal complex, the red nucleus, and the cerebellum. Comparison of control subjects with patients with Parkinson's disease and control animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated animals revealed a loss of parkin-immunoreactive neurons only in the substantia nigra pars compacta. Furthermore, the surviving dopaminergic neurons in the parkinsonian state continued to express parkin at a level similar to that observed in the control situation. These data indicate that parkin is a widely expressed protein. Thus, the degeneration of dopaminergic neurons in familial cases of Parkinson's disease with autosomal recessive transmission cannot be explained solely in terms of an alteration of this protein.

The antioxidant ebselen prevents neurotoxicity and clinical symptoms in a primate model of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), via its major metabolite 1-methyl-4-phenylpyridinium (MPP(+)), produces in primates including humans clinical, biochemical, and neuropathological changes similar to those which occur in idiopathic Parkinson's disease. Ebselen is an antioxidant drug with glutathione peroxidase-like activity and a proven neuroprotective action in stroke patients. Here we show that Ebselen, when administered before, during, and after MPTP injections, prevents both neuronal loss and clinical symptoms in a primate MPTP model of Parkinson's disease. Ebselen also prevents peroxide radical overproduction induced by serum withdrawal in cultured PC12 cells and hydroxyl radical generation induced by the mitochondrial toxin, MPP(+), in vivo in rat brain. Moreover, Ebselen inhibits MPP(+)-induced toxicity in PC12 cells, without interacting with the dopamine uptake system. Our results demonstrate that compounds which prevent mitochondrial dysfunction and free radical production may be useful as preventive treatment of Parkinson's disease.

Characterization of human presenilin 1 transgenic rats: increased sensitivity to apoptosis in primary neuronal cultures.

Mutations in the gene for presenilin 1 are causative for the majority of cases of early onset familial Alzheimer's disease. Yet, the physiological function of presenilin 1 and the pathological mechanisms of the mutations leading to Alzheimer's disease are still unknown. To analyse potential pathological effects of presenilin 1 over-expression, we have generated transgenic rats which express high levels of human presenilin 1 protein in the brain. The over-expression of presenilin 1 leads to saturation of its normal processing and to the appearance of full-length protein in the transgenic rat brain. The transgenic protein is expressed throughout the brain and is predominantly found in neuronal cells. Cultured primary cortical neurons derived from these transgenic rats are significantly more sensitive than non-transgenic controls to apoptosis induced by standard culture conditions and to apoptosis induced by trophic factor withdrawal. Furthermore, the observed apoptosis is directly correlated with the expression of the transgenic protein. The results further emphasize the role of presenilin 1 in apoptotic cell death in native neuronal cultures.

Rapid identification and fingerprinting of Candida krusei by PCR-based amplification of the species-specific repetitive polymorphic sequence CKRS-1.

A PCR method was developed to identify and fingerprint Candida krusei isolates simply and rapidly. The primer pair Arno1 and Arno2 was designed to amplify the polymorphic species-specific repetitive sequence CKRS-1 (C. krusei repeated sequence 1) that we identified in the nontranscribed intergenic regions (IGRs) of rRNA genes in C. krusei LMCK31. The specificity, sensitivity, reproducibility, and fingerprinting ability of the PCR assay were evaluated. Amplification products were obtained from all 131 C. krusei isolates studied. No other yeast species of medical importance (n = 26), including species similar to C. krusei, species of pathogenic filamentous fungi, or a variety of pathogenic bacteria, yielded a PCR product with these primers. This PCR assay allowed for the identification of C. krusei in less than 6 h. The PCR assay was sensitive enough to detect as little as 10 to 100 fg of C. krusei-purified DNA and proved to be reproducible. Since amplification products varied both in number and in molecular weight according to the strains, PCR patterns allowed strains to be distinguished. To ascertain the epidemiological usefulness of this PCR fingerprinting, the patterns of the 131 isolates were compared. A total of 95 types which corresponded to 95 independent strains were delineated (discriminatory power = 1 with n = 95). Comparison of the results of PCR fingerprinting and those of fingerprinting with the CkF1,2 probe showed that they concurred. In addition, this work yields insights into the mechanisms involved in generating polymorphisms in the IGRs of C. krusei. Since this method is simpler and faster than established identification and genotyping methods of this important pathogenic species, it is a critical improvement for clinical microbiology laboratories relevant not only to diagnosis but also to epidemiology.

Immunohistochemical analysis of presenilin 2 expression in the mouse brain: distribution pattern and co-localization with presenilin 1 protein.

Missense mutations of presenilin 1 (PS-1) and presenilin 2 (PS-2) genes cause the majority of early-onset familial forms of Alzheimer's disease (AD). We previously characterized the distribution of the PS-1 protein in the mouse brain by immunohistochemistry using an antibody directed against an epitope located in the large hydrophilic loop [Moussaoui, S., Czech, C., Pradier, L., Blanchard, V., Bonici, B., Gohin, M., Imperato, A. and Revah, F., Immunohistochemical analysis of presenilin 1 expression in the mouse brain, FEBS Lett., 383 (1996) 219-222]. Similarly, we now report the distribution pattern of PS-2 protein in the mouse brain. For these experiments we used a polyclonal antibody raised against a synthetic peptide corresponding to the amino-acid sequence 7-24 of the predicted human PS-2 protein. The specificity of the antibody was evidenced by its ability to recognize PS-2 protein in immunoprecipitation studies and by antigen-peptide competition. In the mouse brain, PS-2 protein was present in numerous cerebral structures, but its distribution in these structures did not correlate with their susceptibility to AD pathology. In all examined structures of the gray matter, PS-2 protein was concentrated in neuronal cell bodies but it was not detected in the glial cells of the white matter. The regional distribution pattern of PS-2 protein was almost identical to that of PS-1 protein. Moreover, PS-2 protein co-localized with PS-1 protein in a large number of neuronal cell bodies. In terms of subcellular localization, PS-2 immunostaining was present almost exclusively in neuronal cell bodies while PS-1 immunostaining was also present in dendrites. This could be explained by the different epitopes of the antibodies and the known proteolytic processing of both presenilins in vivo [Tanzi, R.E., Kovacs, D.M., Kim, T.-W., Moir, R.D., Guenette, S.Y. and Wasco, W., The presenilin genes and their role in early-onset familial Alzheimer's disease, Alzheimer's disease Rev., 1 (1996) 91-98]. Within neuronal cell bodies, the immunostaining of PS-2 protein, as well as that of PS-1 protein, had a reticular and granular appearance. This suggests in agreement with previous observations on PS-1 and PS-2 in COS and H4 cells [Kovacs, D.M., Fausett, H.J., Page, K.J., Kim, T.-W., Moir, R.D., Merriam, D.E., Hollister, R.D., Hallmark, O.G., Mancini, R., Felsenstein, K.M., Hyman, B.T., Tanzi, R.E., Wasco, W., Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells, Nature Med., 2 (1996) 224-229] that these proteins are situated in intracytoplasmic organelles, possibly the endoplasmic reticulum and the Golgi complex.

DA uptake sites, D1 and D2 receptors, D2 and preproenkephalin mRNAs and Fos immunoreactivity in rat striatal subregions after partial dopaminergic degeneration.

Stereotaxic injection of a limited amount of 6-hydroxydopamine in the lateral part of the rat substantia nigra induces a partial degeneration of the nigrostriatal dopaminergic system. This animal model in which the destruction of the dopaminergic nigral cell population reaches approximately 50% could be considered as a preclinical Parkinson's model. Autoradiography of dopaminergic uptake sites performed with a specific marker ([3H]GBR 12935) allowed the precise determination of dopaminergic denervated and non-denervated areas in the striatum 1 month after partial lesion of the substantia nigra pars compacta. In both striatal areas, dopaminergic D1 and D2 receptor densities and dopaminergic D2 and preproenkephalin mRNAs levels were measured by autoradiography and in situ hybridization coupled to an image analysis system. Our results show that in the denervated striatal subregion, none of the dopaminergic targets were modified, contrary to the observations made after complete lesion of the nigrostriatal DA system at the same post-lesion delay. However, striatal Fos activation induced by amphetamine (5 mg/kg i.p., 2 h before killing) revealed that the number of Fos-positive cells detected in the denervated striatal subregion was lower than that observed in the non-denervated one. These data argue in favour of the existence of compensatory mechanisms different from the up-regulation of DA receptor densities, thereby allowing the maintenance of striatal dopaminergic transmission. Such mechanisms could contribute to the delay of the appearance of neurological symptoms (which are reported to be clinically apparent only when depletion of striatal dopamine levels reaches near 80%) in Parkinsonian patients.

Immunohistochemical analysis of presenilin-1 expression in the mouse brain.

At least 22 different mutations associated with early-onset familial Alzheimer's disease (AD) in various kindreds have been reported to occur in a recently identified gene on chromosome 14, presenilin 1 (PS-1) (Sherrington et al. (1995) Nature 375, 754-760 [1] and reviewed by Van Broeckhoven (1995) Nat. Genet. 11, 230-231 [2]). In order to study the localization of PS-1 in the brain, we raised a polyclonal antiserum specific to a fragment of the predicted protein sequence of PS-1. PS-1 immunostaining was found intracellularly, in the perikaria of discrete cells, mostly neurons, appearing as thick granules, resembling large-size vesicles. These granules were located in the periphery of cell bodies and extended into dendrites and neurites. PS-1 expression was found to be broadly distributed throughout the mouse brain, not only in structures involved in AD pathology, but also in structures unaltered by this disease.

Dopaminergic sprouting in the rat striatum after partial lesion of the substantia nigra.

The capacity of the dopaminergic nerve system to reinnervate the denervated adult striatum was analyzed in a model of partial 6-hydroxydopamine-induced unilateral lesion of rat substantia nigra pars compacta. Sprouting of dopaminergic fibers entering the ventrolateral part of the striatum from a narrow zone of the external capsule was detected on the lesioned side 4 and 7 months, but not 10 days, after lesioning. Ultrastructural examination of the zone of sprouting revealed hypertrophic dopaminergic fibers and growth-cone-like structures, confirming the existence of an ongoing process of spontaneous regrowth of dopaminergic fibers. The identification of the factors involved in the regrowth of dopaminergic fibers may help to orientate molecular research into new treatments for Parkinson's disease.

Long-term induction of tyrosine hydroxylase expression: compensatory response to partial degeneration of the dopaminergic nigrostriatal system in the rat brain.

The present study was undertaken to examine the adaptive changes occurring 1 and 6 months after moderate or severe unilateral 6-hydroxydopamine-induced lesions confined to the lateral part of the rat substantia nigra pars compacta (SNC). The expression of tyrosine hydroxylase (TH) enzyme was analyzed in the remaining dopaminergic nigral cell bodies and in the corresponding striatal nerve endings. In the cell bodies of the lesioned SNC, TH mRNA content was increased (+20 to +30%) 6 months after the lesion without changes in cellular TH protein amounts. The depletion of TH protein in the nerve terminal area was less severe than the percentage of cell loss observed in the SNC at 1- and 6-month postlesion intervals. Moreover, the decrease in TH protein in the ipsilateral striatum was less pronounced 6 months after lesion than 1 month after. That no corresponding change in TH protein content was observed in the cell bodies at a time when TH increased in nerve terminals suggests that the newly synthesized protein is probably rapidly transported to the striatal fibers. These results suggest the existence of a sequence of changes in TH expression between cell bodies and fibers, occurring spontaneously after partial denervation of the nigrostriatal pathway.

Biochemistry and molecular biology of the vesicular monoamine transporter from chromaffin granules.

Prior to secretion, monoamines (catecholamines, serotonin, histamine) are concentrated from the cytoplasm into vesicles by vesicular monoamine transporters (VMAT). These transporters also carry non-physiological compounds, e.g. the neurotoxin methyl-4-phenylpyridinium. VMAT acts as an electrogenic antiporter (exchanger) of protons and monoamines, using a proton electrochemical gradient. Vesicular transport is inhibited by specific ligands, including tetrabenazine, ketanserin and reserpine. The mechanism of transport and the biochemistry of VMAT have been analyzed with the help of these tools, using mainly the chromaffin granules from bovine adrenal glands as a source of transporter. Although biochemical studies did not suggest a multiplicity of VMATs, two homologous but distinct VMAT genes have recently been cloned from rat, bovine and human adrenal glands. The VMAT proteins are predicted to possess 12 transmembrane segments, with both extremities lying on the cytoplasmic side. They possess N-glycosylation sites in a putative luminal loop and phosphorylation sites in cytoplasmic domains. In rat, VMAT1 is expressed in the adrenal gland whereas VMAT2 is expressed in the brain. In contrast, we found that the bovine adrenal gland expressed both VMAT1 and VMAT2. VMAT2 corresponds to the major transporter of chromaffin granules, as shown by partial peptidic sequences of the purified protein and by a pharmacological analysis of the transport obtained in transfected COS cells (COS cells are monkey kidney cells possessing the ability to replicate SV-40-origin-containing plasmids). We discuss the possibility that VMAT1 may be specifically addressed to large secretory granules vesicles, whereas VMAT2 may also be addressed to small synaptic vesicles; species differences would then reflect the distinct physiological roles of the small synaptic vesicles in the adrenal gland.