Reconstruction of the fetus face from three-dimensional ultrasound using a newborn face statistical shape model.

BACKGROUND AND OBJECTIVE: The fetal face is an essential source of information in the assessment of congenital malformations and neurological anomalies. Disturbance in early stages of development can lead to a wide range of effects, from subtle changes in facial and neurological features to characteristic facial shapes observed in craniofacial syndromes. Three-dimensional ultrasound (3D US) can provide more detailed information about the facial morphology of the fetus than the conventional 2D US, but its use for pre-natal diagnosis is challenging due to imaging noise, fetal movements, limited field-of-view, low soft-tissue contrast, and occlusions. METHODS: In this paper, we propose the use of a novel statistical morphable model of newborn faces, the BabyFM, for fetal face reconstruction from 3D US images. We test the feasibility of using newborn statistics to accurately reconstruct fetal faces by fitting the regularized morphable model to the noisy 3D US images. RESULTS: The results indicate that the reconstructions are quite accurate in the central-face and less reliable in the lateral regions (mean point-to-surface error of 2.35 mm vs 4.86 mm). The algorithm is able to reconstruct the whole facial morphology of babies from US scans while handle adverse conditions (e.g. missing parts, noisy data). CONCLUSIONS: The proposed algorithm has the potential to aid in-utero diagnosis for conditions that involve facial dysmorphology.

Ovarian Hormone-Dependent Effects of Dietary Lipids on APP/PS1 Mouse Brain.

The formation of senile plaques through amyloid-ß peptide (Aß) aggregation is a hallmark of Alzheimer's disease (AD). Irrespective of its actual role in the synaptic alterations and cognitive impairment associated with AD, different therapeutic approaches have been proposed to reduce plaque formation. In rodents, daily intake of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFAs) is required for neural development, and there is experimental and epidemiological evidence that their inclusion in the diet has positive effects on several neurodegenerative diseases. Similarly, estradiol appears to reduce senile plaque formation in primary mouse cell cultures, human cortical neurons and mouse AD models, and it prevents Aß toxicity in neural cell lines. We previously showed that differences in dietary n-6/n-3 LC-PUFAs ratios modify the lipid composition in the cerebral cortex of female mice and the levels of amyloid precursor protein (APP) in the brain. These effects depended in part on the presence of circulating estradiol. Here we explored whether this potentially synergistic action between diet and ovarian hormones may influence the progression of amyloidosis in an AD mouse model. Our results show that a diet with high n-3 LC-PUFA content, especially DHA (22:6n-3), reduces the hippocampal accumulation of Aß1 - 4 0, but not amyloid Aß1 - 42 in female APPswe/PS1 E9A mice, an effect that was counteracted by the loss of the ovaries and that depended on circulating estradiol. In addition, this interaction between dietary lipids and ovarian function also affects the composition of the brain lipidome as well as the expression of certain neuronal signaling and synaptic proteins. These findings provide new insights into how ovarian hormones and dietary composition affect the brain lipidome and amyloid burden. Furthermore, they strongly suggest that when designing dietary or pharmacological strategies to combat human neurodegenerative diseases, hormonal and metabolic status should be specifically taken into consideration as it may affect the therapeutic response.

Ovarian Function Modulates the Effects of Long-Chain Polyunsaturated Fatty Acids on the Mouse Cerebral Cortex.

Different dietary ratios of n-6/n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) may alter brain lipid profile, neural activity, and brain cognitive function. To determine whether ovarian hormones influence the effect of diet on the brain, ovariectomized and sham-operated mice continuously treated with placebo or estradiol were fed for 3 months with diets containing low or high n-6/n-3 LC-PUFA ratios. The fatty acid (FA) profile and expression of key neuronal proteins were analyzed in the cerebral cortex, with intact female mice on standard diet serving as internal controls of brain lipidome composition. Diets containing different concentrations of LC-PUFAs greatly modified total FAs, sphingolipids, and gangliosides in the cerebral cortex. Some of these changes were dependent on ovarian hormones, as they were not detected in ovariectomized animals, and in the case of complex lipids, the effect of ovariectomy was partially or totally reversed by continuous administration of estradiol. However, even though differential dietary LC-PUFA content modified the expression of neuronal proteins such as synapsin and its phosphorylation level, PSD-95, amyloid precursor protein (APP), or glial proteins such as glial fibrillary acidic protein (GFAP), an effect also dependent on the presence of the ovary, chronic estradiol treatment was unable to revert the dietary effects on brain cortex synaptic proteins. These results suggest that, in addition to stable estradiol levels, other ovarian hormones such as progesterone and/or cyclic ovarian secretory activity could play a physiological role in the modulation of dietary LC-PUFAs on the cerebral cortex, which may have clinical implications for post-menopausal women on diets enriched with different proportions of n-3 and n-6 LC-PUFAs.

Expression and localization of the immunophilin FKBP51 in colorectal carcinomas and primary metastases, and alterations following oxaliplatin-based chemotherapy.

The immunophilin FK506-binding protein 5 (FKBP51) is a scaffold protein that serves a pivotal role in the regulation of multiple signaling pathways, integrating external and internal stimuli into distinct signal outputs. In a previous study, we identified several genes that are significantly up- or downregulated in the peripheral white cells (PWCs) of colorectal adenocarcinoma (CRC) patients undergoing oxaliplatin-based chemotherapy. In our screening, FKBP51 gene expression was downregulated following chemotherapy. In order to determine whether this alteration in gene expression observed in PWCs may be detected at the protein level in tumors and metastases following the administration of adjuvant chemotherapy, an immunohistochemical analysis of FKBP51 in CRC and primary metastasis tissues was performed. The present study confirmed the downregulation of FKBP51 gene expression elicited by chemotherapy with folinic acid (leucovorin), fluorouracil and oxaliplatin in metastasized liver tissue that had been resected after the oxaliplatin-based chemotherapy, compared with tissue section samples of CRC from patients (prior to antineoplastic treatment). Furthermore, the results indicated that, in CRC tissue sections, the expression of FKBP51 protein is associated with an immature phenotype of stromal fibroblasts and with the epithelial-to-mesenchymal transition (EMT) phenotype, suggesting a role for this protein in the EMT process in CRC. Finally, the observation that only certain cells of the stroma express FKBP51 protein suggests a potential role for this immunophilin as a stroma cell subtype marker.

Colocalization of Estrogen Receptors with the Fluorescent Tamoxifen Derivative, FLTX1, Analyzed by Confocal Microscopy.

Tamoxifen is a selective estrogen receptor modulator that competitively binds the ligand-binding domain of estrogen receptors. Binding of tamoxifen displaces its cognate ligand, 17ß-estradiol, thereby hampering the activation of estrogen receptors. Cellular labeling of ER is typically carried out using specific antibodies which require permeabilization of cells, incubation with secondary antibodies, and are expensive and time consuming. In this article, we describe the usefulness of FLTX1, a novel fluorescent tamoxifen derivative, which allows the labeling of estrogen receptors in immunocytochemistry and immunohistochemistry studies, both under permeabilized and non-permeabilized conditions. Further, besides labeling canonical estrogen receptors, this novel fluorescent probe is also suitable for the identification of unconventional targets such membrane estrogen receptors as well as other noncanonical targets, some of which are likely responsible for the number of undesired side effects reported during long-term tamoxifen treatments.

On the influence of the culture conditions in bacterial antifouling bioassays and biofilm properties: Shewanella algae, a case study.

BACKGROUND: A variety of conditions (culture media, inocula, incubation temperatures) are employed in antifouling tests with marine bacteria. Shewanella algae was selected as model organism to evaluate the effect of these parameters on: bacterial growth, biofilm formation, the activity of model antifoulants, and the development and nanomechanical properties of the biofilms.The main objectives were: 1) To highlight and quantify the effect of these conditions on relevant parameters for antifouling studies: biofilm morphology, thickness, roughness, surface coverage, elasticity and adhesion forces. 2) To establish and characterise in detail a biofilm model with a relevant marine strain. RESULTS: Both the medium and the temperature significantly influenced the total cell densities and biofilm biomasses in 24-hour cultures. Likewise, the IC50 of three antifouling standards (TBTO, tralopyril and zinc pyrithione) was significantly affected by the medium and the initial cell density. Four media (Marine Broth, MB; 2% NaCl Mueller-Hinton Broth, MH2; Luria Marine Broth, LMB; and Supplemented Artificial Seawater, SASW) were selected to explore their effect on the morphological and nanomechanical properties of 24-h biofilms. Two biofilm growth patterns were observed: a clear trend to vertical development, with varying thickness and surface coverage in MB, LMB and SASW, and a horizontal, relatively thin film in MH2. The Atomic Force Microscopy analysis showed the lowest Young modulii for MB (0.16 ± 0.10 MPa), followed by SASW (0.19 ± 0.09 MPa), LMB (0.22 ± 0.13 MPa) and MH2 (0.34 ± 0.16 MPa). Adhesion forces followed an inverted trend, being higher in MB (1.33 ± 0.38 nN) and lower in MH2 (0.73 ± 0.29 nN). CONCLUSIONS: All the parameters significantly affected the ability of S. algae to grow and form biofilms, as well as the activity of antifouling molecules. A detailed study has been carried out in order to establish a biofilm model for further assays. The morphology and nanomechanics of S. algae biofilms were markedly influenced by the nutritional environments in which they were developed. As strategies for biofilm formation inhibition and biofilm detachment are of particular interest in antifouling research, the present findings also highlight the need for a careful selection of the assay conditions.

Unique SERM-like properties of the novel fluorescent tamoxifen derivative FLTX1.

Tamoxifen is a selective estrogen receptor modulator extensively used on estrogen receptor-positive breast cancer treatment. However, clinical evidences demonstrate the increased incidence of undesirable side effects during chronic therapies, the most life threatening being uterine cancers. Some of these effects are related to tissue-dependent estrogenic actions of tamoxifen, but the exact mechanisms remain poorly understood. We have designed and synthesized a novel fluorescent tamoxifen derivative, FLTX1, and characterized its biological and pharmacological activities. Using confocal microscopy, we demonstrate that FLTX1 colocalizes with estrogen receptor α (ERα). Competition studies showed that FLTX1 binding was totally displaced by unlabeled tamoxifen and partially by estradiol, indicating the existence of non-ER-related triphenylethylene-binding sites. Ligand binding assays showed that FLTX1 exhibits similar affinity for ER than tamoxifen. FLTX1 exhibited antiestrogenic activity comparable to tamoxifen in MCF7 and T47D cells transfected with 3xERE-luciferase reporter. Interestingly, FLTX1 lacked the strong agonistic effect of tamoxifen on ERα-dependent transcriptional activity. Additionally, in vivo assays in mice revealed that unlike tamoxifen, FLTX1 was devoid of estrogenic uterotrophic effects, lacked of hyperplasic and hypertrophic effects, and failed to alter basal proliferating cell nuclear antigen immunoreactivity. In the rat uterine model of estrogenicity/antiestrogenicity, FLTX1 displayed antagonistic activity comparable to tamoxifen at lower doses, and only estrogenic uterotrophy at the highest dose. We conclude that the fluorescent derivative FLTX1 is not only a suitable probe for studies on the molecular pharmacology of tamoxifen, but also a potential therapeutic substitute to tamoxifen, endowed with potent antiestrogenic properties but devoid of uterine estrogenicity.

Correlation between clinical parameters characterising peri-implant and periodontal health: a practice-based research in Spain in a series of patients with implants installed 4-5 years ago.

OBJECTIVES: To explore peri-implant health (and relation with periodontal status) 4-5 years after implant insertion. STUDY DESIGN: A practice-based dental research network multicentre study was performed in 11 Spanish centres. The first patient/month with implant insertion in 2004 was considered. Per patient four teeth (one per quadrant) showing the highest bone loss in the 2004 panoramic X-ray were selected for periodontal status assessment. Bone losses in implants were calculated as the differences between 2004 and 2009 bone levels in radiographs. RESULTS: A total of 117 patients were included. Of the 408 teeth considered, 73 (17.9%) were lost in 2009 (losing risk: >50% for bone losses ≥7 mm). A total of 295 implants were reviewed. Eight of 117 (6.8%) patients had lost implants (13 of 295 implants installed; 4.4%). Implant loss rate (quadrant status) was 1.4% (edentulous), 3.6% (preserved teeth), and 11.1% (lost teeth) (p=0.037). The percentage of implant loss significantly (p<0.001) increased when the medial/distal bone loss was ≥3 mm. The highest (p≤0.001) pocket depths were found in teeth with ≥5 mm and implants with ≥3 mm bone losses, with similar mean values (≥4 mm), associated with higher rates of plaque index and bleeding by probing. CONCLUSIONS: The significant bi-directional relation between plaque and bone loss, and between each of these two parameters/signs and pocket depths or bleeding (both in teeth and implants, and between them) together with the higher percentage of implants lost when the bone loss of the associated teeth was ≥3 mm suggest that the patient's periodontal status is a critical issue in predicting implant health/lesion.

Efectos del tratamiento con Compvit B, ácido orótico o la combinación de ambos sobre la recuperación de la memoria espacial en ratas con lesión de fimbria-fornix / Effects of treatment with Compvit B, orotic acid or their combination on the recovery of spatial memory in rats with fimbria-fornix lesion

Las vitaminoterapias han sido ampliamente utilizadas en neurología para el tratamiento de neuritis o la correción de déficit metabólicos. En Cuba, se produce desde hace algunos años el preparado vitamínico Compvit®, que contiene vitaminas B1, B6 y B12. El ácido orótico, también llamado vitamina B13, es un producto natural que ha mostrado acciones como nootrópico en estudios con animales jóvenes y viejos que acusan deterioro cognitivo. En el presente trabajo se reportan los resultados de un estudio realizado para evaluar las potencialidades terapéuticas del Compvit® y del ácido orótico, empleando la lesión del sistema fimbria-fornix, que afecta severamente las capacidades de aprendizaje de los animales. Los resultados confirman un efecto positivo de cada uno de los tratamientos vitamónicos mejorando las capacidades cognitivas afectadas por la lesión. Aunque ninguno de los productos empleados o su combinación fue capaz de elevar el rendimiento cognitivo al nivel de los animales sanos, todos logran mejorías signficativas en comparación con el placebo. Este trabajo constituye una evidencia adicional en favor del uso terapéutico de compuestos vitamínicos como parte del tratamiento neurorrestaurativo

Vitamin therapies have been widely used in Neurology for the treatment of neuritis or the correction of metabolic deficits. In Cuba, Compvit® (B1, B6 and B12 vitamins) have been produced since several years. Orotic acid, also called vitamin B13 is a natural product showing nootropic actions in studies with young and old cognitively impaired animals. The present paper reports the results of a study conducted to assess the therapeutic potentials of Compvit® and orotic acid, in the recovery of cognitive abilities in fimbria-fornix lesioned animals, a lesion known to severely impair learning abilities. The results confirm positive effects of each vitamin treatment to improve the cognitive abilities affected by lesion. Although none of the products used, neither their combination, was able to raise the cognitive performance to the level of non-lesioned animals, both of them achieve significant improvement compared to placebo. The present paper constitutes additional evidence favoring the therapeutic use of vitamin compounds as part of neurorestorative treatments

Efectos del tratamiento con Compvit B, ácido orótico o la combinación de ambos sobre la recuperación de la memoria espacial en ratas con lesión de fimbria-fornix / Effects of treatment with Compvit B, orotic acid or their combination on the recovery of spatial memory in rats with fimbria-fornix lesion

Las vitaminoterapias han sido ampliamente utilizadas en neurología para el tratamiento de neuritis o la correción de déficit metabólicos. En Cuba, se produce desde hace algunos años el preparado vitamínico Compvit®, que contiene vitaminas B1, B6 y B12. El ácido orótico, también llamado vitamina B13, es un producto natural que ha mostrado acciones como nootrópico en estudios con animales jóvenes y viejos que acusan deterioro cognitivo. En el presente trabajo se reportan los resultados de un estudio realizado para evaluar las potencialidades terapéuticas del Compvit® y del ácido orótico, empleando la lesión del sistema fimbria-fornix, que afecta severamente las capacidades de aprendizaje de los animales. Los resultados confirman un efecto positivo de cada uno de los tratamientos vitamínicos mejorando las capacidades cognitivas afectadas por la lesión. Aunque ninguno de los productos empleados o su combinación fue capaz de elevar el rendimiento cognitivo al nivel de los animales sanos, todos logran mejorías signficativas en comparación con el placebo. Este trabajo constituye una evidencia adicional en favor del uso terapéutico de compuestos vitamínicos como parte del tratamiento neurorrestaurativo(AU)

Vitamin therapies have been widely used in Neurology for the treatment of neuritis or the correction of metabolic deficits. In Cuba, Compvit® (B1, B6 and B12 vitamins) have been produced since several years. Orotic acid, also called vitamin B13 is a natural product showing nootropic actions in studies with young and old cognitively impaired animals. The present paper reports the results of a study conducted to assess the therapeutic potentials of Compvit® and orotic acid, in the recovery of cognitive abilities in fimbria-fornix lesioned animals, a lesion known to severely impair learning abilities. The results confirm positive effects of each vitamin treatment to improve the cognitive abilities affected by lesion. Although none of the products used, neither their combination, was able to raise the cognitive performance to the level of non-lesioned animals, both of them achieve significant improvement compared to placebo. The present paper constitutes additional evidence favoring the therapeutic use of vitamin compounds as part of neurorestorative treatments(AU)

Voltage-dependent anion channel as a resident protein of lipid rafts: post-transductional regulation by estrogens and involvement in neuronal preservation against Alzheimer's disease.

The voltage-dependent anion channel, VDAC, is present at the neuronal membrane, where it appears to participate, among others, in the extrinsic apoptotic pathway and in the modulation of amyloid-beta induced injury, suggesting the involvement of this channel in Alzheimer's disease (AD) neurotoxicity. VDAC is also highly concentrated in neuronal lipid raft microdomains of different mouse and human cognitive areas, where it has been shown associated with estrogen receptor alpha (ERα), as a part of a `signalosome' that may activate some intracellular signal transduction. At the plasma membrane level, estrogens and antiestrogens (tamoxifen) have been demonstrated to exert rapid antagonist effects on the activation of VDAC, through their distinct effects on the channel post-transductional modulation. Therefore, part of the alternative mechanisms of estrogen related to neuroprotection against amyloid-beta may involve VDAC phosphorylation, in order to maintain the channel in an unactivated (closing) state. Interestingly, VDAC-ERα association has been shown to be disrupted in neuronal lipid rafts of AD brains, in correlation with the aberrant lipid composition observed in these microstructures, suggesting that disturbance of protein interactions may be related to variation in the physico-chemical properties of these microdomains.

Documento de consenso sobre la utilización de profilaxis antibiótica en cirugía y procedimientos dentales / Condensus document on the use of antibiotic prophylaxis in dental surgery and procedures

La profilaxis antibiótica en Odontología tiene como objetivo prevenir la aparición de infección a partir de la puerta de entrada que produce la actuación terapéutica, por lo que se encuentra indicada siempre que exista un riesgo importante de infección, ya sea por las características mismas de la operación o por las condiciones locales o generales del paciente. Sin embargo, los ensayos clínicos con antibióticos en patologías dentarias responden poco a los criterios metodológicos requeridos, y además no son lo suficientemente numerosos. Se presentan los resultados de una conferencia de expertos integrada por los Presidentes de Sociedades científicas españolas más representativas que han analizado la bibliografía existente y han aportado sus valiosas experiencias profesionales. Se describen las circunstancias técnicas, se analizan los fundamentos biológicos y farmacológicos y se aplican a las situaciones médicas más representativas. Se concluye quela profilaxis antibiótica en Odontología cuenta con indicaciones bien fundamentadas y precisas, ofreciendo a la comunidad científica internacional un protocolo práctico de actuación (AU)

The goal of antibiotic prophylaxis in Odontology is to prevent the onset of infections through the entranceway provided by the therapeutic action, therefore it is indicated providing there is a considerable risk of infection, either because of the characteristics of the operation itself or the patient’s local or general condition. Nonetheless, clinical trials with antibiotics in dental pathologies have had scant regard for the required methodological criteria and, in addition, are not sufficiently numerous. This text presents the results of an expert conference comprising the Presidents of the most representative Scientific Societies in Spain who have analyzed the existing literature and have drawn on their valuable professional experience. It describes the technical circumstances, analyzes the biological and pharmacological foundations and their application to the most representative medical situations. It is concluded that antibiotic prophylaxis in Odontology has certain well-founded, precise indications and offers the international scientific community a practical protocol for action (AU)

Modulation of Abeta-induced neurotoxicity by estrogen receptor alpha and other associated proteins in lipid rafts.

Some evidences have demonstrated the participation of estrogen receptors (ERs) in rapid, non-genomic actions of estrogen to promote neuroprotection against different toxic agents. However, there is still very little information about the structural nature of these receptors and the manner these proteins may be integrated into the plasma membrane. One of the plausible possibilities is that they may be localized in lipid rafts microstructures where they would be associated with other, still unknown, molecules which may modulate their physiological activities related to cell survival. In this work, we have identified in caveolar fractions of murine septal and hippocampal neurons a membrane-related ER shown to physically interact with, both, a voltage-dependent anion channel and scaffold protein caveolin-1.

Estrogen inhibition of norepinephrine responsiveness is initiated at the plasma membrane of GnRH-producing GT1-7 cells.

The modulatory action of estradiol (E2) on the GnRH network can be exerted indirectly on presynaptic neurons or directly on estrogen receptors (ERs) located within GnRH hypothalamic neurons. Using the GnRH-producing GT1-7 cell line, we have investigated whether E2 is able to modify the response of these cells to norepinephrine (NE) stimulation. A 48-h exposure of GT1-7 cells to 10 nM E2 reduced NE-induced cAMP accumulation. However, 15-min exposure was enough to induce this inhibitory action, provided that a hormone-free period of 48 h after steroid treatment was allowed. Furthermore, this effect was mimicked by E2 coupled to (E-BSA), indicating that it may be exerted through a membrane-mediated mechanism. In addition, competition experiments using E-BSA coupled to fluorescein isothiocyanate (FITC) revealed the presence of cell membrane-binding sites for E2. Binding of E-BSA coupled to FITC was blocked by preincubation of cells with either E2, antiestrogen ICI 182 780, or tamoxifen. Moreover, fluorescence staining of non-permeabilized cells with antibodies against receptors alpha and beta confirmed the presence of both receptor subtypes at the cell membrane. To determine the nature of the ER involved in this response, specific agonists for ERalpha 4,4',4''-(4-propyl-[1H]pyrazole-1,3,5-triyl)tris-phenol (PPT) and ERbeta 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) were used. Since PPT, but not DPN, reproduced the effect of E2, it is suggested that estrogen-induced modulatory action on NE responsiveness was mediated by the ERalpha isoform. Taken together, these results indicate that E2 modulates the adrenergic sensitivity of GT1-7 cells by a mechanism compatible with the activation of membrane-associated ERs.

Documento de consenso sobre la utilización de profilaxis antibiótica en cirugía y procedimientos dentales / Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures

La profilaxis antibiótica en Odontología tiene como objetivo prevenir la aparición de infección a partir de la puerta de entrada que produce la actuación terapéutica, por lo que se encuentra indicada siempre que exista un riesgo importante de infección, ya sea por las características mismas de la operación o por las condiciones locales o generales del paciente. Sin embargo, los ensayos clínicos con antibióticos en patologías dentarias responden poco a los criterios metodológicos requeridos, y además no son lo suficientemente numerosos. Se presentan los resultados de una conferencia de expertos integrada por los Presidentes de Sociedades científicas españolas más representativas que han analizado la bibliografía existente y han aportado sus valiosas experiencias profesionales. Se describen las circunstancias técnicas, se analizan los fundamentos biológicos y farmacológicos y se aplican a las situaciones médicas más representativas. Se concluye que la profilaxis antibiótica en Odontología cuenta con indicaciones bien fundamentadas y precisas, ofreciendo a la comunidad científica internacional un protocolo práctico de actuación

The goal of antibiotic prophylaxis in Odontology is to prevent the onset of infections through the entranceway provided by the therapeutic action, therefore it is indicated providing there is a considerable risk of infection, either because of the characteristics of the operation itself or the patient’s local or general condition. Nonetheless, clinical trials with antibiotics in dental pathologies have had scant regard for the required methodological criteria and, in addition, are not sufficiently numerous. This text presents the results of an expert conference comprising the Presidents of the most representative Scientific Societies in Spain who have analyzed the existing literature and have drawn on their valuable professional experience. It describes the technical circumstances, analyzes the biological and pharmacological foundations and their application to the most representative medical situations. It is concluded that antibiotic prophylaxis in Odontology has certain well-founded, precise indications and offers the international scientific community a practical protocol for action

Consensus document on the use of antibiotic prophylaxis in dental surgery and procedures.

The goal of antibiotic prophylaxis in Odontology is to prevent the onset of infections through the entranceway provided by the therapeutic action, therefore it is indicated providing there is a considerable risk of infection, either because of the characteristics of the operation itself or the patient s local or general condition. Nonetheless, clinical trials with antibiotics in dental pathologies have had scant regard for the required methodological criteria and, in addition, are not sufficiently numerous. This text presents the results of an expert conference comprising the Presidents of the most representative Scientific Societies in Spain who have analyzed the existing literature and have drawn on their valuable professional experience. It describes the technical circumstances, analyzes the biological and pharmacological foundations and their application to the most representative medical situations. It is concluded that antibiotic prophylaxis in Odontology has certain well-founded, precise indications and offers the international scientific community a practical protocol for action.

Rapid modulatory effect of estradiol on acetylcholine-induced Ca2+ signal is mediated through cyclic-GMP cascade in LHRH-releasing GT1-7 cells.

Hypothalamic luteinizing hormone-releasing hormone neurons (LHRH) form the final pathway for the central control of reproduction through the release of LHRH into the pituitary-hypothalamic system. We previously found that LHRH-producing GT1-7 cells respond to acetylcholine (ACh) with an increase in intracellular calcium ([Ca2+]i) through activation of muscarinic receptors. This effect is acutely modulated by 17beta-estradiol in a manner compatible with specific membrane binding sites. Because increasing evidence suggests that second messengers are involved in the rapid action of estradiol, the aim of the present study was to identify the pathway underlying estrogen actions on ACh-induced Ca2+ signals. 8-Bromoguanosine 3',5'-cyclic monophosphate (10 microm) and C-type natriuretic peptide (10 microm) mimicked the effect of estradiol. On the contrary, neither dibutyryl cAMP (100 microm), forskolin (100 nm or 10 microm), or sodium nitroprusside (10 microm) induced any modification of [Ca2+]i in response to ACh. The effect of estradiol on calcium transients was totally blocked by two different cGMP-dependent protein kinase (PKG) inhibitors. In addition, phosphorylation of inositol 1,4,5-triphosphate (IP3) receptor was rapidly induced by estradiol but totally blocked when the cells were pretreated with a PKG inhibitor. We conclude that physiological concentrations of estradiol reduce ACh-induced Ca2+ transients via a mechanism involving a membrane-associated guanylate cyclase, which finally induces a PKG-dependent IP3 receptor phosphorylation that modifies calcium release from the endoplasmic reticulum.

Estradiol modulates acetylcholine-induced Ca2+ signals in LHRH-releasing GT1-7 cells through a membrane binding site.

Estrogen regulation of the female reproductive axis involves the rapid inhibition (< 30 min) of luteinizing hormone-releasing hormone (LHRH) secretion from hypothalamic neurons. This fast time-course suggests interactions with potential plasma membrane binding sites that could result in short-term effects on LHRH neurons. Because LHRH release is calcium dependent, we have studied the acute effects of 17beta-estradiol (E2) and estradiol-peroxidase (E-HRP) on the elevations of intracellular calcium ([Ca2+]i) induced by acetylcholine (ACh) in LHRH-producing GT1-7 cells. Exposure to ACh (1-100 micro m) induced transient increases of [Ca2+]i, whereas pretreatment with E2 or E-HRP (10 nm) for 2 min reduced this response by 50-60%. The effect was specific for E2 as neither 17alpha-estradiol (1 micro m) nor the synthetic antiestrogens ICI182 780 (1 micro m) or tamoxifen (1 micro m) elicited any change on the ACh-induced Ca2+ signal. Both the latency of the effect and the response to the membrane impermeant conjugate suggested a membrane-mediated mechanism. Such membrane binding sites for E2 in GT1-7 cells were demonstrated by visualizing the binding of E-HRP and estradiol-BSA-fluorescein isothiocyanate (E-BSA-FITC) conjugates. Competition studies showed that E-HRP binding was blocked by preincubation with E2, but not with 17alpha-E2, ICI182 780, tamoxifen or progesterone, indicating that the plasma membrane binding site is highly specific for E2 and exhibits a pharmacological profile different from classical estrogen receptors. We conclude that ACh-induced increase in [Ca2+]i in GT1-7 cells is modulated acutely by physiological E2 concentrations in a manner which is compatible with the existence of an estrogen-specific membrane binding site.

An oestrogen membrane receptor participates in estradiol actions for the prevention of amyloid-beta peptide1-40-induced toxicity in septal-derived cholinergic SN56 cells.

Although oestrogen [17 beta-estradiol (E2)]-related neuroprotection has been demonstrated in different models, the involvement of non-classical oestrogen receptors (ERs) remains unexplored. Using the SN56 cholinergic cell line, we present evidence indicating that an ER associated with the plasma membrane participates in oestrogen-dependent inhibition of cell death induced by amyloid-beta peptide (A beta) toxicity. Similarly to E2 alone, a 15-min exposure to estradiol-horseradish peroxidase (E-HRP) significantly reduced A beta-induced cell death. This effect was decreased by the ER antagonist ICI 182,780 as well as by MC-20 antibody directed to a region neighbouring the ligand-binding domain of ER alpha. Using confocal microscopy on unpermeabilized SN56 cells exposed to MC-20 antibody, we identified a protein at the plasma membrane level. Western blot analysis of purified SN56 cell membrane fractions using MC-20 antibody revealed the presence of one band with the same electrophoretic mobility as intracellular ER alpha. Using conjugated forms of the steroid, E-HRP and E2 conjugated to bovine serum albumin-FITC, we demonstrated by confocal microscopy that SN56 cells contain surface binding sites for E2. Binding of both conjugates was blocked by pre-incubation with E2 and decreased by either ICI 182,780 or MC-20 antibody in a concentration-dependent manner. Thus, a membrane-related ER that shares some structural homologies with ER alpha may participate in oestrogen-mediated neuroprotection.