Silvia Novío

Effects of resveratrol on expression of vascular endothelial growth factor in human gingival fibroblasts stimulated by periodontal pathogens

Abstract Objective. To investigate the effects of resveratrol, a naturally occurring polyphenol, on the expression of vascular endothelial growth factor (VEGF) in human gingival fibroblast culture in response to vesicles and outer membrane proteins from periodontopathic bacteria. Material and methods. Human gingival fibroblasts were stimulated with vesicles and outer membrane proteins from Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. In human gingival fibroblast cultures treated with or without resveratrol, VEGF production was evaluated by means of enzyme-linked immunosorbent assay and VEGF mRNA expression by means of reverse transcription polymerase chain reaction analysis. Vascular permeability enhancement was measured by the leakage of intravenously injected dye at the injection site of supernatant from cultures of human gingival fibroblasts stimulated by vesicles and outer membrane proteins. Results. Resveratrol significantly inhibited the increased production of VEGF by human gingival fibroblasts in response to vesicles and outer membrane proteins from periodontopathic bacteria, as shown by the detection of these proteins and their mRNA in vitro. Moreover, resveratrol treatment significantly decreased vascular permeability enhancement induced by supernatant from human gingival fibroblast cultures stimulated by vesicles and outer membrane proteins. Conclusions. Overall, these findings suggest that resveratrol inhibits production of VEGF by stimulated human gingival fibroblasts and can inhibit vascular permeability, suggesting a therapeutic role for it in pathogenic bacteria-induced periodontal inflammation.

Histomorphometric assessment in human cadavers of the peri‐implant bone density in maxillary tuberosity following implant placement using osteotome and conventional techniques

OBJECTIVE To evaluate and compare peri-implant bone condensation in the maxillary tuberosity of human cadavers following the osteotome and standard drilling techniques, and to determine whether peri-implant bone condensation following the osteotome technique is localized or homogeneous. MATERIAL AND METHODS Twenty-four cylinder-threaded titanium implants (12 on each side) were placed in the left (standard technique) and right (osteotome technique with tapered osteotomes for bone condensation, Straumann) maxillary tuberosities of 12 edentulous posterior maxillae of deceased people who had bequeathed their bodies to the University of Santiago de Compostela for medical-scientific research. After surgery, the implants were removed with the surrounding bone, prepared using sawing and grinding technique and examined histomorphometrically. The bone density (bone area/analyzed area) of the entire, periapical (fifth apical) and pericylinder peri-implant areas was calculated, statistically analyzed and compared with the bone density of the host cancellous maxillary bone. RESULTS The bone density of the entire peri-implant area was statistically found to be greater with the osteotome technique (39.38 +/- 9.67) than with conventional drilling technique (31.06 +/- 5.9). This difference was greatest for the periapical zone (53.32 +/- 12.26 vs. 34.18 +/- 6.34). Nonetheless, in the pericylinder area no significant difference was found between the two techniques (32.30 +/- 8.74 vs. 30.34 +/- 7.2). CONCLUSION Peri-implant bone condensation following the osteotome technique is not homogeneously observed through the entire peri-implant area. A greater bone density was achieved only in the fifth apical peri-implant area.

Effects of Brassicaceae Isothiocyanates on Prostate Cancer

Despite the major progress made in the field of cancer biology, cancer is still one of the leading causes of mortality, and prostate cancer (PCa) is one of the most encountered malignancies among men. The effective management of this disease requires developing better anticancer agents with greater efficacy and fewer side effects. Nature is a large source for the development of chemotherapeutic agents, with more than 50% of current anticancer drugs being of natural origin. Isothiocyanates (ITCs) are degradation products from glucosinolates that are present in members of the family Brassicaceae. Although they are known for a variety of therapeutic effects, including antioxidant, immunostimulatory, anti-inflammatory, antiviral and antibacterial properties, nowadays, cell line and animal studies have additionally indicated the chemopreventive action without causing toxic side effects of ITCs. In this way, they can induce cell cycle arrest, activate apoptosis pathways, increase the sensitivity of resistant PCa to available chemodrugs, modulate epigenetic changes and downregulate activated signaling pathways, resulting in the inhibition of cell proliferation, progression and invasion-metastasis. The present review summarizes the chemopreventive role of ITCs with a particular emphasis on specific molecular targets and epigenetic alterations in in vitro and in vivo cancer animal models.

Inhibitory effects of alprazolam on the development of acute experimental autoimmune encephalomyelitis in stressed rats.

The progression and development of multiple sclerosis (MS) has long been hypothesized to be associated with stress. Benzodiazepines have been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on their effects on MS, or experimental autoimmune encephalomyelitis (EAE), a model for human MS. We designed experiments conducted to ascertain whether alprazolam could modify the clinical, histological and neuroendocrine manifestations of acute EAE in Lewis rats exposed to a chronic auditory stressor. EAE was induced by injection of an emulsion of MBP and complete Freunds adjuvant containing Mycobacterium tuberculosis H37Ra. Stress application and treatment with drugs (placebo or alprazolam) were initiated 5days before inoculation and continued daily for the duration of the experiment (days 14 or 34 postinoculation).Our results show significant increases in the severity of neurological signs, the histological lesions of the spinal cord (inflammation), and the corticosterone plasmatic levels in stressed rats compared to those non-stressed ones. Treatment with alprazolam reversed the adverse effects of stress. These findings could have clinical implications in patients suffering from MS treated with benzodiazepines, so besides the psychopharmacological properties of alprazolam against stress, it has beneficial consequences on EAE.

Effects of Psychological Stress and Fluoxetine on Development of Oral Candidiasis in Rats

ABSTRACT Psychological stress has been found to suppress cell-mediated immune responses that are important for limiting the proliferation of Candida albicans. Fluoxetine has been observed to reduce negative consequences of stress on the immune system in experimental and clinical models, but there are no data on its effects on oral candidiasis. We designed experiments to evaluate the effects of fluoxetine on the development of oral candidiasis in Sprague-Dawley rats exposed to a chronic auditory stressor. Animals were submitted to surgical hyposalivation in order to facilitate the establishment and persistence of C. albicans infection. Stress application and treatment with drugs (placebo or fluoxetine) were initiated 7 days before C. albicans inoculation and lasted until the end of the experiments, on day 15 postinoculation. Establishment of C. albicans infection was evaluated on days 2 and 15 after inoculation. Tissue injury was determined by the quantification of the number and type (normal or abnormal) of papillae on the dorsal tongue per microscopic field. A semiquantitative scale was devised to assess the degree of colonization of the epithelium by fungal hyphae. Our results showed that stress exacerbates C. albicans infection in the tongues of rats. Significant increases in Candida counts, the percentage of the tongues surface covered with clinical lesions, the percentage of abnormal papillae, and the colonization of the epithelium by hyphae were found in stressed rats compared to the nonstressed ones. Treatment with fluoxetine significantly reversed these adverse effects of stress. Besides the psychopharmacological properties of fluoxetine against stress, it has consequences for Candida infection.

Target driven preclinical screening for new antimitotic chemotherapy agents.

Currently approved antimitotic therapies used in chemotherapy are microtubule-targeting agents (MTAs). Despite they achieved some level of success, they have limited efficacy as single agents, with issues of slippages and resistance, and cause significant side effects. The advances in the identification of other mitosis-related targets led to the development of new mitotic regulators aimed to perturb mitosis without interfering with microtubule dynamics in non-dividing cells trying to reduce side effects in patients. Some of these compounds like those targeted to entry and mitotic kinases, mitotic kinesins/motor proteins, and multiprotein complexes have been evaluated in vitro and in animal models, and some of them have reached clinical trials. Despite promising preclinical results, in many cases, the efficacy demonstrated by these new antimitotics was not better than current microtubule inhibitors. In this paper we review present and future strategies on the search for new antimitotic compounds based on identification of new protein targets and development of multifunctional inhibitors of mitosis in cancer cells.

Structure-Based Design of New KSP-Eg5 Inhibitors Assisted by a Targeted Multicomponent Reaction

An integrated multidisciplinary approach that combined structure‐based drug design, multicomponent reaction synthetic approaches and functional characterization in enzymatic and cell assays led to the discovery of new kinesin spindle protein (KSP) inhibitors with antiproliferative activity. A focused library of new benzimidazoles obtained by a Ugi+Boc removal/cyclization reaction sequence generated low‐micromolar‐range KSP inhibitors as promising anticancer prototypes. The design and functional studies of the new chemotypes were assessed by computational modeling and molecular biology techniques. The most active compounds—20 (IC50=1.49 μM, EC50=3.63 μM) and 22 (IC50=1.37 μM, EC50=6.90 μM)—were synthesized with high efficiency by taking advantage of the multicomponent reactions.

Urinary biopyrrins: potential biomarker for monitoring of the response to treatment with anxiolytics.

During periods of psychological stress, excess amounts of free radicals are produced. Bilirubin oxidative metabolites (biopyrrins; BOM) are generated from bilirubin as a result of its scavenging action against free radicals. We investigated whether the urinary excretion of biopyrrins is altered by anxiolytics. In the present study, mice were immobilized for a period of 6 hr. Alprazolam (0.1–1 mg/kg of body‐weight) was administered 30 min. before subjecting the animals to acute stress. The BOM concentrations in urine and the corticosterone levels in serum were measured by ELISA with an anti‐bilirubin antibody and EIA, respectively. We observed an increase in urinary biopyrrins in stressed mice in comparison with non‐stressed mice and a decrease after the treatment of stressed animals with alprazolam. A correlation between urinary BOM and serum corticosterone levels was found. Urinary levels of biopyrrins might be used to assess the response to anxiolytics prescribed during acute stress periods.

Infant Feeding Attitudes and Practices of Spanish Low-Risk Expectant Women Using the IIFAS (Iowa Infant Feeding Attitude Scale)

The Iowa Infant Feeding Attitude Scale (IIFAS) has been shown to have good psychometric properties for English-speaking populations, but it has not been validated among low-risk pregnant women in Spain. The aim of this study was to assess the reliability and validity of the translated version of the IIFAS in order to examine infant feeding attitudes in Spanish women with an uncomplicated pregnancy. Low-risk expectant women (n = 297) were recruited from eight primary public health care centres in Galicia (Spain). Questionnaires including both socio-demographic and breastfeeding characteristics and items about infant feeding were administered during the third trimester. Participants were contacted by telephone during the postpartum period to obtain information regarding their infant feeding status. Prediction validity and internal consistency were assessed. The translated IIFAS (69.76 ± 7.75), which had good psychometric properties (Cronbach’s alpha = 0.785; area under the curve (AUC) of the receiver operating characteristic (ROC) curve = 0.841, CI95% = 0.735–0.948), showed more positive attitudes towards breastfeeding than towards formula feeding, especially among mothers who intended to exclusively breastfeed. This scale was also useful for inferring the intent to breastfeed and duration of breastfeeding. This study provides evidence that the IIFAS is a reliable and valid tool for assessing infant feeding attitudes in Spanish women with an uncomplicated pregnancy.

Adenosine Signaling Pathways as Potential Therapeutic Targets in Prostate Cancer Disease

Prostate cancer (PCa) is the second main cause of death by cancer in men. Although most PCa are initially responsive to treatment, they are difficult to manage clinically after their progression to a hormone independent state. During the last years different approaches to treating PCa have been assessed based mainly on specific targets such as adenosine receptors (AR), since it is known that their activation can modulate tumour growth. This chapter is intended to: (a) review evidences on expression levels of AR subtypes in PCa cells; (b) highlight the molecular mechanisms underlying the regulation of AR functioning during growth, apoptosis, invasion, migration, and/or metastasis of PCa cells; (c) analyse the potential application of AR ligands in oncologic treatment of PCa. The critical analysis of herein highlighted evidences shows that especially A3 AR agonists and to a lesser extent A2b AR antagonists, could be useful clinically in controlling the proliferation and metastasis of hormone sensitive and refractory PCa.