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BACKGROUND: This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC). METHODS: Clinical studies on recurrent OSCC treated with PDT alone were included. Combined treatment strategies were excluded. The search was performed on Medline/Pubmed, Cochrane Library, Embase, Web of Science and ClinicalTrials.gov, manual search, and grey literature. RESULTS: The eleven included studies were observational. The risk of bias and methodological quality were evaluated using the Newcastle-Ottawa Quality Assessment Scale. The studies reported the use of hematoporphyrin derivative, Photofrinâ, Foscanâ and 5-aminolevulinic acid. Data on treatment response and survival was collected. Secondarily, postoperative courses and patient's quality of life/acceptance were reported whenever available. Photofrinâ and Foscanâ were the most used photosensitisers, with more complete responses. Lesions responding less favourably were on posterior regions or deep-seated in the tissue. CONCLUSIONS: Although treatment response differs between treatment protocols, PDT stands as a viable treatment option to be considered, as it can achieve therapeutic results and disease-free, long-lasting periods. Partial treatment responses may be of interest when achieving eligibility for other treatment strategies. Despite this study's limitations, which considered four photosensitisers, Photofrinâ was the most used but more recent photosensitisers like Foscanâ have greater chemical stability, tissue penetration, and may be more efficacious on recurrent OSCC.
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Ácido Aminolevulínico , Carcinoma de Células Escamosas , Neoplasias de la Boca , Recurrencia Local de Neoplasia , Fotoquimioterapia , Fármacos Fotosensibilizantes , Fotoquimioterapia/métodos , Humanos , Neoplasias de la Boca/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Ácido Aminolevulínico/uso terapéutico , Éter de Dihematoporfirina/uso terapéutico , Derivado de la Hematoporfirina/uso terapéutico , Derivado de la Hematoporfirina/farmacología , Mesoporfirinas/uso terapéuticoAsunto(s)
Polen , Incendios Forestales , Polen/inmunología , Región Mediterránea , Humanos , Alérgenos/inmunologíaRESUMEN
This study aimed to evaluate the microbiome, resistome and virulome of two types of Portuguese cheese using high throughput sequencing (HTS). Culture-dependent chromogenic methods were also used for certain groups/microorganisms. Eight samples of raw ewe's milk cheese were obtained from four producers: two producers with cheeses with a PDO (Protected Designation of Origin) label and the other two producers with cheeses without a PDO label. Agar-based culture methods were used to quantify total mesophiles, Enterobacteriaceae, Escherichia coli, Staphylococcus, Enterococcus and lactic acid bacteria. The presence of Listeria monocytogenes and Salmonella was also investigated. The selected isolates were identified by 16S rRNA gene sequencing and evaluated to determine antibiotic resistance and the presence of virulence genes. The eight cheese samples analyzed broadly complied with EC regulations in terms of the microbiological safety criteria. The HTS results demonstrated that Leuconostoc mesenteroides, Lactococcus lactis, Lactobacillus plantarum, Lacticaseibacillus rhamnosus, Enterococcus durans and Lactobacillus coryniformis were the most prevalent bacterial species in cheeses. The composition of the bacterial community varied, not only between PDO and non-PDO cheeses, but also between producers, particularly between the two non-PDO cheeses. Alpha-diversity analyses showed that PDO cheeses had greater bacterial diversity than non-PDO cheeses, demonstrating that the diversity of spontaneously fermented foods is significantly higher in cheeses produced without the addition of food preservatives and dairy ferments. Despite complying with microbiological regulations, both PDO and non-PDO cheeses harbored potential virulence genes as well as antibiotic resistance genes. However, PDO cheeses exhibited fewer of these virulence and antibiotic resistance genes compared to non-PDO cheeses. Therefore, the combination of conventional microbiological methods and the metagenomic approach could contribute to improving the attribution of the PDO label to this type of cheese.
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Queso , Microbiología de Alimentos , Microbiota , Queso/microbiología , Microbiota/genética , Portugal , Animales , Metagenómica , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/clasificación , ARN Ribosómico 16S/genética , Farmacorresistencia Bacteriana/genética , Ovinos , Secuenciación de Nucleótidos de Alto Rendimiento , Leche/microbiología , Enterococcus/genética , Enterococcus/aislamiento & purificaciónRESUMEN
Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, and better characterizations of their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape of 1,298 meningiomas. The clinical and genomic metadata effectively correlated with landscape regions, which led to the identification of meningioma subtypes with specific biological signatures. The time to recurrence also correlated with the map location. Further, we developed an algorithm that maps new patients onto this landscape, where the nearest neighbors predict outcome. This study highlights the utility of combining bulk transcriptomic datasets to visualize the complexity of tumor populations. Further, we provide an interactive tool for understanding the disease and predicting patient outcomes. This resource is accessible via the online tool Oncoscape, where the scientific community can explore the meningioma landscape.
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Neoplasias Meníngeas , Meningioma , Transcriptoma , Meningioma/genética , Meningioma/patología , Humanos , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patología , Masculino , Femenino , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , Algoritmos , Perfilación de la Expresión Génica/métodosRESUMEN
Objectives: The objective of this umbrella review is to evaluate the efficacy and adverse effects of different teeth whitening techniques in-office (IO) and at-home (AH), regarding chromatic changes and teeth sensitivity. Materials and methods: The search was carried out from several databases. The included studies were all systematic reviews with or without meta-analysis of RCT or quasi-RCT. The participants were patients that underwent external dental bleaching in permanent vital teeth. The interventions were in-office (IO) bleaching techniques and at-home (AT) bleaching techniques with different bleaching agents and concentrations. Results: The search resulted in a total of 257 articles, and 28 SR were included in the qualitative analysis and nine in the quantitative analysis. There is no difference between in-office and at-home techniques in terms of color change (p = 0.95) and post-treatment sensitivity (p = 0.85). There is similarity risk and intensity of teeth sensitivity between AH and IO bleaching. IO bleaching with light-activated systems with low concentrations of bleaching agent showed similar results to IO bleaching techniques with high concentrated bleaching gels. With the application of the criteria of the AMSTAR 2 tool, the reviews were considered critically low to high. Conclusions: There are no significant differences in terms of color change between the different bleaching techniques compared. Teeth sensitivity is always present regardless of the technique used. The use of light activation systems did not increase the intensity and risk of post-operative sensitivity.
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Reversine is a purine derivative that has been investigated with regard to its biological effects, such as its anticancer properties and, mostly, its ability to induce the dedifferentiation of adult cells, increasing their plasticity. The obtained dedifferentiated cells have a high potential for use in regenerative procedures, such as regenerative dentistry (RD). Instead of replacing the lost or damaged oral tissues with synthetic materials, RD uses stem cells combined with matrices and an appropriate microenvironment to achieve tissue regeneration. However, the currently available stem cell sources present limitations, thus restricting the potential of RD. Based on this problem, new sources of stem cells are fundamental. This work aims to characterize mouse gingival fibroblasts (GFs) after dedifferentiation with reversine. Different administration protocols were tested, and the cells obtained were evaluated regarding their cell metabolism, protein and DNA contents, cell cycle changes, morphology, cell death, genotoxicity, and acquisition of stem cell characteristics. Additionally, their teratoma potential was evaluated after in vivo transplantation. Reversine caused toxicity at higher concentrations, with decreased cell metabolic activity and protein content. The cells obtained displayed polyploidy, a cycle arrest in the G2/M phase, and showed an enlarged size. Additionally, apoptosis and genotoxicity were found at higher reversine concentrations. A subpopulation of the GFs possessed stem properties, as supported by the increased expression of CD90, CD105, and TERT, the existence of a CD106+ population, and their trilineage differentiation capacity. The dedifferentiated cells did not induce teratoma formation. The extensive characterization performed shows that significant functional, morphological, and genetic changes occur during the dedifferentiation process. The dedifferentiated cells have some stem-like characteristics, which are of interest for RD.
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OBJECTIVES: Treatments that prevent sepsis complications are needed. Circulating lipid and protein assemblies-lipoproteins play critical roles in clearing pathogens from the bloodstream. We investigated whether early inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) may accelerate bloodstream clearance of immunogenic bacterial lipids and improve sepsis outcomes. DESIGN: Genetic and clinical epidemiology, and experimental models. SETTING: Human genetics cohorts, secondary analysis of a phase 3 randomized clinical trial enrolling patients with cardiovascular disease (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402), and experimental murine models of sepsis. PATIENTS OR SUBJECTS: Nine human cohorts with sepsis (total n = 12,514) were assessed for an association between sepsis mortality and PCSK9 loss-of-function (LOF) variants. Incident or fatal sepsis rates were evaluated among 18,884 participants in a post hoc analysis of ODYSSEY OUTCOMES. C57BI/6J mice were used in Pseudomonas aeruginosa and Staphylococcus aureus bacteremia sepsis models, and in lipopolysaccharide-induced animal models. INTERVENTIONS: Observational human cohort studies used genetic PCSK9 LOF variants as instrumental variables. ODYSSEY OUTCOMES participants were randomized to alirocumab or placebo. Mice were administered alirocumab, a PCSK9 inhibitor, at 5 mg/kg or 25 mg/kg subcutaneously, or isotype-matched control, 48 hours prior to the induction of bacterial sepsis. Mice did not receive other treatments for sepsis. MEASUREMENTS AND MAIN RESULTS: Across human cohort studies, the effect estimate for 28-day mortality after sepsis diagnosis associated with genetic PCSK9 LOF was odds ratio = 0.86 (95% CI, 0.67-1.10; p = 0.24). A significant association was present in antibiotic-treated patients. In ODYSSEY OUTCOMES, sepsis frequency and mortality were infrequent and did not significantly differ by group, although both were numerically lower with alirocumab vs. placebo (relative risk of death from sepsis for alirocumab vs. placebo, 0.62; 95% CI, 0.32-1.20; p = 0.15). Mice treated with alirocumab had lower endotoxin levels and improved survival. CONCLUSIONS: PCSK9 inhibition may improve clinical outcomes in sepsis in preventive, pretreatment settings.
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Wine quality maybe understood under two perspectives: (a) commercial quality, intended to satisfy overall consumers, and (b) fine wine quality, aimed at achieving a product with aesthetic value. The current food sensory techniques (e.g. Descriptive Analysis) have been successfully applied to develop wines accepted worldwide and characterized by pleasant sweetish flavours and smooth mouthfeel. On the contrary, these techniques are not suited to characterize fine wines given their dependence on sensory properties with aesthetic value. The conventional tasting approaches follow the sequence of vision, smell (orthonasal), taste and mouthfeel, ending by an overall evaluation. The sensory descriptors tend to be analytic (e.g. different aromas and tastes) or synthetic (e.g. body, structure) and the quality judgement is left for the final step. Some synthetic attributes may have an aesthetic significance (e.g. complexity, harmony, depth) and are more valued when the analytic or synthetic descriptors are highly praised (e.g. oakiness, silkiness, body, minerality). Consequently, these highly praised attributes are regarded as surrogates of fine wine quality. However, commercial wines are frequently judged of higher quality than fine wines irrespective of the taster expertise. We argue that the conventional sensory analysis sequence makes the overall evaluation secondary in relation to the previous analytical steps blurring the assessment of wine's aesthetic properties. Probably due to top-down processing, the initial evaluation of colour or flavours governs the final overall quality evaluation that may be inconsistently rated. Then, to promote the recognition of fine wines, tasting should begin by first acknowledging the aesthetic properties and only proceed to the analytical steps if necessary. A tasting method is proposed to consumer educational programs where emotional responses are used to explain the differences between commercial and fine wine styles. Furthermore, cultural aspects should be included to appreciate the wholeness of wine. Hopefully, this holistic perspective would turn wine appreciation more approachable and facilitate the recognition of fine wines among consumers, increasing their appreciation and enjoyment.
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Vino , Placer , Emociones , Aromatizantes , AlimentosRESUMEN
This study aimed to investigate enterococci recovered from eight Portuguese cheeses made with raw ewe's milk, regarding antibiotic resistance, virulence genes, minimum inhibitory concentration (MIC) of benzalkonium chloride (BAC), biofilm formation capacity, and biofilm eradication (MBEC) by BAC. Antimicrobial resistance against seven antibiotics of five groups was evaluated using the disk diffusion method. The presence of the genes that encode resistance to the antibiotics penicillin (blaZ), erythromycin (ermA, ermB, and ermC), vancomycin (vanA and vanB), aminoglycoside (aac(6')-Ie-aph(2â³)-Ia), and ß-lactam (pbp5) and the genes that encode virulence factors, frsB, cylA, gelE, esp, and agg, were investigated via multiplex PCR. The susceptibility of planktonic cells to BAC was evaluated by the MIC and MBC values of the isolates, using the broth microdilution method. To assess the biofilm-forming ability and resistance of biofilms to BAC, biofilms were produced on stainless steel coupons, followed by exposure to BAC. The results showed a high resistance to the antibiotics vancomycin (87.5%), erythromycin (75%), tetracycline (50%), and penicillin (37.5%). Multidrug resistance was observed in 68.8% of the isolates. Genes encoding the virulence factors FrsB (frsB) and gelatinase E (gelE) were detected in all isolates. The esp and cylA genes were found in 56.3% and 37.5% of the isolates, respectively. All isolates exhibited a biofilm-forming ability, regardless of incubation time and temperature tested. However, after 72 h at 37 °C, E. faecium and E. faecalis biofilms showed significant differences (p ≤ 0.05). Although most isolates (62.5%) were susceptible to BAC (MIC ≤ 10 mg/L), biofilms of the same isolates were, generally, resistant to the higher concentration of BAC (80 mg/mL) tested. This study using Enterococcus isolates from a ready-to-eat food, such as cheese, reveals the high percentages of vancomycin resistance and multidrug resistance, associated with the presence of virulence genes, in isolates also capable of producing biofilms resistant to BAC, an important active ingredient of many disinfectants. These results emphasize the need for effective control measures to ensure the safety and quality of dairy products.
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The sale of ready-to-eat (RTE) street food represents an important source of income in many developing countries. However, these foods are frequently implicated in outbreaks of gastrointestinal diseases. Street food vendors face several constraints that hamper improvement in the microbiological quality of their products. The aim of this review was to update knowledge about the main causes of foodborne illnesses in developing countries, including the growing concern with the microbial transmission of antibiotic resistance. Following PRISMA guidelines, this systematic review was conducted on original articles published from January 2010 to July 2023. The search was carried out using Scopus, PubMed, Web of Science, Food Science and Technology Abstracts (FSTA), the International Information System for Agricultural Sciences and Technology (AGRIS), as well as isolated searches of relevant articles from Google Scholar. The initial search identified 915 articles, 50 of which were included in this systematic review. The results indicate that, in the majority of the 15 countries examined, women constitute the predominant segment of street food vendors, representing more than 55% of the total number of these vendors. In 11 countries, street food vendors under the age of 18 were identified. Most vendors had a low level of education and, consequently, were unaware of good hygiene practices when handling food. The combination of factors such as poor hygiene practices on the part of food handlers and the lack of facilities, namely, the absence of available potable water, were frequently listed as the main causes of food contamination. Enterobacteriaceae such as Escherichia coli (61.9%), Salmonella (30.1%), and Shigella spp. (9.5%), as well as Staphylococcus aureus (30.1%) and Listeria monocytogenes (14.3%), were the most common pathogens found in RTE street foods. In 22 studies from 13 developing countries, 59% (13/22) reported high multidrug resistance in Enterobacteriaceae (40% to 86.4% in E. coli, 16.7 to 70% in Salmonella, and 31 to 76.4% in S. aureus). To address the challenges faced by street vendors and improve their economic activities, it is necessary for government entities, consumers, and vendors to work together collaboratively.
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Single-cell transcriptomic studies have identified a conserved set of neocortical cell types from small postmortem cohorts. We extended these efforts by assessing cell type variation across 75 adult individuals undergoing epilepsy and tumor surgeries. Nearly all nuclei map to one of 125 robust cell types identified in the middle temporal gyrus. However, we found interindividual variance in abundances and gene expression signatures, particularly in deep-layer glutamatergic neurons and microglia. A minority of donor variance is explainable by age, sex, ancestry, disease state, and cell state. Genomic variation was associated with expression of 150 to 250 genes for most cell types. This characterization of cellular variation provides a baseline for cell typing in health and disease.
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Lóbulo Temporal , Transcriptoma , Adulto , Humanos , Epilepsia/metabolismo , Perfilación de la Expresión Génica , Neuronas/metabolismo , Lóbulo Temporal/citología , Lóbulo Temporal/metabolismo , Enfermedades del Sistema Nervioso/genética , Trastornos Mentales/genéticaRESUMEN
Physical activity levels are typically undesirably low in chronic kidney disease patients, especially in those undergoing haemodialysis, and particularly on dialysis days. Intradialytic exercise programmes could be a solution to this issue and have been reported to be safe and relatively easily implemented in dialysis clinics. Nevertheless, such implementation has been failing in part due to barriers such as the lack of funding, qualified personnel, equipment, and patient motivation. Intradialytic aerobic exercise has been the most used type of intervention in dialysis clinics. However, resistance exercise may be superior in eliciting potential benefits on indicators of muscle strength and mass. Yet, few intradialytic exercise programmes have focused on this type of intervention, and the ones which have report inconsistent benefits, diverging on prescribed exercise intensity, absent or subjective load progression, equipment availability, or exercise supervision. Commonly, intradialytic resistance exercise interventions use free weights, ankle cuffs, or elastic bands which hinder load progression and exercise intensity monitoring. Here, we introduce a recently developed intradialytic resistance exercise device and propose an accompanying innovative resistance exercise training protocol which aims to improve the quality of resistance exercise interventions within dialysis treatment sessions.
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Fallo Renal Crónico , Insuficiencia Renal Crónica , Entrenamiento de Fuerza , Humanos , Entrenamiento de Fuerza/métodos , Diálisis Renal , Fallo Renal Crónico/terapia , Ejercicio Físico/fisiología , Calidad de VidaRESUMEN
Thirty controls (C) and 30 IBH-affected (T) Lusitano horses were evaluated. T horses were included based on anamnesis and physical examination, supported by questionnaires. All horses were submitted to skin tests, Intrademal (IDT) and Skin Prick Tests (SPT), on the neck with 14 specific allergens, 13 recombinant proteins (r-proteins) from Culicoides nubeculosus (Cul n) and Culicoides obsoletus (Cul o) salivary glands and Culicoides nubeculosus Whole Body Extract (Cul n WBE). Addicionally, a cluster of six T and six C horses were also tested with Cul n 3 and Cul n 4 produced in insect cells and barley, as well as E. coli produced Cul o 3 and Cul o WBE. Allergen concentrations were 10 µg/mL for IDT and 100 µg/mL for SPT, and wheal diameters assessed at 20 min, 6 and 48 h. IDTs were considered positive when wheal diameter was ≥50% of the histamine wheal and SPT's ≥ 0.9 cm. In vitro tests, allergen-specific serum IgE and sulfidoleukotriene (sLT) release assay were also carried out. Results showed that Cul n WBE, Cul n 7, 8, 9, Cul o1P and Cul o 2P were the best performing allergens for SPTs (p ≤ 0.0001) for the 1st allergen panel and Cul o WBE, Cul n 3 Bar and Cul n 4 Bac (p ≤ 0.05) for the 2nd, presenting a higher discriminatory diagnostic potential than IDTs, at a concentration of 100 µg/mL, with readings assessed at 20 min. Regarding in vitro tests overall, the sLT release assay performed best.
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BACKGROUND: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of CKD-MBD and bone fragility fractures in the COSMOS project. METHODS: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 hemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and PTH (exposure), was assessed using Standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables. RESULTS: During a median follow-up of 24 months 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months respectively. Baseline serum phosphate > 6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models (HR: 1.53[95%CI: 1.10-2.13] and HR: 1.44[95%CI: 1.02-2.05]. The significant association persisted after competitive risk analysis (subHR: 1.42[95%CI: 1.02-1.98]) but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH > 800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis. CONCLUSIONS: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in hemodialysis patients.
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In this study, we leveraged the combined evidence of rare coding variants and common alleles to identify therapeutic targets for osteoporosis. We undertook a large-scale multiancestry exome-wide association study for estimated bone mineral density, which showed that the burden of rare coding alleles in 19 genes was associated with estimated bone mineral density (P < 3.6 × 10-7). These genes were highly enriched for a set of known causal genes for osteoporosis (65-fold; P = 2.5 × 10-5). Exome-wide significant genes had 96-fold increased odds of being the top ranked effector gene at a given GWAS locus (P = 1.8 × 10-10). By integrating proteomics Mendelian randomization evidence, we prioritized CD109 (cluster of differentiation 109) as a gene for which heterozygous loss of function is associated with higher bone density. CRISPR-Cas9 editing of CD109 in SaOS-2 osteoblast-like cell lines showed that partial CD109 knockdown led to increased mineralization. This study demonstrates that the convergence of common and rare variants, proteomics and CRISPR can highlight new bone biology to guide therapeutic development.
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Predisposición Genética a la Enfermedad , Osteoporosis , Humanos , Secuenciación del Exoma , Osteoporosis/genética , Densidad Ósea/genética , Alelos , Factores de Transcripción/genética , Estudio de Asociación del Genoma CompletoRESUMEN
BACKGROUND: Microorganisms and their by-products are responsible for establishing pulpal and periapical diseases. Healing is compromised in patients under bisphosphonate therapy, and the presence of periapical infections can potentially lead to the development of medication-related osteonecrosis of the jaw (MRONJ). This work aimed to evaluate if bisphosphonate therapy is a risk factor for MRONJ development in the presence of periapical lesions. METHODS: Two groups of 10 female Wistar rats were used. The experimental group received zoledronate (0.1 mg/kg) intraperitoneally, and the control received a saline solution, three times a week for three weeks. One week after the last injection, apical periodontitis was induced through pulpal exposure in the mandibular first molars. Twenty-one days later, the animals were intravenously injected with 99mTc-HMDP, and the radioactivity uptake by mandibular specimens was counted. In addition, sample radiographs and a histological examination were performed. RESULTS: The bone loss was higher in the control group when compared to the experimental group (p = 0.027). 99mTc-HMDP uptake in the control was reduced compared with the experimental group, although without statistical significance. CONCLUSIONS: In the presence of zoledronate therapy, apical periodontitis does not increase the risk of MRONJ development, and periapical lesions have lower bone resorption when compared to the control group.