Monoclonal Antibody chP3R99 Reduces Subendothelial Retention of Atherogenic Lipoproteins in Insulin-Resistant Rats: Acute Treatment Versus Long-Term Protection as an Idiotypic Vaccine for Atherosclerosis.

BACKGROUND: Atherosclerosis is triggered by the retention of apolipoprotein B-containing lipoproteins by proteoglycans. In addition to low-density lipoprotein, remnant lipoproteins have emerged as pivotal contributors to this pathology, particularly in the context of insulin resistance and diabetes. We have previously reported antiatherogenic properties of a monoclonal antibody (chP3R99) that recognizes sulfated glycosaminoglycans on arterial proteoglycans. METHODS AND RESULTS: Solid-phase assays demonstrated that chP3R99 effectively blocked >50% lipoprotein binding to chondroitin sulfate and vascular extracellular matrix in vitro. The preperfusion of chP3R99 (competitive effect) resulted in specific antibody-arterial accumulation and reduced fluorescent lipoprotein retention by ~60% in insulin resistant JCR:LA-cp rats. This competitive reduction was dose dependent (25-250 µg/mL), effectively decreasing deposition of cholesterol associated with lipoproteins. In a 5-week vaccination study in insulin resistant rats with (200 µg subcutaneously, once a week), chP3R99 reduced arterial lipoprotein retention, and was associated with the production of antichondroitin sulfate antibodies (Ab3) able to accumulate in the arteries (dot-blot). Neither the intravenous inoculation of chP3R99 (4.5 mg/kg), nor the immunization with this antibody displayed adverse effects on lipid or glucose metabolism, insulin resistance, liver function, blood cell indices, or inflammation pathways in JCR:LA-cp rats. CONCLUSIONS: Both acute (passive) and long-term administration (idiotypic cascade) of chP3R99 antibody reduced low-density lipoprotein and remnant lipoprotein interaction with proteoglycans in an insulin-resistant setting. These findings support the innovative approach of targeting proatherogenic lipoprotein retention by chP3R99 as a passive therapy or as an idiotypic vaccine for atherosclerosis.

Experimental apical periodontitis alters salivary biochemical composition and induces local redox state disturbances in the salivary glands of male rats.

OBJECTIVES: The objective was to evaluate the effects of experimental apical periodontitis on the inflammatory, functional, biochemical, and redox parameters of the parotid and submandibular glands in rats. MATERIALS AND METHODS: Twenty 12-week-old male Wistar rats were randomly divided into two groups (n = 10): a control group and apical periodontitis group. After 28 days, the saliva was collected for salivary flow rate and biochemistry composition. Both glands were sampled for quantification of the tumor necrosis factor-alpha (TNF-α) and biochemical analyses of redox state. RESULTS: TNF-α concentrations were higher in both salivary glands adjacent to the periapical lesions in animals with apical periodontitis and also compared to the control group. The apical periodontitis group increased the salivary amylase, chloride, potassium, calcium, and phosphate. The total oxidant capacity increased in the parotid gland adjacent to the periapical lesions in the same rat and compared to the control group. Conversely, the total antioxidant capacity of the parotid glands on both sides in the apical periodontitis group was lower than that in the control group. Furthermore, glutathione peroxidase activity increased in the submandibular gland adjacent to the apical periodontitis group compared to the control group. CONCLUSIONS: Experimental apical periodontitis alters salivary biochemical composition, in addition to increasing inflammatory marker and inducing local disturbances in the redox state in the parotid and submandibular glands of male rats. CLINICAL RELEVANCE: Apical periodontitis could exacerbate the decline in oral health by triggering dysfunction in the salivary glands.

MicroRNA-138: an emerging regulator of skeletal development, homeostasis, and disease.

Noncoding microRNAs are powerful epigenetic regulators of cellular processes by their ability to target and suppress expression of numerous protein-coding mRNAs. This multitargeting function is a unique and complex feature of microRNAs. It is now well-described that microRNAs play important roles in regulating the development and homeostasis of many cell/tissue types, including those that make up the skeletal system. In this review, we focus on microRNA-138 (miR-138) and its effects on regulating bone and cartilage cell differentiation and function. In addition to its reported role as a tumor suppressor, miR-138 appears to function as an inhibitor of osteoblast differentiation. This review provides additional information on studies that have attempted to alter miR-138 expression in vivo as a means to dampen ectopic calcification or alter bone mass. However, a review of the published literature on miR-138 in cartilage reveals a number of contradictory and inconclusive findings with respect to regulating chondrogenesis and chondrocyte catabolism. This highlights the need for more research in understanding the role of miR-138 in cartilage biology and disease. Interestingly, a number of studies in other systems have reported miR-138-mediated effects in dampening inflammation and pain responses. Future studies will reveal if a multifunctional role of miR-138 involving suppression of ectopic bone, inflammation, and pain will be beneficial in skeletal conditions such as osteoarthritis and heterotopic ossification.

Cytotoxicity of cleaning agents for ocular prostheses.

BACKGROUND: Polymethylmethacrylate (PMMA) is the most used material for the manufacturing of eye prostheses. OBJECTIVES: To investigate the cytotoxicity of different cleaning agents for ocular prostheses on human conjunctival cells. MATERIAL AND METHODS: Six groups of specimens were created (saline, soap, 4% chlorhexidine, hydrogen peroxide, 1% triclosan, and citronella oil). Three specimens were made for each disinfectant at each disinfection period (1, 7, 15, 30, 60, and 90 days), totaling 108 specimens. Thus, the specimens were disinfected, with different disinfectants, for different periods of time. After each disinfection process, the specimens were washed with sterile distilled water. A human conjunctival cell line was grown on the acrylic resin specimens and then cytotoxicity tests (MTT and Neutral Red (NR)) were performed. A negative control (untreated cell cultures) and positive control (Tween 20) were created. Two-way analysis of variance (ANOVA) and Bonferroni test were performed (p < 0.05). RESULTS: For the MTT and NR tests, when there was a significant difference between the disinfectant and negative control, the disinfectant generated a significant reduction in cell proliferation most of the time. CONCLUSIONS: All reductions in cell proliferation caused by the disinfectants were clinically acceptable. All disinfectants tested in this study were found to be non-cytotoxic to human conjunctival cells.

Analysis of salivary flow rate, biochemical composition, and redox status in orchiectomized spontaneously hypertensive rats.

OBJECTIVE: This study aimed to analyze the salivary flow rate, biochemical composition, and redox status in orchiectomized spontaneously hypertensive rats (SHR) compared to normotensive Wistar rats. DESIGN: Thirty-two young adult male SHR and Wistar (3-months-old) rats were randomly distributed into four groups; either castrated bilaterally (ORX) or underwent fictitious surgery (SHAM) as Wistar-SHAM, Wistar-ORX, SHR-SHAM, and SHR-ORX. Two months beyond castration, pilocarpine-induced salivary secretion was collected from 5-month-old rats to analyze salivary flow rate, pH, buffer capacity, total protein, amylase, calcium, phosphate, sodium, potassium, chloride, thiobarbituric acid reactive substances (TBARs), carbonyl protein, nitrite, and total antioxidant capacity. RESULTS: The salivary flow rate was higher in the Wistar-ORX compared to the Wistar-SHAM group, while remaining similar between the SHR-SHAM and SHR-ORX groups. ORX did not affect pH and salivary buffer capacity in both strains. However, salivary total protein and amylase were significantly reduced in the Wistar-ORX and SHR-ORX compared to the respective SHAM groups. In both ORX groups, salivary total antioxidant capacity and carbonylated protein were increased, while lipid oxidative damage (TBARs) and nitrite concentration were higher only in the Wistar-ORX than in the Wistar-SHAM group. In the Wistar-ORX and SHR-ORX, the salivary calcium, phosphate, and chloride were increased while no change was detected in the SHAM groups. Only salivary buffering capacity, calcium, and chloride in the SHR-ORX adjusted to values similar to Wistar-SHAM group. CONCLUSION: Hypertensive phenotype mitigated the orchiectomy-induced salivary dysfunction, since the disturbances were restricted to alterations in the salivary biochemical composition and redox state.

Representação social da malária na perspectiva dos garimpeiros em Boa Vista ­ Roraima / Social representation of malaria from the prespective of miners in Boa Vista ­ Roraima / Representación social de la malaria en la perspectiva de los mineros de Boa Vista ­ Roraima

Objetivo: analisar o núcleo central da representação social acerca da malária na ótica dos garimpeiros e dos indivíduos que exercem atividades laborais em região de garimpo que buscam atendimento no Pronto Atendimento Cosme e Silva em Boa Vista/RR. Método:estudo descritivo exploratório de carácter qualitativo delineado por meio da Teoria das Representações Sociais, formulada por Serge Moscovici em 1961. Foram realizadas 72 entrevistas semiestruturadas com garimpeiros. A análise dos dados ocorreu com o auxílio do software OpenEvoc 0.92 desenvolvido pelo Prof. Dr. Hugo Cristo em 2012. Resultados: foi constatado que as percepções dos garimpeiros acerca da malária está diretamente relacionada com a sintomatologia da doença, principalmente pelos traumas vivenciados devidoa ausência de serviço de saúde disponível no local de trabalho. Enquanto que, as percepções dos garimpeiros sobre o garimpo estão vinculadas a condição econômica deste grupo. Conclusão:observa-se que a busca pelo bem-estar financeiro, faz o garimpeiro se submeter às relações extremamente precárias de trabalho, incluindo a exposição ao vetor da malária.

Objective: to analyze the central nucleus of the social representation about malaria from the perspective of miners and individuals who carry out work activities in a mining region who seek care at the Cosme e Silva Emergency Room in Boa Vista/RR. Method:descriptiveexploratory study of a qualitative nature outlined through the Theory of Social Representations, formulated by Serge Moscovici in 1961. 72 semi-structured interviews were carried out with miners. Data analysis took place with the aid of the OpenEvoc 0.92 software developed by Prof. Dr. Hugo Cristo in 2012. Results:it was found that the prospectors' perceptions about malaria are directly related to the symptoms of the disease, mainly due to the traumas experienced due to the lack of health services available in the workplace. Meanwhile, the prospectors' perceptions about mining are linked to the economic condition of this group. Conclusion:it is observed that the search for financial well-being makes the prospector submit to extremely precarious work relationships, including exposure to the malaria vector.

Objetivo: analizar el núcleo central de la representación social sobre la malaria en la perspectiva de mineros y personas que ejercen actividades laborales en una región minera que buscan atención en el Servicio de Emergencia Cosme e Silva de Boa Vista/RR. Método:estudio descriptivo exploratorio de carácter cualitativo esbozado a través de la Teoría de las Representaciones Sociales, formulada por Serge Moscovici en 1961. Se realizaron 72 entrevistas semiestructuradas con mineros. El análisis de datos se llevó a cabocon la ayuda del software OpenEvoc 0.92 desarrollado por el Prof. Dr. Hugo Cristo en 2012. Resultados:se encontró que las percepciones de los prospectores sobre la malaria están directamente relacionadas con los síntomas de la enfermedad, principalmente debido a los traumas experimentados por la falta de servicios de salud disponibles en el lugar de trabajo. Por su parte, las percepciones de los buscadores sobre la minería están ligadas a la condición económica de este grupo. Conclusión: se observa que labúsqueda de bienestar económico hace que el prospector se someta a relaciones de trabajo extremadamente precarias, incluida la exposición al vector de la malaria.

The Inflammation Level and a Microbiological Analysis of the Anophthalmic Cavities of Unilateral Ocular Prosthesis Users: A Blind, Randomized Observational Study.

Irritation and biofilm adhesion are complaints associated with ocular prosthesis use. This study aimed to evaluate the effects of prosthesis repolishing on several conditions of anophthalmic volunteers. Participants were divided into two groups: intervention (IG, n = 10) and nonintervention (NIG, n = 6) groups. The anophthalmic cavity, contralateral eye, and prosthesis surface were evaluated at initial, day 15, and day 30 after repolishing. Microbiological analysis (colony-forming units), exfoliative cytology (conjunctiva inflammatory cells), sensory analysis (quantitative mechanical sensory test), tear production (Schirmer's test), and conjunctival inflammation (clinical evaluation) were performed. Nonparametric tests were used to compare groups in the initial period and to analyze periods for the IG (p < 0.05). More microorganisms were formed in the anophthalmic socket and prosthesis than in the contralateral eye in the initial period. For IG, the anophthalmic cavity exhibited more microorganisms and inflammatory clinical signs in the initial period than at 15 and 30 after repolishing. The prosthesis showed greater accumulations of total bacteria and Candida albicans in the initial period than at 15 and 30 days after repolishing. The anophthalmic cavity had more palpebral inflammation than the contralateral eye. In conclusion, repolishing reduced the number of microorganisms and inflammatory signs over time.

Patterns of Phenotypic Evolution Associated with Marine/Freshwater Transitions in Fishes.

Evolutionary transitions between marine and freshwater ecosystems have occurred repeatedly throughout the phylogenetic history of fishes. The theory of ecological opportunity predicts that lineages that colonize species-poor regions will have greater potential for phenotypic diversification than lineages invading species-rich regions. Thus, transitions between marine and freshwaters may promote phenotypic diversification in trans-marine/freshwater fish clades. We used phylogenetic comparative methods to analyze body size data in nine major fish clades that have crossed the marine/freshwater boundary. We explored how habitat transitions, ecological opportunity, and community interactions influenced patterns of phenotypic diversity. Our analyses indicated that transitions between marine and freshwater habitats did not drive body size evolution, and there are few differences in body size between marine and freshwater lineages. We found that body size disparity in freshwater lineages is not correlated with the number of independent transitions to freshwaters. We found a positive correlation between body size disparity and overall species richness of a given area, and a negative correlation between body size disparity and diversity of closely related species. Our results indicate that the diversity of incumbent freshwater species does not restrict phenotypic diversification, but the diversity of closely related taxa can limit body size diversification. Ecological opportunity arising from colonization of novel habitats does not seem to have a major effect in the trajectory of body size evolution in trans-marine/freshwater clades. Moreover, competition with closely related taxa in freshwaters has a greater effect than competition with distantly related incumbent species.

Analysis of the femoral neck from rats in the periestropause treated with oxytocin and submitted to strength training.

Among the interventions used to prevent osteoporosis in female organisms, strength training (ST) and oxytocin (OT) stand out, as a promising hormone with anabolic action on bone. This study aimed to verify whether the combined action of OT and ST, compared to isolated interventions, potentiates the bone remodeling process of the femoral neck of Wistar rats during periestropause. Forty Wistar rats (18 months) with irregular estrous cycle were randomly distributed into groups: 1-Vehicle (Veh; NaCl 0.15 mol/L ip); 2-Oxytocin (Ot; 134 µg/kg/ip); 3-Strength training (St); 4-Ot + St. The animals of the 1, 2 and 4 groups received two intraperitoneal injections with an interval of 12 h every 30 days, totaling 8 injections at the end of the experimental period (18 to 21 months). The animals in the St and Ot + St groups performed ST on a ladder 3 times a week, maximal voluntary carrying capacity (MVCC) test monthly. After 120 days, the animals were euthanized; the femur was collected for analysis of biomechanical testing, densitometry, bone microtomography, Raman spectroscopy, tissue PCR, and blood for analysis of bone biomarkers, liver damage, and oxidative stress. The main effects in the Ot group were observed in the maximum load and energy in the compression testing (femoral head), and stiffness and energy in the three-points bending testing (femur diaphysis). In addition, the main effects occurred on the bone mineral density (BMD), cortical thickness (Ct.Th), number of pores (Po.N), polar moment of inertia (J), trabecular thickness (Tb.Th), and connectivity density (Conn.Dn), Bone alkaline phosphatase (Alp), Tumor necrosis factor receptor superfamily member 11b (Opg), Tumor necrosis factor ligand superfamily member 11 (Rankl) and Cathepsin K (Ctsk) expression. There was an effect in the tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP). In the St group, the main effect was observed on the energy (compression and the three-points bending), stiffness, aBMD, BMD, cortical bone area (Ct.Ar), Po.N, trabecular bone volume (BV/TV), Tb.Th and in the mineralization ratio (ѵ1PO4/proline), Runt-related transcription factor 2 (Runx2), Bone morphogenetic protein 2 (Bmp2), Alp, Osteopontin/secreted phosphoprotein 1 (Opn/Spp1), Opg, Tumor necrosis factor receptor superfamily member 11ª (Rank), Rankl, Ctsk expression. There was an effect in the TRAP and ALP. The interaction in the combination of therapies in the Ot + St group was verified in energy to maximum load (compression and three-points bending testing), stiffness, BMD, Ct.Th, J, Tb.Th and ѵ1PO4/proline. In the gene analysis there was interaction in the Runx2, Osterix/Sp7 transcription factor (Osx/Sp7), Bmp2, Alp, Osteocalcin/Bone gamma-carboxyglutamate protein (Ocn/Bglap), Opg, Rankl and Acid phosphatase 5, tartrate resistant (Trap/Acp5) expression. In addition, the combination of OT and ST resulted in a higher maximum load compared to the Veh group, with higher BV/TV than the Ot group, higher Rankl and Ctsk expression than Veh and Ot groups, and lower Po.N and lower activity of TRAP than the other groups. In oxidative stress, total antioxidant capacity (TAC) was lower. These results showed that the combination of interventions is a promising anabolic strategy for the prevention of osteoporosis in the period of periestropause, standing out from the effects of isolated interventions.

Evaluation of Different Polymerisation Methods of Ocular Prosthesis Acrylic Resins on Subcutaneous Tissue Inflammatory Response in Rats.

Objectives: This study aimed to evaluate the influence of different polymerisation methods of acrylic resin for ocular prostheses on the subcutaneous tissue inflammatory response of rats. Methods: The study was conducted at the Basic Sciences Department, Araçatuba Dental School, São Paulo State University (UNESP), Brazil, from 2016 to 2018. The samples were prepared by water bath (WB), microwave energy (MW) or autopolymerisation (AP) (n = 20 samples per group). The inflammatory response (cell count and immunohistochemical analysis of interleukin [IL]-1ß, IL-6, tumour necrosis factor [TNF]-α, IL-17 and macrophage inflammatory protein-3α) was analysed by the implantation of a sample from each group in the subcutaneous tissue of 20 Wistar rats and evaluated after seven, 15, 30 and 60 days. The quantitative and qualitative data were analysed using analysis of variance and Tukey tests (P <0.05) and visual comparison, respectively. Results: There was a moderate inflammatory infiltrate for the MW and AP groups and a light infiltrate for the WB group after seven days. The inflammatory infiltrate and the immunolabeling of tested targets decreased gradually during the 60-day period. The AP group had the highest immunolabeling of TNF-α (seven days), IL-1ß and IL-17 (at 15 and 30 days) and IL-6 (at 30 and 60 days). The WB and MW groups showed greater immunolabeling at 15 and 30 days, while the MW group also had high results at 60 days. Conclusion: Polymerisation by microwave energy and by chemical activation resulted in a higher inflammatory response.

Knee Osteoarthritis: Kinesiophobia and Isometric Strength of Quadriceps in Women.

Introduction: Osteoarthritis is a disease characterized by progressive wear and tear of the joint, with the knee being the most affected region. These patients have reduced mobility and mobility, among other symptoms. Thus, it is necessary to know the variables that influence the ability to walk. Objective: To analyze how much the gait capacity, in the performance of the six-minute walk test, can be influenced by the maximum isometric strength of the quadriceps or by kinesiophobia in women with knee osteoarthritis. Materials and Methods: This is a cross-sectional study with a sample of 49 women diagnosed with osteoarthritis. The evaluation was carried out in a single moment. Variables studied isometric quadriceps strength, level of fear of movement (kinesiophobia), and ability to walk. Simple linear regression analyzes were performed, with gait ability as the dependent variable and maximum isometric strength and kinesiophobia as independent. Data were presented with mean and standard deviation and were analyzed by the SPSS Statistic 22.0 software, considering p < 0.05 as significant. Results: The maximum isometric strength presents a significant difference, directly interfering with the gait ability; as kinesiophobia does not show a statistically significant difference, it does not directly interfere with the ability to walk. Conclusion: Maximal quadriceps isometric strength directly interferes with gait ability in women with knee osteoarthritis, thus suggesting the inclusion of this strategy in treatment programs for this population.

A Collaborative Classroom Investigation of the Evolution of SABATH Methyltransferase Substrate Preference Shifts over 120 My of Flowering Plant History.

Next-generation sequencing has resulted in an explosion of available data, much of which remains unstudied in terms of biochemical function; yet, experimental characterization of these sequences has the potential to provide unprecedented insight into the evolution of enzyme activity. One way to make inroads into the experimental study of the voluminous data available is to engage students by integrating teaching and research in a college classroom such that eventually hundreds or thousands of enzymes may be characterized. In this study, we capitalize on this potential to focus on SABATH methyltransferase enzymes that have been shown to methylate the important plant hormone, salicylic acid (SA), to form methyl salicylate. We analyze data from 76 enzymes of flowering plant species in 23 orders and 41 families to investigate how widely conserved substrate preference is for SA methyltransferase orthologs. We find a high degree of conservation of substrate preference for SA over the structurally similar metabolite, benzoic acid, with recent switches that appear to be associated with gene duplication and at least three cases of functional compensation by paralogous enzymes. The presence of Met in active site position 150 is a useful predictor of SA methylation preference in SABATH methyltransferases but enzymes with other residues in the homologous position show the same substrate preference. Although our dense and systematic sampling of SABATH enzymes across angiosperms has revealed novel insights, this is merely the "tip of the iceberg" since thousands of sequences remain uncharacterized in this enzyme family alone.

Apical periodontitis promotes insulin resistance and alters adaptive immunity markers in rats.

OBJECTIVE: Apical periodontitis (AP) is a chronic or acute inflammatory disease usually developed from endodontic infections, predominantly due to gram-negative anaerobic bacteria invading the dental pulp. This study aimed to evaluate lymphocyte markers to assess the involvement of adaptive immunity in insulin resistance (IR) in a rat model of AP.Design.Forty-five male Wistar albino rats were divided into 3 groups (control, 1AP and 4AP). AP was induced in the upper right first molar (1AP), and in the first and second upper and lower right molars (4AP). The spleen was collected to evaluate the expression of transcription factors involved in lymphocyte polarization, including T-bet (Th1), GATA3 (Th2), and FOXP3 (Treg). Blood samples were assessed for serum cytokine levels transcribed by the respective lymphocyte polarizations, INF-γ (Th1), IL-4 (Th2) and TGF-ß (Treg). In addition, glucose and insulin levels were measured to evaluate IR by the HOMA-IR method. RESULTS: The results showed higher T-bet expression on AP groups, along with lower GATA3 and FOXP3 expression in the 1AP, in addition to increased GATA3 and decreased FOXP3 expression in the 4AP group compared to the CN group. There was no difference in the INF-γ levels, while IL-4 was decreased in the AP groups. Taken together, these results suggest that the adaptive immune system, with a predominance of the Th1 polarization, may be involved in the development of IR in rats with AP. CONCLUSIONS: AP promotes increase in the expression of T-bet (4AP) and decrease of FOXP3 expressions and IL-4 levels (1AP and 4AP). However, depending on the number of lesions (1 or 4 lesions), the expression of GATA3 appears differently. Thus, innate immunity and adaptive immunity may contribute to the IR observed in rats with AP.

Tumor de Klatskin en una paciente con diagnóstico de síndrome de Sjögren / Klatskin tumor in a patient diagnosed with Sjögren's syndrome

El proceso inflamatorio crónico de las enfermedades reumáticas constituye un factor que causa afectación en otros órganos y sistemas de órganos. La afectación puede llegar a producir metaplasia de la mucosa de distintos tejidos y condicionar la aparición de enfermedades neoplásicas. Los pacientes con síndrome de Sjögren tienen un 40 por ciento de aumento de riesgo de padecer una enfermedad tumoral con respecto a los pacientes sanos o con otras enfermedades crónicas no inflamatorias. El objetivo del presente estudio es dar a conocer las características clínico-imagenológicas que posibilitaron el diagnóstico de un tumor de Klatskin en una paciente femenina de 57 años de edad con antecedentes de 5 años de evolución del síndrome de Sjögren. Se realizó una colangiopancreatografía retrógrada endoscópica para eliminar el tumor. A los tres días de la intervención quirúrgicamente la paciente muestra una evolución favorable por lo que se decide dar alta hospitalaria con seguimiento por consulta externa de especialidades de cirugía general y reumatología indistintamente. Durante todo el procedimiento se mantuvo el tratamiento para la enfermedad de base de la paciente. Actualmente la paciente se encuentra incorporada a sus actividades cotidianas y con una evolución favorable de su estado de salud(AU)

The chronic inflammatory process of rheumatic diseases constitutes a factor that causes affectation in other organs and organ systems. The affectation can produce metaplasia of the mucosa of different tissues and condition the appearance of neoplastic diseases. Patients with Sjögren's syndrome have a 40 percent increased risk of developing a tumor disease compared to healthy patients or other non-inflammatory chronic diseases. The objective of this study is to present the clinical-imaging characteristics that made the diagnosis of a Klatskin tumor possible in a 57-year-old female patient with a 5-year history of Sjögren's syndrome. Endoscopic retrograde cholangiopancreatography was performed to remove the tumor. Three days after the surgical intervention, the patient showed a favorable evolution, so it was decided to discharge from the hospital with follow-up by outpatient consultation of specialties of general surgery and rheumatology indistinctly. Treatment for the patient's underlying disease was maintained throughout the procedure. Currently the patient is incorporated into her daily activities and with a favorable evolution of her state of health(AU)

Recomendaciones pre- y posquirúrgicas en pacientes reumáticos / Pre and post-surgical recommendations in rheumatic patients

El acto quirúrgico constituye un elemento de estrés, principalmente en pacientes con enfermedades reumáticas en los que la actividad quirúrgica presenta características distintivas. Mantener un adecuado control de la actividad clínica de los pacientes con enfermedad reumática constituye un pilar fundamental para la recuperación posquirúrgica de las personas sometidas a cirugía electiva. Para ello es necesario orientar correctamente a los pacientes reumáticos tanto en el preoperatorio como en el posoperatorio. Solo de esta forma se logrará una adecuada recuperación quirúrgica sin poner en riesgo el control de la enfermedad reumática. El siguiente reporte tiene como objetivo describir las recomendaciones pre- y posquirúrgicas de la cirugía electiva en pacientes con enfermedades reumáticas, lo que permitirá orientar correctamente a las personas y disminuir la morbilidad relacionada con la realización de procedimientos quirúrgicos en los pacientes diagnosticados con enfermedades reumáticas(AU)

The surgical act constitutes an element of stress, mainly in patients with rheumatic diseases in whom the surgical activity presents distinctive characteristics. Maintaining adequate control of the clinical activity of patients with rheumatic disease constitutes a fundamental pillar for the post-surgical recovery of people undergoing elective surgery. For this, it is necessary to correctly guide rheumatic patients both preoperatively and postoperatively. Only from this will an adequate surgical recovery be achieved without jeopardizing the control of the rheumatic disease. The objective of the following report is to describe the pre and post-surgical recommendations for elective surgery in patients with rheumatic diseases, which will allow people to be correctly oriented and reduce the morbidity related to the performance of surgical procedures in patients diagnosed with rheumatic diseases(AU)

Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats.

Telmisartan (TELM) is an angiotensin II (Ang II) type 1 receptor (Agtr1) antagonist, with partial agonism for Pparg, and has been shown to affect bone metabolism. Therefore, the aim of this study was to investigate the effects of TELM in the in vitro osteogenic differentiation of bone marrow-derived mesenchymal stromal cells (BMSC) from spontaneously hypertensive rats (SHRs). BMSC were obtained from male SHR, and the osteogenic medium (OM) was added to the cells concomitantly with TELM (0.005, 0.05, and 0.5 µM). Undifferentiated BMSC, in control medium (CM), showed an increased viability, while the addition of OM reduced this parameter, and TELM did not show cytotoxicity in the concentrations used. BMSC in OM had an alkaline phosphatase (ALP) activity peak at d10, which decreased at d14 and d21, and TELM reduced ALP at d10 in a dose-dependent manner. Mineralization was observed in the OM at d14, which intensified at d21, but was inhibited by TELM. Agtr1b was increased in the OM, and TELM inhibited its expression. TELM reduced Opn, Ocn, and Bsp and increased Pparg expression, and at the higher concentration TELM also increased the expression of adipogenic markers, Fabp4 and Adipoq. In addition, TELM 0.5 µM increased Irs1 and Glut4, insulin and glucose metabolism markers, known to be regulated by Pparg and to be related to adipogenic phenotype. Our data shows that TELM inhibited the osteogenic differentiation and mineralization of SHR BMSC, by favoring an adipogenic prone phenotype due to Pparg upregulation.

Biological and antimicrobial properties of the association Ambroxol and a water-soluble viscous liquid as a vehicle for a tricalcium silicate-based sealer.

This study aimed to investigate the antimicrobial and biological properties of Ambroxol associated with glycerin (GLI), propylene glycol (PG), and polyethylene glycol (PEG) as a possible vehicle for an experimental tricalcium silicate sealer, with the intention of developing a new biomaterial. Mouse undifferentiated dental pulp cells (OD-21) were cultured, and the effects of different association on cell proliferation and inflammatory cytokine production were investigated. Antimicrobial adhesion of Enterococcus faecalis to setting sealers at 2 h was evaluated. Polyethylene tubes containing experimental sealers and empty tubes were implanted into dorsal connective tissues of 12 male 3- to 4-months-old Wistar rats (250-280 g). After 7 and 30 days, the tubes were removed and processed for histological and immunohistochemical analyses. ANOVA followed by Bonferroni correction and ANOVA followed by Tukey test was used for parametric data and Kruskal-Wallis followed by Dunn for nonparametric (p < 0.05). Cell proliferation was dose-dependent, since all association were cytotoxic at higher concentrations; however, Ambroxol-PEG showed significantly higher cytotoxicity than other association (p < 0.05). In addition, irrespective of the association, no cytokine production was observed in vitro. Ambroxol-GLI reduced bacterial viability, whereas Ambroxol-PEG increased (p < 0.05). Histological examination showed no significant difference in the inflammatory response (p > 0.05) and mineralization ability in all association. Additionally, IL-1ß and TNF-α were upregulated on Ambroxol-PEG in relation to Control at 07 days (p < 0.05). Ambroxol-GLI was the best vehicle for experimental tricalcium silicate sealer, as it promoted an increase in antimicrobial activity without altering the inflammatory response or mineralization ability.

Concomitant Antihyperalgesic and Antitumor Effects of Gabapentin in a Murine Cancer Pain Model.

Cancer pain may be the consequence of physical nerve compression by a growing tumor. We employed a murine model to study whether gabapentin was able to regulate tumor growth, in addition to controlling hyperalgesic symptoms. A fluorescent melanoma cell line (B16-BL6/Zs green) was inoculated into the proximity of the sciatic nerve in male C57BL/6 mice. The tumor gradually compressed the nerve, causing hypersensitivity. Tumor growth was characterized via in vivo imaging techniques. Every other day, gabapentin (100 mg/Kg) or saline was IP administered to each animal. In the therapeutic protocol, gabapentin was administered once the tumor had induced increased nociception. In the preventive protocol, gabapentin was administered before the appearance of the positive signs. Additionally, in vitro experiments were performed to determine gabapentin's effects on cell-line proliferation, the secretion of the chemokine CCL2, and calcium influx. In the therapeutically treated animals, baseline responses to noxious stimuli were recovered, and tumors were significantly reduced. Similarly, gabapentin reduced tumor growth during the preventive treatment, but a relapse was noticed when the administration stopped. Gabapentin also inhibited cell proliferation, the secretion of CCL2, and calcium influx. These results suggest that gabapentin might represent a multivalent strategy to control cancer-associated events in painful tumors.

ß1-adrenergic receptor but not ß2 mediates osteogenic differentiation of bone marrow mesenchymal stem cells in normotensive and hypertensive rats.

The sympathetic nervous system regulates bone remodeling via adrenergic receptors on the surface of bone cells. Herein, we evaluated the role of beta-adrenergic receptors (ADRBs) in osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) derived from normotensive (Wistar) and spontaneously hypertensive rats (SHRs). BMSCs were cultured in a proliferation medium or osteogenic medium (OM). Cells cultured in OM were treated with carvedilol (Cv) or nebivolol (Nb).In OM, cell proliferation was decreased in both strains. In Wistar rats, Cv increased BMSC proliferation and increased alkaline phosphatase (ALP) activity in OM. Both Cv and Nb decreased ALP activity. In addition, Cv and Nb reduced mineral deposition in Wistar rats. Moreover, NB decreased mineralization in SHRs, exhibiting superior efficacy. In OM, cells from Wistar rats and SHRs showed Adrb1 and Adrb2 expression. On day 7, Nb, but not Cv, reduced Adrb1 levels in BMSCs from Wistar rats. Nb inhibited Adrb2 in both strains, and Cv demonstrated superior efficacy. In BMSCs from Wistar rats, both antagonists inhibited Runx2, osterix, and ß-catenin; in SHRs, Cv and Nb inhibited only osterix. Cv decreased osteopontin (Opn), osteocalcin (Ocn), and bone morphogenetic protein (Bmp2) in BMSCs from Wistar rats, inhibiting only Opn in SHRs. Nb effectively inhibited Ocn, bone sialoprotein, and Bmp2, but not Ocn, in BMSCs from Wistar rats, while suppressing Opn in BMSCs from SHRs. In addition, Nb inhibited p-p38 in BMSCs from Wistar rats; Cv inhibited p-p38 in BMSCs from SHRs. In Wistar rats, both antagonists inhibited p-ERK and reduced p-JNK; Cv reduced these expressions only in SHRs. In conclusion, ADRB1, but not ADRB2, could be involved in the osteogenic differentiation of BMSCs from Wistar rats and SHRs. The high ADRB1 expression might suppress the effect of ADRB2 on BMSCs.

Effect of processing methods on the cytotoxicity of methyl methacrylate-based ocular prostheses: An in vitro study.

The study evaluated the influence of cycles and methods of an ocular prosthesis resin on cytotoxicity toward human conjunctival cells. Resins were polymerized by water bath (WB, 74 °C or 100 °C for 30 min to 9 h), microwave (MW, 1200 W, 3 to 14 min and 30 s at 0 to 720 W), or autopolymerization (AP, room temperature for 20 min ± 60 °C for 30 min). Degree of conversion (DC), cytotoxicity, level of inflammatory mediators, gene expression of different markers, and apoptosis were evaluated. Data were submitted to ANOVA and Tukey test (p < 0.05). WB with longer processing time at higher temperature had highest DC (85.6%) and higher TGF ß1-gene expression (1.39); long cycle low power MW showed lowest DC (69.6%), lower cell proliferation (85.4%, MTT), and large IL-2 release (39,297 ng/mL). AP with additional processing time showed lower cell proliferation (75.3%, Alamar Blue), and AP polymerized at room temperature showed higher CASP 9-gene expression (1.21). AP methods showed higher IL-6 release (>277 pg/mL). Short cycle medium power MW had higher IL-23 release (534.2 pg/mL). MW (long and short cycles) and AP polymerizations have triggered a more intense inflammatory response. Among methods recommended by the manufacturer, WB showed high DC and less cytotoxicity.