Abstract Inflammation-related immune responses and bone metabolism lead to extensive tooth loss in periodontitis. Objective: This study aims to investigate the effect of peroxisome proliferator-activated receptor (PPAR) alpha agonist anti-inflammatory treatment in vitro and in ligature-induced experimental periodontitis in vivo . Methodology: Splenocytes were isolated from C57BL/6J mice and cultured for 48 hours under the following conditions: control, P. gingivalis lipopolysaccharide (LPS) (1 µg/ml); experimental, LPS (1 µg/ml) + PPARα agonist (fenofibrate) at 1, 10, 50, 100 µM. MRNA and secreted protein levels of TNF-α expression were detected by RT-qPCR and ELISA, respectively. Silk ligatures (7-0) were tied around maxillary second molars of C57BL/6J mice for two weeks. Optimized doses of fenofibrate (50 µM) and vehicle control were injected into the contralateral side of the palatal gingiva on days three, six, and nine. At day 14, bone resorption, osteoclastogenesis, and gingival mRNA expression levels of TNF-α, IL-1β, IL-6, and RANKL/OPG were measured by micro-computed tomography, Tartrate-resistant acid phosphatase (TRAP) staining, and Real-time quantitative PCR, respectively. Results: TNF-α expression in cultured spleen cells were significantly increased in the presence of LPS, when compared with the control group, and significantly reduced by fenofibrate treatment in a dose-dependent manner from 1-100 µM (p<0.05). Gingival mRNA levels of TNF-α, IL-1β, IL-6, and the ratio of RANKL/OPG, were significantly decreased after injection of fenofibrate, when compared to the control side (p<0.05). Periodontal bone loss and TRAP positive cell formation were significantly decreased on the side with an injection of fenofibrate, as compared to the control side (p<0.05). Conclusions: An anti-inflammatory treatment, PPARα agonist, inhibited inflammation and periodontal bone loss in ligature-induced experimental periodontitis.

Abstract Local administration of toll-like receptor 9 (TLR9), agonist cytidine-phosphate-guanosine oligodeoxynucleotide (CpG ODNs), and CD40 ligand (CD40L) can decrease ligature-induced periodontal inflammation and bone loss in wild type (WT) mouse. Objective: This study aimed to explore whether such effect is dependent on TLR9 signaling. Material and Methods: Purified spleen B cells isolated from WT C57BL/6J mice and TLR9 knockout (KO) mice were cultured for 48 hours under the following conditions: CD40L, CpG+CD40L, CpG at low, medium and high doses. We determined B cell numbers using a hemocytometer at 24 h and 48 h. Percentages of CD1dhiCD5+ B cells were detected by flow cytometry. Interleukin-10 (IL-10) mRNA expression and protein secretion were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and by ELISA, respectively. The silk ligature was tied around the maxillary second molars for 14 days, during which the CpG+CD40L mixture or PBS was injected into palatal gingiva on days 3, 6, and 9. Results: For both WT and TLR9 KO mice, CpG significantly induced B cell proliferation, increased IL-10 mRNA expression and protein secretion of IL-10 but reduced CD1dhiCD5+ B cells population; local injection of CpG+CD40L mixture significantly decreased alveolar bone loss and the number of TRAP-positive cells adjacent to the alveolar bone surface, and significantly increased the gingival mRNA expression of IL-10 and decreased RANKL and IFN-γ mRNA expression. Conclusions: These results indicated that CpG plus CD40L decreased periodontal inflammation and alveolar bone loss in a TLR9-independent manner in ligature-induced experimental periodontitis.

OBJECTIVES: To investigate the association between diastolic function and the different beneficial effects of cardiac resynchronization therapy in patients with heart failure due to different causes. METHODS: The 104 enrolled patients were divided into an ischemic cardiomyopathy group (n=27) and a non-ischemic cardiomyopathy group (n=77) according to the cause of heart failure. Before implantation, left ventricular diastolic function was evaluated in all patients using echocardiography. After six months of follow-up, the beneficial effects of cardiac resynchronization therapy were evaluated using a combination of clinical symptoms and echocardiography parameters. RESULTS: The ischemic cardiomyopathy group included significantly more patients with restrictive filling than the non-ischemic cardiomyopathy group. The response rate after the implantation procedure was significantly higher in the non-ischemic cardiomyopathy group than in the ischemic cardiomyopathy group. Degrees of improvement in echocardiography parameters were significantly greater in the non-ischemic cardiomyopathy group than in the ischemic cardiomyopathy group. Multivariate regression analysis showed that a restrictive filling pattern was an independent factor that influenced responses to cardiac resynchronization therapy. CONCLUSIONS: This study again confirmed that the etiology of heart failure affects the beneficial effects of cardiac resynchronization therapy and a lower degree of improvement in ventricular systolic function and remodelling was observed in ischemic cardiomyopathy patients than in non-ischemic cardiomyopathy patients. In addition, systolic heart failure patients with severe diastolic dysfunction had poor responses to cardiac resynchronization therapy. Ischemic cardiomyopathy patients exhibited more severe diastolic dysfunction than non-ischemic cardiomyopathy patients, which may be a reason for the reduced beneficial effect of cardiac resynchronization therapy.

Abstract Introduction: Alzheimer's disease is one of the most prevalent neurodegenerative dementia in developed world. This fact, coupled with the lack cure, makes new no pharmacological therapeutic strategies such as nutrient management to investigate. In this regard, it stresses the possible influence of coconut oil as alternative energy source capable of stopping the progressively neuronal death that occurs in this disease. Objectives: To assess the cognitive impact of coconut oil in Alzheimer's patients, and specifically in orientation, language-building, fixing, calculation-concentration and memory areas. Methods: Prospective, longitudinal, qualitative, analytical and experimental study through a clinical trial where 44 patients with Alzheimer's in region of Ribera (Valencia), of which half was selected to receive during 21 days, 40 ml coconut oil daily divided between breakfast (20 ml) and food (20 ml). Before and after administration of the oil, they were evaluated through cognitive test Mini-Mental State Examination to determine possible changes. Results: It was observed in patients who received coconut oil, that cognitive improvement after completion of the intervention, statistically significant improved in the orientation and language-construction areas. Conclusions: Coconut oil appears to improve cognitive abilities of Alzheimer's patients, with different intensity depending on the cognitive area.

Resumen Introducción: la enfermedad de Alzheimer es a día de hoy la demencia neurodegenerativa con mayor prevalencia en el primer mundo. Este hecho, unido a la falta de tratamiento farmacológico que cure la enfermedad, hace que se estudien nuevas estrategias terapéuticas no farmacológicas como es la administración de nutrientes. En este sentido, destaca la posible influencia del aceite de coco como fuente energética alternativa, capaz de frenar la muerte neuronal que se produce de modo progresivo en esta enfermedad. Objetivos: valorar el impacto del aceite de coco a nivel cognitivo en pacientes de alzhéimer, y concretamente en las áreas de orientación, lenguaje-construcción, fijación, cálculo-concentración y memoria. Métodos: estudio prospectivo, longitudinal, cualitativo, analítico y experimental a través de un ensayo clínico, donde se seleccionaron a 44 pacientes con alzhéimer de la zona de la Ribera (Comunidad Valenciana), de los cuales a la mitad se le administró durante 21 días, 40 ml diarios de aceite de coco repartidos entre desayuno (20 ml) y comida (20 ml). Antes y después de la administración del aceite, se les valoró a través del test cognitivo Mini-Examen Cognoscitivo, para determinar los posibles cambios. Resultados: en los enfermos que tomaron el aceite de coco se observó una mejora cognitiva tras finalizar la intervención, siendo estadísticamente significativa en las áreas de orientación y lenguaje-construcción. Conclusiones: el aceite de coco parece mejorar la capacidad cognitiva de los enfermos de alzhéimer, variando la intensidad de la misma en función del área cognitiva.

Abstract IL-10 expressing regulatory B cells (B10) play a key role in immune system balance by limiting excessive inflammatory responses. Effects of toll-like receptor signaling and co-stimulatory molecules on B10 activity during innate and adaptive immune responses are not fully understood. Objective This study is to determine the effects of P. gingivalis LPS and CpG on B10 cell expansion and IL-10 competency in vitro. Material and Methods Spleen B cells were isolated from C57BL/6J mice with or without formalin-fixed P. gingivalis immunization. B cells were cultured for 48 hours under the following conditions: CD40L, CD40L+LPS, CD40L+CpG, and CD40L+LPS+CpG in the presence or absence of fixed P. gingivalis. Percentages of CD1dhiCD5+ B cells were measured by flow cytometry. IL-10 mRNA expression and secreted IL-10 were measured by real-time quantitative PCR and by ELISA respectively. Results P. gingivalis LPS plus CD40L significantly increased CD1dhiCD5+ B cell percentages and secreted IL-10 levels in both immunized and non-immunized mice B cells in the presence or absence of P. gingivalis, compared with control group. Secreted IL-10 levels were significantly increased in CD40L+LPS treated group compared with CD40L treatment group in the absence of P. gingivalis. CpG plus CD40L significantly decreased CD1dhiCD5+ B cell percentages, but greatly elevated secreted IL-10 levels in immunized and non-immunized mice B cells in the absence of P. gingivalis, compared with CD40L treatment group. Conclusions P. gingivalis LPS and CpG differentially enhance IL-10 secretion and expansion of mouse B10 cells during innate and adaptive immune responses.

Abstract This study was conducted to investigate the roles of different Toll-like receptor (TLR) signaling in Porphyromonas gingivalis (P. gingivalis)-induced and ligature-induced experimental periodontal bone resorption in mice. Wild-type (WT), TLR2 knockout (KO), TLR4KO, and TLR2&4 KO mice with C57/BL6 background were divided into three groups: control, P. gingivalis infection, and ligation. Live P. gingivalis or silk ligatures were placed in the sulcus around maxillary second molars over a 2-week period. Images were captured by digital stereomicroscopy, and the bone resorption area was measured with ImageJ software. The protein expression level of gingival RANKL was measured by ELISA. The gingival mRNA levels of RANKL, IL-1β, TNF-α, and IL-10 were detected by RT-qPCR. The results showed that P. gingivalis induced significant periodontal bone resorption in WT mice and TLR2 KO mice but not in TLR4 KO mice or TLR2&4 KO mice. For all four types of mice, ligation induced significant bone loss compared with that in control groups, and this bone loss was significantly higher than that in the P. gingivalis infection group. RANKL protein expression was significantly increased in the ligation group compared with that in the control group for all four types of mice, and in the P. gingivalis infection group of WT, TLR2 KO, and TLR4 KO mice. Expression patterns of RANKL, IL-1β, TNF-α, and IL-10 mRNA were different in the P. gingivalis infection group and the ligation group in different types of mice. In summary, P. gingivalis-induced periodontal bone resorption is TLR4-dependent, whereas ligation-induced periodontal bone resorption is neither TLR2- nor TLR4-dependent.

Background: Alzheimer's dementia is the most prevalent nowadays. As for treatment, there is no definitive cure drug, thus new therapies are needed. In this regard the medium chain triglycerides are a direct source of cellular energy and can be a nonpharmacological alternative to the neuronal death for lack of it, that occurs in Alzheimer patients. Objective: to evaluate the impact of coconut oil in the development of Alzheimer's dementia, in any degree of dementia. Also determine whether this improvement influences within variables such as sex and suffering or not Type II Diabetes Mellitus. Material and methods: a prospective study was conducted in patients with Alzheimer's dementia, with a control and an intervention group which was administered 40 ml/day of extra virgin coconut oil. The parameters evaluated were the mini test scores Lobo cognitive test, pre and post intervention in both groups. Results: it was observed in subjects taking the product, a statistically significant increase in test score MECWOLF and therefore an improvement in cognitive status, improving especially women's, those without diabetes mellitus type II, and severe patients. Conclusion: this study, although preliminary, demonstrated the positive influence of coconut oil at the cognitive level of patients with Alzheimer's, this improvement being dependent on sex, presence or absence of diabetes and degree of dementia.

Introducción: la enfermedad de Alzheimer es la demencia más prevalente en la actualidad. En cuanto al tratamiento, no existe cura farmacológica definitiva, con lo cual son necesarias nuevas alternativas terapéuticas. En este sentido, los triglicéridos de cadena media suponen una fuente directa de energía celular y pueden ser una alternativa no farmacológica a la muerte neuronal por falta de la misma, que se produce en los enfermos de Alzheimer. Objetivo: evaluar el impacto que tiene el aceite de coco en la evolución de la demencia tipo Alzheimer, en cualquier grado de demencia. Asimismo, determinar si existe influencia en dicha mejora, de variables como el sexo y padecer o no diabetes mellitus tipo II. Material y métodos: estudio prospectivo realizado en pacientes con demencia tipo Alzheimer, con un grupo control y un grupo de intervención al que se le administró 40 ml/día de aceite de coco virgen extra. Los parámetros evaluados han sido las puntuaciones del test del miniexamen cognoscitivo de Lobo, pre y postintervención en ambos grupos. Resultados: se observó en los sujetos que tomaban el producto un aumento estadísticamente significativo de la puntuación del test MEC-LOBO y, por consiguiente, una mejoría del estado cognitivo, mejorando sobre todo las mujeres, los que no tenían diabetes mellitus tipo II y los pacientes graves. Conclusión: este estudio, aunque preliminar, demuestra la influencia positiva del aceite de coco a nivel cognitivo en los pacientes con Alzheimer, siendo esta mejoría dependiente del sexo, de la existencia o no de diabetes y del grado de demencia.