Lacticaseibacillus casei decrease long-chain fatty acids and most substances in an experimental model of intestinal mucositis.

PURPOSE: To evaluate the long-chain fatty acid and major compounds levels in the feces after prophylactic oral use of Lacticaseibacillus casei in an experimental model of intestinal mucositis. METHODS: Fifteen Swiss mice were randomly divided into three groups (n=5/group): The negative or positive control groups (n = 5) received saline orally for 18 days and an the intraperitoneal (i.p.) of saline or 5 Fluorouracil (450 mg/kg) in 15th day, respectability. L. casei group received oral concentration of L. casei (1x109 CFU/mL) for 18 days, the i.p. injection of 5-fluorouracil (450 mg/kg) in 15th days. Tissue samples from colon and each small intestine segment were collected for histopathological analysis. Stool samples were collected. Fecal composition of long-chain fatty acids and sterols were analysed by gas chromatography-mass spectrometry on the 15th and the 18th day. RESULTS: The mucosa layer of all small intestine segments of animals from L. casei showed well preserved epithelium and glands, without necrosis signs, but Goblet cells number decreased. Several long-chain fatty acids and sterols have been identified before and after in the groups. L. casei administration after 5-FU treatment reduced concentrations of linoleic acid (18:2) (p < 0.001) and oleic acid (18:1) (p < 0.001) in feces. CONCLUSIONS: L. casei prevented the mucosal damage associated with 5-FU-induced intestinal mucositis reduced long-chain fatty acid levels in the feces.

L-glutamine supplementation reduced morphological damage in the renal glomerulus of rats with Walker-256 tumor.

PURPOSE: To evaluate the effects of the experimental subcutaneous Walker-256 tumor and L-glutamine supplementation, an antioxidant, on the glomerular morphology of rats. METHODS: Twenty Wistar rats were distributed into four groups (n = 5): control (C); control treated with 2% L-glutamine (CG); rats with Walker-256 tumor (WT); and rats with Walker-256 tumor treated with 2% L-glutamine (WTG). Renal histological samples were submitted to periodic acid-Schiff and Masson's Trichrome staining to analyze glomerular density, morphometry of glomerular components and glomerulosclerosis; and to immunohistochemistry for fibroblast growth factor-2 (FGF-2). RESULTS: WT showed 50% reduction in body mass gain and cachexia index > 10%, while WTG demonstrated reduction in cachexia (p < 0.05). WT revealed reduction of glomerular density, increase in the glomerular tuft area, mesangial area, matrix in the glomerular tuft, decrease in the urinary space and synechia, and consequently higher glomerulosclerosis (p < 0.05). L-glutamine supplementation in the WTG improved glomerular density, and reduced glomerular tuft area, urinary space, mesangial area, and glomerulosclerosis compared to WT(p < 0.05). WT showed higher collagen area and FGF-2 expression compared to C (p < 0.05). WTG presented lower collagen fibers and FGF-2 expression compared to WT (p < 0.05). CONCLUSIONS: L-glutamine supplementation reduced cachexia and was beneficial for glomerular morphology of the rats, as well as it reduced kidney damage and improved the remaining glomeruli morphology.

Perfil do consumo dos benzodiazepínicos nos anos de 2019 e 2020 no brasil e regiões / Profile of the benzodiazepines in the years 2019 e 2020 in Brazil and regions / Perfil de consume y hospitalizaciones de los benzodiacepinas en los años 2019 y 2020 enBrasil y regiones

Os benzodiazepínicos estão entre os medicamentos mais prescritos, principalmente em países ocidentais, onde estimativas mostram um consumo anual de 1% a 3% da população.Objetivo:Estudar o perfil do consumo dos benzodiazepínicosnos anos de 2019-2020. Metodologia:Foram estudadas a taxa de desocupação segundo o Instituto Brasileiro de Geografia e Estatística, consumo dos benzodiazepínicosa partir do Sistema Nacional de Gerenciamento de Produtos Controlados da Agencia de Vigilância Sanitáriae quantidade de internações por envenenamento com exposição (acidental ou proposital), auto-intoxicação e efeitos adversos aos anticonvulsivantes, sedativos, hipnóticos, antiparkinsonianos e psicotrópicos segundo o Departamento de Informática do Sistema Único de Saúde no Brasil. Resultados:A região Norte e Nordeste apresentou um aumento na taxa de desocupação. O rendimento nominal mensal domiciliar per capitada população residente nas regiões Norte e Nordeste se manteveabaixo de 01 salário-mínimo nos anos de 2019 e 2020. De 2019 para 2020, o princípio ativo mais utilizado dos benzodiazepínicos industrializados foi o Clonazepam com incremento de 9,81% no Brasil e 22,52% na região Nordeste. Todas as formas farmacêuticas manipuladas apresentaram umaredução no consumo de 2019 para 2020, com exceção da forma em mililitros que apresentou um incremento para o bromazepam (42,1%), clonazepam (8,76%) e diazepam (5,27%). De 2020 em relação a 2019, ocorreu um incrementode 119,05% e 25% nas regiões Nordeste e Centro-Oeste, respectivamente, nasinternações por envenenamento [intoxicação] por exposição, a anticonvulsivantes (antiepilépticos), sedativos, hipnóticos, antiparkinsonianos e psicotrópicos não classificados em outra parte, intenção não determinada. Conclusões:Ocorreu um aumento no consumo de benzodiazepínicosindustrial no ano de 2020 sendo o envenenamento [intoxicação] umadas principais causasde internação. Há necessidade de um controle do consumo e vigilância aos psicotrópicos visto que estes fármacos estão dentre aqueles com risco de internações devido àexposição acidental ou não, autointoxicaçãoou efeitos adversos (AU).

Benzodiazepines are among the most prescribed drugs, especially in Western countrieswhere estimates show an annual consumption of 1% to 3% of the population.Objective: To study the profile of benzodiazepinesconsumptionfrom the National Controlled Products Management System of the Sanitary Surveillance Agencyin the years 2019 and 2020.Methodology:The unemployment rate,according to theBrazilian Institute of Geography and Statistics,benzodiazepines consumptionfrom the National Controlled Products Management System of the Sanitary Surveillance Agency, and the number of hospitalizations due to poisoning with exposure (accidental or intentional), self-intoxication, and adverse effects to anticonvulsants, sedatives, hypnotics, antiparkinsonian drugs and psychotropic drugs according to the Department of Informatics of the Unified Health System in Brazil were studied.Results:The North and Northeast regions showed an increase in the unemployment rate. The nominal monthly household income per capita of the population residing in the North and Northeast regions remained below 01 minimum wage in the years 2019 and 2020. From 2019 to 2020, the most used active substanceof industrialized benzodiazepines was Clonazepam with an increase of 9.81% in Brazil and 22.52% in the Northeast region. All compounded pharmaceutical forms showed a reduction in consumption from 2019 to 2020, with the exception of the form in milliliters which showed an increase for bromazepam (42.1%), clonazepam (8.76%) and diazepam (5.27%). In 2020 compared to 2019, there was an increase of 119.05% and 25% in the Northeast and Midwest regions, respectively, in hospitalizations for poisoning[intoxication] due to exposure toanticonvulsants (antiepileptics), sedatives, hypnotics, antiparkinsonian drugs,and psychotropic drugs not elsewhere classified with intent undetermined.Conclusions:There was an increase in the consumption of industrial benzodiazepines in 2020, with poisoning [intoxication] being one of the main causes of hospitalization. There is a need to control the consumption andincrease the surveillance of psychotropic drugs becausethese drugs are among those that involverisk of hospitalization due to accidental or non-accidental exposure, self-intoxication or adverse effects (AU).

ntroducción: Las benzodiacepinas se encuentran entre los fármacos más recetados, especialmente en los países occidentales, donde se estima que de 1% al 3% de la poblaciónde estos países los consumen. Objetivo: Estudiar el perfil del consumo de benzodiacepinas en los años 2019-2020.Metodología: Se midieron la tasa de desempleo según elInstituto Brasileño de Geografía y Estadística, el consumo de benzodiacepinasdel Sistema Nacional de Gestión de Productos Controlados de la Agencia de Vigilancia Sanitariay el número de hospitalizaciones por intoxicación con exposición (accidental o intencional), además se estudiaron autointoxicaciones y efectos adversos a los anticonvulsivos, sedantes, hipnóticos, drogas contra el mal de Parkinsony psicotrópicossegún elDepartamento de Informática del Sistema Único de Salud de Brasil.Resultados: Las regiones Norte y Nordeste presentaron aumento de la tasa de desempleo. El ingreso nominal mensual de los hogares per cápita de la población residente en las regiones Norte y Nordeste se mantuvo por debajo de 01 salario mínimo en los años 2019-2020. De 2019 a 2020, el principio activo más utilizado de las benzodiacepinas industrializadas fue el clonazepam con un aumento de 9,81% en Brasil y de22,52% en la región Nordeste. Todas las formas farmacéuticas compuestas mostraron una reducción en su consumo de 2019-2020, a excepción de la forma en mililitros que mostró un aumento para bromazepam (42,1%), clonazepam (8,76%) y diazepam (5,27%). En 2020 respecto a 2019, hubo un aumento del 119,05% y 25% en las regiones Noreste y Medio Oeste, respectivamente, en las hospitalizaciones por intoxicación por exposición aanticonvulsivos (antiepilépticos), sedantes, hipnóticos, drogas contra el mal de Parkinsony psicofármacos no clasificados en otra parte conintención indeterminada.Conclusiones: Hubo un aumento en el consumo de benzodiacepinas industriales en 2020, siendo las intoxicaciones una de las principales causas de hospitalización. Existe la necesidad de controlar el consumo y vigilancia de los psicofármacos, ya que estos fármacos se encuentran entre los de riesgo de hospitalización por exposición accidental o no accidental, autointoxicación o efectos adversos (AU).

Lacticaseibacillus casei decrease long-chain fatty acids and most substances in an experimental model of intestinal mucositis

Purpose: To evaluate the long-chain fatty acid and major compounds levels in the feces after prophylactic oral use of Lacticaseibacillus casei in an experimental model of intestinal mucositis. Methods: Fifteen Swiss mice were randomly divided into three groups (n=5/group): The negative or positive control groups (n = 5) received saline orally for 18 days and an the intraperitoneal (i.p.) of saline or 5 Fluorouracil (450 mg/kg) in 15th day, respectability. L. casei group received oral concentration of L. casei (1x109 CFU/mL) for 18 days, the i.p. injection of 5-fluorouracil (450 mg/kg) in 15th days. Tissue samples from colon and each small intestine segment were collected for histopathological analysis. Stool samples were collected. Fecal composition of long-chain fatty acids and sterols were analysed by gas chromatography-mass spectrometry on the 15th and the 18th day. Results: The mucosa layer of all small intestine segments of animals from L. casei showed well preserved epithelium and glands, without necrosis signs, but Goblet cells number decreased. Several long-chain fatty acids and sterols have been identified before and after in the groups. L. casei administration after 5-FU treatment reduced concentrations of linoleic acid (18:2) (p < 0.001) and oleic acid (18:1) (p < 0.001) in feces. Conclusions: L. casei prevented the mucosal damage associated with 5-FU-induced intestinal mucositis reduced long-chain fatty acid levels in the feces.

L-glutamine supplementation reduced morphological damage in the renal glomerulus of rats with Walker-256 tumor

ABSTRACT Purpose: To evaluate the effects of the experimental subcutaneous Walker-256 tumor and L-glutamine supplementation, an antioxidant, on the glomerular morphology of rats. Methods: Twenty Wistar rats were distributed into four groups (n = 5): control (C); control treated with 2% L-glutamine (CG); rats with Walker-256 tumor (WT); and rats with Walker-256 tumor treated with 2% L-glutamine (WTG). Renal histological samples were submitted to periodic acid-Schiff and Masson's Trichrome staining to analyze glomerular density, morphometry of glomerular components and glomerulosclerosis; and to immunohistochemistry for fibroblast growth factor-2 (FGF-2). Results: WT showed 50% reduction in body mass gain and cachexia index > 10%, while WTG demonstrated reduction in cachexia (p < 0.05). WT revealed reduction of glomerular density, increase in the glomerular tuft area, mesangial area, matrix in the glomerular tuft, decrease in the urinary space and synechia, and consequently higher glomerulosclerosis (p < 0.05). L-glutamine supplementation in the WTG improved glomerular density, and reduced glomerular tuft area, urinary space, mesangial area, and glomerulosclerosis compared to WT(p < 0.05). WT showed higher collagen area and FGF-2 expression compared to C (p < 0.05). WTG presented lower collagen fibers and FGF-2 expression compared to WT (p < 0.05). Conclusions: L-glutamine supplementation reduced cachexia and was beneficial for glomerular morphology of the rats, as well as it reduced kidney damage and improved the remaining glomeruli morphology.

Curcuma longa extract protects against 5-fluorouracil-induced oral mucositis in hamsters

Abstract Curcumin, contained at Turmeric (Curcumalonga), can exert many beneficial pleiotropic activities in the gastrointestinal tract. This study evaluated the antioxidant and anti-inflammatory activity of C. longa on 5-fluorouracil (5-FU)-induced oral mucositis (OM) in hamsters. Phytochemical analysis of crude C. longa extract (CLE) was performed to detect the presence of curcumin by TLC and HPLC. Golden Syrian hamsters were orally pre-treated with CLE (5, 50, or 100mg/kg). Cheek pouch samples were subjected to macroscopic and histopathological evaluation. ELISA was performed to quantify the inflammatory cytokines IL-1ß and TNF-α. Superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels were assessed by ultraviolet-visible spectroscopy analysis. Behavior analysis was conducted by the open field test. Curcumin content in the CLE was 0.55%m/m ± 0.0161 (2.84%). The group treated with 5mg/kg CLE showed healing evidence with macroscopic absence of ulceration (p<0.05) and microscopic aspect of re-epithelialization, discrete inflammatory infiltrate and absence of edema. Treatment with 5mg/kg CLE significantly increased GSH levels, and reduced MDA levels and SOD activity (p˂0.05), and decreased IL-1ß (p˂0.05) and TNF-α (p˂0.01) levels. A significant reduction in walking distance, ambulation, speed, and rearing was observed for motor activity. Curcumin reduced oxidative stress, inflammation, and motor activity in hamsters with 5-FU-induced OM.

Qualidade de vida, sintomas de depressão e adesão ao tratamento em pacientes com trantorno depressivo maior / Quality of life, depression symptoms and adherence to treatment in patients with major depressive disorder / Calidad de vida, síntomas depresión y adhesión al tratamiento en pacientes con trastorno depresivo mayor

Introdução:Pacientes com depressão maior geralmente respondem ao tratamento com medicamentos antidepressivos, no entanto em 10% a 30% dos casos há apenas uma resposta parcial ou nenhuma resposta, entre os fatores que podem influenciar encontra-se o perfil das enzimas hepáticas metabolizadoras dos antidepressivos, tal como a CYP2C19.Objetivo:Caracterizar os indivíduos quanto ao perfil genético dospolimorfismos CYP2C19*2 ou CYP2C19*17 em pacientes com transtorno depressivo maior (TDM) tratados com citalopram ou escitalopram e compará-los em relação a adesão ao tratamento, sintomas de depressão e qualidade de vida.Metodologia:Trata-se de um estudo transversal realizado com 29 pacientes com TDM. Amostras de sangue foram coletadas para genotipagem de CYP2C19 por discriminação alélica TaqMan®. Após caracterização do perfil genético, os indivíduos foram comparados quanto aos dados demográfico e socioeconômico, adesão ao tratamento (TestedeMorisky-Green),sintomas de depressão (escala de Hamilton) e qualidade de vida (WHOQoL-BREF).Resultados:Quatro pacientes (13.8%) apresentaram polimorfismo para CYP2C19*2 e 10 pacientes (34.4%) para CYP2C19*17, com maior prevalência de CYP2C19*17 (p>0.05). Nenhuma associação significativa de características socioeconômicas, demográficas e clínicas entre os genótipos do CYP2C19.No TestedeMorisky-Green, aadesão moderada ao tratamento foi predominante nos pacientes CYP2C19*2 e CYP2C19*17 (p>0.05). Não foi observada associação entre sintomas de depressão e polimorfismos genéticos (p>0.05). Uma associação significativa entre o genótipo polimórfico CC do CYP2C19*17 com a satisfação com a saúde, enquanto o genótipo CT foi associado ao estado "nem satisfeito/nem insatisfeito" (p<0.05). A maioria dos indivíduos CYP2C19*2 e CYP2C19*17 relatou "necessidade de melhorar" em relação aos domínios de qualidade de vida físico, psicológico, social e ambiental (p>0.05).Conclusões:Os pacientes apresentaram maior prevalência do polimorfismo CYP2C19*17, com moderada adesão ao tratamento. Alguns pacientes, mesmo sob efeito da medicação, apresentaram sintomas de depressão moderado a intenso e relataram uma indefinição na satisfação da sua qualidade de vida (AU).

Introduction:Patients with major depression usually respond to treatment with antidepressant drugs, however in 10% to 30% of cases there is only a partial response or no response, among the factors that can influence is the profile of liver enzymes metabolizing antidepressants, such as CYP2C19.Objective:To characterize the individuals regarding the genetic profile ofCYP2C19*2or CYP2C19*17 polymorphisms in patients with major depressive disorder (MDD) treated with citalopram or escitalopram, and to compare themaccording to treatment adherence, symptoms of depression and quality of life.Methodology:This is cross-sectionalstudy carried out with 29 patients with MDD. Blood samples were collected for CYP2C19 genotyping by TaqMan® allelic discrimination. After characterization of the genetic profile, the individuals were compared regarding the demographic and socioeconomic data, treatment adherence (Morisky-GreenTest), symptoms of depression (Hamilton scale) and quality of life (WHOQoL-BREF).Results:Four patients showed (13.8%) CYP219*2 and 10 patients (34.4%) CYP219*17 polymorphisms.,withhigher prevalence of CYP219*17 (p>0.05). No association between socioeconomic, demographic, and clinical features with CYP2C19 genotypes was observed. In Morisky-GreenTest, moderate adherence to treatment was predominant for CYP2C19*2 and CYP219*17 patients (p>0.05). No statistically significant association was observed between symptoms of depression and genetic polymorphisms (p>0.05). A significant association between polymorphic CC genotype of CYP219*17 with health satisfaction, while the CT genotype was associated with "neither satisfied/nor dissatisfied" status (p<0.05). Most of the CYP2C19*2 and CYP2C19*17 subjects reported "need to improve" or "regular" regarding physical, psychological, social, and environmental domainsof quality of life(p>0.05).Conclusions:The patients showed a higher prevalence of CYP219*17 polymorphism, with moderate treatment adherence. Some subjects, even under the effect of the medication, presented moderate to intense symptoms of depression, and reported a lack of definition in the satisfaction of their quality of life (AU).

Introducción:Los pacientes con depresión mayor responder al tratamiento con antidepresivos, en 10% al 30% de los casos existe una respuesta parcial o nula, entre los factores que pueden influir se encuentra el perfil de enzimas hepáticas metabolizadoras de antidepresivos, como CYP2C19.Objetivo: Caracterizar a los individuos en cuanto al perfil genético depolimorfismos CYP2C19 *2 o CYP2C19 * 17 en pacientes con trastorno depresivo mayor (TDM) tratados con citalopram o escitalopram y compararlos en relaciónpara la adherencia al tratamiento, síntomas de depresión y la calidad de vida.Metodología: Estudio transversalcon 29 pacientes con TDM. Se recogieron muestras de sangre para la determinación del genotipo CYP2C19 mediante discriminación alélica TaqMan®, los individuos fueron comparados en cuanto a los datosdemográficosy socioeconómicos, adherencia (Prueba de Morisky-Green), síntomas de depresión (escala de Hamilton) y calidad de vida (WHOQoL-BREF).Resultados: Cuatro pacientes (13,8%) con polimorfismo CYP2C19*2 y 10 (34,4%) con CYP2C19 * 17,(p> 0,05). No existe una asociación significativa de las características socioeconómicas, demográficas y clínicas con los genotipos CYP2C19. La adherencia moderada al tratamiento fue predominante en los pacientes con CYP2C19*2 y CYP2C19*17 (p> 0,05). No hubo asociación entre síntomas de depresión y polimorfismos genéticos (p> 0.05). Una asociación significativa entre el genotipo polimórfico CYP2C19 * 17 CC con la satisfacción con la salud, mientras que el genotipo CT se asoció con el estado "ni satisfecho / no insatisfecho" (p <0.05). La mayoría de CYP2C19 * 2 y CYP2C19 * 17 individuos informaron "necesidad de mejorar" en relación con los dominios físico, psicológico, social y ambientalde calidad de vida(p> 0,05).Conclusiones: Los pacients mostraron una mayor prevalencia del CYP2C19 * 17, con adherencia moderada al tratamiento, síntomas de depresión moderada a intensay informaron una falta de definición en la satisfacción de su calidad de vida (AU).

The Receptor AT1 Appears to Be Important for the Maintenance of Bone Mass and AT2 Receptor Function in Periodontal Bone Loss Appears to Be Regulated by AT1 Receptor.

A large number of experimental studies has demonstrated that angiotensin II (Ang II) is involved in key events of the inflammatory process. This study aimed to evaluate the role of Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors on periodontitis. Methods: Experimental periodontitis was induced by placing a 5.0 nylon thread ligature around the second upper left molar of AT1 mice, no-ligature or ligature (AT1-NL and AT1-L), AT2 (AT2-NL or AT2-L) and wild type (WT-NL or L). Alveolar bone loss was scanned using Micro-CT. Cytokines, peptides and enzymes were analyzed from gingival tissues by Elisa and RT-PCR. Results: The blockade of AT1 receptor resulted in bone loss, even in healthy animals. Ang II receptor blockades did not prevent linear bone loss. Ang II and Ang 1-7 levels were significantly increased in the AT2-L (p < 0.01) group compared to AT2-NL and AT1-L. The genic expression of the Mas receptor was significantly increased in WT-L and AT2-L compared to (WT-NL and AT2-NL, respectively) and in AT1-L. Conclusions: Our data suggest that the receptor AT1 appears to be important for the maintenance of bone mass. AT2 receptor molecular function in periodontitis appears to be regulated by AT1.

Defocused high-power diode laser accelerates skin repair in a murine model through REDOX state modulation and reepithelization and collagen deposition stimulation.

Skin wounds represent a burden in healthcare. Our aim was to investigate for the first time the effects of defocused high-power diode laser (DHPL) on skin healing in an animal experimental model and compare it with gold standard low-level laser therapy. Male Wistar rats were divided into 5 groups: Negative control; Sham; 0.1 W laser (L0.1 W); DHPL Dual 1 W (DHPLD1 W); and DHPL Dual 2 W (DHPLD2 W). Rats were euthanized on days 3, 5, 10, 14 and 21. Clinical, morphological, PicroSirus, oxidative stress (MDA, SOD and GSH) and cytokines (IL-1ß, IL-10 and TNF-α) analyses were performed. A faster clinical repair was observed in all laser groups at D10 and D14. DHPLD1 W exhibited lower inflammation and better reepithelization compared to other groups at D10. DHPL protocols modulated oxidative stress by decreasing MDA and increasing SOD and GSH. Collagen maturation was triggered by all protocols tested and L0.1 W modulated cytokines release (IL-1ß and TNF-α) at D3. In conclusion, DHPL, especially DHPL1 W protocol, accelerated skin healing by triggering reepithelization and collagen maturation and modulating inflammation and oxidative stress.

AT1 and AT2 Receptor Knockout Changed Osteonectin and Bone Density in Mice in Periodontal Inflammation Experimental Model.

BACKGROUND: The aim of this study was to evaluate the role of AT1 and AT2 receptors in a periodontal inflammation experimental model. METHODS: Periodontal inflammation was induced by LPS/Porphyromonas gingivalis. Maxillae, femur, and vertebra were scanned using Micro-CT. Maxillae were analyzed histopathologically, immunohistochemically, and by RT-PCR. RESULTS: The vertebra showed decreased BMD in AT1 H compared with WT H (p < 0.05). The femur showed increased Tb.Sp for AT1 H and AT2 H, p < 0.01 and p < 0.05, respectively. The Tb.N was decreased in the vertebra (WT H-AT1 H: p < 0.05; WT H-AT2 H: p < 0.05) and in the femur (WT H-AT1 H: p < 0.01; WT H-AT2 H: p < 0.05). AT1 PD increased linear bone loss (p < 0.05) and decreased osteoblast cells (p < 0.05). RANKL immunostaining was intense for AT1 PD and WT PD (p < 0.001). OPG was intense in the WT H, WT PD, and AT2 PD when compared to AT1 PD (p < 0.001). AT1 PD showed weak immunostaining for osteocalcin compared with WT H, WT PD, and AT2 PD (p < 0.001). AT1 H showed significantly stronger immunostaining for osteonectin in fibroblasts compared to AT2 H (p < 0.01). CONCLUSION: AT1 receptor knockout changed bone density, the quality and number of bone trabeculae, decreased the number of osteoblast cells, and increased osteonectin in fibroblasts.

Gliclazide reduced oxidative stress, inflammation, and bone loss in an experimental periodontal disease model.

OBJECTIVE: The aim of this study was to evaluate the effects of gliclazide on oxidative stress, inflammation, and bone loss in an experimental periodontal disease model. MATERIAL AND METHODS: Male albino Wistar rats were divided into no ligature, ligature, and ligature with 1, 5, and 10 mg/kg gliclazide groups. Maxillae were fixed and scanned using micro-computed tomography to quantify linear and bone volume/tissue volume (BV/TV) and volumetric bone loss. Histopathological, immunohistochemical and immunofluorescence analyses were conducted to examine matrix metalloproteinase-2 (MMP-2), cyclooxygenase 2 (COX-2), cathepsin K, members of the receptor activator of the nuclear factor kappa-Β ligand (RANKL), receptor activator of nuclear factor kappa-Β (RANK), osteoprotegerin (OPG) pathway, macrophage migration inhibitory factor (MIF), superoxide dismutase-1 (SOD-1), glutathione peroxidase-1 (GPx-1), NFKB p 50 (Cytoplasm), NFKB p50 NLS (nuclear localization signal), PI3 kinase and AKT staining. Myeloperoxidase activity, malondialdehyde and glutathione levels, while interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) levels were evaluated by spectroscopic ultraviolet-visible analysis. A quantitative reverse transcription polymerase chain reaction was used to quantify the gene expression of the nuclear factor kappa B p50 subunit (NF-κB p50), phosphoinositide 3-kinase (PI3k), protein kinase B (AKT), and F4/80. RESULTS: Micro-computed tomography showed that the 1 mg/kg gliclazide treatment reduced linear bone loss compared to the ligature, 5 mg/kg gliclazide, and 10 mg/kg gliclazide treatments. All concentrations of gliclazide increased bone volume/tissue volume (BV/TV) compared to the ligature group. Treatment with 1 mg/kg gliclazide reduced myeloperoxidase activity, malondialdehyde, IL-1ß, and TNF-α levels (p≤0.05), and resulted in weak staining for COX-2, cathepsin k, MMP-2, RANK, RANKL, SOD-1, GPx-1,MIF and PI3k. In addition, down-regulation of NF-κB p50, PI3k, AKT, and F4/80 were observed, and OPG staining was strong after the 1 mg/kg gliclazide treatment. CONCLUSIONS: This treatment decreased neutrophil and macrophage migration, decreased the inflammatory response, and decreased bone loss in rats with ligature-induced periodontitis.

Gliclazide reduced oxidative stress, inflammation, and bone loss in an experimental periodontal disease model

Abstract Objective The aim of this study was to evaluate the effects of gliclazide on oxidative stress, inflammation, and bone loss in an experimental periodontal disease model. Material and Methods Male albino Wistar rats were divided into no ligature, ligature, and ligature with 1, 5, and 10 mg/kg gliclazide groups. Maxillae were fixed and scanned using micro-computed tomography to quantify linear and bone volume/tissue volume (BV/TV) and volumetric bone loss. Histopathological, immunohistochemical and immunofluorescence analyses were conducted to examine matrix metalloproteinase-2 (MMP-2), cyclooxygenase 2 (COX-2), cathepsin K, members of the receptor activator of the nuclear factor kappa-Β ligand (RANKL), receptor activator of nuclear factor kappa-Β (RANK), osteoprotegerin (OPG) pathway, macrophage migration inhibitory factor (MIF), superoxide dismutase-1 (SOD-1), glutathione peroxidase-1 (GPx-1), NFKB p 50 (Cytoplasm), NFKB p50 NLS (nuclear localization signal), PI3 kinase and AKT staining. Myeloperoxidase activity, malondialdehyde and glutathione levels, while interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels were evaluated by spectroscopic ultraviolet-visible analysis. A quantitative reverse transcription polymerase chain reaction was used to quantify the gene expression of the nuclear factor kappa B p50 subunit (NF-κB p50), phosphoinositide 3-kinase (PI3k), protein kinase B (AKT), and F4/80. Results Micro-computed tomography showed that the 1 mg/kg gliclazide treatment reduced linear bone loss compared to the ligature, 5 mg/kg gliclazide, and 10 mg/kg gliclazide treatments. All concentrations of gliclazide increased bone volume/tissue volume (BV/TV) compared to the ligature group. Treatment with 1 mg/kg gliclazide reduced myeloperoxidase activity, malondialdehyde, IL-1β, and TNF-α levels (p≤0.05), and resulted in weak staining for COX-2, cathepsin k, MMP-2, RANK, RANKL, SOD-1, GPx-1,MIF and PI3k. In addition, down-regulation of NF-κB p50, PI3k, AKT, and F4/80 were observed, and OPG staining was strong after the 1 mg/kg gliclazide treatment. Conclusions This treatment decreased neutrophil and macrophage migration, decreased the inflammatory response, and decreased bone loss in rats with ligature-induced periodontitis.

Metformin Hydrochloride-Loaded PLGA Nanoparticle in Periodontal Disease Experimental Model Using Diabetic Rats.

Evidence shows that metformin is an antidiabetic drug, which can exert favorable anti-inflammatory effects and decreased bone loss. The development of nanoparticles for metformin might be useful for increased therapeutic efficacy. The aim of this study was to evaluate the effect of metformin hydrochloride-loaded Poly (d,l-Lactide-co-glycolide) (PLGA)/(MET-loaded PLGA) on a ligature-induced periodontitis model in diabetic rats. MET-loaded PLGA were characterized by mean diameter, particle size, polydispensity index, and entrapment efficiency. Maxillae were scanned using Microcomputed Tomography (µCT) and histopathological and immunohistochemical analysis. IL-1ß and TNF-α levels were analyzed by ELISA immunoassay. Quantitative RT-PCR was used (AMPK, NF-κB p65, HMGB1, and TAK-1). The mean diameter of MET-loaded PLGA nanoparticles was in a range of 457.1 ± 48.9 nm (p < 0.05) with a polydispersity index of 0.285 (p < 0.05), Z potential of 8.16 ± 1.1 mV (p < 0.01), and entrapment efficiency (EE) of 66.7 ± 3.73. Treatment with MET-loaded PLGA 10 mg/kg showed low inflammatory cells, weak staining by RANKL, cathepsin K, OPG, and osteocalcin, and levels of IL-1ß and TNF-α (p < 0.05), increased AMPK expression gene (p < 0.05) and decreased NF-κB p65, HMGB1, and TAK-1 (p < 0.05). It is concluded that MET-loaded PLGA decreased inflammation and bone loss in periodontitis in diabetic rats.

Protective effect of angiotensin II receptor blocker against oxidative stress and inflammation in an oral mucositis experimental model.

BACKGROUND: The aim of this study was to evaluate the effect of olmesartan medoxomil (Olme), an angiotensin II receptor antagonist, on oral mucositis (OM) experimental model. METHODS: Oral mucositis was induced in hamsters with 5-fluorouracil (5-FU; 60 mg/kg day 1 and 40 mg/kg day 2). Animals (n = 10/group) were pretreated with oral Olme (1, 5, or 10 mg/kg) or vehicle 30 minutes before 5-FU injection and daily, until day 10. Cheek pouch samples were subjected to histopathological and immunostaining analysis of IL-1ß, TNF-α, IL-10, TGF-ß, macrophage migration inhibitory factor (MIF), SOD, MMP-2 and FGF-2. In addition, IL-1ß and TNF-α levels were evaluated by ELISA. Myeloperoxidase activity (MPO), glutathione (GSH) and malondialdehyde (MDA) levels were investigated by spectroscopic UV/VIS analysis. Reverse transcriptase polymerase chain reactions (RT-PCRs) were used to quantify the expression of IL-1ß, TNF-α, NF-κBp65, MKP1 and ACE2. Inducible nitric oxide synthase (iNOS) and extracellular regulated kinase (ERK)1/2 protein levels were analysed by Western blot. RESULTS: Treatment with 10 mg/kg Olme reduced ulceration, inflammatory cell infiltration, MPO activity, MDA levels, iNOS and ERK1/2 proteins levels, MIF expression and TNF-α and IL-1ß of levels and gene expression. These findings were associated with a significant increase in the immunostaining of IL-10, FGF-2 and TGF-ß. In addition, gene expression of IL-1ß, TNF-α, NF-κBp65 MKP1 and ACE2 was decreased. CONCLUSION: Olmesartan at a dose of 10 mg/kg prevented the mucosal damage and inflammation associated with 5-FU-induced OM, increasing granulation and tissue repair.

In-office tooth bleaching with 38% hydrogen peroxide promotes moderate/severe pulp inflammation and production of ll-1ß, TNF-ß, GPX, FGF-2 and osteocalcin in rats.

OBJECTIVES: To study the intensity of inflammatory infiltrate and production of interleukin-1ß (ll-1ß), tumor necrosis factor-ß (TNF-ß), fibroblast growth factor-2 (FGF-2), glutathione peroxidase (GPX), and osteocalcin in response to in-office tooth bleaching in rats. MATERIAL AND METHODS: Twenty male Wistar rats were randomized into four groups (n=5) according to the received treatment (tooth bleaching or no treatment - control) and the period of euthanasia after treatment (24 h or 10 days). We performed tooth bleaching using a 38% hydrogen peroxide gel on maxillary and mandibular incisors. After euthanasia, incisors (20 per group) were processed for histological analysis, immunohistochemistry staining of ll-1ß, TNF-ß, FGF-2 and GPX and osteocalcin by immunofluorescence. We analyzed data using the Mann-Whitney and Kruskal-Wallis/Dunn tests (p<0.05). RESULTS: The bleached groups presented statistically significant differences regarding the pulp inflammation stage compared with the control groups. Bleached teeth showed moderate/severe inflammatory infiltrate and control groups presented absent inflammatory cells or a negligible number of mononuclear cells (p<0.001) at two times (24 h and 10 days). There was strong staining for ll-1ß, TNF-ß, and GPX in bleached groups at 24 h and strong staining for ll-1ß, TNF-ß, GPX and FGF-2 at 10 days. After 10 days of tooth bleaching, the bleached group showed a statistically superior amount of osteocalcin than the other groups (p<0.01). CONCLUSIONS: Tooth bleaching with 38% hydrogen peroxide causes severe pulp inflammation, but characteristics of tissue repair after 10 days.

Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis.

AIM: To evaluate the effects of metformin (Met) on inflammation, oxidative stress, and bone loss in a rat model of ligature-induced periodontitis. MATERIALS & METHODS: Male albino Wistar rats were divided randomly into five groups of twenty-one rats each, and given the following treatments for 10 days: (1) no ligature + water, (2) ligature + water, (3) ligature + 50 mg/kg Met, (4) ligature + 100 mg/kg Met, and (5) ligature + 200 mg/kg Met. Water or Met was administered orally. Maxillae were fixed and scanned using Micro-computed Tomography (µCT) to quantitate linear and bone volume/tissue volume (BV/TV) volumetric bone loss. Histopathological characteristics were assessed through immunohistochemical staining for MMP-9, COX-2, the RANKL/RANK/OPG pathway, SOD-1, and GPx-1. Additionally, confocal microscopy was used to analyze osteocalcin fluorescence. UV-VIS analysis was used to examine the levels of malondialdehyde, glutathione, IL-1ß and TNF-α from gingival tissues. Quantitative RT-PCR reaction was used to gene expression of AMPK, NF-κB (p65), and Hmgb1 from gingival tissues. Significance among groups were analysed using a one-way ANOVA. A p-value of p<0.05 indicated a significant difference. RESULTS: Treatment with 50 mg/kg Met significantly reduced concentrations of malondialdehyde, IL-1ß, and TNF-α (p < 0.05). Additionally, weak staining was observed for COX-2, MMP-9, RANK, RANKL, SOD-1, and GPx-1 after 50 mg/kg Met. OPG and Osteocalcin showed strong staining in the same group. Radiographically, linear measurements showed a statistically significant reduction in bone loss after 50 mg/kg Met compared to the ligature and Met 200 mg/kg groups. The same pattern was observed volumetrically in BV/TV and decreased osteoclast number (p<0.05). RT-PCR showed increased AMPK expression and decreased expression of NF-κB (p65) and HMGB1 after 50 mg/kg Met. CONCLUSIONS: Metformin, at a concentration of 50 mg/kg, decreases the inflammatory response, oxidative stress and bone loss in ligature-induced periodontitis in rats.

Libidibia ferrea presents antiproliferative, apoptotic and antioxidant effects in a colorectal cancer cell line.

Colorectal cancer is noted for being one of the most frequent of tumors, with expressive morbidity and mortality rates. In new drug discovery, plants stand out as a source capable of yielding safe and high-efficiency products. Well known in Brazilian popular medicine, Libidibia ferrea (Mart. Ex Tul.) L.P. Queiroz var. ferrea (better known as "ironwood" or "jucá"), has been used to treat a wide spectrum of conditions and to prevent cancer. Using methodologies that involved flow cytometry, spectrophotometry and RT-qPCR assays, crude extracts of the fruits of L. ferrea (20T, 40T, 60T and 80T) were evaluated at 24h and/or 48h for: their ability to inhibit cell proliferation; induce apoptosis through Bcl-2, caspase-3 and Apaf-1; their antioxidant activity and effects on important targets related to cell proliferation (EGFR and AKT) in the HT-29 human colorectal cancer lineage. The results revealed high antiproliferative potential as compared to the controls, induction of apoptosis through the intrinsic pathway, and probable tumor inhibition activity under the mediation of important targets in tumorigenesis. In addition, L. ferrea revealed antioxidant, lipid peroxidation and chemoprotective effects in healthy cells. Thus, L. ferrea derivatives have important anticancer effects, and may be considered promising candidate for colorectal cancer therapy.

[Consumption of anxiolytic benzodiazepines: a correlation between SNGPC data and sociodemographic indicators in Brazilian capitals]. / Consumo de ansiolíticos benzodiazepínicos: uma correlação entre dados do SNGPC e indicadores sociodemográficos nas capitais brasileiras.

The scope of this article is to determine the distribution and frequency of consumption of anxiolytic benzodiazepines and the correlation between consumption and demographic, epidemiological, economic and social characteristics. It is an ecological study with a sample of 27 state capitals. Data collection was performed through the ANVISA database for the dispensation of Alprazolam, Bromazepam, Clonazepam, Diazepam and Lorazepam in 2010-2012, the 2010 Demographic Census (IBGE), DATASUS and Medical Demographic Research. Descriptive statistical analysis and multiple linear regression analyses were performed for data analysis. The northern region has capitals with the lowest and the southeast has capitals with the highest average consumption of these products. The average consumption for the population of all capitals was 3.60 DHD. Alprazolam is the drug most dispensed by pharmacies and private drugstores with average 2.00 DHD for the capitals. Multiple linear regression analysis showed that 76% of the variation was explained by population density (ß = 0.310 p = 0.045) and percentage of physicians (ß = 0.507 p = 0.016). The consumption of short half-life anxiolytics has been on the increase, mainly in the cities of greater population density and concentration of physicians.

Consumo de ansiolíticos benzodiazepínicos: uma correlação entre dados do SNGPC e indicadores sociodemográficos nas capitais brasileiras / Consumption of anxiolytic benzodiazepines: a correlation between SNGPC data and sociodemographic indicators in Brazilian capitals

Resumo O objetivo do artigo é conhecer a distribuição e a frequência de consumo de ansiolíticos benzodiazepínicos, bem como avaliar a correlação entre consumo e características demográficas, epidemiológicas, econômicas e sociais. Estudo ecológico tendo como unidade amostral as 27 capitais brasileiras. A coleta de dados foi executada através do banco da Anvisa, para a dispensação do Alprazolam, Bromazepam, Clonazepam, Diazepam e Lorazepam, de 2010 a 2012, do Censo Demográfico 2010 (IBGE), Datasus e da pesquisa Demografia Médica. A análise estatística descritiva e a de regressão linear múltipla foram realizadas para análise dos dados. A região Norte possui as capitais com menores médias de consumo desses medicamentos e o Sudeste as mais elevadas. O consumo médio para a população de todas as capitais foi de 3,60 DHD. O Alprazolam é o mais dispensado pelas farmácias e drogarias particulares, com média de 2,00 DHD para as capitais. A análise de regressão linear múltipla demonstrou que 76% da variância do consumo foi explicada pela variação da densidade demográfica (β = 0,310 p = 0,045) e percentual de médicos (β = 0,507 p = 0,016). O consumo de ansiolíticos de meia vida curta vem crescendo ao longo dos anos, principalmente nas capitais de maior densidade demográfica e concentração de médicos.

Abstract The scope of this article is to determine the distribution and frequency of consumption of anxiolytic benzodiazepines and the correlation between consumption and demographic, epidemiological, economic and social characteristics. It is an ecological study with a sample of 27 state capitals. Data collection was performed through the ANVISA database for the dispensation of Alprazolam, Bromazepam, Clonazepam, Diazepam and Lorazepam in 2010-2012, the 2010 Demographic Census (IBGE), DATASUS and Medical Demographic Research. Descriptive statistical analysis and multiple linear regression analyses were performed for data analysis. The northern region has capitals with the lowest and the southeast has capitals with the highest average consumption of these products. The average consumption for the population of all capitals was 3.60 DHD. Alprazolam is the drug most dispensed by pharmacies and private drugstores with average 2.00 DHD for the capitals. Multiple linear regression analysis showed that 76% of the variation was explained by population density (β = 0.310 p = 0.045) and percentage of physicians (β = 0.507 p = 0.016). The consumption of short half-life anxiolytics has been on the increase, mainly in the cities of greater population density and concentration of physicians.

Azilsartan increases levels of IL-10, down-regulates MMP-2, MMP-9, RANKL/RANK, Cathepsin K and up-regulates OPG in an experimental periodontitis model.

AIMS: The aim of this study was to evaluate the effects of azilsartan (AZT) on bone loss, inflammation, and the expression of matrix metallo proteinases (MMPs), receptor activator of nuclear factor κB ligand (RANKL), receptor activator of nuclear factor κB (RANK), osteoprotegerin (OPG), cyclooxygenase-2 (COX-2), and cathepsin K in periodontal tissue in a rat model of ligature-induced periodontitis. MATERIALS AND METHODS: Male Wistar albino rats were randomly divided into 5 groups of 10 rats each: (1) nonligated, water; (2) ligated, water; (3) ligated, 1 mg/kg AZT; (4) ligated, 5 mg/kg AZT; and (5) ligated, 10 mg/kg AZT. All groups were treated with saline or AZT for 10 days. Periodontal tissues were analyzed by histopathology and immunohistochemical detection of MMP-2, MMP-9, COX-2, RANKL, RANK, OPG, and cathepsin K. Levels of IL-1ß, IL-10, TNF-α, myeloperoxidase (MPO), and glutathione (GSH) were determined by ELISA. RESULTS: Treatment with 5 mg/kg AZT resulted in reduced MPO (p<0.05) and IL-1ß (p<0.05), increased levels of IL-10 (p<0.05), and reduced expression of MMP-2, MMP-9, COX-2, RANK, RANKL, cathepsin K, and increased expression of OPG. CONCLUSIONS: These findings reveal that AZT increases anti-inflammatory cytokines and GSH and decreases bone loss in ligature-induced periodontitis in rats.