Relación de IMC con marcadores de inflamación y hemoglobina glicosilada en niños y jóvenes con diabetes mellitus 1 / Relationship of BMI with markers of inflammation and glycosylated hemoglobin in children and young adults with diabetes mellitus 1

La diabetes mellitus tipo 1 (DM1) es una enfermedad autoinmune que genera dependencia exógena de insulina de forma permanente, presenta inflamación subclínica crónica lo que conlleva a una elevación de marcadores de inflamación como factor de necrosis tumoral alfa (TNF-α), proteína C reactiva (PCR) e interleuquina 6 (IL-6). OBJETIVO: determinar la relación entre el IMC sobre los marcadores de inflamación y el control metabólico en niños y jóvenes con DM1 entre 5 a 15 años de edad. METODOLOGÍA: Se realizó un estudio clínico, observacional, exploratorio. A partir de La recolección de datos de fichas clínicas y muestras de sangre en el Instituto de Investigaciones Materno Infantil (IDIMI) del Hospital San Borja Arriarán de la Universidad de Chile. Clasificación del estado nutricional utilizando datos registrados en ficha clínica. Marcadores de inflamación por medio de ELISA, hemoglobina glicosilada mediante métodos estándares. El análisis estadístico incluyó correlaciones mediante test de Spearman y diferencia de medias mediante test de Kruskal-Wallis seguido de post hoc Dunns. RESULTADOS: Un 30% de los pacientes con DM1 presentaron malnutrición por exceso. Al analizar la relación entre los niveles de marcadores inflamatorios y Hb glicosilada se observó la existencia de asociacion positiva entre usPCR y HbA1c (r= 0,30; p=0,0352) y entre IL-6 y HbA1c (r= - 0,038; p=0,0352). CONCLUSIONES: este estudio describe una posible asociación entre parámetros clásicos de inflamación con la hemoglobina glicosilada en las categorias de sobrepeso y obesidad en pacientes con DM1.

Type 1 diabetes mellitus (T1D) is an autoimmune disease that generates permanent exogenous insulin dependence, accompanied by chronic subclinical inflammation that leads to an elevation of inflammation markers such as tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP) and interleukin-6 (IL-6). OBJECTIVE: To determine the relationship between BMI on markers of inflammation and metabolic control in children and young people with T1D between 5 and 15 years of age. METHODOLOGY: A clinical, observational and exploratory study was carried out, based on the collection of data from clinical records and blood samples of children and adolescents with DM1 at the Instituto de Investigaciones Materno Infantil (IDIMI) of the Hospital San Borja Arriarán of the Universidad de Chile. Nutritional status, levels of inflammation markers and glycosylated hemoglobin were determined by standardized methods. Statistical analysis included correlations by Spearman test and mean difference by Kruskal-Wallis test followed by post hoc Dunns test. RESULTS: A total of 56 patients with T1D were analyzed, 30% of whom presented excess malnutrition. Those children or adolescents with obesity presented significantly higher usPCR levels compared to underweight patients or patients at risk of malnutrition (p=0.039). In addition, HbA1c levels were determined which were negatively associated with usPCR (r= 0.30; p=0.0352) and IL-6 (r= - 0.038; p=0.0352) levels. CONCLUSIONS: This study points out that nutritional status is associated with usPCR levels, in agreement with what is described in the literature and shows a possible association between classical parameters of inflammation with glycosylated hemoglobin in children and adolescents with nutritional diagnosis of overweight or obesity.

Protective effects of melatonin in cisplatin-induced cardiac toxicity: possible role of BDNF-TNF-α signaling pathway

Purpose: The present study explored the role of melatonin in cisplatin-induced cardiac injury along with the possible role of brain-derived neurotrophic factor (BDNF) in melatonin-mediated effects. Methods: Wistar rats were administered cisplatin (10 mg/kg), and cardiac injury was assessed by measuring the levels of cardiac troponin (cTnT) and lactate dehydrogenase (LDH-1).The extent of apoptosis was measured by measuring caspase-3 (pro-apoptotic) and Bcl-2 (anti-apoptotic) in hearts. The levels of BDNF, tumour necrosis factor α (TNF-α) and reduced glutathione were measured in heart. Melatonin (5 and 10 mg/kg) was administered for 15 days, and the role of BDNF was identified by co-administering BDNF inhibitor, ANA-12 (0.25 and 0.5 mg/kg). Results: Melatonin attenuated cTnT and LDH-1 levels along with reduction in caspase-3 and increase in Bcl-2. It also increased cisplatin-induced decrease in BDNF, increase in TNF-α and decrease in reduced glutathione levels. Moreover, ANA-12 abolished the cardioprotective effects, anti-inflammatory and antioxidant effects of melatonin suggesting the role of BDNF in melatonin-mediated effects in cisplatin-induced cardiac injury. Conclusions: Melatonin is useful in cisplatin-induced cardiac injury, which may be due to an increase in BDNF, decrease in inflammation and increase in antioxidant activities.

Detection of respiratory viruses and expression of inflammatory cytokines in patients with acute exacerbation chronic obstructive pulmonary disease in Mongolia China / Detecção de vírus respiratórios e expressão de citocinas inflamatórias em pacientes com doença pulmonar obstrutiva crônica de exacerbação aguda na Mongólia, China

Chronic obstructive pulmonary disease (COPD) was estimated to be the third cause of global mortality by 2020. Acute exacerbation COPD (AECOPD) is a sudden worsening of COPD symptoms and could be due to virus/bacterial infections and air pollution. Increased expression of inflammatory markers in patients with AECOPD is associated with viral infection. This study aimed to detect different viruses and analyze the expression of various inflammatory markers associated with AECOPD patients. Three hundred and forty-seven patients diagnosed with COPD according to GOLD criteria were included in this study. Swab samples and blood were collected for the detection of viruses by RT-PCR and expression of inflammatory markers, respectively. Of the swab samples, 113 (32.6%) of samples were positive for virus detection. Of these, HRV (39.8%) was the predominant virus detected followed by FluB (27.4%) and FluA (22.1%). The presence of HRV was significantly higher (p=0.044) among the other detected viruses. When compared to healthy controls the expression levels of TNF-α, IL-6 and IL-8 were significantly higher (p<0.05) in virus-positive patients. The IL-6 and IL-8 were the next predominantly expressed in markers among the samples. The higher expression rate of IL-8 was significantly (p<0.05) associated with patients having COPD GOLD III severity level and smoking history. Although HRV was the predominant virus detected the combined prevalence of Influenza A and B surpassing the rate of HRV. The high-level expression of well known inflammatory markers of AECOPD, TNF-α, IL-6 and IL-8 indicates a chronic severe illness. These markers play an important role and could be used as a marker for determining the severity of AECOPD.

Estima-se que a doença pulmonar obstrutiva crônica (DPOC) seja a terceira causa de mortalidade global em 2020. A exacerbação aguda DPOC (AECOPD) é um agravamento súbito dos sintomas da DPOC e pode ser devido a infecções por vírus/bactérias e poluição do ar. O aumento da expressão de marcadores inflamatórios em pacientes com AECOPD está associado à infecção viral. Este estudo teve como objetivo detectar diferentes vírus e analisar a expressão de vários marcadores inflamatórios associados a pacientes com AECOPD. Trezentos e quarenta e sete pacientes com diagnóstico de DPOC de acordo com os critérios GOLD foram incluídos neste estudo. Amostras de swab e sangue foram coletadas para detecção de vírus por RT-PCR e expressão de marcadores inflamatórios, respectivamente. Das amostras de esfregaço, 113 (32,6%) amostras foram positivas para detecção de vírus. Nestas, o HRV (39,8%) foi o vírus predominante detectado, seguido do FluB (27,4%) e do FluA (22,1%). A presença de VFC foi significativamente maior (p = 0,044) entre os demais vírus detectados. Quando comparados a controles saudáveis, os níveis de expressão de TNF-α, IL-6 e IL-8 foram significativamente maiores (p <0,05) em pacientes com vírus positivo. A IL-6 e a IL-8 foram as próximas predominantemente expressas em marcadores entre as amostras. A maior taxa de expressão de IL-8 foi significativamente (p <0,05) associada a pacientes com grau de gravidade GOLD III da DPOC e história de tabagismo. Embora o HRV tenha sido o vírus predominante, a prevalência combinada de Influenza A e B ultrapassou a taxa de HRV. O alto nível de expressão de marcadores inflamatórios bem conhecidos de AECOPD, TNF-α, IL-6 e IL-8 indica uma doença crônica grave. Esses marcadores desempenham um papel importante e podem ser usados como um marcador para determinar a gravidade da AECOPD.

Changes in somatic cell count, composition and cytokine levels in milk from cows with mastitis due to mixed infections

Mastitis is a mammary gland inflammation that is very common worldwide, mostly caused by bacteria, and causes enormous economic losses. Many microorganisms cause this disease. The most common causes of mastitis by these microorganisms are Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and Streptococcus agalactiae (S. agalactiae). The anti-inflammatory properties of transforming growth factor (TGF)-ß include: 1) limiting interferon (IFN)-γ production; 2) increasing the expression of the interleukine (IL)-1 receptor antagonist; 3) inhibiting macrophage production of chemokines, pro-inflammatory cytokines, nitric oxide, and reactive oxygen intermediates; and 4) increasing macrophage clearance of bacterial debris and damaged parenchymal cells. It is stated that cytokines and milk composition change in case of mastitis. In this study, it was aimed to reveal the changes in milk TGF-ß1 and Tumor necrosis factor (TNF)-α concentrations and milk composition in mixed infections caused by three pathogens causing mastitis. In this study, milk samples from 90 cows were divided into 5 groups. Tumor necrosis factor (TNF)-α and TGF-ß1 concentrations and milk composition were determined in these milk samples. The California Mastitis Test (CMT) was applied to the cows included in the study and scoring was done. According to the CMT results of the milk samples taken, CMT(-) cows were included in group 1 (n = 22). Those with the CMT(+) were sent to the microbiology laboratory for analysis within 2 h. After the bacteria was determined, combination groupings were formed. Group 2 (n = 17), in which S. aureus and E. coli grew together, group 3 (n = 21), in which S. aureus and S. agalactiae grew together, group 4 (n = 8), in which S. agalactiae and E. coli grew together in milk samples, and milk samples without any bacterial growth in CMT (+) formed group 5 (n = 22), respectively. Somatic cell count was measured with the DeLaval Cell Counter® (Cell Counter DCC) device. Mineral matter, fat, protein, lactose, electrical conductivity and specific gravity were measured in milk samples using Lactoscan Milk Analyzer (Milkotronic/EUROPE). Milk samples were then stored at -80°C to measure TGF-ß1 and TNF-α. Tumor necrosis factor-α and TGF-ß1 concentrations in milk samples were measured using ELISA kits (Sunred Biological Technology). Changes in milk TNF-α and TGF-ß1 concentration and milk composition were determined in milk samples with mastitis caused by mixed infection. The TNF-α concentration of group 4 was higher than the other groups. On the other hand, the highest concentration of TGF-ß1 was found in group 2. While the number of somatic cells in group 1 was lower than in groups 2, 3, and 4, there was no statistical difference between groups 1 and 5. The lowest milk fat ratio was found in group 1, and it was found to be statistically lower than groups 2, 3, and 4. While the rate of solid-non-fat of group 1 increased compared to groups 2 and 3, the highest protein ratio was found in groups 1 and 5. There was no difference between the 5 groups in terms of mineral matter ratios. While the specific gravity was highest in group 1, there was no statistical difference between the other 4 groups. Overall, it was concluded that there was an increase in TNF-α and TGF-ß1 concentrations and a change in milk composition in samples with bacterial growth.(AU)

Suppression of thioacetamide-induced hepatic injury in rats treatment with resveratrol: role of mammalian target of rapamycin (mTOR) cell signaling / Supresión de la lesión hepática inducida por tioacetamida en ratas tratadas con resveratrol: rol de la vía de señalización mTOR (mammalian target of rapamycin)

Chronic hepatotoxicity is a debilitating and frequently life-threatening disease resulting in progressive liver failure. The toxic chemical, thioacetamide (TAA) is used to evaluate hepatoprotective agents, and the polyphenolic compound, resveratrol was proposed as a novel treatment for diseases with hyperactivation of the mammalian target of rapamycin (mTOR) cell signaling pathway. This analysis sought to investigate the potential protective effect of resveratrol against liver injury induced by TAA via the inhibition of hepatic mTOR. Model group rats received several injections of TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed at week 10 and the protective group was pretreated with resveratrol (20 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment. Harvested liver tissues were examined using light microscopy and liver homogenates were assayed for biomarkers of inflammation and assessed the levels of mTOR protein in all animal groups. In addition, blood samples were assayed for biomarkers of liver injury enzyme. TAA substantially damaged the hepatic tissue of the model group such as infiltration of inflammatory cells, vacuolated cytoplasm, dark pyknotic nuclei, and dilated congested blood vessel that were effectively protected by resveratrol. Resveratrol also significantly (p<0.05) inhibited TAA-induced mTOR, high sensitivity c-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in harvested liver homogenates and blood samples. Thus, we conclude that resveratrol effectively protects against TAA-induced hepatotoxicity in rats, possibly due to the inhibition of mTOR and inflammation.

La hepatotoxicidad crónica es una enfermedad debilitante y potencialmente mortal que produce insuficiencia hepática progresiva. La toxicidad del químico de la tioacetamida (TAA) se utiliza para evaluar los agentes hepatoprotectores y el compuesto polifenólico, resveratrol, se propuso como un nuevo tratamiento para enfermedades con hiperactivación de la vía de señalización celular mTOR (mammalian Target of Rapamycin). Aquí buscamos investigar el posible efecto protector del resveratrol contra la lesión hepática inducida por TAA a través de la inhibición de la vía de señalización mTOR en hepatocitos. Las ratas del grupo modelo recibieron varias inyecciones de TAA (200 mg / kg; dos veces por semana durante 8 semanas) antes de ser sacrificadas en la semana 10 y el grupo protector se trató previamente con resveratrol (20 mg / kg) diariamente durante dos semanas antes de las inyecciones de TAA y continuó recibiendo ambos agentes hasta el final del experimento. Se examinaron los tejidos hepáticos recolectados usando microscopía óptica y se analizaron los homogeneizados hepáticos para detectar biomarcadores de inflamación y se evaluaron los niveles de proteína mTOR en todos los grupos de animales. Además, se analizaron muestras de sangre para detectar biomarcadores de la enzima de lesión hepática. TAA dañó sustancialmente el tejido hepático del grupo modelo, con infiltración de células inflamatorias, citoplasma vacuolado, núcleos picnóticos oscuros y vasos sanguíneos congestionados dilatados que estaban efectivamente protegidos por el resveratrol. El resveratrol también inhibió significativamente (p <0.05) mTOR, proteína C-reactiva (hs-CRP), factor de necrosis tumoral alfa (TNF-α), interleucina-6 (IL-6), alanina aminotransferasa (ALT ) y aspartato aminotransferasa (AST) en las muestras de sangre y de hígados recolectados. En conclusión, el resveratrol protege eficazmente contra la hepatotoxicidad inducida por TAA en ratas, posiblemente debido a la inhibición de mTOR y de la inflamación.

Aspects of Langerhans cells and TNF-α in the cutaneous immunity of anogenital warts

Abstract Background: Anogenital warts are the leading sexually transmitted infection in patients seeking care at specialized clinics. They may display a vast array of forms, according to the interaction of the virus with the host's immunity. Cellular immunity is the epithelium's main form of defense against the virus, involving an active participation of the Langerhans cells and pro-inflammatory cytokines such as TNF-α. Objective: To assess the epithelial immune response of anogenital warts in males, according to the number of lesions presented. Methods: This is a prospective, cross-sectional study carried out at the dermatology outpatient clinic in a tertiary hospital. We included male patients over 18 years of age without comorbidities who had anogenital condylomata and no previous treatments.In order to evaluate the local epithelial immunity, the lesions were quantified, then removed and employed in CD1a immunohistochemistry assays for assessing the morphometry and morphology of Langerhans cells; TNF-α; reaction was used for determining cytokine positivity in the epithelium. Results: 48 patients were included in the study. There was no statistically significant difference as to the number of Langerhans cells, in their morphology, or the presence of TNF-α. However, patients presenting with more Langerhans cells in the lesions had cells with a star-like and dendritic morphology, whereas in those with a lower cell count had cells with a rounded morphology and no dendrites (p < 0.001). Study limitations: Small number of patients analyzed. Conclusion: There was no difference in epithelial immunity between patients having few or many anogenital condyloma lesions as measured by the morphology and morphometry of Langerhans cells and TNF-α; positivity. Such an assessment employing immunity markers differing from the usual ones is expected to yield useful results.

Inflammatory markers in palatine tonsils of children with obstructive sleep apnea syndrome / Marcadores inflamatórios em tonsilas palatinas de crianças com síndrome da apneia obstrutiva do sono

Abstract Introduction Obstrutive sleep apnea syndrome is characterized by repeated episodes of upper airway obstruction, associated with intermittent hypoxia and hypercapnia, and the main risk factor in childhood is adenotonsillar hypertrophy. The lymphocytes in these structures are responsible for local and systemic immune responses. Objective Verify the levels of the inflammatory markers, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, CRP and α1-GP, in the tonsils of children with and without obstructive sleep apnea syndrome. Methods This cross-sectional prospective study included 34 children with complains of snoring, difficulty breathing during sleep or recurrent tonsillitis. Patients underwent to a complete otorhinolaryngological examination, nasal endoscopy and polysomnography and were divided into two groups with 17 children each: obstructive sleep apnea syndrome group and control group. All underwent an adenotonsillectomy. Cytokines were measured in the collected tonsils (ELISA and Multiplex methods). Results Statistically significant increasing were observed between IL-8 and IL-10 cytokines of patients with obstructive sleep apnea when compared to the control group; also between c-reactive protein and α1-GP of the tonsils cortical region in children with obstructive sleep apnea syndrome when compared with the medullary region. There were no statistically significant differences for the remaining inflammatory mediators. Conclusion After the analysis of the levels of pro and anti-inflammatory markers (IL-1β, IL-4, IL-6, IL-8, IL-10, Il-15, TNF-α, CRP, α1-GP) in the tonsils, we observed higher levels of markers IL-8 and IL-10 in pediatric patients with obstructive sleep apnea syndrome.

Resumo Introdução A síndrome da apneia obstrutiva do sono é caracterizada por episódios repetidos de obstrução das vias aéreas superiores, associados a hipóxia intermitente e hipercapnia, e o principal fator de risco na infância é a hipertrofia adenotonsilar. Os linfócitos nessas estruturas são responsáveis por respostas imunes locais e sistêmicas. Objetivo Dosar os marcadores inflamatórios, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-15, TNF-α, PCR e α1-GP, nas tonsilas de crianças com e sem síndrome da apneia obstrutiva do sono. Método Estudamos prospectivamente 34 crianças que se queixavam de ronco, dificuldade para respirar durante o sono ou tonsilites recorrentes. Os pacientes foram submetidos a exame otorrinolaringológico completo, endoscopia nasal e polissonografia e foram divididos em dois grupos com 17 crianças cada: síndrome de apneia obstrutiva do sono e controle. Todos foram submetidos à adenotonsilectomia. As citocinas foram medidas nas tonsilas coletadas (métodos ELISA e Multiplex). Resultados Com diferenças estatisticamente significantes, observou-se aumento das citocinas IL-8 e IL-10 em pacientes com apneia obstrutiva do sono em comparação ao grupo controle, assim como aumento dos níveis de proteína C reativa e de α1-GP na região cortical das tonsilas de crianças portadoras de síndrome da apneia obstrutiva do sono em comparação com a região medular. Não houve diferenças estatisticamente significantes para o restante dos mediadores inflamatórios. Conclusão Após a análise dos níveis de marcadores pró e anti-inflamatórios (IL-1β, IL-4, IL-6, IL-8, IL-10, Il-15, TNF-α, PCR, α1-GP) nas tonsilas, observamos níveis mais altos de marcadores IL-8 e IL-10 em pacientes pediátricos com síndrome da apneia obstrutiva do sono.

Muscular resistance, hypertrophy and strength training equally reduce adiposity, inflammation and insulin resistance in mice with diet-induced obesity / Exercícios físicos de resistência, hipertrofia e força muscular reduzem igualmente adiposidade, inflamação e resistência à insulina em camundongos obesos por dieta hiperlipídica

ABSTRACT Objective To evaluate the effect of three types of muscular resistance training on adiposity, inflammation levels and insulin activity in Swiss mice with fat-rich diet-induced obesity. Methods Lean and obese male Swiss mice were selected and allocated to one of eight groups comprising eight mice each, as follows: standard diet + no training; standard diet + muscular resistance training; standard diet + hypertrophy training; standard diet + strength training; high-fat diet + no training; high-fat diet + muscular resistance training; high-fat diet + hypertrophy training; high-fat diet + strength training. The training protocol consisted of stair climbing for a 10-week period. Blood samples were collected for lactate analysis, glucose level measurement and insulin tolerance test. After euthanasia, adipose tissues were removed and weighed for adiposity index determination. Fragments of epididymal adipose tissue were then embedded for histological analysis or homogenized for tumor necrosis factor alpha level determination using the ELISA method. Results Ausency of differences in total training volume and blood lactate levels overall emphasize the similarity between the different resistance training protocols. Body weight loss, reduced adipocyte area and lower adiposity index were observed in trained obese mice, regardless of training modality. Different training protocols also improved insulin sensitivity and reduced inflammation levels. Conclusion Resistance training protocols were equally effective in reducing body fat, inflammation levels and insulin resistance in obese mice.

RESUMO Objetivo Avaliar os efeitos de três tipos de treinamentos de resistência na adiposidade, na inflamação e na ação da insulina em camundongos Swiss obesos por dieta hiperlipídica. Métodos Camundongos Swiss machos magros e obesos foram selecionados e posteriormente separados em oito grupos com oito animais em cada: dieta padrão + não treinado; dieta padrão + treinamento de resistência muscular; dieta padrão + treinamento de hipertrofia; dieta padrão + treinamento de força; dieta hiperlipídica + não treinado; dieta hiperlipídica + treinamento de resistência muscular; dieta hiperlipídica + treinamento de hipertrofia; e dieta hiperlipídica + treinamento de força. O protocolo de treinamento consistiu em escaladas, por um período de 10 semanas. Amostras de sangue foram coletadas para análises de lactato, glicemia e teste de tolerância à insulina. Após eutanásia, os tecidos adiposos foram retirados e pesados para determinar o índice de adiposidade. Em seguida, parte do tecido adiposo epididimal foi emblocado para análises histológicas, e outra parte foi homogeneizada para análises de fator de necrose tumoral alfa por ELISA. Resultados O volume total de treinamento e a concentração sanguínea de lactato não diferiram entre os três treinos resistidos, sugerindo similaridade entre eles. Nos animais obesos, as três modalidades de treinamento reduziram o peso corporal, a área adipocitária e o índice de adiposidade. Os três tipos de treinamentos ainda melhoraram a tolerância à insulina e reduziram a inflamação. Conclusão Os protocolos de treinamento resistido foram igualmente efetivos em reduzir a adiposidade, a inflamação e a resistência à ação da insulina em camundongos obesos.

Impact of history of periodontitis on gene expression of bone-related factors in young patients

Abstract Although dental implants and bone regenerative procedures are important approaches for the reestablishment of esthetics and function in young patients with a history of generalized aggressive periodontitis (GAP), no predictable outcomes have been reported, and the host osteo-immunoinflammatory response may play a relevant role in this context. In view of the lack of molecular investigations into the bone tissue condition of young patients with periodontitis, the aim of this study was to evaluate the gene expression of bone-related factors in this population. Bone biopsies were obtained from the posterior mandible in 16 individuals previously diagnosed with GAP and on periodontal support therapy and from 17 periodontally healthy (PH) patients. The gene expression of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, receptor activator of the NF-κB ligand (RANKL), osteoprotegerin (OPG), osteocalcin (OC), bone sialoprotein (BSP), and type I collagen (COL-I), important biomarkers of bone turnover, was evaluated by qRT-PCR. Lower TGF-β and OPG mRNA levels were observed in GAP patients compared to PH individuals (p ≤ 0.05). There were no between-group differences in levels of TNF-α, BSP, RANKL, OC, or COL-I mRNA (p>0.05). In young adults, a history of periodontal disease can negatively modulate the gene expression of important bone-related factors in alveolar bone tissue. These molecular outcomes may contribute to the future development of therapeutic approaches to benefit bone healing in young patients with history of periodontitis via modulation of osteo-immuno-inflammatory biomarkers.

Characteristics of neutrophil extracellular traps in patients with periodontitis and gingivitis

Abstract We sought to compare the characteristics and clinical significance of neutrophil extracellular traps in gingival samples from patients with periodontitis and those with gingivitis. The clinical indexes of gingival samples from patients with periodontitis and gingivitis were measured; the expression of TNF-alpha and IL-8 was measured by real-time fluorescent quantitative PCR; and the expression of TLR-8 and MMP-9 was measured by western blotting assays. Chemotaxis, phagocytosis and phagocytic activity of neutrophils were measured. Compared with the healthy group, the expression of TNF-α and IL-8 in the periodontitis group and the gingivitis group increased significantly (p < 0.05), and TNF-α in the gingivitis group was significantly lower than that in the healthy group (p < 0.05). The expression of IL-8 in the periodontitis group was significantly higher than that in the periodontitis group (p < 0.05). Furthermore, the expression of TLR-8 and MMP-9 in the periodontitis group was different from that in the gingivitis group and the healthy group, and the expression of TLR-8 and MMP-9 in the gingivitis group was significantly different from that in the healthy group (p < 0.05). In addition, the neutrophil mobility index in healthy people was 3.02 ± 0.53, that in the periodontitis group was 2.21 ± 0.13, and that in the gingivitis group was 2.31 ± 0.12. In conclusion, the chemotaxis of neutrophils in gingival samples of patients with periodontitis and gingivitis was decreased, the phagocytotic ability and activity of neutrophils were reduced, and the release of the extracellular trap-releasing inducible factors TNF-alpha and IL-8 also declined.

Therapeutic effects of vitamin D on acetic acid-induced colitis in rats

Abstract Purpose To analyze the effect of calcitriol treatment on acute colitis in an experimental rat model. Methods A total of 24 adult Sprague Dawley albino rats were randomly separated into 3 equal groups: control group (n:8), colitis group (n:8), calcitriol administered group (n:8). A single dose of acetic acid (1 ml of 4% solution) was administered intrarectally to induce colitis. Group 1 was given 1 ml/kg 0.9% NaCl intraperitoneally; rats belonging to Group 2 were administered calcitriol 1 µg/kg for 5 days. Results Plasma tumor necrosis factor alpha, Pentraxin 3, and malondialdehyde levels were significantly lower in the calcitriol administered colitis group than in the standard colitis group (p<0.01). In the Calcitriol group, there was a significant histological improvement in hyperemia, hemorrhage and necrotic areas in the epithelium compared to the placebo group (p <0.000). Conclusion The findings suggest that calcitriol may be an agent that could be used in acute colitis treatment.

Perillyl alcohol has antibacterial effects and reduces ROS production in macrophages

Abstract Natural products have emerged as a rich source of bioactive compounds for adjunctive treatments of many infectious and inflammatory conditions, including periodontitis. Among the monoterpenes with significant biological properties, there is the perillyl alcohol (POH), which can be found in several essential oils and has shown immunomodulatory properties in recent studies, which may be interesting in the treatment of non-neoplastic inflammatory disorders. Objective To determine the antibacterial and immune modulatory activities of the POH. Methodology The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the POH for two significant Gram-negative periodontal pathogens were determined by macrodilution and subculture, respectively. Cell proliferation and cytotoxicity in RAW 264.7 macrophages were determined by Trypan Blue and mitochondrial enzymatic activity assay. The modulation of reactive oxygen species (ROS) was analyzed by flow cytometry and expression of TNF and arginase-1 by real-time PCR. Results The POH was effective against P. gingivalis (ATCC 33277) and F. nucleatum (ATCC 25586) with MIC= MBC=1600 μM. No cytotoxicity up to 100 µM was observed on macrophages. The cell proliferation was inhibited from 48 hours at 100 μM (p<0.05) and 250 μM (p<0.01). The POH increased ROS production at both 10 μM and 100 μM (p<0.05) in unstimulated cells. The PMA-induced ROS production was not affected by POH, whereas 100 μM significantly reduced lipopolysaccharide-induced (LPS-induced) ROS. The expression of TNF was not affected by POH in unstimulated cells or in cells polarized to M1 phenotype, whereas both concentrations of POH reduced (p<0.05) the expression of arginase-1 in M2-polarized macrophages. Conclusion The POH has antibacterial activity against periodontal pathogens and reduced proliferation of murine macrophages without significant cytotoxicity at concentrations up to 100 μM. In addition, the POH reduced the LPS-induced ROS and the expression of arginase-1 in M2-polarized macrophages.

Ginger extract ameliorates renal damage in high fat diet-induced obesity in rats: biochemical and ultrastructural study / El extracto de jengibre mejora el daño renal en la obesidad inducida por la dieta alta en grasas en ratas: estudio bioquímico y ultraestructural

Obesity is a modifiable risk factor for the development and progression of kidney disease. Obesity may harm kidneys in individuals without hypertension, diabetes, or pre-existing renal disease. Ginger, Zingiber officinale, has many beneficial pharmaceutical benefits. This study aimed to evaluate the Zingiber officinale protective effect against obesity complications which induced by high fat diet and caused renal dysfunctions. The study period was two months, and the experimental animals' groups were four, 80 Wistar rats were appropriated similarly 20 animals/group: control group; ginger extract group (GE); high-fat diet (HFD); and GE+HFD group. Body and fat weight, creatinine, leptin, TNF-α, total antioxidants, renal histopathological and ultrastructure were investigated. Rats in group of HFD showed a significant increase (P<0.05) in the body and fat weights, creatinine, leptin and TNF-α, and significant decrease (P<0.05) in total antioxidants (TAS). Ginger administration significantly showed the protective restoring the altered parameters. Furthermore, rats co-treated with ginger extract improved the histopathological and ultrastructural renal injury induced by obesity. The study concluded that the ginger extract used could suppress and decrease the renal damage induced by high-fat diet as it possesses potential medicinal values.

La obesidad es un factor de riesgo modificable para el desarrollo y la progresión de la enfermedad renal. La obesidad puede dañar los riñones en personas sin hipertensión, diabetes o enfermedad renal preexistente. El jengibre, Zingiber officinale, tiene muchos beneficios farmacéuticos. Este estudio tuvo como objetivo evaluar el efecto protector de Zingiber officinale en las complicaciones de la obesidad inducida por una dieta alta en grasas y las enfermedad renal. El período de estudio fue de dos meses, y los grupos de animales experimentales fueron cuatro, se asignaron 80 ratas Wistar de manera similar, 20 animales por grupo: grupo de control; grupo de extracto de jengibre (GE); dieta alta en grasas (DAG); y el grupo GE + DAG. Se evaluó el peso corporal y la grasa, creatinina, leptina, TNF-α, antioxidantes totales, histopatología renal y ultraestructura. Las ratas en el grupo de DAG mostraron un aumento significativo (P<0,05) en el peso corporal y de grasa, creatinina, leptina y TNF-a, y una disminución significativa (P<0,05) en los antioxidantes totales. La administración de jengibre mostró una protección significativa restaurando los parámetros alterados. Además, las ratas tratadas conjuntamente con extracto de jengibre mejoraron la lesión renal histopatológica y ultraestructural inducida por la obesidad. El estudio concluyó que el extracto de jengibre podría suprimir y disminuir el daño renal inducido por la dieta alta en grasas, ya que posee potenciales valores medicinales.

Resistance Exercise Modulates Oxidative Stress Parameters and TNF-α Content in the Heart of Mice with Diet-Induced Obesity / Exercício Resistido Modula Parâmetros de Estresse Oxidativo e Conteúdo de TNF-α no Coração de Camundongos com Obesidade Induzida por Dieta

Abstract Background: Obesity can be characterized by low-grade chronic inflammation and is associated with an excesso production of reactive oxygen species, factors that contribute to coronary heart disease and other cardiomyopathies. Objective: To verify the effects of resistance exercise training on oxidative stress and inflammatory parameters on mice with obesity induced by a high-fat diet (HFD). Methods: 24 Swiss mice were divided into 4 groups: standard diet (SD), SD + resistance exercise (SD + RE), diet-induced obesity (DIO), DIO + RE. The animals were fed SD or HFD for 26 weeks and performed resistance exercises in the last 8 weeks of the study. The insulin tolerance test (ITT) and body weight monitoring were performed to assess the clinical parameters. Oxidative stress and inflammation parameters were evaluated in the cardiac tissue. Data were expressed by mean and standard deviation (p < 0.05). Results: The DIO group had a significant increase in reactive oxygen species levels and lipid peroxidation with reduction after exercise. Superoxide dismutase and the glutathione system showed no significant changes in DIO animals, with an increase in SD + RE. Only catalase activity decreased with both diet and exercise influence. There was an increase in tumor necrosis factor-alpha (TNF-α) in the DIO group, characterizing a possible inflammatory condition, with a decrease when exposed to resistance training (DIO+RE). Conclusion: The DIO resulted in a redox imbalance in cardiac tissue, but the RE was able to modulate these parameters, as well as to control the increase in TNF-α levels.

Resumo Fundamento: A obesidade pode ser caracterizada por uma inflamação crônica de baixo grau e está associada à produção excessiva de espécies reativas de oxigênio, fatores que contribuem para doenças coronarianas e outras cardiomiopatias. Objetivo: Verificar os efeitos do treinamento resistido sobre os parâmetros de estresse oxidativo e parâmetro inflamatório em camundongos com obesidade induzida por dieta hiperlipídica (DIO). Métodos: 24 camundongos Swiss foram divididos em 4 grupos: dieta padrão (DP), DP + exercício resistido (DP+ER), obesidade induzida por DIO, DIO + ER. Os animais foram alimentados por 26 semanas com DP ou hiperlipídica realizando treinamento resistido nas 8 semanas finais do estudo. Para avaliar parâmetros clínicos foi realizado o teste de tolerância à insulina (TTI) e monitoramento do peso corporal. No tecido cardíaco foram avaliados parâmetros de estresse oxidativo e inflamação. Dados expressos por média e desvio padrão (p < 0,05). Resultados: O grupo DIO teve um aumento significativo nos níveis espécies reativas e peroxidação lipídica com redução após o exercício. A superóxido dismutase e o sistema glutationa não demonstraram alterações importantes nos animais DIO, com elevação perante DP+ER. Somente a atividade da catalase reduziu tanto com influência da dieta como do exercício. Ocorreu um aumento do fator de necrose tumoral-alfa (TNF-α) no grupo DIO, caracterizando um possível quadro inflamatório, com redução quando expostos ao treino resistido (DIO+ER). Conclusão: A DIO ocasionou um desequilíbrio redox no tecido cardíaco, porém o ER foi capaz de modular estes parâmetros, bem como controlar o aumento do TNF-α.

[Artigo Parcialmente Retratado] Prevalência da infecção por Helicobacter pylori em pacientes dispépticos e associação com fatores de riscos clínicos para o desenvolvimento de adenocarcinoma gástrico / [article partial retraction] prevalence of helicobacter pylori infection in dyspeptic patients and its association with clinical risk factors for developing gastric adenocarcinoma

ABSTRACT BACKGROUND: In Brazil, particularly in the underdeveloped localities, the prevalence of Helicobacter pylori (H. pylori) infections can range up to 90%. These rates are higher in older individuals and vary by country region. H. pylori infections are linked to the development of gastric pathologies, namely mild to moderate gastritis, gastroenteritis, peptic ulcer, intestinal metaplasia, and gastric cancer. In 1994, this organism was classified by the International Agency for Research on Cancer (IARC) as pertaining to the Group 1 carcinogen for gastric adenocarcinoma etiology. Gastric cancer represents a significant public health problem, being the fourth most common malignant tumor and the second largest cause of cancer-related deaths. OBJECTIVE: To investigate the prevalence of H. pylori infection in dyspeptic patients and determine the link between clinical risk factors and gastric adenocarcinoma diagnosis. METHODS: Polymerase chain reaction (PCR) analysis was employed for molecular diagnosis of gastric tissue biopsies collected from 113 dyspeptic patients at the University Hospital of Federal University of Goiás. Molecular analyses allowed the identification of H. pylori infections. Furthermore, histopathological examinations were performed to determine the clinical risks of developing gastric malignancies. RESULTS: The test results identified 69 individuals older than 44 years, from 75 (66.4%) positive H. pylori infection samples. The prevalence of gastric adenocarcinoma in this study was 1.3%. Among the infected patients, six (8.2%) had high risk, and 67 (91.8%) had a low risk of developing gastric cancer (P<0.05). CONCLUSION: This study shows a high prevalence of H. pylori infection and identifies its contribution to gastric inflammations, which in the long term are manifested in high-risk clinical factors for the development of gastric adenocarcinoma.

RESUMO CONTEXTO: No Brasil, particularmente nas áreas mais pobres, a prevalência da infecção por Helicobacter pylori pode variar até 90%. Esses índices aumentam com o envelhecimento da população e são distintos entre as diferentes regiões do país. Podendo manifestar diferentes sintomatologias, essa infecção está diretamente relacionada com o desenvolvimento de patologias gástricas como gastrite leve a moderada, gastroenterites, úlcera péptica, metaplasia intestinal e principalmente, o câncer gástrico. Em 1994 a bactéria foi categorizada pela International Agency for Research on Cancer (IARC) como carcinógeno do Grupo 1 para adenocarcinoma gástrico, tipo de câncer que representa um importante problema de saúde pública, sendo o quarto tumor maligno mais comum e a segunda maior causa de mortes por câncer no mundo. OBJETIVO: Analisar a prevalência da bactéria em pacientes dispépticos e avaliar a associação de fatores de risco clínicos para desenvolvimento de adenocarcinoma gástrico. MÉTODOS: Biópsias de tecido gástrico coletadas de 113 pacientes dispépticos, atendidos no Hospital das Clínicas da Universidade Federal de Goiás, foram submetidas a diagnóstico molecular por meio de Reação em Cadeia da Polimerase, para identificação da infecção por Helicobacter pylori, e exame histopatológico, para avaliar o risco clínico de desenvolvimento de adenocarcinoma gástrico. RESULTADOS: Foram diagnosticadas 75 (66,4%) amostras positivas para infecção por Helicobacter pylori, sendo 69 indivíduos maiores de 44 anos de idade. A prevalência do adenocarcinoma gástrico nesse estudo foi de 1,3% e dentre os pacientes positivos para a infecção bacteriana seis (8,2%) possuem alto risco e 67 (91,8%) baixo risco de desenvolver esse tipo de câncer (P<0,05). CONCLUSÃO: Esse estudo mostra uma alta prevalência da infecção por H. pylori na população estudada e identifica sua intrínseca contribuição para inflamações gástricas, que a longo prazo se manifestam em fatores clínicos de alto risco para o desenvolvimento de adenocarcinoma gástrico.

An immunohistochemistry and histopathological study of ankaferd blood stopper in a rat model of cervical inflammation

SUMMARY OBJECTIVE: Ankaferd Blood Stopper (ABS) is a medicinal plant extract used topically as a hemostatic, anti-inflammatory, and anti-oxidant agent. Its cytoprotective effect mainly depends on its pleiotropic properties by modulating inflammatory mediators such as IL-1β, IL-6, and TNF-α. This study aims to test the possible therapeutic effect of ABS in the treatment of erosive and inflammatory conditions occurring in the uterine cervix. METHODS: Twenty-four female Wistar Albino rats were used in the present study. Trichloracetic acid was applied intravaginally to establish an experimental rat model of cervicitis. The rats were randomly divided into three groups: group I (injury), group II (injury+isotoinc saline), and group III (injury+ABS). After 3 estrous cycles of ABS and isotonic saline treatment, the amount of inflammation, vascular congestion and erosion were evaluated in the cervical tissues by using a modified semi-quantitative scale of 0-3. Immunohistochemical staining with monoclonal antibodies against IL-1β was also performed. RESULTS: Compared with group I and II, the ABS group showed the least inflammatory cell infiltration, vascular congestion and cervical erosion, compared with the ABS group prominent IL-1β staining observed in group I and group II. CONCLUSION: Our data suggest that ABS is a highly effective alternative to induce normal cervical epithelium and can be used safely in the treatment of cervical inflammation with or without cervical erosion.

RESUMO OBJETIVO: Ankaferd Blood Stopper (ABS) é um extrato de plantas medicinais utilizado topicamente como um agente hemostático, anti-inflamatório e antioxidante. O seu efeito citoproteico depende principalmente das suas propriedades pleiotrópicas por meio da modulação de mediadores inflamatórios tais como IL-1β, IL-6 e TNF-a. O objetivo deste estudo é testar o possível efeito terapêutico do ABS no tratamento de condições erosivas e inflamatórias que ocorrem no colo uterino. MÉTODOS: Vinte e quatro ratas Wistar Albino foram utilizadas no presente estudo. O ácido tricloroacético foi aplicado intravaginalmente para estabelecer um modelo experimental de cervicite em ratos. Os ratos foram divididos aleatoriamente em três grupos: grupo I (lesão), grupo II (lesão + fisiológico sérico) e grupo III (lesão + ABS). Após três ciclos estrais de ABS e tratamento fisiológico sérico, as quantidades de inflamação, congestionamento vascular e erosão foram avaliadas nos tecidos cervicais usando uma escala semiquantitativa modificada de 0-3. Coloração imuno-histoquímica com anticorpos monoclonais contra IL-1β também foi realizada. RESULTADOS: Em comparação com os grupos I e II, o grupo ABS mostrou menos infiltração de células inflamatórias, congestionamento vascular e erosão cervical. Além disso, em comparação com o grupo ABS, observou-se uma coloração proeminente de IL-1β no grupo I e no grupo II. CONCLUSÃO: Nossos dados sugerem que o ABS é uma alternativa altamente eficaz para induzir o epitélio cervical normal e pode ser utilizado com segurança no tratamento da inflamação cervical com ou sem erosão cervical.

Comparative study on the efficacy of non-steroidal, steroid and non-use of anti-inflammatory in the treatment of acute epidemic conjunctivitis

Abstract Purpose To evaluate the effects of prednisolone against sodium diclofenac both with ciprofloxacin compared to artificial tears on the symptoms and signs of acute viral conjunctivitis. Methods Study included 37 patients diagnosed with acute conjunctivitis and distributed by three groups: A (1% prednisolone acetate + ciprofloxacin (0.3%); B (Sodium diclofenac (0.1%) + ciprofloxacin (0.3%) and C (artificial tears + ciprofloxacin (0.3%). Patients received medication 6/6 hours daily. Signs and symptoms (e.g. lacrimation, burning, photophobia, etc.) were scored at baseline and on the first, third, fifth and seventh days and in the end of treatment using a standardized questionnaire and slit lamp anterior segment examination. Results All three groups demonstrated an improvement in the signs and symptoms of conjunctivitis in their follow-up visits. There was no significant difference in symptom and sign scores between Group A and B and B and C in the study visits ( p >0.05). However, the comparison between groups A and C showed a clinical trend (p=0.05) on third evaluation suggesting better clinical action using the corticosteroids. Conclusion The prednisolone acetate was not superior to the use of sodium diclofenac or artificial tears in relieving the signs and symptoms of viral conjunctivitis.

Hypercapnia attenuates ventilator-induced lung injury through vagus nerve activation

Abstract Purpose: To investigate the role of vagus nerve activation in the protective effects of hypercapnia in ventilator-induced lung injury (VILI) rats. Methods: Male Sprague-Dawley rats were randomized to either high-tidal volume or low-tidal volume ventilation (control) and monitored for 4h. The high-tidal volume group was further divided into either a vagotomy or sham-operated group and each surgery group was further divided into two subgroups: normocapnia and hypercapnia. Injuries were assessed hourly through hemodynamics, respiratory mechanics and gas exchange. Protein concentration, cell count and cytokines (TNF-α and IL-8) in bronchoalveolar lavage fluid (BALF), lung wet-to-dry weight and pathological changes were examined. Vagus nerve activity was recorded for 1h. Results: Compared to the control group, injurious ventilation resulted in a decrease in PaO2/FiO2 and greater lung static compliance, MPO activity, enhanced BALF cytokines, protein concentration, cell count, and histology injury score. Conversely, hypercapnia significantly improved VILI by decreasing the above injury parameters. However, vagotomy abolished the protective effect of hypercapnia on VILI. In addition, hypercapnia enhanced efferent vagus nerve activity compared to normocapnia. Conclusion: These results indicate that the vagus nerve plays an important role in mediating the anti-inflammatory effect of hypercapnia on VILI.

The role of visfatin levels in gingival crevicular fluid as a potential biomarker in the relationship between obesity and periodontal disease

Abstract Objectives Visfatin is an adipokine that plays an important role in immune functions as a growth factor, enzyme, and pro-inflammatory mediator. We aimed to determine the levels of visfatin, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in gingival crevicular fluid (GCF) in both obese/non-obese patients, with/without generalized chronic periodontitis (GCP). Methodology Patients were categorized as obese (O) (n=31) or non-obese (nO) (n=19). Groups were divided into four subgroups according to periodontal conditions: (1) periodontally healthy without obesity (nO-Ctrl); (2) GCP without obesity (nO-CP); (3) periodontally healthy with obesity (O-Ctrl); and (4) GCP with obesity (O-CP). Demographic variables, anthropometric and laboratory data were recorded. Periodontal parameters were measured at baseline and 3rd months after either non-surgical periodontal treatment or calorie -restricted diet therapy. At the same time, GCF samples were taken from patients to analyze TNF-alpha, IL-6,and visfatin levels. Results Periodontal parameters were significantly higher in the O group than in the nO group (P<0.05). IL-6 levels were higher in the O group than in the nO group (P<0.001). The visfatin levels of the obese patients were reduceddecreased following the treatments (P<0.05). Cholesterol levels were higher in the O group than in the nO groups (P<0.05). IL-6 levels were higher in O-CP and O-Ctrl groups than in the nO-Ctrl group (P<0.05). Compared to the other groups, visfatin levels were significantly higher in the O-CP group but decreased following treatment (P<0.05). Conclusions Our findings suggest that visfatin and IL-6 levels in GCF are associated with the pathogenesis of obesity and periodontitis. Within the limits of this study, we considered that there might be an association between the lipid profile and periodontitis on systemically healthy individuals.

Inflammatory markers in the saliva of cerebral palsy individuals with gingivitis after periodontal treatment

Abstract The aim of this study was to evaluate the effect of periodontal treatment on the salivary cytokine levels and clinical parameters of individuals with cerebral palsy (CP) with gingivitis. A non-randomized, clinical trial was conducted in individuals diagnosed with spastic CP. Thirty-eight individuals were enrolled in the study and were categorized according to gingival index scores between 0-1 or 2-3, assigned to groups G2 or G1, respectively. Periodontal treatment comprised oral hygiene instructions, conventional mechanical treatment and 0.12% chlorhexidine applied as an adjunct. Clinical parameters and saliva samples were collected at baseline and at the 15-day follow-up visit. Bleeding on probing and periodontal screening and recording were determined. Non-stimulated saliva samples were obtained, and the salivary flow rate, the osmolality and the levels of cytokines IL-1β, IL-6, IL-8, IL-10, TNF-α and IL-12p70 were evaluated by a cytometric bead array. The Wilcoxon test, the Mann-Whitney test, Spearman correlation analysis, Poisson regression analysis and an adjusted analysis were performed (α = 0.05). The groups differed significantly in periodontal clinical parameters at baseline and at follow-up. Salivary flow rate and osmolality were similar in both groups at both timepoints. However, TNF-α and IL-1β levels were higher in G1 than in G2 at baseline. Mechanical treatment resulted in improved clinical parameters for both groups. Furthermore, mechanical treatment resulted in a significant reduction in salivary IL-1β and IL-8 levels for both groups after treatment. Periodontal treatment performed in individuals with CP and gingivitis reduces the levels of TNF-α, IL-1β, IL-6 and IL-8.