Nutritional strategies cause memory damage and alter biochemical parameters without causing neuroinflammation.

Obesity results from an energy imbalance and has been considered an epidemic due to its increasing rates worldwide. It is classified as a low-grade chronic inflammatory disease and has associated comorbidities. Different nutritional strategies are used for the purpose of weight loss, highlighting low-carbohydrate (LC) diets, ketogenic diets, and intermittent fasting (IF). These strategies can lead to metabolic and behavioral changes as they stimulate different biochemical pathways. Therefore, this study evaluated memory, energy metabolism, neuroinflammation, oxidative stress, and antioxidant defense parameters in mice subjected to an LC diet, ketogenic diet (KD), or IF. Eighty male Swiss mice, 60 days old, were divided into 4 groups: control, LC, KD, or IF. Body weight was measured weekly, and food intake every 48 h. After 15 days of nutritional interventions, the animals were subjected to the behavioral object recognition test and subsequently euthanized. Then, visceral fat was removed and weighed, and the brain was isolated for inflammatory and biochemical analysis. We concluded from this study that the LC and KD strategies could damage memory, IF improves the production of adenosine triphosphate (ATP), and the LC, KD, and IF strategies do not lead to neuroinflammatory damage but present damage at the level of oxidative stress.

PHASE ANGLE AS A PREDICTOR OF MUSCLE MASS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE.

BACKGROUND: Malnutrition/sarcopenia is frequent in patients with inflammatory bowel diseases (IBD), and results in muscle catabolism, impacting treatment response, postoperative complications, and quality of life. OBJECTIVE: This study aims to assess whether the phase angle (PhA) is a parameter for predicting reduced muscle mass in patients with IBD. METHODS: Adult patients with IBD were included in this cross-sectional study. For the estimation of muscle mass and the calculation of the PhA, we used bioelectrical impedance analysis (BIA). Crohn's disease (CD) and ulcerative colitis (UC) activity scores were defined using the Harvey-Bradshaw index and partial Mayo score, respectively. The area under the ROC curve was calculated to identify the PhA cut-off point for reduced muscle mass. RESULTS: The sample consisted of 145 patients, with 39 (26.9%) with IBD in the active phase. There was a correlation of the PhA with skeletal muscle mass (SMM) (rs 0.35, P<0.001) and with the skeletal muscle mass index (SMI) (rs 0.427, P<0.001), and the associations remained in the most active form (moderate or severe) of IBD. The ROC curve analysis indicated that the cut-offs points of the PhA ≤5.042 for female and PhA ≤6.079 for male can be used to predict muscle mass reduction. CONCLUSION: The PhA can be considered a predictor of muscle mass reduction in IBD patients, and we can use it for screening and monitoring the evolution of malnutrition. BACKGROUND: • This study aims to assess whether the phase angle is a parameter for predicting reduced muscle mass in patients with inflammatory bowel disease. BACKGROUND: • There was a correlation of the phase angle with skeletal muscle mass and the associations remained in disease activity. BACKGROUND: • The ROC curve analysis indicated that the cut-off point of the PhA ≤5.042° for women and PhA ≤6,079° for men can be used to predict muscle mass reduction. BACKGROUND: • The phase angle can be considered a predictor of muscle mass reduction in inflammatory bowel disease.

Ângulo de fase como preditor de massa muscular em pacientes com doença inflamatória intestinal / Phase angle as a predictor of muscle mass in patients with inflammatory bowel disease

ABSTRACT Malnutrition/sarcopenia is frequent in patients with inflammatory bowel diseases (IBD), and results in muscle catabolism, impacting treatment response, postoperative complications, and quality of life. Objective: This study aims to assess whether the phase angle (PhA) is a parameter for predicting reduced muscle mass in patients with IBD. Methods: Adult patients with IBD were included in this cross-sectional study. For the estimation of muscle mass and the calculation of the PhA, we used bioelectrical impedance analysis (BIA). Crohn's disease (CD) and ulcerative colitis (UC) activity scores were defined using the Harvey-Bradshaw index and partial Mayo score, respectively. The area under the ROC curve was calculated to identify the PhA cut-off point for reduced muscle mass. Results: The sample consisted of 145 patients, with 39 (26.9%) with IBD in the active phase. There was a correlation of the PhA with skeletal muscle mass (SMM) (rs 0.35, P<0.001) and with the skeletal muscle mass index (SMI) (rs 0.427, P<0.001), and the associations remained in the most active form (moderate or severe) of IBD. The ROC curve analysis indicated that the cut-offs points of the PhA ≤5.042 for female and PhA ≤6.079 for male can be used to predict muscle mass reduction. Conclusion: The PhA can be considered a predictor of muscle mass reduction in IBD patients, and we can use it for screening and monitoring the evolution of malnutrition.

RESUMO A desnutrição/sarcopenia é frequente em pacientes com doenças inflamatórias intestinais (DII), resultando em catabolismo muscular, com impacto nas respostas aos tratamentos, complicações cirúrgicas e na qualidade de vida. Objetivo: Este estudo tem como objetivo, avaliar se o ângulo de fase (AF) é um parâmetro para a predição de redução de massa muscular em pacientes com DII. Métodos: Pacientes adultos com DII foram incluídos neste estudo transversal. A estimativa da massa muscular e o cálculo do AF foram realizados a partir do exame de bioimpedância elétrica (BIA). As atividades da doença de Crohn e retocolite ulcerativa foram definidas pelo índice Harvey-Bradshaw e escore parcial de Mayo, respectivamente. A área de curva ROC foi calculada para identificar o ponto de corte do AF para a massa muscular reduzida. Resultados: A amostra foi composta por 145 pacientes, sendo 39 (26.9%) com DII em fase ativa. Houve correlação do AF com massa muscular esquelética (MME) (rs 0.35, P<0.001) e com o índice de massa muscular esquelética (IMME) (rs 0.427, P<0.001), mantendo-se as associações na forma mais ativa (moderada ou grave) da DII. A análise da curva ROC indicou que os pontos de corte de AF ≤5.042 para mulheres e ≤6.079 para homens podem ser usados para prever a redução da massa muscular. Conclusão: O AF pode ser considerado um preditor de redução de massa muscular nos pacientes com DII e ser utilizado para triagem e acompanhamento da evolução da desnutrição.

Prophylactic Minocycline for Delirium in Critically Ill Patients: A Randomized Controlled Trial.

BACKGROUND: Delirium is a potentially severe form of acute encephalopathy. Minocycline has neuroprotective effects in animal models of neurologic diseases; however, data from human studies remain scarce. RESEARCH QUESTION: Does the neuroprotective effect of minocycline prevent delirium occurrence in critical ill patients?. STUDY DESIGN AND METHODS: This study was a randomized, placebo-controlled, double-blind trial conducted in four ICUs. Patients aged 18 years or older were eligible and randomized to receive minocycline (100 mg, twice daily) or placebo. The primary outcome was delirium incidence within 28 days or before ICU discharge. Secondary outcomes included days in delirium during ICU stay, delirium/coma-free days, length of mechanical ventilation, ICU length of stay, ICU mortality, and hospital mortality. The kinetics of various inflammatory (IL-1ß, IL-6, IL-10, and C-reactive protein) and brain-related biomarkers (brain-derived neurotrophic factor and S100B) were used as exploratory outcomes. RESULTS: A total of 160 patients were randomized, but one patient in the placebo group died before treatment; thus the data from 159 patients were analyzed (minocycline, n = 84; placebo, n = 75). After the COVID-19 pandemic it was decided to stop patient inclusion early. There was a small but significant decrease in delirium incidence: 17 patients (20%) in the minocycline arm compared with 26 patients (35%) in the placebo arm (P = .043). No other delirium-related outcomes were modified by minocycline treatment. Unexpectedly, there was a significant decrease in hospital mortality (39% vs. 23%; P = .029). Among all analyzed biomarkers, only plasma levels of C-reactive protein decreased significantly after minocycline treatment (F = 0.75, P = .78, within time; F = 4.09, P = .045, group × time). INTERPRETATION: Our findings in this rather small study signal a possible positive effect of minocycline on delirium incidence. Further studies are needed to confirm the benefits of this drug as a preventive measure in critically ill patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04219735; URL: www. CLINICALTRIALS: gov.

The II Brazilian Guidelines for the pharmacological treatment of patients hospitalized with COVID-19 Joint Guidelines of the Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia and Sociedade Brasileira de Reumatologia.

OBJECTIVE: To update the recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil. METHODS: Experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method. RESULTS: Twenty-one recommendations were generated, including strong recommendations for the use of corticosteroids in patients using supplemental oxygen and conditional recommendations for the use of tocilizumab and baricitinib for patients on supplemental oxygen or on noninvasive ventilation and anticoagulants to prevent thromboembolism. Due to suspension of use authorization, it was not possible to make recommendations regarding the use of casirivimab + imdevimab. Strong recommendations against the use of azithromycin in patients without suspected bacterial infection, hydroxychloroquine, convalescent plasma, colchicine, and lopinavir + ritonavir and conditional recommendations against the use of ivermectin and remdesivir were made. CONCLUSION: New recommendations for the treatment of hospitalized patients with COVID-19 were generated, such as those for tocilizumab and baricitinib. Corticosteroids and prophylaxis for thromboembolism are still recommended, the latter with conditional recommendation. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and to promote resource economy.

Enoxaparin improves COVID-19 by reducing Neutrophils Extracellular Traps (NETs) production.

BACKGROUND: COVID-19 causes consequences such as imbalance of the immune system and thrombotic events. During the infection process, NETs in excess induce a pro-inflammatory response and disseminated intravascular coagulation. We evaluated the role of enoxaparin as a potential inhibitor of NETs. METHODS: K18-hACE2 animals infected with the SARS-CoV-2 virus and a group of 23 individuals admitted to the hospital with COVID-19 treated with enoxaparin or without treatment and controls without the disease were included. RESULTS: Enoxaparin decreased the levels of NETs, reduced the signs of the disease and mitigated lung damage in the animals infected with SARS-CoV-2. These effects were partially associated with prevention of SARS-CoV-2 entry and NETs synthesis. Clinical data revealed that treatment with enoxaparin decreased the levels of inflammatory markers, the levels of NETs in isolated neutrophils and the organ dysfunction. CONCLUSION: This study provides evidence for the beneficial effects of enoxaparin in COVID-19 in addition to its anticoagulant role.

Biomarkers of neuropsychiatric dysfunction in intensive care unit survivors: a prospective cohort study.

OBJECTIVE: To assess factors associated with long-term neuropsychiatric outcomes, including biomarkers measured after discharge from the intensive care unit. METHODS: A prospective cohort study was performed with 65 intensive care unit survivors. The cognitive evaluation was performed through the Mini-Mental State Examination, the symptoms of anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale, and posttraumatic stress disorder was evaluated using the Impact of Event Scale-6. Plasma levels of amyloid-beta (1-42) [Aß (1-42)], Aß (1-40), interleukin (IL)-10, IL-6, IL-33, IL-4, IL-5, tumor necrosis factor alpha, C-reactive protein, and brain-derived neurotrophic factor were measured at intensive care unit discharge. RESULTS: Of the variables associated with intensive care, only delirium was independently related to the occurrence of long-term cognitive impairment. In addition, higher levels of IL-10 and IL-6 were associated with cognitive dysfunction. Only IL-6 was independently associated with depression. Mechanical ventilation, IL-33 levels, and C-reactive protein levels were independently associated with anxiety. No variables were independently associated with posttraumatic stress disorder. CONCLUSION: Cognitive dysfunction, as well as symptoms of depression, anxiety, and posttraumatic stress disorder, are present in patients who survive a critical illness, and some of these outcomes are associated with the levels of inflammatory biomarkers measured at discharge from the intensive care unit.

The II Brazilian Guidelines for the pharmacological treatment of patients hospitalized with COVID-19 Joint Guidelines of the Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia and Sociedade Brasileira de Reumatologia / II Diretrizes Brasileiras para o tratamento farmacológico de pacientes hospitalizados com COVID-19 Diretriz conjunta da Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia e Sociedade Brasileira de Reumatologia

ABSTRACT Objective: To update the recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil. Methods: Experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method. Results: Twenty-one recommendations were generated, including strong recommendations for the use of corticosteroids in patients using supplemental oxygen and conditional recommendations for the use of tocilizumab and baricitinib for patients on supplemental oxygen or on noninvasive ventilation and anticoagulants to prevent thromboembolism. Due to suspension of use authorization, it was not possible to make recommendations regarding the use of casirivimab + imdevimab. Strong recommendations against the use of azithromycin in patients without suspected bacterial infection, hydroxychloroquine, convalescent plasma, colchicine, and lopinavir + ritonavir and conditional recommendations against the use of ivermectin and remdesivir were made. Conclusion: New recommendations for the treatment of hospitalized patients with COVID-19 were generated, such as those for tocilizumab and baricitinib. Corticosteroids and prophylaxis for thromboembolism are still recommended, the latter with conditional recommendation. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and to promote resource economy.

RESUMO Objetivo: Atualizar as recomendações para embasar as decisões para o tratamento farmacológico de pacientes hospitalizados com COVID-19 no Brasil. Métodos: A elaboração desta diretriz foi feita por especialistas, incluindo representantes do Ministério da Saúde e metodologistas. O método utilizado para o desenvolvimento rápido de diretrizes baseou-se na adoção e/ou adaptação de diretrizes internacionais existentes (GRADE ADOLOPMENT) e contou com o apoio da plataforma e-COVID-19 RecMap. A qualidade das evidências e a elaboração das recomendações seguiram o método GRADE. Resultados: Chegaram-se a 21 recomendações, incluindo recomendações fortes quanto ao uso de corticosteroides em pacientes em uso de oxigênio suplementar e recomendações condicionais para o uso de tocilizumabe e baricitinibe, em pacientes com oxigênio suplementar ou ventilação não invasiva, e de anticoagulantes, para prevenção de tromboembolismo. Devido à suspensão da autorização de uso, não foi possível fazer recomendações para o tratamento com casirivimabe + imdevimabe. Foram feitas recomendações fortes contra o uso de azitromicina em pacientes sem suspeita de infecção bacteriana, hidroxicloroquina, plasma convalescente, colchicina e lopinavir + ritonavir, além de recomendações condicionais contra o uso de ivermectina e rendesivir. Conclusão: Foram criadas novas recomendações para o tratamento de pacientes hospitalizados com COVID-19, como as recomendações de tocilizumabe e baricitinibe. Ainda são recomendados corticosteroides e profilaxia contra tromboembolismo, esta em caráter condicional. Vários medicamentos foram considerados ineficazes e não devem ser usados, no intuito de proporcionar o melhor tratamento segundo os princípios da medicina baseada em evidências e promover a economia de recursos.

Sepsis exacerbates Alzheimer's disease pathophysiology, modulates the gut microbiome, increases neuroinflammation and amyloid burden.

While our understanding of the molecular biology of Alzheimer's disease (AD) has grown, the etiology of the disease, especially the involvement of peripheral infection, remains a challenge. In this study, we hypothesize that peripheral infection represents a risk factor for AD pathology. To test our hypothesis, APP/PS1 mice underwent cecal ligation and puncture (CLP) surgery to develop a polymicrobial infection or non-CLP surgery. Mice were euthanized at 3, 30, and 120 days after surgery to evaluate the inflammatory mediators, glial cell markers, amyloid burden, gut microbiome, gut morphology, and short-chain fatty acids (SCFAs) levels. The novel object recognition (NOR) task was performed 30 and 120 days after the surgery, and sepsis accelerated the cognitive decline in APP/PS1 mice at both time points. At 120 days, the insoluble Aß increased in the sepsis group, and sepsis modulated the cytokines/chemokines, decreasing the cytokines associated with brain homeostasis IL-10 and IL-13 and increasing the eotaxin known to influence cognitive function. At 120 days, we found an increased density of IBA-1-positive microglia in the vicinity of Aß dense-core plaques, compared with the control group confirming the predictable clustering of reactive glia around dense-core plaques within 15 µm near Aß deposits in the brain. In the gut, sepsis negatively modulated the α- and ß-diversity indices evaluated by 16S rRNA sequencing, decreased the levels of SCFAs, and significantly affected ileum and colon morphology in CLP mice. Our data suggest that sepsis-induced peripheral infection accelerates cognitive decline and AD pathology in the AD mouse model.

Coagulation biomarkers and coronavirus disease 2019 phenotyping: a prospective cohort study.

BACKGROUND: Because severe acute respiratory syndrome coronarivus 2 (SARS-CoV-2) leads to severe conditions and thrombus formation, evaluation of the coagulation markers is important in determining the prognosis and phenotyping of patients with COVID-19. METHODS: In a prospective study that included 213 COVID-19 patients admitted to the intensive care unit (ICU) the levels of antithrombin, C-reactive protein (CRP); factors XI, XII, XIII; prothrombin and D-dimer were measured. Spearman's correlation coefficient was used to assess the pairwise correlations between the biomarkers. Hierarchical and non-hierarchical cluster analysis was performed using the levels of biomarkers to identify patients´ phenotypes. Multivariate binary regression was used to determine the association of the patient´s outcome with clinical variables and biomarker levels. RESULTS: The levels of factors XI and XIII were significantly higher in patients with less severe COVID-19, while factor XIII and antithrombin levels were significantly associated with mortality. These coagulation biomarkers were associated with the in-hospital survival of COVID-19 patients over and above the core clinical factors on admission. Hierarchical cluster analysis showed a cluster between factor XIII and antithrombin, and this hierarchical cluster was extended to CRP in the next step. Furthermore, a non-hierarchical K-means cluster analysis was performed, and two phenotypes were identified based on the CRP and antithrombin levels independently of clinical variables and were associated with mortality. CONCLUSION: Coagulation biomarkers were associated with in-hospital survival of COVID-19 patients. Lower levels of factors XI, XII and XIII and prothrombin were associated with disease severity, while higher levels of both CRP and antithrombin clustered with worse prognosis. These results suggest the role of coagulation abnormalities in the development of COVID-19 and open the perspective of identifying subgroups of patients who would benefit more from interventions focused on regulating coagulation.

Sepsis sensitizes behavioural amphetamine responses while inducing inflammatory and neurotrophic vulnerability in the cecal ligation and puncture model.

The present study aimed to evaluate if sepsis sensitizes behavioural and biochemical responses induced by m-amphetamine. For this, Wistar rats were submitted to the cecal ligation and puncture. After 30 days of cecal ligation and puncture procedure, the animals were submitted to a single intraperitoneal injection of saline or m-amphetamine (.25, .50, or 1.0 mg/kg). Locomotor behaviour was assessed 2 h after the administration. Interleukin (IL)-1ß, IL-6, IL-10, tumour necrosis factor-α, dopamine-cAMP-regulated phosphoprotein of 32,000 kDa (DARPP-32) and neuronal calcium sensor (NCS-1) levels were evaluated in the frontal cortex, hippocampus and striatum. Also, brain-derived neurotrophic factor (BDNF), neuronal growth factor and glial-derived neurotrophic factor levels were assessed in the hippocampus. M-amphetamine alone (.25 and 1.0 mg/kg) increased rats' locomotion and exploratory behaviour compared with the Sham + Sal. Animals from the cecal ligation and puncture + m-amphetamine (.5 and/or 1.0 mg/kg) group showed an increase in locomotion, exploratory and risk-like behaviour when compared with the Sham + Saline group and with its respective Sham groups. Cecal ligation and puncture increased interleukin levels compared with the Sham + Sal. However, cecal ligation and puncture animals that received m-amphetamine (1 mg/kg) increased even more, these inflammatory parameters compared with the Sham + Sal and the cecal ligation and puncture + saline group. M-amphetamine at lower doses increased neurotrophic factors, but higher doses decreased these parameters in the brain of cecal ligation and puncture rats. M-amphetamine dose-dependently increased DARPP-32 and NCS-1 levels in cecal ligation and puncture rats in some structures. In conclusion, these results demonstrate that sepsis sensitizes behavioural amphetamine responses while inducing inflammatory and neurotrophic vulnerability in the cecal ligation and puncture model.

Neurochemical effects of sepsis on the brain.

Sepsis is a life-threatening organ dysfunction triggered by a dysregulated host immune response to eliminate an infection. After the host immune response is activated, a complex, dynamic, and time-dependent process is triggered. This process promotes the production of inflammatory mediators, including acute-phase proteins, complement system proteins, cytokines, chemokines, and antimicrobial peptides, which are required to initiate an inflammatory environment for eliminating the invading pathogen. The physiological response of this sepsis-induced systemic inflammation can affect blood-brain barrier (BBB) function; subsequently, endothelial cells produce inflammatory mediators, including cytokines, chemokines, and matrix metalloproteinases (MMPs) that degrade tight junction (TJ) proteins and decrease BBB function. The resulting BBB permeability allows peripheral immune cells from the bloodstream to enter the brain, which then release a range of inflammatory mediators and activate glial cells. The activated microglia and astrocytes release reactive oxygen species (ROS), cytokines, chemokines, and neurochemicals, initiate mitochondrial dysfunction and neuronal damage, and exacerbate the inflammatory milieu in the brain. These changes trigger sepsis-associated encephalopathy (SAE), which has the potential to increase cognitive deterioration and susceptibility to cognitive decline later in life.

Paraprobiotics strains accelerate wound repair by stimulating re-epithelialization of NIH-3T3 cells, decreasing inflammatory response and oxidative stress.

The present study aimed to evaluate the potential and specificity of the inflammatory and antioxidant response of Microbe-Associated Molecular Patterns (MAMPs) in NIH-3T3 fibroblast cells, as well as in the healing process of skin wounds. Cells (NIH-3T3) were cultivated in supplemented specific medium. NIH-3T3 cells were treated with MAMPs (Bifidobacterium lactis or Lactobacillus casei or Lactobacillus gasseri or Lactobacillus paracasei or Streptococcus thermophilus), at two concentrations and insulted with LPS or H2O2. Cell viability, myeloperoxidase activity, nitrite/nitrate, oxidative damage and inflammatory parameters were measured. In addition, scratch assay was performed. Significant scratch closure was observed after 24 h and 48 h, and the effect of 0.1 g/mL MAMPs on wound healing was found to be highly statistically significant. In the viability cellular assay, Lactobacillus showed better response in 0.1 g/mL dose, whereas B. lactis and S. thermophilus showed better response in 0.01 g/mL dose. There was reduction in IL-6 and IL-1ß levels in all treatments insulted with LPS. MAMP's showed preventive efficacy in reducing the effects caused by LPS. The MAMP's action in decreasing the production of ROS, inflammatory activity and increasing cell viability, besides significant cell proliferation during wound healing processes suggests remodeling mechanisms and new possibilities for wound healing.

Bacillus strains prevent lipopolysaccharide-induced inflammation in gut and blood of male mice.

AIMS: The protective effects of Bacillus amyloliquefaciens(CCT7935), Bacillus subtilis(CCT7935), Bacillus licheniformis (CCT 7836), and Bacillus coagulans (CCT 0199) against lipopolysaccharide (LPS)-induced intestinal inflammation were investigated. METHODS AND RESULTS: Male Swiss mice were assigned into six groups: control group, LPS group, LPS + B. subtilis (CCT7935) group, LPS +   B. licheniformis (CCT 7836) group, LPS +   B. amyloliquefaciens (CCT7935) group, and LPS   + B. coagulans (CCT 0199) group. Each mouse of the groups Bacillus received 1 × 109 colony-forming units of Bacillus once daily by oral gavage during 30 days. Twenty-four hours after the last dose of Bacillus, all groups, except the control group, were intraperitoneally injected with LPS in the single dose of 15 mg kg-1. The mice were euthanized 24 h after the LPS administration. Histological alterations, myeloperoxidase activity, and nitrite levels were analyzed in the gut of mice and the inflammatory cytokines were analyzed in the gut and in the blood. The results demonstrate that the mice challenged with LPS presented the villi shortened and damaged, which were significantly protected by B. coagulans and B. amyloliquefaciens. Furthermore, all Bacillus tested were effective in preventing against the increase of myeloperoxidase activity, while B. amyloliquefaciens and B. subtilis prevented the increase of nitrite and IL-1ß levels in the gut of mice induced with LPS was decreased only B. subtilis. LPS also elevated the IL-1 ß, IL-6, and IL-10 levels in the blood, and these alterations were significantly suppressed by Bacillus, especially by B. subtilis. CONCLUSIONS: The study suggests that the Bacillus investigated in this study might be effective therapeutic agents for preventing intestinal inflammation, because they decrease the inflammatory process an protect against tissue damage.

How to use biomarkers of infection or sepsis at the bedside: guide to clinicians.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In this context, biomarkers could be considered as indicators of either infection or dysregulated host response or response to treatment and/or aid clinicians to prognosticate patient risk. More than 250 biomarkers have been identified and evaluated over the last few decades, but no biomarker accurately differentiates between sepsis and sepsis-like syndrome. Published data support the use of biomarkers for pathogen identification, clinical diagnosis, and optimization of antibiotic treatment. In this narrative review, we highlight how clinicians could improve the use of pathogen-specific and of the most used host-response biomarkers, procalcitonin and C-reactive protein, to improve the clinical care of patients with sepsis. Biomarker kinetics are more useful than single values in predicting sepsis, when making the diagnosis and assessing the response to antibiotic therapy. Finally, integrated biomarker-guided algorithms may hold promise to improve both the diagnosis and prognosis of sepsis. Herein, we provide current data on the clinical utility of pathogen-specific and host-response biomarkers, offer guidance on how to optimize their use, and propose the needs for future research.

Bifidobacterium lactis CCT 7858 Improves Gastrointestinal Symptoms by Antibiotics Treatment: a Double-Blind, Randomized, Placebo-Controlled Trial.

Diarrhea is one of the most frequent side effects of antibiotic treatment and occurs in 25 to 40% of patients in use. One potential strategy to prevent this side effect is the concurrent use of probiotics. This study evaluated the efficacy of the strain Bifidobacterium lactis CCT 7858 in the prevention of diarrhea and improvement of gastrointestinal symptoms in hospitalized patients using antibiotics. This was a randomized, blinded, placebo-controlled clinical trial. This study included 104 patients in antibiotic treatment. Patients were randomized into two groups: placebo (maltodextrin) and intervention (strain Bifidobacterium lactis CCT 7858 at 9 × 1010 CFU concentration; GABBIA® Biotecnology, Santa Catarina, Brazil). Patients were supplemented depending on the duration of antibiotic therapy, and both were evaluated with scales in two moments: before and after treatment. We included 104 hospitalized patients. In follow-up, 38 (74.5%) of the B. lactis group have no reported diarrhea. In secondary outcomes, in five day strong abdominal distension was reported in 4 (7,3) placebo group and not reported in B. lactis. Abdominal noises, nausea, and vomiting were not registered in any group. B. lactis strain has been considered safe and with several benefits, including reduction of soft stools and gastrointestinal symptoms how abdominal noise, pain and distension, as well reduction of diarrhea.

Zebrafish as a potential model for stroke: A comparative study with standardized models.

Animal models of cerebral ischemia have improved our understanding of the pathophysiology and mechanisms involved in stroke, as well as the investigation of potential therapies. The potential of zebrafish to model human diseases has become increasingly evident. The availability of these models allows for an increased understanding of the role of chemical exposure in human conditions and provides essential tools for mechanistic studies of disease. To evaluate the potential neuroprotective properties of minocycline against ischemia and reperfusion injury in zebrafish and compare them with other standardized models. In vitro studies with BV-2 cells were performed, and mammalian transient middle cerebral artery occlusion (tMCAO) was used as a comparative standard with the zebrafish stroke model. Animals were subjected to ischemia and reperfusion injury protocols and treated with minocycline. Infarction size, cytokine levels, oxidative stress, glutamate toxicity, and immunofluorescence for microglial activation, and behavioral test results were determined and compared. Administration of minocycline provided significant protection in the three stroke models in different parameters analyzed. Both experimental models complement each other in their particularities. The proposal also strengthens the findings in the literature in rodent models and allows the validation of alternative models so that they can be used in further research involving diseases with ischemia and reperfusion injury.

Intra-articular Treatment with Triamcinolone Hexacetonide Associated with Gold Nanoparticles Reduces Cartilage Degeneration in an Animal Model of Osteoarthritis.

INTRODUCTION: The association between triamcinolone hexacetonide (TH) and gold nanoparticles (GNPs) represents a promising treatment due to the potential anti-inflammatory and antioxidant effects of these compounds. In this study, we evaluated the effects of intra-articular treatment of TH associated with GNPs in a mechanical model of osteoarthritis (OA). METHODS: Fifty Wistar rats were divided into five groups: Sham; OA; OA+TH; OA+GNPs; OA+TH-GNPs. Both applications were performed 30 and 60 days after the model was induced. After 30 days of the last application, the animals were euthanized. RESULTS: Only the combined treatment with TH and GNPs promoted a reduction in proinflammatory cytokines and an increase in anti-inflammatory cytokines. The OA+TH-GNPs group obtained a significant reduction in the production of oxidants and oxidative damage markers while an increase in antioxidants. Histologically, all treated groups showed results of a significant increase in cartilage thickness and chondrocyte count, the OA+TH-GNPs group had similar behavior to the group without osteoarthritis, with significantly smaller amounts of chondrocytes than the OA group. CONCLUSION: The intra-articular use of TH associated with GNPs may be able to prevent the progression of the pathology and minimize joint degradation.