Effects of Pera Orange Juice and Moro Orange Juice in Healthy Rats: A Metabolomic Approach.

Cardiovascular disease is a leading cause of death worldwide. Heart failure is a cardiovascular disease with high prevalence, morbidity, and mortality. Several natural compounds have been studied for attenuating pathological cardiac remodeling. Orange juice has been associated with cardiovascular disease prevention by attenuating oxidative stress. However, most studies have evaluated isolated phytochemicals rather than whole orange juice and usually under pathological conditions. In this study, we evaluated plasma metabolomics in healthy rats receiving Pera or Moro orange juice to identify possible metabolic pathways and their effects on the heart. METHODS: Sixty male Wistar rats were allocated into 3 groups: control (C), Pera orange juice (PO), and Moro orange juice (MO). PO and MO groups received Pera orange juice or Moro orange juice, respectively, and C received water with maltodextrin (100 g/L). Echocardiogram and euthanasia were performed after 4 weeks. Plasma metabolomic analysis was performed by high-resolution mass spectrometry. Type I collagen was evaluated in picrosirius red-stained slides and matrix metalloproteinase (MMP)-2 activity by zymography. MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, TIMP-4, type I collagen, and TNF-α protein expression were evaluated by Western blotting. RESULTS: We differentially identified three metabolites in PO (N-docosahexaenoyl-phenylalanine, diglyceride, and phosphatidylethanolamine) and six in MO (N-formylmaleamic acid, N2-acetyl-L-ornithine, casegravol isovalerate, abscisic alcohol 11-glucoside, cyclic phosphatidic acid, and torvoside C), compared to controls, which are recognized for their possible roles in cardiac remodeling, such as extracellular matrix regulation, inflammation, oxidative stress, and membrane integrity. Cardiac function, collagen level, MMP-2 activity, and MMP-9, TIMP-2, TIMP-4, type I collagen, and TNF-α protein expression did not differ between groups. CONCLUSION: Ingestion of Pera and Moro orange juice induces changes in plasma metabolites related to the regulation of extracellular matrix, inflammation, oxidative stress, and membrane integrity in healthy rats. Moro orange juice induces a larger number of differentially expressed metabolites than Pera orange juice. Alterations in plasma metabolomics induced by both orange juice are not associated with modifications in cardiac extracellular matrix components. Our results allow us to postulate that orange juice may have beneficial effects on pathological cardiac remodeling.

Administration of enteral nutrition and gastrointestinal complications in Covid-19 critical patients in prone position.

Background: The prone position (PP) used in the treatment of critically ill patients infected with SARS-CoV-2, may be a barrier to enteral nutrition (EN). This study aimed to analyze the effectiveness and complications of EN in the PP, as well as clinical outcomes. Methods: Prospective cohort study with patients in EN and coronavirus disease 2019 (COVID-19), on mechanical ventilation (MV), which whom needed or not PP. Gastrointestinal intolerances (GII) related to PP were evaluated, and correlated with possible confounding factors. EN, days on MV, Intensive Care Unit (ICU) length of stay, hospital length of stay, ventilator-associated pneumonia (VAP) and mortality were analyzed. The data were evaluated daily and compared prone group (PG=57) and supine group (SG=69). Results: The PP was associated with GII (P=0.000) and presented in 32 patients (26,44%) with no difference among groups. Association between epinephrine (P=0.003), vasopressin (P=0.018), and GII was observed. There was no difference between the total volume of enteral nutrition (TVEN) infused in the groups. However, the mean EN infused for the days when the patient was on PP was (70.0% ± 31.5) and for the days in supine position was (74.8% ± 27.3), P= 0.006. The PG had a longer time on MV (P=0.005) and ICU (P=0.003) and PP was associated with VAP (P=<0.001). The infused TVEN showed no association with VAP (P=0.09). Conclusion: PP was a determining factor in GII and proved to be a risk factor for VAP, but the EN protocol seems to have ensured an adequate EN supply in PP and be a safe alternative.

Doxycycline Attenuates Doxorubicin-Induced Cardiotoxicity by Improving Myocardial Energy Metabolism in Rats.

AIM: Evaluate the influence of doxycycline, an anti-inflammatory and matrix metalloproteinase (MMP) inhibitor, on the attenuation of chronic doxorubicin-induced cardiotoxicity in rats. METHODS: We allocated male Wistar rats into four groups: control (C), doxorubicin (D), doxycycline (inhibitor of MMP, IM), and Dox + doxycycline (DIM). Groups IM and DIM received doxycycline (5 mg/kg, IP) once a week for 4 weeks. In addition, 48 h after every doxycycline injection, groups D and DIM received Dox (5 mg/kg, IP). We performed echocardiogram and evaluated TIMP-4 and collagen I protein expression, MMP-2 activity, and oxidative stress and myocardial metabolism. RESULTS: Doxorubicin promotes left atrium (LA) and left ventricle (LV) dilatation and decreases in LV fractional shortening, which was improved by doxycycline. Moreover, doxycycline attenuated the LV cardiomyocyte hypertrophy and collagen type I expression. Doxorubicin increased phosphofructokinase and decreased beta-hydroxyacyl Co-A dehydrogenase, pyruvate dehydrogenase, citrate synthase, and ATP synthase activity, which was partially attenuated by doxycycline. Lastly, doxycycline improved antioxidant enzyme activity in the DIM group. CONCLUSION: Doxorubicin increases oxidative stress and promotes changes in myocardial energy metabolism, accompanied by structural and functional changes. Doxycycline attenuated the doxorubicin-induced cardiotoxicity, at least in part, through changes in myocardial energy metabolism.

Pera orange (Citrus sinensis) and Moro orange (Citrus sinensis (L.) Osbeck) juices attenuate left ventricular dysfunction and oxidative stress and improve myocardial energy metabolism in acute doxorubicin-induced cardiotoxicity in rats.

OBJECTIVES: Doxorubicin is a highly effective chemotherapeutic agent for treating several types of cancer; however, it can induce cardiotoxicity. We evaluated the influence of Pera and Moro orange juices on cardiac remodeling induced by acute administration of doxorubicin in rats. METHODS: We allocated 120 male Wistar rats into six groups: control (C), Pera orange juice (PO), Moro orange juice (MO), doxorubicin (D), doxorubicin + Pera orange juice (DPO), and doxorubicin + Moro orange juice (DMO). Groups PO and DPO received Pera orange juice, MO and DMO received Moro orange juice, and C and D received water with maltodextrin (100 g/L) for 4 wk. Subsequently, groups D, DPO, and DMO received 20 mg/kg doxorubicin and C, PO, and MO received saline. Echocardiogram and euthanasia were performed 48 h after doxorubicin injection. Juice and animal-serum flavonoid identification and quantification were evaluated by liquid chromatography/electrospray ionization multistage mass spectrometry. Oxidative stress and myocardial metabolism were evaluated by spectrophotometry. RESULTS: Systolic and diastolic left ventricular dysfunction increased oxidative stress and pathologic changes in myocardial energy metabolism of rats treated with doxorubicin. Intake of both orange juices improved left ventricular function, decreased oxidative stress, and attenuated the myocardial energy metabolism changes. Moro orange juice had a more pronounced effect than Pera orange juice in glutathione peroxidase activity, citrate synthase, and ß-hydroxyacyl-CoA dehydrogenase activity. CONCLUSIONS: Pera and Moro orange juices attenuated cardiac remodeling induced by doxorubicin, improved myocardial energy metabolism, and attenuated oxidative stress. However, Moro orange juice was more effective than Pera orange juice in modifying energy metabolism.

Influence of negative pressure on the viability of adipocytes and mesenchymal stem cell, considering the device method used to harvest fat tissue.

BACKGROUND: Transplanted adipose tissue has many applications in regenerative medicine. However, fat grafting yields unpredictable results because the fat that is transferred can suffer variable degrees of fat reabsorption. It is necessary to identify methods and maneuvers to minimize reabsorption rates and provide predictable long-term results. OBJECTIVES: Our study aimed to identify the optimal method of harvesting, as well as the optimal pressure regime for fat aspiration. The primary objective was to assess the degree of adipocyte and mesenchymal stem cell death that occurred with the various devices and pressure levels used to harvest fat. METHODS: This study was a prospective, randomized, comparative study in 15 healthy male and female subjects aged 25 to 60 who were undergoing abdominal cosmetic surgery. Various apparatuses and pressure regimens were used to harvest 8 samples of fat tissue. These samples (R1 = R8) underwent histological analysis in order to verify the integrity and functionality of the adipocytes and mesenchymal stem cells that had been harvested. RESULTS: A total of 14 females and 1 male underwent abdominal cosmetic surgery. Quantitative analysis revealed that the adipocytes in all 8 samples had homogeneous quantitative profiles. The adipose mesenchymal stem cell (AMSC) analysis, according to Friedman ANOVA, revealed no significant variation in the percentage of mesenchymal stem cells (P = .045) between the various samples. CONCLUSIONS: The type of device, nozzle diameter tip, and pressure regimen used in this study for harvesting fat tissue did not significantly affect the number of the adipocytes or viable AMSC harvested. LEVEL OF EVIDENCE: 3 Therapeutic.

Prevalência de dor e fatores associados em pacientes com úlcera venosa / Prevalence of pain and associated factors in venous ulcer patients

Justificativa e objetivos: A dor é um sintoma muito frequente em pacientes com úlceras venosas e pode ser persistente e/ou ser exacerbada durante as trocas de curativo. A presença de dor afeta a qualidade de vida e pode influenciar negativamente a cicatrização da ferida. O objetivo deste estudo foi identificar a prevalência de dor e verificar os principais fatores associados à dor em pacientes com úlceras venosas. Métodos: Estudo transversal, desenvolvido em um Hospital Universitário em Natal, RN. A amostra, de conveniência, foi constituída por 100 pacientes com úlcera venosa atendidos no ambulatório de angiologia do referido hospital. Utilizou-se um formulário estruturado de entrevista com características sociodemográficas e de saúde, características da assistência e da lesão, além de duas questões sobre dor do Medical Outcome Study Short Form 36 (SF-36). Para a comparação das variáveis categóricas, foi utilizado o teste Mann-Whitney. O nível de significância estabelecido foi p<0,05. Resultados: A dor esteve presente em 86% dos pacientes avaliados. Pacientes com profissão/ocupação, de baixa renda e que não fumavam/bebiam, que usavam terapia compressiva, que receberam orientações sobre uso de terapia compressiva e elevação de membros inferiores, com lesões menores, em fase de epitelização, sem odor e sem sinais de infecção apresentaram menor intensidade da dor e menor impacto da dor nas atividades do dia a dia. Conclusao: Fatores sociodemográficos, relacionados à assistência e à lesão influenciaram a dor relacionada a úlceras venosas. Intervenções que visem influenciar esses fatores tem potencial para auxiliar no controle da dor desses pacientes.

Background and objectives: Pain is a very frequent symptom in venous ulcer patients and may be persistent and/or exacerbated during dressing change. Pain affects quality of life and may negatively impact wound healing. This study aimed at identifying the prevalence of pain and at evaluating major painassociated factors in venous ulcer patients. Methods: This is a transversal study carried out in a Teaching Hospital of Natal, RN. Convenience sample was made up of 100 venous ulcer patients seen by the angiology ambulatory of this hospital. A structured interview form with socio-demographic and health characteristics, and assistance and injury characteristics was used, in addition to two questions about pain from the Medical Outcome Study Short Form 36 (SF-36). Mann-Whitney test was used to compare categorical variables. Significance level was p<0.05. Results: Pain was referred by 86% of evaluated patients. Patients with profession/occupation, low income and who did not smoke/drank, using compressive therapy, who were oriented about using compressive therapy and leg lifting, with minor injuries, in epithelialization stage, with no odor and without signs of infection had lower pain intensity and lower impact of pain on daily life activities. Conclusion: Socio-demographic factors and aspects regarding assistance and injury have influenced venous ulcer-related pain. Interventions aiming at influencing such factors might help controlling these patients' pain.

Lipase production by Aspergillus ibericus using olive mill wastewater.

Olive mill wastewater (OMW) characteristics make it a suitable resource to be used as a microbial culture media to produce value-added compounds, such as enzymes. In this work, the ability of the novel species Aspergillus ibericus to discolor OMW and produce lipase was studied. An initial screening on plates containing an OMW-based agar medium and an emulsified olive oil/rhodamine-B agar medium was employed to select the strain A. ibericus MUM 03.49. Then, experiments in conical flasks with liquid OMW-based media showed that the fungus could growth on undiluted OMW, with a chemical oxygen demand (COD) of 97 ± 2 g/L, and to produce up to 2,927 ± 54 U/L of lipase. When pure OMW was used in the media, the maximum COD and color reduction achieved were 45 and 97 %, respectively. When OMW diluted to 10 % was used, A. ibericus was able to reduce phenolic and aromatic compounds by 37 and 39 %, respectively. Additionally, lipase production was found to be promoted by the addition of mineral nutrients. When the fermentations were scaled up to a 2-L bioreactor, A. ibericus produced up to 8,319 ± 33 U/L of lipase, and the maximum COD and color reduction were 57 and 24 %, respectively.

The extracellular matrix of the lateral pharyngeal wall in obstructive sleep apnea.

STUDY OBJECTIVES: To compare the components of the extracellular matrix in the lateral pharyngeal muscular wall in patients with and without obstructive sleep apnea (OSA). This may help to explain the origin of the increased collapsibility of the pharynx in patients with OSA. DESIGN: Specimens from the superior pharyngeal constrictor muscle, obtained during pharyngeal surgeries, were evaluated using histochemical and immunohistochemical analyses to determine the fractional area of collagen types I and III, elastic fibers, versican, fibronectin, and matrix metalloproteinases 1 and 2 in the endomysium. SETTING: Academic tertiary center. PATIENS: A total of 51 nonobese adult patients, divided into 38 patients with OSA and 13 nonsnoring control subjects without OSA. INTERVENTIONS: Postintervention study performed on tissues from patients after elective surgery. MEASUREMENTS AND RESULTS: Pharyngeal muscles of patients with OSA had significantly more collagen type I than pharyngeal muscles in control subjects. Collagen type I was correlated positively and independently with age. The other tested components of the extracellular matrix did not differ significantly between groups. In a logistic regression, an additive effect of both the increase of collagen type I and the increase in age with the presence of OSA was observed (odds ratio (OR), 2.06; 95% confidence interval (CI), 1.17-3.63), when compared with the effect of increased age alone (OR, 1.11; 95% CI, 1.03-1.20). CONCLUSION: Collagen type I in the superior pharyngeal constrictor muscle was more prevalent in patients with OSA and also increased with age. It was hypothesized that this increase could delay contractile-relaxant responses in the superior pharyngeal constrictor muscle at the expiratory-inspiratory phase transition, thus increasing pharyngeal collapsibility.

Tonsil volume, tonsil grade and obstructive sleep apnea: is there any meaningful correlation?

OBJECTIVES: The aims of this study were to evaluate the correlation between oropharyngeal examination and objective palatine tonsil volume in snoring adults and verify the influence of the oropharyngeal anatomy, body mass index, age, and severity of obstructive sleep apnea on actual tonsil volume. In addition, we aimed to assess the influence of tonsil size on obstructive sleep apnea in adults. INTRODUCTION: Pharyngeal wall geometry is often altered in adults who have obstructive sleep apnea, and this might influence the findings of the oropharyngeal examination that, in turn, are the key factors when considering surgical management for this condition. Furthermore, the correlation between the actual tonsil volume and the severity of obstructive sleep apnea in adults is currently unknown. METHODS: We prospectively studied 130 patients with obstructive sleep apnea or primary snoring who underwent pharyngeal surgery with intraoperative measurement of tonsil volume. We compared tonsil volume with preoperative polysomnography, oropharyngeal examination, and anthropometric data. RESULTS: We found a significant correlation between actual tonsil volume and subjective tonsil grade. We also found a significant correlation between tonsil volume and the apnea-hypopnea index. Using a multivariate linear regression model, tonsil volume was found to be significantly correlated with age, body mass index, and oropharyngeal examination, but not with polysomnography. Clinically, only the rare tonsil grade IV was indicative of more severe obstructive sleep apnea. CONCLUSIONS: There is a strong correlation between clinical tonsil grade and objective tonsil volume in snoring adults, and this correlation exists regardless of the presence or severity of obstructive sleep apnea. Pharyngeal tissue volume likely reflects the body mass index rather than obstructive sleep apnea severity.

Tonsil volume, tonsil grade and obstructive sleep apnea: is there any meaningful correlation?

OBJECTIVES: The aims of this study were to evaluate the correlation between oropharyngeal examination and objective palatine tonsil volume in snoring adults and verify the influence of the oropharyngeal anatomy, body mass index, age, and severity of obstructive sleep apnea on actual tonsil volume. In addition, we aimed to assess the influence of tonsil size on obstructive sleep apnea in adults. INTRODUCTION: Pharyngeal wall geometry is often altered in adults who have obstructive sleep apnea, and this might influence the findings of the oropharyngeal examination that, in turn, are the key factors when considering surgical management for this condition. Furthermore, the correlation between the actual tonsil volume and the severity of obstructive sleep apnea in adults is currently unknown. METHODS: We prospectively studied 130 patients with obstructive sleep apnea or primary snoring who underwent pharyngeal surgery with intraoperative measurement of tonsil volume. We compared tonsil volume with preoperative polysomnography, oropharyngeal examination, and anthropometric data. RESULTS: We found a significant correlation between actual tonsil volume and subjective tonsil grade. We also found a significant correlation between tonsil volume and the apnea-hypopnea index. Using a multivariate linear regression model, tonsil volume was found to be significantly correlated with age, body mass index, and oropharyngeal examination, but not with polysomnography. Clinically, only the rare tonsil grade IV was indicative of more severe obstructive sleep apnea. CONCLUSIONS: There is a strong correlation between clinical tonsil grade and objective tonsil volume in snoring adults, and this correlation exists regardless of the presence or severity of obstructive sleep apnea. Pharyngeal tissue volume likely reflects the body mass index rather than obstructive sleep apnea severity.

Avaliação do papel da matriz extracelular na musculatura da parede lateral da faringe na fisiopatologia da síndrome da apnéia obstrutiva do sono / Extracellular matrix of the lateral pharyngeal wall in obstructive sleep apnea syndrome

A parede lateral da faringe parece ser a estrutura central envolvida no colapso da faringe nos pacientes com síndrome da apnéia obstrutiva do sono (SAOS). Os pacientes com roncos e apnéia têm uma faringe mais colapsável associada a um espessamento da musculatura da parede lateral da faringe, em grande parte formada pelo músculo constritor superior da faringe. O endomísio da matriz extracelular do músculo esquelético tem uma íntima relação com as células musculares, influenciando suas propriedades mecânicas e biológicas, podendo modificar seu comportamento e função. As fibras colágenas e elásticas formam o arcabouço do tecido conectivo, enquanto os proteoglicanos e as glicoproteínas estruturais (fibronectina) têm importante papel na propriedade de adesão e hidratação dos tecidos e as metaloproteínas são responsáveis pela degradação dos componentes da matriz extracelular. Os fatores determinantes da complacência excessiva da musculatura da parede lateral são desconhecidos. É possível que a MEC tenha um papel relevante neste aspecto. O objetivo deste estudo é descrever e comparar a densidade dos componentes da matriz extracelular do endomísio da musculatura da parede lateral da faringe em controles, roncadores e apnéicos. Neste estudo prospectivo foram avaliados 61 pacientes maiores de 18 anos e não obesos do Departamento de Otorrinolaringologia do Hospital das Clínicas da Faculdade de medicina da Universidade de São Paulo, com indicação de cirurgias faríngeas no período de 2005 e 2006. Os pacientes foram divididos em três grupos: controles (14 pacientes sem roncos ou SAOS), 18 roncadores primários e 29 pacientes com SAOS...

The lateral muscular pharyngeal wall appears to be the predominant structure involved in the collapse of the pharynx in obstructive sleep apnea (OSA). OSA patients and snorers have a narrower pharynx which is more susceptible to collapse and is associated with muscle thickening in the lateral pharyngeal wall, largely formed by superior pharyngeal constrictor. The endomysial extracellular matrix of skeletal muscle has an intimate relationship with the muscle cells and has an important influence on its mechanical and biological properties and can modify their behavior and function. Collagen and elastic fibers form the scaffolding of the connective tissue and proteoglycans and structural glycoproteins (fibronectin) have important roles in hydration, resiliency and adhesive properties of the tissues and the matrix metalloproteinases are involved in extracellular matrix components degradation. The determining factors in the compliance of lateral muscular pharyngeal wall are also unknown. It is possible that the ECM has a relevant role in this aspect. Our objective was to determine and compare the density of the components of the extracellular matrix in the deep, structural lateral pharyngeal muscular walls in snorers, OSA and control patients and correlate with age and weight. In this prospective study we evaluated 61 patients older than 18 and nonobese with indications for pharyngeal surgery at the department of Otolaryngology of the Hospital das Clínicas of the São Paulo University, between 2005 and 2006. The patients were divided in three groups: controls (14 patients), 18 primary snorers and 29 OSA patients. We obtained specimens from the lateral pharyngeal muscular wall (superior constrictor muscle) during pharyngeal surgeries...