RESUMO
Cryptosporidiosis is a waterborne protozoal infection that may cause life-threatening diarrhea in undernourished children living in unsanitary environments. The aim of this study is to identify new biomarkers that may be related to gut-brain axis dysfunction in children suffering from the malnutrition/infection vicious cycle, necessary for better intervention strategies. Myeloperoxidase (MPO) is a well-known neutrophil-related tissue factor released during enteropathy that could drive gut-derived brain inflammation. We utilized a model of environmental enteropathy in C57BL/6 weanling mice challenged by Cryptosporidium and undernutrition. Mice were fed a 2%-Protein Diet (dPD) for eight days and orally infected with 107-C. parvum oocysts. C. parvum oocyst shedding was assessed from fecal and ileal-extracted genomic DNA by qRT-PCR. Ileal histopathology scores were assessed for intestinal inflammation. Prefrontal cortex samples were snap-frozen for MPO ELISA assay and NF-kb immunostaining. Blood samples were drawn by cardiac puncture after anesthesia and sera were obtained for serum amyloid A (SAA) and MPO analysis. Brain samples were also obtained for Iba-1 prefrontal cortex immunostaining. C. parvum-infected mice showed sustained stool oocyst shedding for six days post-infection and increased fecal MPO and inflammation scores. dPD and cryptosporidiosis led to impaired growth and weight gain. C. parvum-infected dPD mice showed increased serum MPO and serum amyloid A (SAA) levels, markers of systemic inflammation. dPD-infected mice showed greater MPO, NF-kB expression, and Iba-1 immunolabeling in the prefrontal cortex, an important brain region involved in executive function. Our findings suggest MPO as a potential biomarker for intestinal-brain axis dysfunction due to environmental enteropathy.
Assuntos
Criptosporidiose , Cryptosporidium parvum , Cryptosporidium , Desnutrição , Animais , Camundongos , Encéfalo/patologia , Criptosporidiose/complicações , Criptosporidiose/patologia , Fezes , Inflamação , Desnutrição/patologia , Camundongos Endogâmicos C57BL , NF-kappa B , Peroxidase , Proteína Amiloide A SéricaRESUMO
A crucial etiological component in fetal programming is early nutrition. Indeed, early undernutrition may cause a chronic increase in blood pressure and cardiovascular diseases, including stroke and heart failure. In this regard, current evidence has sustained several pathological mechanisms involving changes in central and peripheral targets. In the present review, we summarize the neuroendocrine and neuroplastic modifications that underlie maladaptive mechanisms related to chronic hypertension programming after early undernutrition. First, we analyzed the role of glucocorticoids on the mechanism of long-term programming of hypertension. Secondly, we discussed the pathological plastic changes at the paraventricular nucleus of the hypothalamus that contribute to the development of chronic hypertension in animal models of prenatal undernutrition, dissecting the neural network that reciprocally communicates this nucleus with the locus coeruleus. Finally, we propose an integrated and updated view of the main neuroendocrine and central circuital alterations that support the occurrence of chronic increases of blood pressure in prenatally undernourished animals.
Assuntos
Hipertensão , Desnutrição , Efeitos Tardios da Exposição Pré-Natal , Animais , Pressão Sanguínea , Feminino , Glucocorticoides/fisiologia , Humanos , Desnutrição/patologia , Núcleo Hipotalâmico Paraventricular , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologiaRESUMO
The intensity damages caused by nutritional deficiency in growing plants can vary with nutrients. The effects caused by nutrient omission in the plant nutritional efficiency in relation to the absorption and use of the missing nutrient, and the reasons why these damages reflect in other nutrients have not yet been reported in the culture of scarlet eggplant. A better understanding of the nutritional mechanisms involved may clarify why certain nutrients cause greater limitations than other during plants growth. Thus, this study was designed with the aim of evaluating the damages caused by macronutrients deficiency in the culture of scarlet eggplant in the accumulation of these nutrients, nutritional deficiency, plants growth and in visual symptoms. The experiment was carried out in a controlled environment where plants were cultivated in a hydroponic system. Treatments consisted of supplying a complete Hoagland and Arnon solution (CS), and other nutrient solutions with individual omissions of nitrogen (-N), phosphorus (-P), potassium (-K), calcium (-Ca), magnesium (-Mg) and sulphur (-S). When a nutrient deficiency arose, nutritional analyses, growth and visual symptoms were analyzed. The omissions of N, S and K in the nutrient solution resulted in lower accumulation of all macronutrients in both the above and below ground biomass. Individual omissions resulted in nutritional imbalances with reflexes in the absorption efficiencies and use of the missing nutrient, as well as of other nutrients, revealing that the metabolism involves multiple nutritional interactions. Losses of nutritional efficiencies of macronutrients caused detrimental effects on plants growth, with reduced height, stem diameter, number of leaves, leaf area, and biomass production in above ground and below ground. From the losses in production in above ground biomass, the order of macronutrients limitation was N, S, K, Ca, Mg, and P, with reductions of 99, 96, 94, 76, 51 and 46%, respectively, in comparison to plants cultivated in CS. The most limiting nutrients were N, S, and K, seen that its deficiencies affected the metabolism of all other nutrients. This study demonstrates the importance of an adequate nutritional management of N, S, and K in the cultivation of scarlet eggplant.
Assuntos
Desnutrição/patologia , Nutrientes/análise , Nutrientes/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Solanum melongena/crescimento & desenvolvimento , Magnésio/análise , Nitrogênio/análise , Fósforo/análise , Folhas de Planta/metabolismo , Potássio/análise , Solanum melongena/metabolismo , Enxofre/análiseRESUMO
BACKGROUND & AIMS: Malnutrition is prevalent among hospitalized patients, but there is no universally accepted consensus regarding its diagnosis. Recently, the Global Leadership Initiative on Malnutrition (GLIM) proposed a new framework for the malnutrition diagnosis and until this moment there is scarce evidence regarding its validity. This study aimed to evaluate the concurrent and predictive validity of GLIM criteria for malnutrition diagnosis in hospitalized patients. METHODS: Prospective cohort study involving adult/elderly hospitalized patients. The malnutrition diagnoses according to Subjective Global Assessment (SGA) and GLIM criteria were performed within 48 h of admission. Patients were followed up until hospital discharge to assess the length of hospital stay (LOS) and in-hospital mortality. Six months post discharge; the patients were contacted to collect the outcomes readmission and death. Agreement and accuracy tests, Cox and Logistic regression analysis were performed for testing criterion validity. RESULTS: 601 patients (55.7 ± 14.8 years, 51.3% men) were evaluated. Malnutrition was diagnosed in 33.9% and 41.6% of patients, by SGA and GLIM criteria, respectively. GLIM criteria presented a satisfactory accuracy, (AUC = 0.842; CI95% 0.807-0.877) with a sensitivity of 86.6%, and a specificity of 81.6%. The presence of malnutrition by GLIM criteria increased the chance of prolonged hospitalization by 1.76 (CI95% 1.23-2.52) times, and the risk of in-hospital deaths by 5.1 (CI95% 1.14-23.14) times. It was also associated with death within six months (RR = 3.96, CI95% 1.49-10.53). CONCLUSION: GLIM criteria for malnutrition diagnosis presented satisfactory criterion validity and should be applied during clinical practice.
Assuntos
Desnutrição/diagnóstico , Avaliação Nutricional , Estado Nutricional , Índice de Massa Corporal , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Desnutrição/patologia , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Estudos Prospectivos , Sensibilidade e Especificidade , Redução de PesoRESUMO
BACKGROUND/AIMS: Chronic malnutrition (M) affects >1 billion people worldwide. Epidemiological data point to long-term renal and cardiovascular outcomes (e.g. arterial hypertension, cardiorenal syndromes). The renin-angiotensin-aldosterone system (RAAS) has been implicated in the physiopathology of these disturbances, but M-induced alterations in RAAS-modulated renal Na+ handling and their cardiovascular repercussions are not known. Moreover, altered tissue-specific histone deacetylases (HDAC) results in arterial hypertension and the use of sodium Valproate (Val; a HDAC inhibitor) reduces blood pressure. However, there are no reports regarding the renal and cardiovascular effects of HDAC inhibition in M, or on the signaling pathways involved. The central aim of our study has been to investigate whether alterations in the HDAC/RAAS axis underpin alterations in active Na+ transport in the kidney and heart, and affects blood pressure. METHODS: Male rats aged 28 days were given either a control (C) or a multideficient diet (Regional Basic Diet, RBD), which mimics alimentary habits from developing countries. Subgroups received Losartan (Los), a blocker of type 1 Angiotensin II receptors. When the rats reached 70 days, new subgroups received Val until they were 90 days of age. Homogenates and enriched plasma membrane fractions from renal cortex corticis and cardiomyocytes were obtained by differential centrifugation of the tissues. The activity of renal and cardiac deacetylases was assayed by measuring - after incubation with the membranes - the amount of deacetylated lysines in a substrate containing an acetylated lysine side chain. Protein kinases activities were measured following the incorporation of the γ-phosphoryl group of [γ-32P]ATP into Ser/Thr residues of histone type III-S. The activity of Na+-transporting ATPases (kidney and heart) was quantified by measuring the release of Pi from ATP that was sensitive to ouabain ((Na++K+)ATPase), or sensitive to furosemide (Na+-ATPase). Tail-cuff plethysmography was used to measure systolic blood pressure and heart rate. RESULTS: M provoked HDAC downregulation, which was reversed by Los and Val, either alone or in combination, with selective upregulation of protein kinases C and A (PKC, PKA) in renal cortex corticis, but not in left ventricle cardiomyocytes. The 2 kinases were strongly inhibited by Los and Val in both organs. Malnourished rats developed elevated systolic arterial pressure (SAP) and heart rate (HR) at 70 days of age; Los and Val restored the control SAP, but not HR. Functional and the above biochemical alterations were associated with the deregulation of renal and cardiac Na+-transporting ATPases. (Na++K+)ATPase activities were downregulated in M rats in both organs, and were further inhibited by the pharmacological treatments in the renal cortex corticis (C and M groups) and the left ventricle (only in C rats). No additional effect was found in cardiac (Na++K+)ATPase from M rats. Ouabain-resistant Na+-ATPase was upregulated in renal cortex corticis and downregulated in cardiomyocytes, returning to C values after administration of Los and Val. CONCLUSION: The HDAC/RAAS axis appears to be a key regulator of Na+-transporting ATPases in renal cortex corticis and cardiomyocytes via an appropriate balance of PKC and PKA activities. Modifications within the HDAC/RAAS axis provoked by chronic M - with repercussions in renal and cardiac Na+ transport - underpin alterations in bodily Na+ homeostasis that culminate with the onset of arterial hypertension and potential cardiorenal syndrome.
Assuntos
Histona Desacetilases/metabolismo , Córtex Renal/metabolismo , Desnutrição/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Sistema Renina-Angiotensina , Adenosina Trifosfatases/metabolismo , Animais , Proteínas de Transporte de Cátions/metabolismo , Doença Crônica , Feminino , Córtex Renal/patologia , Masculino , Desnutrição/patologia , Miocárdio/patologia , Miócitos Cardíacos/patologia , RatosRESUMO
Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1ß immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.
Assuntos
Apolipoproteína A-I/sangue , Dieta/efeitos adversos , Inflamação/metabolismo , Desnutrição/metabolismo , Animais , Apolipoproteína A-I/metabolismo , Brasil , Doença Crônica , Humanos , Inflamação/sangue , Inflamação/patologia , Fígado/metabolismo , Masculino , Desnutrição/sangue , Desnutrição/patologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Malnutrition in cancer is an independent factor associated with negative clinical outcomes. The objective of this study was to evaluate the prevalence of malnutrition across different age groups in patients with cancer in Brazil and to identify associations with nutrition impact symptoms (NIS). METHODS: In this observational, cross-sectional, multicenter study, the authors evaluated 4783 patients with cancer aged ≥20 years who were admitted to 45 public hospitals in Brazil. Nutritional status, nutritional risk, and NIS were evaluated using the Patient-Generated Subjective Global Assessment. RESULTS: More than one-fourth (25.5%) of all participants were aged ≥65 years. In patients aged ≥65 years, the prevalence of moderate/suspected and severe malnutrition was 55%, it was 45.4% in those aged 51 to 64 years, and it was 36.1% in those aged ≤50 years. Among the NIS with a higher risk of occurrence in patients aged ≥65 years were no appetite (odds ratio [OR], 1.90; 95% CI, 1.62-2.22; P < .05) and dry mouth (OR, 1.40; 95% CI, 1.1-1.67; P < .05). In patients between ages 51 and 64 years, compared with those aged ≤50 years, the NIS with a higher risk of occurrence were no appetite (OR, 1.45; 95% CI, 1.23-1.69; P < .05), dry mouth (OR, 1.22; 95% CI, 1.02-1.45; P < .05), and problems with swallowing (OR, 1.56; 95% CI, 1.25-1.96; P < .05). CONCLUSIONS: The prevalence of malnutrition and the occurrence of NIS are high in hospitalized Brazilian patients aged ≥65 years who have cancer. The occurrence of NIS was higher in the population aged >50 years than in those aged ≤50 years. Nutritional screening and assessment should be performed immediately after hospitalization to enable early diagnosis and multidisciplinary or interdisciplinary intervention(s).
Assuntos
Desnutrição/epidemiologia , Neoplasias/epidemiologia , Estado Nutricional , Adulto , Idoso , Idoso de 80 Anos ou mais , Apetite/fisiologia , Índice de Massa Corporal , Brasil/epidemiologia , Feminino , Hospitalização , Humanos , Tempo de Internação , Masculino , Desnutrição/complicações , Desnutrição/patologia , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/patologia , Avaliação NutricionalRESUMO
Malnutrition is still considered endemic in many developing countries. Malnutrition-enteric infections may cause lasting deleterious effects on lipid metabolism, especially in children living in poor settings. The regional basic diet (RBD), produced to mimic the Brazilian northeastern dietary characteristics (rich in carbohydrate and low in protein) has been used in experimental malnutrition models, but few studies have explored the effect of chronic RBD on liver function, a central organ involved in cholesterol metabolism. This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1β immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alanine aminotransferase (ALT) was measured to assess liver function. RBD markedly impaired body weight gain compared with the control group (P<0.05). Higher hepatic TNF-α (P<0.0001) and IL-10 (P=0.001) mRNA levels were found in RBD-challenged mice, although without detectable non-alcoholic fatty liver disease. Marked IBA-1 immunolabeling and increased number of positive-IBA-1 cells were found in the undernourished group. No statistical difference in serum ALT was found. There was also a significant increase in ApoA mRNA expression in the undernourished group, but not ApoE and LCAT, compared with the control. Altogether our findings suggested that chronic RBD-induced malnutrition leads to liver inflammation with increased ApoA-I activity.
Assuntos
Humanos , Animais , Masculino , Coelhos , Ratos , Apolipoproteína A-I/sangue , Desnutrição/metabolismo , Dieta/efeitos adversos , Inflamação/metabolismo , Brasil , Doença Crônica , Apolipoproteína A-I/metabolismo , Desnutrição/patologia , Desnutrição/sangue , Inflamação/patologia , Inflamação/sangue , Fígado/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Environmental enteric dysfunction (EED) is associated with chronic undernutrition. Efforts to identify minimally invasive biomarkers of EED reveal an expanding number of candidate analytes. An analytic strategy is reported to select among candidate biomarkers and systematically express the strength of each marker's association with linear growth in infancy and early childhood. 180 analytes were quantified in fecal, urine and plasma samples taken at 7, 15 and 24 months of age from 258 subjects in a birth cohort in Peru. Treating the subjects' length-for-age Z-score (LAZ-score) over a 2-month lag as the outcome, penalized linear regression models with different shrinkage methods were fitted to determine the best-fitting subset. These were then included with covariates in linear regression models to obtain estimates of each biomarker's adjusted effect on growth. Transferrin had the largest and most statistically significant adjusted effect on short-term linear growth as measured by LAZ-score-a coefficient value of 0.50 (0.24, 0.75) for each log2 increase in plasma transferrin concentration. Other biomarkers with large effect size estimates included adiponectin, arginine, growth hormone, proline and serum amyloid P-component. The selected subset explained up to 23.0% of the variability in LAZ-score. Penalized regression modeling approaches can be used to select subsets from large panels of candidate biomarkers of EED. There is a need to systematically express the strength of association of biomarkers with linear growth or other outcomes to compare results across studies.
Assuntos
Biomarcadores/sangue , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/patologia , Doença Ambiental/diagnóstico , Doença Ambiental/patologia , Desnutrição/diagnóstico , Desnutrição/patologia , Bioestatística , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , PeruRESUMO
OBJECTIVES: Adductor pollicis muscle thickness (APMT) has been used as a simple index for muscle mass for the assessment of nutritional status among hospitalized patients to identify malnutrition. The aim of this study was to evaluate the association between APMT and nutritional status in clinical patients diagnosed with congestive heart failure (CHF). METHODS: APMT was measured in 500 patients with CHF on the dominant side. Nutritional status was assessed means of by the Subjective Global Assessment (SGA). Functional classification was performed according to guidelines provided by the New York Heart Association (NYHA), which establishes four categories of CHF severity. Poisson regression was used to verify the association of APMT, malnutrition, and severity of CHF. P ≤ 0.05 was considered statistically significant. RESULTS: The malnutrition prevalence varied from 1.5% in patients with functional class I CHF to 96.2% in patients classified as functional class IV (P ≤ 0.001). In both sexes, APMT values were significantly lower in patients who were malnourished (P< 0.001). The proportion of patients with CHF and malnutrition was higher among women than men (47.2 versus 37.4%, Pâ¯=â¯0.027). Malnutrition was slightly more common among patients ≥60 y of age compared with other age groups (48.3%, P ≤ 0.001). APMT is a significant protective factor for malnutrition even after controlling for sex, age, body mass index, and CHF functional class. CONCLUSIONS: Malnutrition is highly prevalent among patients with CHF and is associated with functional class. APMT may be used as a simple index for muscle mass for the assessment of nutritional status in these patient populations, and is also associated with malnutrition in these patients, even after controlling for other risk factors.