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2.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445710

RESUMO

Cancer cachexia displays a complex nature in which systemic inflammation, impaired energy metabolism, loss of muscle and adipose tissues result in unintentional body weight loss. Cachectic patients have a poor prognosis and the presence of cachexia reduces the tolerability of chemo/radio-therapy treatments and it is frequently the primary cause of death in advanced cancer patients. Early detection of this condition could make treatments more effective. However, early diagnostic biomarkers of cachexia are currently lacking. In recent years, although solid biopsy still remains the "gold standard" for diagnosis of cancer, liquid biopsy is gaining increasing interest as a source of easily accessible potential biomarkers. Moreover, the growing interest in circulating microRNAs (miRNAs), has made these molecules attractive for the diagnosis of several diseases, including cancer. Some muscle-derived circulating miRNA might play a pivotal role in the onset/progression of cancer cachexia. This topic is of great interest since circulating miRNAs might be easily detectable by means of liquid biopsies and might allow an early diagnosis of this syndrome. We here summarize the current knowledge on circulating muscular miRNAs involved in muscle atrophy, since they might represent easily accessible and promising biomarkers of cachexia.


Assuntos
Caquexia/diagnóstico , Caquexia/genética , MicroRNAs/genética , Tecido Adiposo/metabolismo , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , MicroRNA Circulante/análise , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Metabolismo Energético/fisiologia , Humanos , Inflamação/patologia , Biópsia Líquida/métodos , MicroRNAs/análise , MicroRNAs/sangue , Músculo Esquelético/metabolismo , Atrofia Muscular/patologia , Neoplasias/complicações , Neoplasias/genética , Transdução de Sinais/genética , Perda de Peso/genética
3.
Nutrients ; 13(7)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34371806

RESUMO

BACKGROUND AND AIM: Sarcopenia is considered an important risk factor for morbidity and mortality in liver cirrhosis. Beta-hydroxy-beta-methylbutyrate (HMB) has the potential to increase muscle mass and performance by stimulating protein synthesis and reducing muscle catabolism. The present study aimed at evaluating the effect of HMB supplementation on muscle mass and function in patients with liver cirrhosis. Changes in frailty during the study were also estimated, and the safety of HMB supplementation was verified. METHODS: This is a randomized, single-blind, placebo-controlled pilot trial. Twenty-four patients (14 HMB and 10 placebo) affected by liver cirrhosis were enrolled in the study. Each patient received dedicated counseling, which included nutrition and physical activity recommendations for chronic liver disease patients. Patients were randomized to receive 3 g/day of HMB or placebo (sorbitol powder) for 12 consecutive weeks. A diet interview, anthropometry, electrical bioimpedance analysis (BIA), quadriceps ultrasound, physical performance battery, Liver Frailty Index (LFI), and cognitive tests were completed at enrolment (T0), at 12 weeks (T1), and 24 weeks after enrolment (T2). RESULTS: At baseline, the two groups were similar in demography, severity of liver disease, muscle mass, muscle function, and cognitive tests. LFI at baseline was higher in patients in the HMB group vs. those in the placebo group (4.1 ± 0.4 vs. 3.4 ± 0.6, p < 0.01). After treatment, a statistically significant increase in muscle function was seen in the HMB group (chair stand test: 14.2 ± 5 s vs. 11.7 ± 2.6 s, p < 0.05; six-minute walk test: 361.8 ± 68 m vs. 409.4 ± 58 m, p < 0.05). Quadriceps muscle mass measured by ultrasound also increased (4.9 ± 1.8 vs. 5.4 ± 1.8 mm, p < 0.05) after HMB, while LFI decreased (4.1 ± 0.4 vs. 3.7 ± 0.4, p < 0.05). HMB was well tolerated by patients, and no adverse events were documented. CONCLUSIONS: Our study suggests the efficacy of 12-week beta-hydroxy-beta-methylbutyrate supplementation in promoting improvements in muscle performance in compensated cirrhotic patients. LFI was also ameliorated. Further studies with a greater number of patients are required to reinforce this hypothesis.


Assuntos
Suplementos Nutricionais , Cirrose Hepática/terapia , Força Muscular/efeitos dos fármacos , Sarcopenia/prevenção & controle , Valeratos/administração & dosagem , Antropometria , Impedância Elétrica , Exercício Físico/fisiologia , Feminino , Fragilidade/etiologia , Fragilidade/prevenção & controle , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Projetos Piloto , Sarcopenia/etiologia , Método Simples-Cego , Resultado do Tratamento
5.
Clin Nutr ; 40(6): 4037-4042, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676774

RESUMO

BACKGROUND & AIMS: Anorexia is a frequent symptom in cancer and we aimed to assess its prevalence among patients at their first cancer diagnosis by different appetite tools and the relationship between each tool with self-reports of food intake. We also tested whether cancer anorexia influences outcomes independently of reduced food intake or body weight loss (BWL) overtime and whether BWL was associated with complications during anticancer-therapy. METHODS: Functional Assessment of Anorexia/Cachexia Therapy (FAACT) score, self-assessment of appetite, Anorexia Questionnaire (AQ) and Visual Analog Scale (VAS) were administered. Percent of food intake was used as a criterion measure of anorexia. We registered BWL and anticancer-therapy complications over 3-month-follow-up. RESULTS: 438 cancer patients from 7 cancer-centers worldwide were included. The prevalence of anorexia was 39.9% by FAACT score, 40.2% by VAS, 40.6% by the self-assessment of appetite and 65.4% by AQ. Low food intake (≤50%) was reported in 28% of patients. All appetite tools correlated with food intake percent (P < 0.0001). We documented a correlation between self-assessment of appetite, FAACT score, VAS and BWL overtime (P < 0.04). The self-assessment of appetite (P = 0.0152) and the FAACT score (P = 0.043) were associated with BWL independently of anticancer therapies. Among patients with BWL, the risk to develop complications was greater with respect to those who maintained a stable or gained body weight (P = 0.03). CONCLUSIONS: In our sample of cancer patients, FAACT score and self-assessment of appetite performed well when low food intake was used as a criterion measure, and revealed an association of anorexia with BWL, which was, in turn, related to the development of anticancer-therapy complications.

7.
J Clin Med ; 9(12)2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33297455

RESUMO

The prevalence of renal disease is constantly increasing in older adults and a prognostic evaluation by a valid tool may play a key role in treatment management. We aimed to assess the association(s) between the multidimensional prognostic index (MPI) and both the hospitalization and mortality among older adults with renal disease. Patients with chronic kidney disease (CKD) (stage 3-5 KDOQI) and on dialysis were considered. Clinical parameters were registered at baseline and after 2 years. In all the patients, the MPI was calculated and divided into grade 0 (low risk), 1 (moderate risk), and 2 (severe risk). Hospitalizations and mortality were recorded during the follow-up and analyzed according to MPI grade. A total of 173 patients, with a median age of 76 years, on conservative (n = 105) and replacement therapy (32 patients on hemodialysis, 36 patients on peritoneal dialysis) were enrolled. Of them, 60 patients were in MPI grade 0, 102 in grade 1, and 11 in grade 2. The median duration of all the hospitalizations was 6 days and the number of deaths was 33. MPI significantly correlated with days of hospitalization (r = 0.801, p < 0.00001) and number of hospitalizations per year (r = 0.808, p < 0.00001), which was higher in MPI grade 2 compared to grade 1 (p < 0.001) and to grade 0 (p < 0.001). We found a significant association between MPI grades and mortality (p < 0.001). Our results indicate that MPI was associated with outcomes in patients with renal disease, suggesting that a multidimensional evaluation should be implemented in this clinical setting.

8.
J Pers Med ; 10(4)2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33202793

RESUMO

Although they cannot be considered curative, the new therapeutic integrated advances in metastatic breast cancer (MBC) have substantially improved patient outcomes. Traditionally, surgery was confined to palliation of symptomatic or ulcerating lumps. Data suggest, in some cases, a possible additive role for more aggressive locoregional surgical therapy in combination with systemic treatments in the metastatic setting, although a low level of evidence has been shown in terms of improvement in overall survival in MBC patients treated with surgery and medical treatment compared to medical treatment alone. In this light, tumor heterogeneity remains a challenge. To effectively reshape the therapeutic approach to MBC, careful consideration of who is a good candidate for locoregional resection is paramount. The patient's global health condition, impacting on cancer progression and morbidity and their associated molecular targets, have to be considered in treatment decision-making. In particular, more recently, research has been focused on the role of metabolic derangements, including the presence of metabolic syndrome, which represent well-known conditions related to breast cancer recurrence and distant metastasis and are, therefore, involved in the prognosis. In the present article, we focus on locoregional surgical strategies in MBC and whether concomitant metabolic derangements may have a role in prognosis.

9.
Nutrients ; 12(9)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32961917

RESUMO

Malnutrition is common in older adults and is associated with functional impairment, reduced quality of life, and increased morbidity and mortality. The aim of this study was to explore the association between health (including depression), physical functioning, disability and cognitive decline, and risk of malnutrition. Participants were recruited from nursing homes in Italy and completed a detailed multidimensional geriatric evaluation. All the data analyses were completed using Stata Version 15.1. The study included 246 participants with an age range of 50 to 102 (80.4 ± 10.5). The sample was characterised by a high degree of cognitive and functional impairment, disability, and poor health and nutritional status (according to Mini Nutritional Assessment (MNA), 38.2% were at risk for malnutrition and 19.5% were malnourished). Using a stepwise linear regression model, age (B = -0.043, SE = 0.016, p = 0.010), depression (B = -0.133, SE = 0.052, p = 0.011), disability (B = 0.517, SE = 0.068, p < 0.001), and physical performance (B = -0.191, SE = 0.095, p = 0.045) remained significantly associated with the malnutrition risk in the final model (adjusted R-squared = 0.298). The logistic regression model incorporating age, depression, disability, and physical performance was found to have high discriminative accuracy (AUC = 0.747; 95%CI: 0.686 to 0.808) for predicting the risk of malnutrition. The results of the study confirm the need to assess nutritional status and to investigate the presence of risk factors associated with malnutrition in order to achieve effective prevention and plan a better intervention strategy.


Assuntos
Desnutrição , Casas de Saúde , Estado Nutricional , Idoso , Idoso de 80 Anos ou mais , Feminino , Avaliação Geriátrica/métodos , Humanos , Masculino , Avaliação Nutricional , Qualidade de Vida , Fatores de Risco
10.
Nutrition ; 78: 110952, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32866900

RESUMO

OBJECTIVES: Anorexia represents a common and debilitating clinical problem in patients with several forms of cancer, in particular lung cancer, but its mechanisms are not completely understood. Recently, the caseinolytic-protease-B (ClpB) homologue protein, produced by common gut bacteria, such as Escherichia coli, was identified as an antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide. ClpB was previously detected in human plasma and displayed satietogenic properties; however, its possible relevance to cancer anorexia has not yet been investigated. METHODS: To address this question, we analyzed plasma ClpB concentrations as well as levels and affinities of anti-ClpB and α-MSH-reactive antibodies in patients with lung cancer with and without anorexia as compared with body mass index-matched healthy controls with normal appetite. RESULTS: We found that plasma ClpB concentrations were significantly lower in non-anorexic patients with cancer than those of the control group (P = 0.028). In contrast, patients with cancer and anorexia had lower levels of anti-ClpB immunoglobulins (Ig)M (P < 0.0001) and of both α-MSH IgM and IgG (P < 0.05) with respect to controls. Moreover, in patients with cancer and anorexia, anti-ClpB IgG showed a trend of lower affinities compared with non-anorexic patients (P = 0.05). CONCLUSIONS: Taken together, the results revealed a reduced humoral immune response to ClpB in patients with cancer and anorexia, which may lead to an enhanced satietogenic effect of this enterobacterial protein contributing to the mechanisms of reduced appetite.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Neoplasias Pulmonares , Anorexia , Enterobacteriaceae , Humanos , Neoplasias Pulmonares/complicações , alfa-MSH
11.
Nutrients ; 12(8)2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32764484

RESUMO

Nutritional guidelines suggest specific energy and protein requirements for patients with cancer. However, cancer patients, often malnourished, use self-made or web-based diets to ameliorate the prognosis of their disease. This review aimed to investigate the associations between post-diagnostic diet and prognostic outcomes in cancer patients. A systematic literature search was performed in Pubmed and Web of Science databases from inception to 30 October 2019, based on fixed inclusion and exclusion criteria. The risk of bias was assessed. A total of 29 prospective studies was identified. Breast (n = 11), colorectal (n = 9), prostate (n = 8) cancers are the most studied. Low- fat diet, healthy quality diet, regular consumption of fiber such as vegetables and high-quality protein intake are beneficial while Western diet (WD) and high consumption of saturated fats could be associated with a higher risk of mortality. Bladder (n = 1), gynecological (n = 1), lung, stomach, and pancreatic cancers still remain almost unexplored. This systematic review suggested that detrimental dietary patterns such as WD should be avoided but none of the food categories (meat, dairy products) should be eliminated in cancer patients' diet. Further large prospective studies are needed to assess the role of post-diagnostic diet in patients with cancer.


Assuntos
Dieta/estatística & dados numéricos , Comportamento Alimentar , Neoplasias/epidemiologia , Estudos de Coortes , Laticínios , Dieta com Restrição de Gorduras/estatística & dados numéricos , Dieta Ocidental/estatística & dados numéricos , Gorduras na Dieta/administração & dosagem , Fibras na Dieta/administração & dosagem , Progressão da Doença , Feminino , Microbioma Gastrointestinal , Humanos , Masculino , Carne , Neoplasias/mortalidade , Prognóstico , Estudos Prospectivos , Verduras
12.
Artigo em Inglês | MEDLINE | ID: mdl-32849295

RESUMO

Rationale: Studies suggest a relation between exposure to air particulate matter (PM)2.5 pollution and greater cardiovascular morbidity, as well as increased risk for obesity and diabetes. We aimed to identify association(s) between nutritional and metabolic status and exposure to environmental pollution in a cohort of policemen exposed to high levels of air pollution. Methods: We considered adult municipal policemen, working in an urban area at high-traffic density with documented high levels of air PM2.5 (exposed group) compared to non-exposed policemen. Clinical characteristics, including the presence/absence of metabolic syndrome, were recorded, and serum biomarkers, including adiponectin, leptin, and ghrelin, were assessed. Results: One hundred ninety-nine participants were enrolled, 100 in the exposed group and 99 in the non-exposed group. Metabolic syndrome was documented in 32% of exposed group and in 52.5% of non-exposed group (P = 0.008). In the exposed group, we found a positive correlation between body mass index and serum leptin as well as in the non-exposed group (P < 0.0001). Within the exposed group, subjects with metabolic syndrome showed lower serum adiponectin (P < 0.0001) and higher leptin (P = 0.002) levels with respect to those without metabolic syndrome, whereas in the non-exposed group, subjects with metabolic syndrome showed only higher leptin levels when compared to those without metabolic syndrome (P = 0.01). Among the participants with metabolic syndrome, we found lower adiponectin levels in those of the exposed group with respect to the non-exposed ones (P = 0.007). When comparing the exposed and non-exposed groups, after stratifying participants for Homeostatic Model Assessment for Insulin Resistance >2.5, we found lower adiponectin levels in those of the exposed group with respect to the non-exposed ones (P = 0.038). Conclusions: Exposure to air PM pollution was associated with lower levels of adiponectin in adult males with metabolic syndrome.


Assuntos
Poluição do Ar/efeitos adversos , Biomarcadores/sangue , Resistência à Insulina , Síndrome Metabólica/etiologia , Obesidade/complicações , Material Particulado/efeitos adversos , Poluição Relacionada com o Tráfego/efeitos adversos , Adiponectina/sangue , Índice de Massa Corporal , Estudos Transversais , Grelina/sangue , Humanos , Leptina/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/patologia , Pessoa de Meia-Idade
13.
Artigo em Inglês | MEDLINE | ID: mdl-32794588

RESUMO

BACKGROUND: Systemic sclerosis (SSc) may be associated with protein-energy malnutrition. It was demonstrated that left ventricular mass (LVM) reflected poor nutrition status in SSc patients, and no data are available on LVM as a surrogate measure of muscularity. We aimed to evaluate, in SSc patients, the relationship between muscle mass and LVM as a novel indicator of muscularity in this setting. METHODS: SSc patients and healthy controls (HCs) were considered and underwent echocardiography to assess LVM and LVM index (LVMI). Body composition, including fat-free mass index (FFMI), phase angle (PhA), and body cell mass index (BCMI), was analyzed by multifrequency bioelectrical impedance analysis. RESULTS: Sixty-four SSc patients (aged 51 ± 13 years) and 30 HCs (aged 46 ± 13 years) were enrolled. BCMI and PhA were lower in SSc patients compared with HCs (P < .001). LVM and LVMI were not different between SSc patients and HCs (P = .068, P = .14, respectively). In SSc patients, a significant correlation was shown between LVMI and FFMI (τ = 0.192, P = .026); in multiple regression analysis, FFMI was significantly associated with the Malnutrition Universal Screening Tool (P < .0001), LVMI (P = .01), and disease severity scale (P = .02). CONCLUSION: Changes in body composition were present in SSc patients, particularly in terms of BMCI and PhA. A correlation between LVMI and FFMI as indexes of muscularity exists in this cohort, suggesting that cardiac mass might be used as a surrogate of nutrition status in this setting.

14.
Toxins (Basel) ; 12(6)2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32526852

RESUMO

A relationship between dysbiotic gut microbiome and chronic kidney disease (CKD) has been recently documented; it contributes to CKD-related complications, including cardiovascular disease. Aim: We tested how a low-protein diet (LPD)-with or without oral inulin supplementation as a prebiotic-modulates some inflammatory, atherosclerosis and endothelial dysfunction indices and nutritional markers, as well as psychocognitive functions in CKD patients. We conducted a prospective, case-control study on CKD patients on conservative therapy, divided in two groups: the intervention group treated with LPD (0.6 g/kg/day) plus inulin (19 g/day) and a control group treated with LPD without inulin, for six consecutive months. Clinical and hematochemical parameters as well as instrumental, and psychocognitive assessments (by SF-36 survey and MMSE, HAM-D, BDI-II) were recorded in all the participants at baseline (T0), at three months (T1) and at six months (T2). A total of 41 patients were enrolled: 18 in the intervention group and 23 in the control group. At T2, in both groups, we observed a significant reduction of serum nitrogen and phosphorus (p ≤ 0.01) and serum uric acid (p ≤ 0.03), and an improvement in metabolic acidosis (bicarbonates, p ≤ 0.01; base excess, p ≤ 0.02). Moreover, at T2 the intervention group showed a reduction in serum insulin (p = 0.008) and fasting glucose levels (p = 0.022), HOMA-IR (p = 0.004), as well as lower total serum cholesterol (p = 0.012), triglycerides (p = 0.016), C-reactive protein (p = 0.044) and homocysteine (p = 0.044) and higher HDL (p < 0.001) with respect to baseline. We also observed a significant amelioration of some quality of life and functional status indices (SF-36 survey) among the intervention group compared to controls, without a significant improvement in the cognitive state (MMSE). On the other hand, an amelioration in mood (by HAM-D and BDI-II) was found in the intervention group and in controls (only by BID-II). In conclusion, LPD in association with oral inulin supplementation improved glycemic and lipid metabolism and ameliorated the systemic inflammatory state, likely reducing cardiovascular risk in CKD patients and this may represent a promising therapeutic option, also improving quality of life and mood.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta com Restrição de Proteínas , Inulina/uso terapêutico , Saúde Mental , Estado Nutricional , Prebióticos , Insuficiência Renal Crônica/dietoterapia , Afeto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Estudos de Casos e Controles , Cognição , Feminino , Estado Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/psicologia , Fatores de Tempo , Resultado do Tratamento
15.
Cancer Med ; 9(11): 3752-3757, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32270594

RESUMO

BACKGROUND: Sunitinib is a standard treatment for metastatic renal cell carcinoma (RCC). Currently, the data available on the effects of sunitinib on endothelial dysfunction, metabolic changes, and cardiovascular (CV) risk factors are limited, and we aimed to evaluate these aspects in patients with RCC after a short period of treatment. METHODS: Patients affected by metastatic RCC were enrolled and evaluated before starting sunitinib (T0) and after 40 days of treatment (T1) by the flow-mediated dilation (FMD), carotid intima media thickness (IMT), ankle-brachial pressure index (ABI), and 24-hour proteinuria. We also assessed serum metabolic and nutritional parameters at T0 and T1. RESULTS: Twenty patients (7 female), with a mean age of 61.4 ± 12.0 years, were studied. Overtime, we observed a reduction in estimated glomerular filtration rate (P = .002), FMD (P = .001) and in fasting plasma glucose levels (P = .04), as well as an increase in plasma insulin (P < .001), HOMA-IR (P < .01), and serum total cholesterol levels (P = .01). Moreover at T1 we found a significant increase in systolic and diastolic blood pressure (P ≤ .001) and 24-hour proteinuria (P < .001) compared to baseline, whereas no changes in IMT and ABI were detected. CONCLUSION: The changes observed overtime after sunitinib treatment in terms of markers of early endothelial dysfunction, blood pressure, as well as in glucose/insulin metabolism and proteinuria may contribute to increase CV risk in RCC patients and suggest a strict follow-up in this setting. Larger evidences are mandatory to confirm our observations.


Assuntos
Biomarcadores/sangue , Carcinoma de Células Renais/tratamento farmacológico , Doenças Cardiovasculares/patologia , Taxa de Filtração Glomerular , Neoplasias Renais/tratamento farmacológico , Sunitinibe/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Pressão Sanguínea , Carcinoma de Células Renais/patologia , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/metabolismo , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Feminino , Seguimentos , Glucose/metabolismo , Fatores de Risco de Doenças Cardíacas , Humanos , Insulina/sangue , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto Jovem
16.
Nutrition ; 71: 110594, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31790890

RESUMO

OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease characterized by multiple and bilateral cystic dilation of renal tubules. Hypertension, endothelial dysfunction, systemic inflammation, and accelerated atherosclerosis are alterations found at a very early stage of the disease and are responsible for increasing both cardiovascular risks and progression toward end-stage renal disease. The aim of the study was to evaluate the effects of the use of 1.6 g α-lipoic acid (ALA) daily for 3 and 6 on the main markers of systemic inflammation, endothelial dysfunction, and atherosclerosis, as well as on nutritional, cardiovascular, and psychocognitive parameters, in ADPKD patients with CKD stage G2/G3 Kidney Disease Improving Global Outcomes chronic kidney disease (KDIGO) compared to controls. METHODS: This was a controlled, longitudinal, prospective, interventional study with 59 patients with ADPKD. Of the patients, 33 were treated with ALA (1.6 g/d) for 6 mo and 26 were controls. Clinical, laboratory (inflammation and metabolic indexes), instrumental parameters (intima media thickness (IMT), renal resistive index (RRI), flow-mediated dilation (FMD), ankle-brachial index (ABI), and psycho-cognitive tests (Mini-Mental State Examination [MMSE], Hamilton Depression Rating Scale [HAM-D], Beck Depression Inventory-II [BDI-II]) were evaluated at baseline (T0), 3 mo (T1), and 6 mo (T2). RESULTS: Patients treated with ALA at T1 and T2 showed a significant reduction in serum glucose, insulin, homeostatic model assessment-insulin resistance, and serum uric acid (P = 0.013, P = 0.002, P = 0.002, P <0.001; respectively) and significantly higher values of base excess (P < 0.001), compared with the control group. Moreover, the results showed a significant increase in bicarbonates (P = 0.009) and FMD (P < 0.001), and a significant reduction of C-reactive protein (P <0.001) and RRI (P = 0.013). On the other hand, we did not assess a significant difference in IMT and ABI at T1 and T2. Psychocognitive tests (BDI-II, HAM-D, and MMSE) were significantly improved (P = 0.007, P < 0.001, P < 0.001; respectively) in patients treated with ALA for 6 mo compared with the control group. A significant difference in nicotinamide adenine dinucleotide phosphate oxidase 2 concentrations was observed between T0 and T2 only in ADPKD patients treated with ALA (P = 0.039, P = 0.039; respectively), although we did not find a significant difference in interleukin-6, interleukin -1ß, and tumor necrosis factor-α concentrations in either group. CONCLUSIONS: We suggest an early and careful monitoring of traditional and non-traditional cardiovascular risk factors in patients with ADPKD. Moreover, we suggest the use of ALA, an anti-inflammatory and antioxidant nutraceutical with few side effects. Additionally, it is important to evaluate the cognitive abilities, psychological health, and quality of life of patients with ADPKD, especially at the early stage of disease.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Suplementos Nutricionais , Rim Policístico Autossômico Dominante/terapia , Ácido Tióctico/administração & dosagem , Adulto , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Proteína C-Reativa/efeitos dos fármacos , Espessura Intima-Media Carotídea , Cognição/efeitos dos fármacos , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Resistência à Insulina , Rim/fisiopatologia , Estudos Longitudinais , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/fisiopatologia , Estudos Prospectivos , Qualidade de Vida , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/terapia , Índice de Gravidade de Doença , Resultado do Tratamento , Ácido Úrico/sangue
17.
Nutrients ; 11(12)2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818021

RESUMO

INTRODUCTION: The gut microbiota has coevolved with humans for a mutually beneficial coexistence and plays an important role in health and disease. A dysbiotic gut microbiome may contribute to progression to chronic kidney disease (CKD) and CKD-related complications such as cardiovascular disease. Microbiota modulation through the administration of prebiotics may represent an important therapeutic target. AIM: We sought to evaluate the effects of a low-protein diet (LPD) (0.6 g/kg/day) with or without the intake of the prebiotic inulin (19 g/day) on microbiota and clinical parameters in CKD patients. MATERIALS AND METHODS: We performed a longitudinal, prospective, controlled, and interventional study on 16 patients: 9 patients treated with LPD (0.6 g/kg/day) and inulin (19 g/day) and 7 patients (control group) treated only with LPD (0.6 g/kg/day). Clinical evaluations were performed and fecal samples were collected for a subsequent evaluation of the intestinal microbiota in all patients. These tests were carried out before the initiation of LPD, with or without inulin, at baseline (T0) and at 6 months (T2). The microbiota of 16 healthy control (HC) subjects was also analyzed in order to identify potential dysbiosis between patients and healthy subjects. RESULTS: Gut microbiota of CKD patients was different from that of healthy controls. The LPD was able to significantly increase the frequencies of Akkermansiaceae and Bacteroidaceae and decrease the frequencies of Christensenellaceae, Clostridiaceae, Lactobacillaceae, and Pasteurellaceae. Only Bifidobacteriaceae were increased when the LPD was accompanied by oral inulin intake. We showed a significant reduction of serum uric acid (SUA) and C-reactive protein (CRP) in patients treated with LPD and inulin (p = 0.018 and p = 0.003, respectively), an improvement in SF-36 (physical role functioning and general health perceptions; p = 0.03 and p = 0.01, respectively), and a significant increase of serum bicarbonate both in patients treated with LPD (p = 0.026) or with LPD and inulin (p = 0.01). Moreover, in patients treated with LPD and inulin, we observed a significant reduction in circulating tumor necrosis factor alpha (TNF-α) (p = 0.041) and plasma nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) (p = 0.027) levels. We did not find a significant difference in the circulating levels of Interleukin (IL)-1ß (p = 0.529) and IL-6 (p = 0.828) in the two groups. CONCLUSIONS: LPD, associated or not with inulin, modified gut microbiota and modulated inflammatory and metabolic parameters in patients with CKD. Our results suggest that interventions attempting to modulate the gut microbiome may represent novel strategies to improve clinical outcomes in CKD patients and may provide useful therapeutic effects.


Assuntos
Dieta com Restrição de Proteínas , Microbioma Gastrointestinal , Inulina/administração & dosagem , Insuficiência Renal Crônica/dietoterapia , Insuficiência Renal Crônica/microbiologia , Proteína C-Reativa/metabolismo , Estudos Controlados Antes e Depois , Fezes/microbiologia , Inquéritos Epidemiológicos , Humanos , Estudos Longitudinais , NADPH Oxidases/metabolismo , Estudos Prospectivos , Fator de Necrose Tumoral alfa/metabolismo , Ácido Úrico/sangue
18.
Front Physiol ; 10: 805, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293456

RESUMO

Rationale: Low physical activity is frequent in end stage renal disease. We evaluated the longitudinal change in physical activity and its barriers in hemodialysis (HD) patients and the association between the patterns of physical activity change, body composition, and beta-aminoisobutyric acid (BAIBA), as circulating myokine. Methods: This is an observational study, where HD patients were considered in a 24-month follow-up. We assessed overtime the change of physical inactivity and its barriers by validated questionnaires, body composition by bioimpedance analysis, muscle strength by hand-dynamometer, and plasma BAIBA levels by liquid chromatography spectrometry. Parametric and non-parametric analyses were performed, as appropriate. Results: Out of the 49 patients studied at baseline, 39 completed the first-year follow-up, and 29 completed the second year. At month 12, active patients had higher intracellular water (ICW) (P = 0.001) and cellular mass (P < 0.001), as well as at month 24 (P = 0.012, P = 0.002; respectively) with respect to inactive. A significant reduction in ICW was shown at month 12 (P = 0.011) and month 24 (P = 0.014) in all patients. The barrier "reduced walking ability" was more frequent in inactive patients with respect to active at month 12 (P = 0.003) and at month 24 (P = 0.05). At month 24, plasma BAIBA levels were higher among active patients with respect to inactive (P = 0.043) and a correlation was seen between muscle strength and ICW (r = 0.51, P = 0.005); normalizing BAIBA per body mass index, we found it lower with respect to baseline (P = 0.004), as well as after correcting per ICW (P = 0.001), as marker of muscle mass. Conclusion: A high prevalence of physical inactivity persisted during a 24-month follow-up in this cohort. We found an association between physical activity and a decline in marker of muscularity and reduced plasma BAIBA levels.

19.
Expert Opin Investig Drugs ; 28(8): 733-740, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31347405

RESUMO

Introduction: Cachexia is frequent in chronic diseases and especially during cancer development. Multiple definitions of cachexia have been proposed; it may be considered a multifactorial complex syndrome that presents with progressive unintentional weight loss and wasting of muscle mass and adipose tissue. Area covered: This article covers phase-I and phase-II clinical trials of investigational drugs for cancer cachexia. We performed a search on PubMed with keywords as cancer cachexia, phase-I/phase-II trial, drug, identifying articles relevant to this review. Studies were conducted using compounds, including anabolic agents such as ghrelin analogs, selective androgen receptor modulators, as well as anti-inflammatory drugs such as thalidomide, OHR, anti-interleukin antibody, cannabinoids, and omega-3 supplements. We also describe the mechanisms of action of these molecules and their phase-I and phase-II study design. The major outcomes were appetite stimulation, weight gain, improvement of muscle mass and function, modulation of inflammation, and quality of life. Expert opinion: The molecules discussed act on molecular pathways involved in cancer cachexia; they modulate appetite, anabolic effects, inflammation and direct interaction with muscle. Considering the multifactorial aspects of the cachexia syndrome, the combination of these drugs with metabolic and nutritional interventions may represent the most promising therapeutic approach to cancer cachexia.


Assuntos
Caquexia/tratamento farmacológico , Drogas em Investigação/uso terapêutico , Neoplasias/complicações , Apetite/efeitos dos fármacos , Caquexia/etiologia , Caquexia/fisiopatologia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Drogas em Investigação/farmacologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Apoio Nutricional/métodos , Qualidade de Vida , Projetos de Pesquisa
20.
Front Physiol ; 10: 897, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354530

RESUMO

Sarcopenia is the age-related progressive loss of skeletal muscle mass and strength finally leading to poor physical performance. Impaired myogenesis contributes to the pathogenesis of sarcopenia, while mitochondrial dysfunctions are thought to play a primary role in skeletal muscle loss during aging. Here we studied the link between myogenesis and metabolism. In particular, we analyzed the effect of the metabolic modulator trimetazidine (TMZ) on myogenesis in aging. We show that reprogramming the metabolism by TMZ treatment for 12 consecutive days stimulates myogenic gene expression in skeletal muscle of 22-month-old mice. Our data also reveal that TMZ increases the levels of mitochondrial proteins and stimulates the oxidative metabolism in aged muscles, this finding being in line with our previous observations in cachectic mice. Moreover, we show that, besides TMZ also other types of metabolic modulators (i.e., 5-Aminoimidazole-4-Carboxamide Ribofuranoside-AICAR) can stimulate differentiation of skeletal muscle progenitors in vitro. Overall, our results reveal that reprogramming the metabolism stimulates myogenesis while triggering mitochondrial proteins synthesis in vivo during aging. Together with the previously reported ability of TMZ to increase muscle strength in aged mice, these new data suggest an interesting non-invasive therapeutic strategy which could contribute to improving muscle quality and neuromuscular communication in the elderly, and counteracting sarcopenia.

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