RESUMO
OBJECTIVES: The aim of the review was to elucidate the adverse effects of chronic treatment with the main subclasses of highly active antiretroviral therapy (HAART). METHODS: A systematic review was carried out using the methods recommended in the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P). Searches of articles in MEDLINE, SCIELO, Web of Science and LILACS were conducted from January to October 2018 based on the following descriptors and keywords: 'HIV' [AND]; 'AIDS' [OR]; 'HAART' [AND]; 'Highly Active Antiretroviral Therapy' [OR]; 'Adverse Effects' [AND]. All articles selected described the biochemical changes produced by, and the main adverse effects of, using one or more of the following HAART subclasses: nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and other new drugs. The selected articles included patients living with HIV (PLWH) initiating or continuing any type of HAART. The results are presented qualitatively and discussed. RESULTS: Twenty-one articles found in the searches were selected for the review, and they included a total of 5626 participants. Seven of the studies investigated mainly NRTIs, three studies mainly NNRTIs, eight studies predominantly PIs, and three studies other antiretroviral drugs as the main treatment. The most common adverse effects on biochemical parameters were the emergence of anaemia for NRTIs as well as NNRTIs and PIs, and plasma lipid alterations caused by their prolonged use. In general, it was found that biological differences among individuals can cause differences in adverse effects, such as virological and treatment failure. CONCLUSIONS: One or more occurrences of adverse effects of the chronic utilization of drugs were found for all subclasses of HAART, and certain combinations of drugs from different subclasses were also found to be associated with adverse events.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Inibidores de Proteases/efeitos adversos , Inibidores de Proteases/uso terapêutico , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Resultado do TratamentoRESUMO
Cachexia, a paraneoplastic syndrome markedly associated with worsened prognosis in cancer patients, provokes profound wasting of both lean and adipose mass in an association with a state of metabolic "chaos". The white adipose tissue responds to cachexia with marked local inflammation and may be thus a relevant contributor to systemic inflammation. To address this hypothesis we examined the correlation between tissue expression of adipokines and plasma concentration in cachectic and stable weight patients with or without cancer. Adiponectin and liver-derived CRP concentration were significantly higher in the cachectic groups when compared with stable weight patients (P<0.01). The concentration of plasma IL-6 was higher (11.4-fold) in the cancer cachectic group when compared with weight-stable controls, and presented a significant correlation with the presence of cancer (P<0.001). A marked increase (5-fold) in IL-6 as a result of the interaction between the presence of cachexia and the presence of tumour was observed in the subcutaneous tissue of the patients, yet not in the visceral depot. Plasma adiponectin levels were higher in cachectic cancer patients, compared with stable weight cancer patients individually matched by age, sex, and BMI, and the subcutaneous depot was found to be the main contributing tissue, rather than the visceral pad. Based on the results we concluded that the subcutaneous adipose tissue is associated with plasma changes that may function as markers of cachexia.
Assuntos
Tecido Adiposo/metabolismo , Biomarcadores Tumorais/sangue , Caquexia/sangue , Neoplasias/sangue , Adiponectina/sangue , Adiponectina/genética , Tecido Adiposo/patologia , Idoso , Caquexia/complicações , Caquexia/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-6/sangue , Interleucina-6/genética , Leptina/genética , Leptina/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/complicações , Neoplasias/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Cancer cachexia is a multifaceted syndrome whose aetiology is extremely complex and is directly related to poor patient prognosis and survival. Changes in lipid metabolism in cancer cachexia result in marked reduction of total fat mass, increased lipolysis, total oxidation of fatty acids, hyperlipidaemia, hypertriglyceridaemia, and hypercholesterolaemia. These changes are believed to be induced by inflammatory mediators, such as tumour necrosis factor-α (TNF-α) and other factors. Attention has recently been drawn to the current theory that cachexia is a chronic inflammatory state, mainly caused by the host's reaction to the tumour. Changes in expression of numerous inflammatory mediators, notably in white adipose tissue (WAT), may trigger several changes in WAT homeostasis. The inhibition of adipocyte differentiation by PPARγ is paralleled by the appearance of smaller adipocytes, which may partially account for the inhibitory effect of PPARγ on inflammatory gene expression. Furthermore, inflammatory modulation and/or inhibition seems to be dependent on the IKK/NF-κB pathway, suggesting that a possible interaction between NF-κB and PPARγ is required to modulate WAT inflammation induced by cancer cachexia. In this article, current literature on the possible mechanisms of NF-κB and PPARγ regulation of WAT cells during cancer cachexia are discussed. This review aims to assess the role of a possible interaction between NF-κB and PPARγ in the setting of cancer cachexia as well as its significant role as a potential modulator of chronic inflammation that could be explored therapeutically.
Assuntos
Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Caquexia/complicações , Núcleo Celular/metabolismo , Inflamação/complicações , Neoplasias/complicações , Fatores de Transcrição/metabolismo , Animais , Caquexia/patologia , Humanos , Inflamação/patologia , Neoplasias/patologiaRESUMO
Evaluate the effect of 12 wks of concurrent training (CT) in the extracellular matrix (ECM) of subcutaneous adipose tissue (SAT) in people living with HIV/AIDS (PLWHA). In the non-randomized clinical trial, 19 participants, 11 healthy (HIV-) and 18 PLWHA under the use of highly active antiretroviral therapy (HAART) for at least 1 year (HIV+). All participants engaged in a moderate-intensity CT program for 12 weeks, 3 times a week. Before and after CT, aerobic and strength performance were assessed, as well as anthropometric and biochemical blood profiles. In addition, SAT biopsies were performed for histologic and morphometric analyses. Statistical analysis was carried out with R Studio, using descriptive and inferential analysis, ANOVA test, and mixed-effect model (P < 0.05). HIV+ showed higher levels of very-low-density lipoproteins and triglycerides and lower levels of high-density lipoproteins at baseline than HIV- (P < 0.05). All groups showed improved aerobic and strength performances (P < 0.05). Both groups showed reduced adipocyte sizes after CT (P < 0.05). Lastly, HIV+ presented smaller adipocytes and higher elastic fiber deposition at baseline and decreased after training only in HIV+, similar to the HIV group. Thus, CT in PLWHA promoted a decrease in the size heterogeneity of adipocytes and elastic fiber deposition, remodeling the ECM, and improving the SAT fibrosis profile. Brazilian Clinical Trials Registry (ensaiosclinicos.gov.br - UTN: U1111-1214-3022). Novelty: Adipose tissue fibrosis is improved by training in people living with HIV. Concurrent training remodels adipose tissue extracellular matrix.
Assuntos
Exercício Físico/fisiologia , Matriz Extracelular/metabolismo , Infecções por HIV/metabolismo , Infecções por HIV/patologia , Gordura Subcutânea/metabolismo , Adipócitos/patologia , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Colágeno/metabolismo , Tecido Elástico/patologia , Infecções por HIV/tratamento farmacológico , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Pessoa de Meia-Idade , Força Muscular/fisiologia , Condicionamento Físico Humano/métodos , Condicionamento Físico Humano/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Triglicerídeos/sangueRESUMO
Cancer cachexia induces loss of fat mass that accounts for a large part of the dramatic weight loss observed both in humans and in animal models; however, the literature does not provide consistent information regarding the set point of weight loss and how the different visceral adipose tissue depots contribute to this symptom. To evaluate that, 8-week-old male Wistar rats were subcutaneously inoculated with 1âml (2×10(7)) of tumour cells (Walker 256). Samples of different visceral white adipose tissue (WAT) depots were collected at days 0, 4, 7 and 14 and stored at -80â°C (seven to ten animals/each day per group). Mesenteric and retroperitoneal depot mass was decreased to the greatest extent on day 14 compared with day 0. Gene and protein expression of PPARγ2 (PPARG) fell significantly following tumour implantation in all three adipose tissue depots while C/EBPα (CEBPA) and SREBP-1c (SREBF1) expression decreased over time only in epididymal and retroperitoneal depots. Decreased adipogenic gene expression and morphological disruption of visceral WAT are further supported by the dramatic reduction in mRNA and protein levels of perilipin. Classical markers of inflammation and macrophage infiltration (f4/80, CD68 and MIF-1α) in WAT were significantly increased in the later stage of cachexia (although showing a incremental pattern along the course of cachexia) and presented a depot-specific regulation. These results indicate that impairment in the lipid-storing function of adipose tissue occurs at different times and that the mesenteric adipose tissue is more resistant to the 'fat-reducing effect' than the other visceral depots during cancer cachexia progression.
Assuntos
Tecido Adiposo/metabolismo , Caquexia/metabolismo , Neoplasias/complicações , Adipocinas/sangue , Tecido Adiposo/patologia , Animais , Western Blotting , Caquexia/sangue , Caquexia/patologia , Masculino , Neoplasias/sangue , Neoplasias/fisiopatologia , PPAR gama/metabolismo , Reação em Cadeia da Polimerase , Ratos , Ratos WistarRESUMO
Creatine is widely used by athletes as an ergogenic resource. The aim of this study was to evaluate the influence of creatine supplementation on the duodenum of rats submitted to physical training. The number and myenteric neuronal cell bodies as well mucosal and muscular tunic morphometry were evaluated. Control animals received a standard chow for 8 weeks, and the treated ones received the standard chow for 4 weeks and were later fed with the same chow but added with 2% creatine. Animals were divided in groups: sedentary, sedentary supplemented with creatine, trained and trained supplemented with creatine. The training consisted in treadmill running for 8 weeks. Duodenal samples were either processed for whole mount preparations or for paraffin embedding and hematoxylin-eosin staining for histological and morpho metric studies of the mucosa, the muscular tunic and myenteric neurons. It was observed that neither creatine nor physical training alone promoted alterations in muscular tunic thickness, villus height or crypts depth, however, a reduction in these parameters was observed when both were associated. The number of myenteric neurons was unchanged, but the neuronal cell body area was reduced in trained animals but not when training and creatine was associated, suggesting a neuroprotector role of this substance.