Ana Lúcia dos Anjos Ferreira

Anthracycline-Induced Cardiotoxicity

The anthracyclines constitute a group of drugs widely used for the treatment of a variety of human tumors. However, the development of irreversible cardiotoxicity has limited their use. Anthracycline-induced cardiotoxicity can persist for years with no clinical symptoms. However, its prognosis becomes poor after the development of overt heart failure, possibly even worse than ischemic or idiopathic dilated cardiomyopathies. Due to the successful action of anthracyclines as chemotherapic agents, several strategies have been tried to prevent/attenuate their side effects. Although anthracycline-induced injury appears to be multifactorial, a common denominator among most of the proposed mechanisms is cellular damage mediated by reactive oxygen species. However, it remains controversial as to whether antioxidants can prevent such side effects given that different mechanisms may be involved in acute versus chronic toxicity. The present review applies a multisided approach to the critical evaluation of various hypotheses proposed over the last decade on the role of oxidative stress in cardiotoxicity induced by doxorubicin, the most used anthracycline agent. The clinical diagnosis and treatment is also discussed.

Site-specific concentrations of carotenoids in adipose tissue: relations with dietary and serum carotenoid concentrations in healthy adults

BACKGROUND Dietary carotenoids are related to a decreased risk of certain diseases. Serum and adipose tissue carotenoid concentrations are used as biomarkers of intake. OBJECTIVES The objectives of this study were to evaluate site-specific concentrations of carotenoids in adipose tissue and to examine relations between carotenoid concentrations in the diet, serum, and adipose tissue. DESIGN Healthy adults (12 women and 13 men) participated in this cross-sectional study. Dietary carotenoids over the past year were assessed with a food-frequency questionnaire. Serum and adipose tissue biopsy samples were collected from the abdomen, buttock, and inner thigh for the measurement of carotenoids by HPLC. RESULTS Many adipose carotenoids were inversely related to percentage body fat, although lycopene was the only carotenoid inversely correlated with all 3 sites. Most of the carotenoids were significantly higher in the abdominal adipose tissue than in the thigh (P < 0.05). Concentrations of alpha-carotene, beta-carotene, 5-cis-lycopene, and total carotenoids were significantly higher in the buttocks than in the thigh (P < 0.05). Concentrations of alpha-carotene, cis-lycopene, and lutein (with or without zeaxanthin) were significantly higher in the abdomen than in the buttocks (P < 0.05). Dietary intake was significantly correlated with serum concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, and total carotenoids. Carotenoid intake was significantly correlated with adipose tissue concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, cis-lycopene, and total carotenoids (P < 0.05) but varied by site. Of all the adipose tissue sites evaluated, the abdomen showed the strongest correlation with long-term dietary carotenoid intakes and with serum (indicator of short-term intake) for most carotenoids. CONCLUSIONS Body fat may influence the tissue distribution of carotenoids. Abdominal adipose tissue carotenoid concentrations may be a useful indicator of carotenoid status.

Predictors of Beta-Blocker Intolerance and Mortality in Patients After Acute Coronary Syndrome

Purpose To investigate the predictors of intolerance to beta-blockers treatment and the 6-month mortality in hospitalized patients with acute coronary syndrome (ACS). Methods This was a single-center, prospective, and longitudinal study including 370 consecutive ACS patients in Killip class I or II. BBs were prescribed according to international guidelines and withdrawn if intolerance occurred. The study was approved by the institutional ethics committee of our university. Statistics: the clinical parameters evaluated at admission, and the related intolerance to BBs and death at 6 months were analyzed using logistic regression (p<0.05)in PATIENTS. Results BB intolerance was observed in 84 patients and was associated with no prior use of statins (OR: 2.16, 95%CI: 1.26–3.69, p= 0.005) and Killip class II (OR: 2.5, 95%CI: 1.30-4.75, p=0.004) in the model adjusted for age, sex, blood pressure, and renal function. There was no association with ST-segment alteration or left anterior descending coronary artery plaque. Intolerance to BB was associated with the greatest risk of death (OR: 4.5, 95%CI: 2.15–9.40, p<0.001). Conclusions After ACS, intolerance to BBs in the first 48 h of admission was associated to non previous use of statin and Killip class II and had a high risk of death within 6 months.

Ischaemia and reperfusion effects on skeletal muscle tissue: morphological and histochemical studies

This was a study on the oxidative stress due to ischaemia (I) and reperfusion (R) in skeletal muscle tissue. Using a tourniquet, groups of rats were submitted to ischaemia for 4 h, followed by different reperfusion periods. The animals were divided in four groups: control; 4 h of ischaemia (IR); 4 h of ischaemia plus 1 h reperfusion (IR‐1 h); 4 h of ischaemia plus 24 h reperfusion (IR‐24 h); and 4 h of ischaemia plus 72 h reperfusion (IR‐72 h). At the end of the procedures, samples of soleus muscle were collected and frozen in n‐hexane at −70 °C. Cryostat sections were submitted to haematoxylin–eosin, succinate dehydrogenase (SDH) and nicotinamide adenine dinucleotide‐tetrazolium reductase (NADH‐TR) stains. An additional muscle sample was processed for electron microscopy. No alterations were found in control animals. IR group showed fibres had normal aspect besides some round, acidophilic and hypertrophic fibres. There were several fibres with angular outlines and smaller diameters in this group compared with control group. NADH‐TR/SDH reaction was moderately intense in most fibres. In some fibres, cytoplasm showed areas without activity and other fibres had very intense reactivity. IR‐1 h group showed oedema hypercontracted fibres with disorganized myofibrils, mitochondria with focal lesions and dilated sarcoplasmic reticulum. NADH‐TR/SDH reaction was moderate to weak. IR‐24 h showed intense inflammatory infiltrate in the endomysium and perimysium. NADH‐TR/SDH reaction was similar to IR‐1 h. IR‐72 h showed necrotic fibres, areas with inflammatory infiltrate, reduced muscle fibres at different stages of necrosis and phagocytosis, and many small round and basophilic fibres characterizing a regeneration process. NADH‐TR/SDH reaction was weak to negative. Our results suggest that ischaemia and the subsequent 1‐, 24‐ and 72‐h reperfusions induced progressive histological damage. Although progressive, it may be reversible because there were ultrastructural signs of recovery after 72‐h reperfusion. This recovery could in part be due to the low oxidative stress identified by the morphological and histochemical analysis.

Lycopene supplementation modulates plasma concentrations and epididymal adipose tissue mRNA of leptin, resistin and IL-6 in diet-induced obese rats

Obesity is characterised by chronic low-grade inflammation, and lycopene has been reported to display anti-inflammatory effects. However, it is not clear whether lycopene supplementation modulates adipokine levels in vivo in obesity. To determine whether lycopene supplementation can regulate adipokine expression in obesity, male Wistar rats were randomly assigned to receive a control diet (C, n 6) ora hyperenergetic diet (DIO, n 12) for 6 weeks. After this period, the DIO animals were randomised into two groups: DIO (n 6) and DIO supplemented with lycopene (DIO + L, n 6). The animals received maize oil (C and DIO) or lycopene (DIO + L, 10 mg/kg body weight(BW) per d) by oral administration for a 6-week period. The animals were then killed by decapitation, and blood samples and epididymal adipose tissue were collected for hormonal determination and gene expression evaluation (IL-6, monocyte chemoattractant protein-1(MCP-1), TNF-α, leptin and resistin). There was no detectable lycopene in the plasma of the C and DIO groups. However, the mean lycopene plasma concentration was 24 nmol in the DIO + L group. Although lycopene supplementation did not affect BW or adiposity, it significantly decreased leptin, resistin and IL-6 gene expression in epididymal adipose tissue and plasma concentrations. Also, it significantly reduced the gene expression of MCP-1 in epididymal adipose tissue. Lycopene affects adipokines by reducing leptin, resistin and plasma IL-6 levels. These data suggest that lycopene may be an effective strategy in reducing inflammation in obesity.

Oxidative stress status of highly prolific sows during gestation and lactation

Elevated oxidative stress is reported to be associated with pregnancy complications in highly prolific sows. Oxidative DNA damage and the antioxidant status were determined in blood samples collected during the course of gestation and lactation in multiparous sows. Blood samples were drawn from sows (n = 5) on days 30, 60, 90 and 110 of gestation (G30, G60, G90 and G110, respectively), on day 3, 10 and 18 of lactation (L3, L10 and L18, respectively) and on day 5 of postweaning (W5). Lymphocytes were isolated from the fresh blood and cryopreserved in each time point. Lymphocyte DNA damage was analyzed by alkaline single-cell gel electrophoresis (comet assay) to determine the single- and double-strand brakes and endogenous antioxidant concentrations using an HPLC system with UV detection. The comet assay showed elevated (P < 0.05) DNA damage (between 38% and 47%) throughout the gestational and lactational periods than during early gestation (G30; 21%). Plasma retinol concentration was reduced (P < 0.05) at the end of gestation (G110) compared with G30. Plasma α-tocopherol concentrations also showed a similar trend as to retinol. This study indicates that there is an increased systemic oxidative stress during late gestation and lactation, which are not fully recovered until the weaning compared with the G30, and that antioxidant nutrients in circulation substantially reduced in the mother pig at G110.

Hiperinsuflação manual combinada com compressão torácica expiratória para redução do período de internação em UTI em pacientes críticos sob ventilação mecânica

OBJECTIVE Although manual hyperinflation (MH) is widely used for pulmonary secretion clearance, there is no evidence to support its routine use in clinical practice. Our objective was to evaluate the effect that MH combined with expiratory rib cage compression (ERCC) has on the length of ICU stay and duration of mechanical ventilation (MV). METHODS This was a prospective randomized controlled clinical trial involving ICU patients on MV at a tertiary care teaching hospital between January of 2004 and January of 2005. Among the 49 patients who met the study criteria, 24 and 25 were randomly assigned to the respiratory physiotherapy (RP) and control groups, respectively. Of those same patients, 6 and 8, respectively, were later withdrawn from the study. During the 5-day observation period, the RP patients received MH combined with ERCC, whereas the control patients received standard nursing care. RESULTS The two groups were similar in terms of the baseline characteristics. The intervention had a positive effect on the duration of MV, as well as on the ICU discharge rate and Murray score. There were significant differences between the control and RP groups regarding the weaning success rate on days 2 (0.0% vs. 37.5%), 3 (0.0% vs. 37.5%), 4 (5.3% vs. 37.5%), and 5 (15.9% vs. 37.5%), as well as regarding the ICU discharge rate on days 3 (0% vs. 25%), 4 (0% vs. 31%), and 5 (0% vs. 31%). In the RP group, there was a significant improvement in the Murray score on day 5. CONCLUSIONS Our results show that the use of MH combined with ERCC for 5 days accelerated the weaning process and ICU discharge.OBJECTIVE: Although manual hyperinflation (MH) is widely used for pulmonary secretion clearance, there is no evidence to support its routine use in clinical practice. Our objective was to evaluate the effect that MH combined with expiratory rib cage compression (ERCC) has on the length of ICU stay and duration of mechanical ventilation (MV). METHODS: This was a prospective randomized controlled clinical trial involving ICU patients on MV at a tertiary care teaching hospital between January of 2004 and January of 2005. Among the 49 patients who met the study criteria, 24 and 25 were randomly assigned to the respiratory physiotherapy (RP) and control groups, respectively. Of those same patients, 6 and 8, respectively, were later withdrawn from the study. During the 5-day observation period, the RP patients received MH combined with ERCC, whereas the control patients received standard nursing care. RESULTS: The two groups were similar in terms of the baseline characteristics. The intervention had a positive effect on the duration of MV, as well as on the ICU discharge rate and Murray score. There were significant differences between the control and RP groups regarding the weaning success rate on days 2 (0.0% vs. 37.5%), 3 (0.0% vs. 37.5%), 4 (5.3% vs. 37.5%), and 5 (15.9% vs. 37.5%), as well as regarding the ICU discharge rate on days 3 (0% vs. 25%), 4 (0% vs. 31%), and 5 (0% vs. 31%). In the RP group, there was a significant improvement in the Murray score on day 5. CONCLUSIONS: Our results show that the use of MH combined with ERCC for 5 days accelerated the weaning process and ICU discharge.

Remodelação miocárdica na sobrecarga crônica de pressão ou de volume no coração de ratos

OBJECTIVE To compare cardiac structural changes in experimental pressure and volume overload models. METHODS The study analysis included renovascular hypertensive rats (RVH, n = 8), normotensive rats with volume overload caused by an aortocaval fistula (ACF, n = 10) and control rats (CONT, n = 8). After four weeks, tail cuff blood pressure (SBP) was recorded. Rats were killed, the hearts were excised and the right and left ventricles (RV&LV) were weighed (RVW&LVW). Using histological sections, myocyte cross sectional areas (MA). LV wall thickness (LVWT) LV cavity diameter (LVD), normalized LVWT (LVWT/LVD) and collagen volume fraction (CVF) were measured. The comparisons were made using the ANOVA and Tukey test for a significance level of 5%. RESULTS Tail cuff blood pressure (mmHg) was higher in the RVH group (RVH = 187 +/- 22; CONT = 125 +/- 10; ACF = 122 +/- 6, p < 0.05). LV hypertrophy was observed in the RVH and ACF groups. The ACF group presented a significant increase in size of LVD, compared to CONT and RVH. The absolute and normalized ventricular wall thickness were similar among the groups. The RVH group presented a significant increase in CVF compared to CONT group and ACF group. CONCLUSION Cardiac remodeling patterns following volume or pressure overload are distinct, suggesting that their implications on ventricular dysfunction are not interchangeable.

Avaliação do desempenho diagnóstico e do valor de corte para o índice de respiração rápida e superficial na predição do insucesso da extubação

OBJECTIVE: To evaluate the diagnostic performance of the rapid shallow breathing index (RSBI) in predicting extubation failure among adult patients in the intensive care unit and to determine the appropriateness of the classical RSBI cut-off value. METHODS: This was a prospective study conducted in the adult intensive care unit of the Botucatu School of Medicine Hospital das Clinicas. The RSBI was evaluated in 73 consecutive patients considered clinically ready for extubation. RESULTS: The classical RSBI cut-off value (105 breaths/min/L) presented a sensitivity of 20% and a specificity of 95% (sum = 115%). Analysis of the receiver operator characteristic (ROC) curve revealed a better cut-off value (76.5 breaths/min/L), which presented a sensitivity of 66% and a specificity of 74% (sum = 140%). The area under the ROC curve for the RSBI was 0.78. CONCLUSIONS: The classical RSBI cut-off value proved inappropriate, predicting only 20% of the cases of extubation failure in our sample. The new cut-off value provided substantial improvement in sensitivity, with an acceptable loss of specificity. The area under the ROC curve indicated that the discriminative power of the RSBI is satisfactory, which justifies the validation of this index for use.

Infecção em idosos internados em instituição de longa permanência

OBJECTIVE: To evaluate the occurrence of infection in elderly interned in long-term care facilities (LTCF) during 13 consecutive months. METHODS: Fifty five elderly were evaluated according to infection and, reporting was standardized. RESULTS: The median age was 75 (66 81) years. The data set consisted of 20,896 patients-day (PD) of care during the period, with a total of 76 infections for a pooled mean rate of infections 3.20 per 1,000 PD of care. Patient infection rate was 63.6%. Prevalent topographies of infection were respiratory (50%), urinary tract (32%), skin and soft tissue (12%) and gastroenteritis (7%), with an infection rate for specific categories/1000 PD of 1.60, 1.01, 0.38, 0.21, respectively. Mortality infection rate was 5%. Microbiological agents were isolated in 30.5% of the infection episodes. Escherichia coli and Staphylococcus aureus were prevalent. CONCLUSION: Infection presented an elevated incidence in the elderly interned, but no unusual problem with infections was disclosed.