Phase angle and cellular health: inflammation and oxidative damage.

Phase angle is a composite measure that combines two raw bioelectrical impedance analysis measures: resistance and reactance. Phase angle has been considered an indicator of cellular health, integrity, and hydration. As inflammation and oxidative stress can damage cellular structures, phase angle has potential utility in early detecting inflammatory and oxidative status. Herein, we aimed to critically review the current understanding on the determinants of phase angle and its relationship with markers of inflammation and oxidative stress. We also discussed the potential role of phase angle in detecting chronic inflammation and related adverse outcomes. Several factors have been identified as predictors of phase angle, including age, sex, extracellular to intracellular water ratio, and fat-free mass. In addition to these factors, body mass index (BMI) also seems to influence phase angle. Available data also show that lower phase angle values are correlated (negligible to high correlation coefficients) with higher c-reactive protein, tumour necrosis factor-α, interleukin-6, and interleukin-10 in studies involving the general and aging populations, as well as patients with chronic conditions. Although fewer studies have evaluated the relationship between phase angle and markers of oxidative stress, available data also suggest that phase angle has potential to be used as an indicator (for screening) of oxidative damage. Future studies including diverse populations and bioelectrical impedance devices are required to confirm the validity and accuracy of phase angle as a marker of inflammation and oxidative stress for clinical use.

An Evaluation of Metabolic, Dietetic, and Nutritional Status Reveals Impaired Nutritional Outcomes in Breast Cancer Patients.

Nutritional status can change in breast cancer patients after treatment. However, the metabolic implications of those alterations are poorly understood. We used a cross-sectional study design to compare body composition, lipids, glucose levels, and adiposity indices in breast cancer patients with a matched control and a healthy group. We recruited women who completed their chemotherapy (BC group) and compared them with a group of women without cancer age and body mass index-paired (MC group) and a group of healthy women (HC group). We estimated body composition by bioelectrical impedance analysis, physical function by handgrip strength, and food consumption by 24-hour food record. A blood sample was collected. We calculated visceral obesity indices (VAI and LAP) and insulin resistance-triglyceride glucose (TyG). Eighty-eight women were included (BC = 36, MC = 36, HC = 16). BC patients demonstrated worse phase angle values, nutritional risk index and lower handgrip strength. Additionally, according to the indices, BC had impairments in lipids, worse glucose levels, and elevated visceral fat adiposity and presented important unhealthy dietary patterns characterized by under-recommended protein consumption and higher caloric intake than the other groups. No differences were observed between both control groups. Further investigations are required to examine the underlying mechanisms and the potential longitudinal changes during surveillance.

Effect of chocolate on older patients with cancer in palliative care: a randomised controlled study.

BACKGROUND: Older advanced stage cancer patients, with changes in nutritional status, represent an important demand for palliative care. The aim was to determine the effects of 4 weeks of chocolate consumption on the nutritional status of older cancer patients in palliative care. METHODS: Older cancer patients in palliative care with ambulatory (n = 46) monitoring were randomized to control (CG, n = 15), intervention with 55% cocoa chocolate (IG1, n = 16) and intervention with white chocolate (IG2, n = 15) groups and evaluated before and after 4 weeks for nutritional status (primary outcome), evaluated by the Mini Nutritional Assessment tool (MNA). Food consumption, anthropometry, body composition, laboratory parameters and quality of life (QL) with the European Organization for the Research and Treatment of Cancer instrument were also evaluated. RESULTS: IG1 progressed with increased screening (estimated difference [95% CI]: - 1.3 [- 2.2;-0.4], p < 0.01), and nutritional (estimated difference [95% CI]: - 1.3 [- 2.5;-0.1], p = 0.04) scores on the MNA, with no change in anthropometry and body composition. Regarding antioxidant capacity, reduced glutathione levels increased (estimated difference [95% CI]: - 0.8 [- 1.6;-0.02], p = 0.04) and malondealdehyde levels decreased in IG2 (estimated difference [95% CI]:+ 4.9 [+ 0.7;+ 9.1], p = 0.02). Regarding QL, functionality improved in IG1, with higher score in the functional domain (estimated difference [95% CI]:-7.0 [- 13.3;-0.7], p = 0.03). CONCLUSIONS: The consumption of chocolate with a greater cocoa content may contribute to the improvement of the nutritional status and functionality among older cancer patients in palliative care. The consumption of white chocolate was associated with improved oxidative stress. TRIAL REGISTRATION: A randomized clinical trial (ClinicalTrials.gov NCT04367493 ).

Oocyte oxidative DNA damage may be involved in minimal/mild endometriosis-related infertility.

Early endometriosis is associated with infertility, and oxidative stress may play a role in the pathogenesis of disease-related infertility. This prospective case-control study aimed to compare the presence of oxidative stress markers in the follicular microenvironment and systemic circulation of infertile women with minimal/mild endometriosis (EI/II) versus individuals undergoing controlled ovarian stimulation for intracytoplasmic sperm injection (ICSI). Seventy-one blood samples (27 from infertile women with EI/II and 44 controls with tubal and/or male infertility factor) and 51 follicular fluid samples (19 EI/II and 32 controls) were obtained on the day of oocyte retrieval. Total hydroperoxides (FOX1 ), reduced glutathione, vitamin E, Superoxide dismutase, total antioxidant capacity, malondialdehyde, advanced oxidation protein products, and 8-hydroxy-2'-deoxyguanosine (8OHdG) concentrations were measured in both fluids. Women with EI/II showed higher FOX1 (8.48 ± 1.72 vs. 7.69 ± 1.71 µmol/g protein) and lower total antioxidant capacity (0.38 ± 0.18 vs. 0.46 ± 0.15 mEq Trolox/L) concentrations in serum, and higher 8OHdG concentrations (24.21 ± 8.56 vs. 17.22 ± 5.6 ng/ml) in follicular fluid compared with controls. These data implicate both systemic and follicular oxidative stress may in infertile women with EI/II undergoing controlled ovarian stimulation for ICSI. Furthermore, the elevated 8OHdG concentrations in follicular fluid of women with EI/II may be related to compromised oocyte quality.

Dietary docosahexaenoic acid and eicosapentaenoic acid influence liver triacylglycerol and insulin resistance in rats fed a high-fructose diet.

This study aimed to examine the benefits of different amounts of omega-3 (n-3) polyunsaturated fatty acids from fish oil (FO) on lipid metabolism, insulin resistance and gene expression in rats fed a high-fructose diet. Male Wistar rats were separated into two groups: Control (C, n = 6) and Fructose (Fr, n = 32), the latter receiving a diet containing 63% by weight fructose for 60 days. After this period, 24 animals from Fr group were allocated to three groups: FrFO2 (n = 8) receiving 63% fructose and 2% FO plus 5% soybean oil; FrFO5 (n = 8) receiving 63% fructose and 5% FO plus 2% soybean oil; and FrFO7 (n = 8) receiving 63% fructose and 7% FO. Animals were fed these diets for 30 days. Fructose led to an increase in liver weight, hepatic and serum triacylglycerol, serum alanine aminotransferase and HOMA1-IR index. These alterations were reversed by 5% and 7% FO. FO had a dose-dependent effect on expression of genes related to hepatic ß-oxidation (increased) and hepatic lipogenesis (decreased). The group receiving the highest FO amount had increased markers of oxidative stress. It is concluded that n-3 fatty acids may be able to reverse the adverse metabolic effects induced by a high fructose diet.

Homocysteine and nitrite levels are modulated by MTHFR 677C>T polymorphism in obese women treated with simvastatin.

Higher homocysteine (Hcy) levels are associated with cardiovascular risk. The aim of the present study was to evaluate the effect of simvastatin treatment on circulating Hcy levels in obese women without hypertension, diabetes or dyslipidaemia; and to determine whether the 677C>T polymorphism located in methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR) gene modulates the effects of this treatment on Hcy and nitrite (as a biomarker of nitric oxide (NO) bioavailability). Twenty-five obese women (body mass index ≥ 30 kg/m(2) ) who had received 20 mg/day simvastatin for 6 weeks were enrolled in the study. Venous blood samples were collected to measure plasma biomarkers and gene polymorphisms. Simvastatin treatment significantly reduced total cholesterol, low-density lipoprotein-cholesterol, thiobarbituric acid-reactive substances, high-sensitivity C-reactive protein and Hcy, whereas nitrite levels were increased. The reduction in Hcy levels in carriers of the T allele was -20.3% compared with -9.4% in patients with the CC genotype. Importantly, before treatment, nitrite levels were significantly higher in patients with the CC genotype compared with T allele carriers, whereas after treatment these levels were similar between groups. Our findings demonstrate that obese women without comorbidities and carrying the T variant of the 677C>T polymorphism of MTHFR exhibit benefits with simvastatin treatment, mainly in terms of increased NO levels.

Phase angle is related to oxidative stress and antioxidant biomarkers in breast cancer patients undergoing chemotherapy.

PURPOSE: The study aimed to analyze the influence of chemotherapy on health biomarkers and examine the relationship between phase angle (PhA) and oxidative stress. METHODS: A prospective study was performed. Women who were starting chemotherapy were recruited. Also, this study included a control group of women without cancer. Bioelectrical impedance multiple-frequency (BIS) analysis, 24h food recall, and blood samples were collected at 2-time points: diagnosis (T0) and after one month of completion of therapy (T1) for the main study group and one-time point for the control group. T-tests or Mann-Whitney Wilcoxon Test was used to compare variables. Linear regression analysis was conducted to test if PhA is related to the dependent variables after adjusting for age and body mass index. RESULTS: 119 women were included (61 with breast cancer and 58 healthy). There was no difference between the groups concerning anthropometrics, fat mass, and fat-free mass. Breast cancer patients had a worsening in PhA (p<0.001) after chemotherapy completion. PhA was positive statistically correlated with extracellular water, albumin, and the antioxidant markers at both times. The linear model showed that PhA was significantly predicted by C reactive protein, 2,2-Diphenyl-1-picrylhydrazyl (DPPH), Malondialdehyde (MDA), total body water/extracellular water, and body mass index fat mass. This model explained 58% of PhA variability (p<0.001). CONCLUSION: Our findings show that PhA is an easy and affordable tool that correlates oxidative stress markers in breast cancer patients, regardless of age or body mass index.

Oxidative stress biomarker responses to an acute session of hypertrophy-resistance traditional interval training and circuit training.

We have studied circuit resistance schemes with high loads as a time-effective alternative to hypertrophy-traditional resistance training. However, the oxidative stress biomarker responses to high-load circuit training are unknown. The aim of the present study was to compare oxidative stress biomarker response with an acute session of hypertrophy-resistance circuit training and traditional interval training. A week after the 1 repetition maximum (1RM) test, 11 healthy and well-trained male participants completed hypertrophy-resistance acute sessions of traditional interval training (3 × 10 repetitions at 75% of the 1RM, with 90-second passive rest) and circuit training (3 × 10 repetitions at 75% of the 1RM, in alternating performance of 2 exercises with different muscle groups) in a randomized and cross-over design. Venous blood samples were collected before (pre) and 10 minutes after (post) the resistance training sessions for oxidative stress biomarker assays. As expected, the time used to complete the circuit training (20.2 ± 1.6) was half of that needed to complete the traditional interval training (40.3 ± 1.8). Significant increases (p < 0.05) in thiobarbituric acid reactive substances (40%), creatine kinase (CK) (67%), glutathione (14%), and uric acid (25%) were detected posttraditional interval training session in relation to pre. In relation to circuit training, a significant increase in CK (33%) activity postsession in relation to pre was observed. Statistical analysis did not reveal any other change in the oxidative stress biomarker after circuit training. In conclusion, circuit resistance-hypertrophy training scheme proposed in the current study promoted lower oxidative stress biomarkers and antioxidant modulations compared with resistance traditional interval training.

Performance of functionality measures and phase angle in women exposed to chemotherapy for early breast cancer.

PURPOSE: The study aimed to analyze the influence of chemotherapy on nutritional status and the phase angle (PhA) as nutritional indicator for breast cancer women undergoing chemotherapy. METHODS: A prospective study was performed. Women who were starting chemotherapy with no previous chemotherapy treatment were recruited. Quality of life (QoL) was collected using the EORTC QLQ-BR23 questionnaire. Bioelectrical impedance analysis, performance tests, and blood sample to albumin analyzes were collected at 2-time points: diagnosis (T0) and after 1 month of completion of therapy (T1). Mean, standard deviation, linear regression, and ANOVA in R were used to explore the results. RESULTS: 61 women were included. We did not find any changes in body composition. However, PhA, nutritional risk index (NRI), gait speed (GS), and handgrip strength (HGS) had expressive changes (p < 0.001). 75.4% of women had PhA values below the cut-off point of 5.6°, and the group that had a lower average of PhA also expressed low NRI. PhA was a nutritional status marker and its values were influenced by changes in NRI (p < 0.05). CONCLUSION: We have found supporting evidence for chemotherapy treatment resulting in worsening of prognostic factors such as PhA, and yet PhA was related to no nutritional risk. Besides a higher prevalence of obesity, 80% of the sample showed some nutritional risk level, implying the possibility of a sub-notification candidate who might benefit, for instance, from nutritional intervention in obesity groups. Further investigation about this theme may improve health measures for the prevention and screening of disease among breast cancer.

Metabolic syndrome and unfavorable outcomes on body composition and in visceral adiposities indexes among early breast cancer women post-chemotherapy.

PURPOSE: The study objected to investigate potential changes in metabolic, dietary, and nutritional status in women with stages I-III breast cancer exposed to chemotherapy. METHODS: Women who were starting chemotherapy with no previous treatment were recruited. Anthropometrics, bioelectrical impedance analysis, handgrip strength, blood pressure and blood sample were collected. Visceral adiposity index and lipid accumulation product were calculated. Dietary intake was evaluated, and the multiple source methods program was applied. Metabolic syndrome (MetS) was assessed following the NCEP-ATP III criteria (defined as 3 of 5 components of MetS). All data were collected at 2-time points: diagnosis (T0) and after 1 month of completion of therapy (T1). Mean, standard deviation, percentage, and ANOVA in SAS Studio® were used to explore the results. RESULTS: 61 women were included. We did not find any changes in anthropometrics and body composition. However, phase angle, extracellular water (EX) and ratio EX to total body water had expressive changes (p < 0.001). The results showed changes in lipid profile (p < 0.001), and greater unfavorable outcomes on adiposities index (p < 0.001). At the end of the study, 68,8% (N = 42) of the women developed MetS post-chemotherapy. CONCLUSION: We have found supporting evidence for chemotherapy treatment resulting in worsening of nutritional markers, lipid profile and adiposity markers. After chemotherapy part of the sample developed MetS, even without changes in body weight, fat mass, and food intake. Breast cancer patients may benefit from targeted interventions before starting chemotherapy to prevent MetS post-treatment, and therefore reduce the risk of cardiovascular disease. Further investigation into this theme is needed.

Antioxidant Effect of Standardized Extract of Propolis (EPP-AF®) in Healthy Volunteers: A "Before and After" Clinical Study.

BACKGROUND: Propolis is rich in polyphenols, especially flavonoids and phenolic acids, and has significant antioxidant activity, shown mainly in "in vitro" studies. OBJECTIVE: The aim of this study was to evaluate the antioxidant efficacy and safety of a standardized propolis extract in healthy volunteers. DESIGN: A two-phase sequential, open-label, nonrandomized, before and after clinical trial. METHODS: Healthy participants received two EPP-AF® doses (375 and 750 mg/d, P.O, tid) during 7 ± 2 days, starting with the lower doses. Immediately before starting EPP-AF® administration and at the end of each 7-day dosing schedule, blood and urine samples were collected for quantification of 8-OHDG (8-hydroxydeoxyguanosine) and 8-ISO (8-isoprostanes) in urine and GSH (reduced glutathione), GSSG (oxidized glutathione), SOD (superoxide dismutase), FRAP (Ferric Reducing Antioxidant Power), vitamin E, and MDA (malondialdehyde) in plasma. RESULTS: In our study, we had 34 healthy participants (67.7% women, 30 ± 8 years old, 97% white). The 8-ISO, a biomarker of lipid peroxidation, decreased with both doses of EPP-AF® compared to baseline (8-ISO, 1.1 (0.9-1.3) versus 0.85 (0.75-0.95) and 0.89 (0.74-1.0), ng/mg creatinine, P < 0.05, for 375 and 750 mg/d EPP-AF® doses versus baseline, mean and CI 95%, respectively). 8-OHDG, a biomarker of DNA oxidation, was also reduced compared to baseline with 750 mg/d doses (8-OHDG, 15.7 (13.2-18.1) versus 11.6 (10.2-13.0), baseline versus 750 mg/d, respectively, ng/mg creatinine, P < 0.05). Reduction of biomarkers of oxidative stress damage was accompanied by increased plasma SOD activity (68.8 (66.1-73.3) versus 78.2 (72.2-80.5) and 77.7 (74.1-82.6), %inhibition, P < 0.0001, 375 and 750 mg/d versus baseline, median and interquartile range 25-75%, respectively) and by increased GSH for 375 mg/d EPP-AF® doses (1.23 (1.06-1.34) versus 1.33 (1.06-1.47), µmol/L, P < 0.05). CONCLUSION: EPP-AF® reduced biomarkers of oxidative stress cell damage in healthy humans, with increased antioxidant enzymatic capacity, especially of SOD. This trial is registered with the Brazilian Registry of Clinical Trials (ReBEC, RBR-9zmfs9).

Effect of NFkappaB inhibition by CAPE on skeletal muscle ischemia-reperfusion injury.

BACKGROUND/AIMS: Nuclear factor kappa B (NFkappaB) plays important role in the pathogenesis of skeletal muscle ischemia/reperfusion (I/R) injury. Caffeic acid phenyl ester (CAPE), a potent NFkappaB inhibitor, exhibits protective effects on I/R injury in some tissues. In this report, the effect of CAPE on skeletal muscle I/R injury in rats was studied. METHODS: Wistar rats were submitted to sham operation, 120-min hindlimb ischemia, or 120-min hindlimb ischemia plus saline or CAPE treatment followed by 4-h reperfusion. Gastrocnemius muscle injury was evaluated by serum aminotransferase levels, muscle edema, tissue glutathione and malondialdehyde measurement, and scoring of histological damage. Apoptotic nuclei were determined by a terminal uridine deoxynucleotidyl transferase dUTP nick end labeling assay. Muscle neutrophil and mast cell accumulation were also assessed. Lipoperoxidation products and NFkappaB were evaluated by 4-hydroxynonenal and NFkappaB p65 immunohistochemistry, respectively. RESULTS: Animals submitted to ischemia showed a marked increase in aminotransferases after reperfusion, but with lower levels in the CAPE group. Tissue glutathione levels declined gradually during ischemia to reperfusion, and were partially recovered with CAPE treatment. The histological damage score, muscle edema percentage, tissue malondialdehyde content, apoptosis index, and neutrophil and mast cell infiltration, as well as 4-hydroxynonenal and NFkappaB p65 labeling, were higher in animals submitted to I/R compared with the ischemia group. However, the CAPE treatment significantly reduced all of these alterations. CONCLUSIONS: CAPE was able to protect skeletal muscle against I/R injury in rats. This effect may be associated with the inhibition of the NFkappaB signaling pathway and decrease of the tissue inflammatory response following skeletal muscle I/R.

The protective effect of CAPE on hepatic ischemia/reperfusion injury in rats.

BACKGROUND/AIMS: The transcription factor nuclear factor-kappa B (NF-kappaB) exerts a pivotal role in the pathogenesis of hepatic ischemia/reperfusion (I/R) injury. Caffeic acid phenyl ester (CAPE), a potent and specific NF-kappaB inhibitor, presents protective effects on I/R injury in some tissues. This study aimed to evaluate the effect of CAPE on hepatic I/R injury in rats. MATERIALS AND METHODS: Wistar rats were submitted to a sham operation, 60 min ischemia, or 60 min ischemia plus saline or CAPE treatment followed by 6 h reperfusion. Liver tissue injury was evaluated by alanine aminotransferase, aspartate aminotransferase, and tissue glutathione measurement, and histological damage score. Apoptotic hepatocytes were determined by the transferase-mediated dUTP-biotin nick-end labeling assay. Hepatic neutrophil accumulation was assessed by the naphthol method. Lipid peroxidation and NF-kappaB activation were evaluated by 4-hydroxynonenal and NF-kappaB p65 immunohistochemistry, respectively. RESULTS: Animals submitted to ischemia showed a marked increase of alanine aminotransferase and aspartate aminotransferase after reperfusion, but with lower levels in CAPE group. Tissue glutathione content declined gradually during ischemia to reperfusion and was partially recovered with CAPE treatment. The histological damage score, apoptosis index, and neutrophil infiltration, as well as 4-hydroxynonenal and NF-kappaB p65 nuclear labeling, were higher in the liver of animals submitted to I/R compared to the ischemia group. However, the CAPE treatment significantly reduced all of these alterations. CONCLUSIONS: CAPE was able to protect the liver against normothermic I/R injury in rats. This effect may be associated with the inhibition of the NF-kappaB signaling pathway and decrease of the acute inflammatory response following I/R in the liver.

Cutoff Points of BMI for Classification of Nutritional Status Using Bioelectrical Impedance Analysis.

The objective of this study was to improve the cutoff points of the traditional classification of nutritional status and overweight / obesity based on the BMI in a Brazilian sample. A cross-sectional study was conducted on 1301 individuals of both genders aged 18 to 60 years. The subjects underwent measurement of weight and height and bioelectrical impedance analysis. Simple linear regression was used for statistical analysis, with the level of significance set at p < 0.05. The sample consisted of 29.7% men and 70.3% women aged on averaged 35.7 ± 17.6 years; mean weight was 67.6 ± 16.0 kg, mean height was 164.9 ± 9.5 cm, and mean BMI was 24.9 ± 5.5 kg/m2. As expected, lower cutoffs were found for BMI than the classic reference points traditionally adopted by the WHO for the classification of obesity, i.e., 27.15 and 27.02 kg/m2 for obesity for men and women, respectively. Other authors also follow this tendency, Romero-Corral et al. (2008) suggested 25.8 to 25.5 kg/m2 for American men and women as new values for BMI classification of obesity. Gupta and Kapoor (2012) proposed 22.9 and 28.8 kg/m2 for men and women of North India. The present investigation supports other literature studies which converge in reducing the BMI cutoff points for the classification of obesity. Thus, we emphasize the need to conduct similar studies for the purpose of defining these new in populations of different ethnicities.

Human milk enriched with human milk lyophilisate for feeding very low birth weight preterm infants: A preclinical experimental study focusing on fatty acid profile.

BACKGROUND: Human milk, with essential nutrients and long chain polyunsaturated fatty acids (LC-PUFAs) such as the omega 3 and 6 fatty acids is important for development of the central nervous system and the retina in very low birth weight infants (<1,500 g). However, breast milk may not be sufficient to meet these needs. The possibility of supplementing breast milk with a lyophilisate of human milk was explored in this study. The objectives of this study were to determine the total lipid content and the lipid profile of the Human Milk on Baseline (HMB) and that of the Concentrates with the Human Milk + lyophilisate (with lyophilisate of milk in the immediate period (HMCI), at 3 months (HMC3m), and at 6 months (HMC6m) of storage). METHODS: Fifty donors from the Human Milk Bank of Children's Hospital provided consent, and donated milk samples. Macronutrient (including total lipids) quantification was performed using the MIRIS® Human Milk Analyzer, and the fatty acid profile was determined by gas chromatography (CG-FID, SHIMADZU®). RESULTS: There was a higher lipid concentration in HMCI relative to HMB. The concentrations of the main fatty acids (% of total) were as follows: palmitic acid (C16:0) HMB, 22.30%; HMCI, 21.46%; HMC3m, 21.54%; and HMC6m, 21.95% (p<0.01); oleic acid (C18:1n-9) HMB, 30.41%; HMCI, 30.47%; HMC3m, 30.55%; and HMC6m, 29.79% (p = 0.46); linoleic acid (C18:2n-6) HMB, 19.62%; HMCI, 19.88%; HMC3m, 19.49%; and HMC6m, 19.45% (p = 0.58); arachidonic acid (C20:4n-6) HMB, 0.35%; HMCI, 0.16%; HMC3m, 0.13%; and HMC6m, 0.15% (p<0.01); α-linolenic acid (C18:3n-3) HMB,1.32%; HMCI, 1.37%; HMC3m, 1.34%; and 1.34% HMC6m (p = 0.14); docosahexaenoic acid (C22:6n-3) HMB, 0.10%; HMCI, 0.06%; HMC3m, 0.05%; and HMC6m, 0.06% (p<0.01). There were no significant changes in the lipid profile when stored. There was no evidence of peroxidation during storage. CONCLUSIONS: Freeze-dried human milk fortified with a human milk concentrate brings potential benefits to newborns, mainly by preserving the essential nutrients present only in breast milk; however, further clinical studies are required to evaluate the safety and efficacy of the concentrate as a standard nutritional food option for very low birth weight infants.

Influence of thyroid hormone on thyroid hormone receptor beta-1 expression and lacrimal gland and ocular surface morphology.

PURPOSE: Hormone diseases induce changes in the lacrimal gland (LG) and ocular surface (OS). Thyroid hormone (TH) induces cell proliferation and lipid metabolism through the activation of TH receptors. The aim of the present study was to evaluate the location and comparative expression of TH receptor beta-1 (Thrb) in LG of rats with hypothyroidism and in controls and to evaluate the impact of this disease on LG and OS structure and function. METHODS: Hypothyroidism was induced in Wistar male rats by the long-term use of tiamazole. Ten weeks later corneal cells were collected for impression cytology (IC). Rats were humanely killed, and tissues were evaluated by immunoperoxidase staining and Western blot for Thrb. The content of malondialdehyde (MDA) and acetylcholine (ACh) in LG was determined by spectrophotometry (n = 5/group in all experiments). RESULTS: LG weight was significantly lower in hypothyroid rats (P < 0.05). Western blot analysis indicated that LGs express Thrb and that hypothyroidism induces a higher expression of this receptor. IC was significantly different and ACh was significantly lower in hypothyroid rats (P < 0.05). CONCLUSIONS: Chronically reduced levels of TH lead to biochemical and structural changes and modulate the levels of Thrb in LG. These events confirm that LG is a target organ for TH and may facilitate understanding of the mechanism related to dry eye in hypothyroidism.

Zinc serum levels and their association with vitamin A deficiency in preschool children.

OBJECTIVES: To identify the prevalence of zinc deficiency in a population with high prevalence of vitamin A deficiency; to verify whether zinc deficiency is associated with vitamin A deficiency in the population studied; to verify risk factors for zinc deficiency (sex, age, diarrhea and fever). METHOD: Cross-sectional study of 182 healthy children aged > or = 24 months and < 72 months. Peripheral blood samples were obtained from fasting children to determine zinc serum levels. Information about presence of diarrhea and/or fever during the 15 days preceding the study was also obtained. Vitamin A deficiency was identified by a serum 30-day dose-response test (+S30DR). RESULTS: Of the children studied, 0.5% (1/182) presented zinc serum levels < 65 microg/dL; however, 74.7% (136/182) of them had vitamin A deficiency. Zinc serum levels were not correlated with retinol serum levels. Zinc serum levels were not changed by previous diarrhea and/or fever. There was no difference in zinc levels between boys and girls. Children aged between > or = 48 and < 60 months tended to have lower zinc serum levels than children of other ages. CONCLUSION: Zinc deficiency prevalence was low and did not represent a risk factor for vitamin A deficiency. Children aged between > or = 48 and < 60 months tended to have lower zinc serum levels than children of other ages. Zinc serum levels were not changed by previous diarrhea and/or fever.

Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment.

OBJECTIVES:: The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated. METHODS:: The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression. RESULTS:: CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice. CONCLUSION:: Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice.

Recommended dose for repair of serum vitamin A levels in patients with HIV infection/AIDS may be insufficient because of high urinary losses.

OBJECTIVE: Retinol deficiency is quite frequent in the population of human immunodeficiency virus (HIV)-infected individuals. Serum retinol levels of less than 1.05 micromol/L determine a 3.5 to five times higher death risk. However, studies evaluating the efficacy of retinol supplementation in HIV-seropositive individuals have reported conflicting results. The World Health Organization recommends the treatment of vitamin A deficiency in seropositive individuals in the same manner as for seronegative individuals, but clinical studies proving the efficacy of this scheme are lacking. The proposal of the present study was to assess the efficacy of supplementation with high retinol doses in HIV-infected patients with vitamin A deficiency. METHODS: Twenty-five adult HIV-seropositive individuals were monitored over a period of 9 months, with determination of serum and urinary retinol every 3 months. The subjects received retinol palmitate doses ranging from 300,000 IU to 600,000 IU. Patients whose retinol levels were higher than 1.60 micromol/L were only observed. RESULTS: Eighteen patients received supplementation during clinical monitoring. The dose of 600,000 IU induced a significant mean increase in serum levels of 0.47 micromol/L (P = 0.049) within a period of three months. Those who received 300,000 IU presented a mean increase of 0.29 micromol/L. In contrast, the patients who did not receive replacement therapy presented a significant decrease (P = 0.017) in serum retinol levels, with initial and final values of 1.77 micromol/L and 1.55 micromol/L. The individuals with the worst response to supplementation presented a higher urinary loss of retinol at the beginning of the study. Even with a mean retinol supplementation of 771,428 IU during the study period, six patients had marginal serum retinol levels at the end of the study. CONCLUSION: We conclude that, in view of the high urinary loss of this nutrient, there is the need to redefine the ideal dose for the treatment of HIV-infected individuals.

[Prevalence of iron deficiency and its association with vitamin A deficiency in preschool children]. / Prevalência da carência de ferro e sua associação com a deficiência de vitamina A em pré-escolares.

OBJECTIVES: To identify the prevalence of iron deficiency in the population studied, as well as verifying if such deprivation is associated with vitamin A deficiency. METHODS: One hundred seventy-nine children, > or = 24 months and < 72 months of age, with no diarrhea and/or fever at collection were studied. Vitamin A deficiency identification was carried out through serum 30-day dose-response test. Samples of peripheral blood from fasting children was obtained for hemoglobin counts, serum iron, and unsaturated iron binding capacity assays. Information about the presence of diarrhea and/or fever during the 15 days preceding the study was also obtained. RESULTS: 35.8% (64/179) of the children presented iron deficiency and 75.4% (135/179), vitamin A deficiency. 29.1% (52/179) of the children presented both iron and vitamin A deficiencies. Iron deficiency was not associated with vitamin A deficiency. A separate analysis for each hematimetric index also demonstrated no significant difference between children with or without vitamin A deficiency. Children aged 24 to 36 months presented significantly higher prevalence rates of iron deficiency (p = 0.0005) as did children with diarrhea and/or fever during the 15 days preceding the study (p = 0.003). CONCLUSIONS: Although iron deficiency was not associated with vitamin A deficiency, high rates of both deficiencies were exhibited in a "healthy" population with low malnutrition indices. Such situations are known as "hidden hunger". Younger children presented a higher risk of iron deficiency as did children with diarrhea and/or fever during the 15 days preceding the study.