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Anti-inflammatory effect of antioxidant pequi (caryocar brasiliense) oil capsules and antioxidant effect of vitamin d and physical activity on systemic lupus erythematosus patients

Montalvão et al. J Rheum Dis Treat 2016, 2:029 Journal of
Rheumatic Diseases and Treatment
Case Series: Open Access
Anti-inflammatory Effect of Antioxidant Pequi (Caryocar Brasiliense)
Oil Capsules and Antioxidant Effect of Vitamin D and Physical Activity
on Systemic Lupus Erythematosus Patients
Thaís Muniz Montalvão1,2, Ana Luisa Miranda-Vilela2,3*, Cesar Koppe Grisolia2 and Leopol-

do Luiz Santos-Neto1,4
1University Hospital of Brasília, University of Brasília, Brasília, Brazil
2Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Brasilia, Brazil
3Department of Medicine, Faciplac, Campus Gama/DF, Brazil
4Department of Medicine, University of Brasilia, Brasília, Brazil
*Corresponding author: Ana Luisa Miranda-Vilela, Department of Genetics and Morphology, Institute of Biological
Sciences, University of Brasilia, Brasilia/DF, Brazil, Tel: +55 (61) 3107-3085, Fax: +55 (61) 3107-2923, E-mail: Objectives: Verifying in SLE patients whether antioxidant
Systemic Lupus Erythematosus, Antioxidant, Oxidative stress, supplementation with pequi oil capsules could reduce oxidative Inflammatory marker, High-sensitivity C-reactive protein (hs-CRP), DNA damage and inflammation in SLE patients.
DNA damage, Comet assay, Pequi oil. Crossover Patients and Methods: A controlled randomized, crossover,
double-blind study was conducted with 38 SLE patients aged 18 to 60, with SLE Disease Activity Index (SLEDAI) below 10, chosen from 73 lupus patients consecutively seen in the University Hospital Systemic lupus erythematosus (SLE) is a chronic inflammatory, of Brasília (HUB) Rheumatology Clinic. They were randomized into complex, multisystem autoimmune disease of multifactorial origin. two groups: one group of 22 patients received one placebo capsule It is characterized by a large set of antibodies, especially antinuclear per day for 60 consecutive days, and the other 16 patients received antibodies. Its incidence rate varies from 1 to 10 per 100,000 persons/ one 400 mg pequi oil in capsule per day over the same period. year and its prevalence rate is 20-70 per 100,000. It is a more frequent There was a 60-day wash-out, and then the patients switched rare disease in women between 15 and 45 years old [ groups: those who had received pequi oil received placebo and vice versa, also for 60 consecutive days. We collected blood, urine, of SLE is still unknown; however, there is a loss of the regulatory anthropometric and social data from patients before and after each mechanisms which maintain self-tolerance to nuclear antigens, period, totaling four collections.
SLE expression is also influenced by non-genetic factors, such as Results: Twenty-nine women finished this clinical trial. The mean
environment, ultra-violet light, smoking and sex hormones, since age was 33.66 years, the mean BMI was 24.1 kg/m2 and the mean disease duration was 7.8 years. The irreversible damage index of the frequency of this disease is 10 times higher in women during the the disease and the SLEDAI had no influence on DNA damage reproductive years than in men. Thus, the interactions of genetic, index (DDI). A correlation was found between DDI and HDL (r = hormonal and environmental factors act together to activate helper −0.414, p = 0.029). A significant difference was detected in the T cells and B cells, causing the production of various autoantibodies average rate of DDI between physical activity practitioners and non-practitioners (p = 0.045) and between users and non-users of vitamin D (p = 0.006). Moreover, high-sensitivity C-reactive protein Oxidative stress is also important in the pathophysiology (hs-CRP) fell significantly after treatment with pequi oil (p = 0.0161).
of autoimmune diseases because reactive oxygen species (ROS) and reactive nitrogen species attack macromolecules such as Conclusions: Although pequi oil did not significantly reduce
the DNA damage index, it effectively reduced hs-CRP levels in carbohydrates, proteins, lipids and DNA, causing cell damage []. The these patients, indicating reduced inflammation with the use of increase in production of these species may favor the development antioxidant supplementation. Furthermore, the practice of physical activity and the use of vitamin D in patients with SLE could have an imbalance can contribute to impairing immune cells, producing independent antioxidant effect.
autoantigens and autoantibody reactivity. Moreover, proteins Citation: Montalvão TM, Miranda-Vilela AL, Grisolia CK, Santos-Neto LL (2016) Anti-
inflammatory Effect of Antioxidant Pequi (Caryocar Brasiliense) Oil Capsules and Antioxidant C l i n M e d Effect of Vitamin D and Physical Activity on Systemic Lupus Erythematosus Patients. J Rheum International Library Received: November 26, 2015: Accepted: January 07, 2016: Published: January 09, 2016
Copyright: 2016 Montalvão TM, et al. This is an open-access article distributed under the
terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
modified by oxidation are responsible for additional disorders for the classification of SLE [ in autoimmune diseases, since they represent potential targets 60 years. Exclusion criteria were: patients with renal impairment for the immune system by breaking B cell tolerance [ (creatinine ≥ 3 mg/dl); with prior kidney transplant; active inflammation is also associated with increased oxidative stress [] infection; diabetes mellitus; Sjögren's syndrome; multiple sclerosis; and patients with SLE are in a state of chronic inflammation in the pregnancy; kidney, liver or lung disease (defined as organ damage course of the disease. Furthermore, oxidative stress also contributes requiring immunosuppressive therapy or high-dose corticosteroids); gastroesophageal reflux disease, malabsorptive intestinal diseases, secondary consequences of oxidative stress in patients with SLE, history of typical angina pectoris or myocardial infarction; a history such as its association with the atherogenic lipid profile []. This of transient ischemic attack; Systemic Lupus Erythematosus Disease state plays a central role in dyslipidemia and atherosclerosis [] and it is an important mediator of hypertension-mediated autoimmune drugs to reduce cholesterol (the last 3 months); taking prednisone mechanisms [].
above 10 mg per day in pulse therapy with methylprednisolone and/ or use of multivitamin supplementation. After exclusion during the The comet assay is a rapid, simple, visual and sensitive technique research in accordance with the presented criteria, four patients widely used to measure and analyze DNA damage [ quit to participate in this survey, three had dyslipidemia, one had detect both simple and double-strand breaks [hemolysis and the other increased dose of corticosteroids higher in vivo]. We showed in a than 10 mg, so 29 patients were selected. The pequi oil capsules previous study that DNA damage index (DDI) by comet assay rose in were produced by cold mechanical extraction, done by pressing and SLE patients when compared with healthy individuals, which reflects centrifugation. Once ready, the capsules were sterilized by radiation, the oxidant/antioxidant imbalance in these patients, independently each one containing 400 mg of pequi oil.
of disease activity. These findings support an association between oxidative stress and SLE [ Afterwards, a controlled randomized, crossover, double- blind clinical trial was conducted and consisted of two phases. The Dietary factors are important regulators of immune function randomization was done through the generation of randomized ], and a diet with moderate protein and energy content, rich in /). The pequi oil and placebo antioxidants like vitamin E, vitamin A, selenium, calcium, mono and capsules were supplied by Farmacotécnica - a compounding polyunsaturated fatty acids/omega 3 can promote a protective effect pharmacy industry located in the Federal District - in separate against tissue damage and inflammatory activity, besides helping boxes: one contained the pequi oil capsules and the other placebo. treat comorbidities and adverse medicine reactions. Thus, some For each box a color was assigned. On delivery of the capsules recommendations may offer a better quality of life to SLE patients to patients, a questionnaire was used to collect social data from ] and using antioxidants may protect against the development patients, medications in use and physical activity, classified using the Caryocar American College of Sports Medicine [ brasiliense Camb., known as pequi, is a typical tree of the Brazilian and Systemic Lupus International Collaborating Clinics (SLICC) Cerrado biome. All its parts are widely used, especially the fruit ]. [ Besides lipids (including fatty acids, such as linolenic), protein, fibers, assessment of respondents performed. The patient ingested a daily carbohydrates, the pequi contains, antioxidants such as carotenoids, capsule containing 400 mg of pequi oil or placebo containing including β-carotene, lycopene, ζ-carotene, criptoflavona, colloidal silicon dioxide alone - Aerosil® - for 60 consecutive days. anteroxantina, zeaxanthin, mutatoxantina, violoxantina, lutein An interval of 60 days before the beginning of the second stage and neoxanthin, besides vitamin E, and phenolic compounds was established. Then, patients switched groups so that those who (flavonoids and tannins) [had received placebo in the first phase received the pequi oil and of both genders who received 14 days' supplementation of 400 mg vice versa, starting the second stage. So, before and after each stage, of pequi oil, extracted with chloroform, showed that there was a totaling four periods, we collected blood and urine and we assessed anthropometric parameters and SLEDAI.
and significant reduction of total cholesterol (TC) and low density The duration of capsule use was defined using some studies lipoprotein (LDL) in the group aged over 45, mostly in men. The of antioxidants in humans. One study investigated the action of authors suggested that the oil works in reducing the inflammation isoflavones and phytic acid in postmenopausal women for 6 weeks caused by exercise, measured by C-reactive protein and thiobarbituric (42 days) in TC and fractions and three markers of oxidative stress acid reactive substances (TBARS) [ (protein carbonyl, oxidized LDL and 8-iso-prostaglandin F2α]. As (1) patients with SLE have an imbalance in the oxidant/ Another study evaluated the antioxidant effect (through the comet anti-oxidant system, promoting the formation of ROS ]; (2) the assay and TBARS) 400 mg of pequi oil capsule in healthy runners for antioxidant status of the plasma is directly related to diet and is defined by antioxidants such as carotenoids (the most powerful suppressors than that reported in the literature, establishing 60 days of treatment of biological singlet oxygen), flavonoids and vitamin E [with 400 mg of pequi oil capsule.
(3) pequi contains such substances [ Laboratory tests were performed in the morning after rest period patients whether antioxidant supplementation with pequi pulp oil and fasting for at least eight hours. The following laboratory tests were capsules could reduce oxidative damage to DNA (evaluated by comet performed by the Clinical Laboratory of HUB: complete blood count, assay) and inflammation (evaluated by high-sensitivity C-reactive urea, alkaline phosphatase, gamma glutamyl transferase (GGT), protein - hs-CRP). As there are secondary consequences of oxidative glucose, aspartate aminotransferase (AST); alanine aminotransferase stress in patients with SLE, such as its association with atherogenic (ALT), complement C3, complement C4, hs-CRP, uric acid, TC, lipid profile ], we also analyzed total cholesterol, low density LDL, high density lipoprotein (HDL), very low density lipoprotein lipoprotein, hemogram and other biochemical markers.
(VLDL), triglycerides, total protein and fraction (albumin and globulin) and abnormal elements of sediment (EAS). Sabin Clinical Patients and Methods
Analysis Laboratories analyzed the anti-DNA. The comet assay Patients and study design
was carried out according to Singh et with modifications according to Montalvão et al. [ Initially, 73 patients attended consecutively in the University Hospital of Brasília (HUB) Rheumatology Clinic from June to October Current weight measurement was by digital scale Filizola®, model 2011 were recruited. Of these, 38 individuals were selected within the Personal Line, capacity for 150 kg and precision of 0.1 kg, with the inclusion criteria: diagnosis of SLE, according to the classification patient standing motionless and barefoot at the center of the scale of the American College of Rheumatology (ACR) revised criteria platform, wearing light clothes. Height was measured in stadiometer Montalvão et al. J Rheum Dis Treat 2016, 2:029 • Page 2 of 7 • Table 1: Demographic, anthropometric, laboratory and patients' disease SLE in
crossover study before starting treatment and placebo.
Initially, the continuous variables were tested for normal Standard
distribution with  the Kolmogorov-Smirnov test. Then exploratory data analysis took place, which involved drawing up tables, graphs and descriptive analysis (mean, median, standard deviation - Ilness duration (months) SD, correlation, etc.). An association was made between the quantitative variables of the sample through Pearson's correlation. Education (years) The comparison between qualitative and quantitative variables was Number of medications in use performed through two tests. When there were only two categories of the qualitative variable, the t-test for independent samples was done. When there were more than two categories of qualitative variable, DNA damage index (%) ANOVA followed by the post hoc Tukey test was applied. A multiple regression analysis model was used to verify that the qualitative Waist circumference (cm) independent variables explained certain quantitative dependent Hip circumference (cm) variables. It was also performed to calculate the power of the post hoc test to verify that the sample size used in the two studies was sufficient to detect a statistically significant difference at 5%. All the steps described here were performed using the Statistical Package for Social Sciences (SPSS) version 20.0. We also used the Statistical Analysis System (SAS) for modeling the study data. To this end, the technique of generalized linear models with a single dependent variable was Complement C3 mg/dL applied to analyze the effect of treatment during the crossover study. Complement C4 mg/dL Thus, effects were considered: treatment period, patient and also a Total cholesterol mg/dL residual treatment effect between applications (carry-over). A p-value Triglycerides mg/dL below 0.05 was considered significant for all analyses.
The demographic characteristics of the 29-woman crossover study immediately before starting the use of pequi oil or placebo SLICC: Systemic Lupus International Collaborating Clinics; SLEDAI: Systemic Lupus Erythematosus Disease Activity Index; BMI: Body Mass Index; AC: Arm 69% of patients were between the second and third decade of life. The Circumference; TS: Triceps Skinfold; AMC: Arm Muscle Circumference; HDL: mean BMI was 24.05 Kg/m2. The average WC was 88.82 cm and 41.4% High-Density Lipoprotein; LDL: Low-Density Lipoprotein; VLDL: Very-Low- had this measure as ≥ 88 cm. The mean disease duration was 7.81 Density Lipoprotein; hs-CRP: high-sensitivity C-reactive protein (hs-CRP).
years. Both the average of irreversible damage index of the disease vertical plane with vertical metric scale of 2.10 m and precision of 1 (0.36) and the SLEDAI (3.85) were low. However, the percentage of mm, according to the Frankfurt plan. The midpoint of the arm was patients with SLEDAI zero (no disease activity) was 22.2% and the measured with an extendable tape measure with accuracy of 0.1 cm rate of patients with some degree of irreversible damage from the and maximum length of 150 cm to enable the measurement of arm disease (SLICC > 0) was 21.4%. The average of the laboratory findings circumference (AC) with the tape measure around the stretched and and their range values show that patients did not have anemia, kidney relaxed arm, placed horizontally without squeezing the arm. The or liver impairment and had no glucose intolerance. The percentage triceps skinfold (TS) was taken on the back of the arm 1 cm above of patients who had leukopenia was 6.9% and lymphopenia 17.2%. the midpoint quoted with the Lange® caliper to within 1 mm; three No patient had thrombocytopenia. Regarding the lipid profile, we measurements were taken and their average used. The arm muscle observed threshold values for all the parameters; however, when circumference (AMC) was calculated using the formula: AMC = considering this profile for each patient dyslipidemia was not AC − (0.314 × TS). The percentage adequacy of AC, TS and AMC detected. Only 20.7% of patients had anti-DNA reagent and 75.9% was calculated by multiplying the measure by 100 and dividing that had negative test before starting the use of the capsules. With respect result by the 50th percentile of each measure, according to the age to the amounts of complements, 48.3% of patients had complement and gender of the individual. For statistical analysis four parameters C3 below the reference value and only 10.3% had complement C4 were considered, based on classification by Blackburn and Thornton, below the reference.
1979 [with the proviso that there is no overweight and obesity Furthermore, most patients are single (55.2%), work (51.7%) have classification for AMC.
a family income between 1 and 5 minimum wages (69%), finished The waist circumference (WC) and hip circumference (HC) were high school (55.2%) and do not practice any activity physical (72.4%). measured with the individual in standing position, with the same tape Regarding nutritional parameters, such as TS adequacy, most patients used before without tightening it and without leaving gaps. The WC was were classified as overweight and obese (51.7%). In other parameters, taken at the navel and the HC was measured at the maximum extension most were classified as normal weight: BMI (65.5%), AC adequacy of the buttocks. The WC measurement in umbilical height was chosen to (58.6%) and AMC adequacy (82.8%). The medicine most used for the study patients was hydroxychloroquine or chloroquine diphosphate ratio (WC/HC) was calculated. The body mass index (BMI) was obtained (89.7%), followed by prednisone (72.4%) and azathioprine (34.5%). by dividing weight by the square of height, and for statistical analysis, we Only two patients used methotrexate and amitriptyline. Of the 21 considered four rating parameters: malnutrition (< 18, 5 kg/m2), normal patients taking prednisone, the mean dose was 4.9 mg (SD 0.56).
weight (between 18.5 to 24.99 kg/m2), pre-obesity (between 25 kg/m2 Pearson correlation tests were performed (coefficient = r) between and 29.99 kg/m2) and obese (> 30kg/m2]. All measurements were DDI (%) and age, time of diagnosis, age at diagnosis, education performed by a single evaluator.
(years), SLICC, SLEDAI, BMI, WC, HC, WC/HC, adequacy of AC, This study was approved by the Research Ethics Committee of TS and AMC, hs-CRP, uric acid, glucose, GGT, TC and fractions, the Faculty of Medicine at the University of Brasilia (UnB), project total protein and fractions. The only correlation was found between registration 058/2010, approval number 75 on 10/26/12, and all the DDI (%) and HDL (r = −0.414, p = 0.029): the higher the HDL, the selected individuals authorized the study by signing the free and lower the DDI (%). We performed Pearson correlation test also for informed consent.
BMI and age, age at diagnosis, duration of illness, education in years, Montalvão et al. J Rheum Dis Treat 2016, 2:029 • Page 3 of 7 •

Vitamin D
Mean DNA Damage Index (%) Physically active=39.1 Not physically active=44.9 Mean DNA Damage Index (%) Users of vitamin D=37.2 Nonusers of vitamin D=45.3 Damage Index (%)
Damage Index (%)
Figure 2: DNA damage index in SLE patients using and not using vitamin D.
Not physically active
Figure 1: DNA damage index in SLE patients physically active and not
with lower educational levels [ physically active.
association exists because the environmental conditions associated with low levels of education limit the knowledge of nutritious SLICC, SLEDAI, prednisone dose. An inverse correlation was found food and safe means for physical exercise, which causes metabolic between BMI and years of study (r = −0.537, p = 0.03): the more years studied, the lower the BMI.
Another important finding was the significant difference in the When comparing the average DDI (%) among the various DDI between physical activity practitioners and non-practitioners qualitative variables (medicines in use, marital status, household observed in this study. Regular physical activity, besides functioning income, race, occupation, education level, physical activity, as an antioxidant to increase the expression of antioxidant enzymes, classification of nutritional parameters and anti-DNA reagent), also induces a systemic increase in many cytokines with anti- a significant difference (p = 0.045) was detected among those who inflammatory properties that protect against chronic disorders practiced physical exercise (mean = 39.1% DDI) and those who did associated with low-grade systemic inflammation [ results also confirm the protective effect of physical activity against difference (p = 0.006) was found between vitamin D users (mean = oxidative stress. It is well documented in the literature that regular exercise results in adaptations in the antioxidant capacity protecting . However, there was no statistical significance between the mean cells against the deleterious effects of oxidative stress and preventing hs-CRP among the same qualitative variables.
subsequent cell damage [ A multiple regression analysis model was used to check whether is associated with a reduction in markers of oxidative stress in the independent variables: occupation, family income, education, rodents ], has a modulating effect on the antioxidant balance in physical activity, azathioprine, prednisone, chloroquine, folic acid women [ and vitamin D explain the variable DDI. As the only independent circumference in obese women [ variables that were statistically significant were physical activity stimulate DNA repair in healthy adults and the elderly, probably due and use of vitamin D, these were examined to determine if one had an oxygen radical scavenger enzyme or repair enzyme mechanism influence over the other with regard to DDI, and no such interference was found. However, these two independent variables explain 38.53% endogenous antioxidant defenses and in reducing oxidative DNA of the total variation of DDI. Thus, the patients in this study that were ]. However, the current study is not physically active showed DDI 5.71% higher than the practitioners. the first to demonstrate this relationship in SLE patients.
Furthermore, patients using no vitamin D showed DDI 7.97% higher Our study also demonstrated that SLE patients using vitamin than users. The other independent variables were not statistically D had DDI (%) that was significantly lower than non-users. This significant and therefore were removed from the model.
information indicates that supplementation with vitamin D could The anthropometric parameters, DDI (%), inflammatory markers reduce oxidative stress in these patients. This fact has also been and lipid profile of patients with SLE before and after treatment after suggested in a study conducted with type 2 diabetic black Americans completion of the crossover study are showed in The data were analyzed considering the effect of the patient as random. This test of oxidative stress in older people who had compromised glucose showed no significant effect of the pequi oil treatment for almost any metabolism and obtained an inverse association between these two variable analyzed, except for hs-CRP (p = 0.0161), which presented a parameters [ statistically significant reduction compared to the placebo. For a 5% There are no reports of clinical studies in the literature showing the significance level a power of post hoc test for DDI was estimated to relationship with SLE, but the protective effect of vitamin D against be 0.9887; for WC/HC of 0.9999 and the hs-CRP of 1.0000 to detect oxidative stress in these patients has been reported ]. Multiple clinically important differences between treatments (pequi oil and regression analysis with qualitative independent variables and the DDI shows that only physical activity and vitamin D reduced DNA Patients with SLE have an imbalance in the oxidant/anti-oxidant An inverse correlation was detected between DDI (%) and HDL system  independent of disease activity.  In a previous study we levels in this study, also reported in other studies. One study compared demonstrated by comet assay that DDI  increased in SLE patients individuals with normal TC, LDL, triglycerides and glucose, but when compared with healthy individuals, supporting an association with lowered HDL normolipidemic with controls, and observed ]. So,  the present study that the former had high oxidative stress (measured by the plasma analyzed if pequi oil in capsule, a rich antioxidant supplementation, 8-isoprostanes) [has an antioxidant effect on patients with SLE, by means of comet that synergy may occur in the inactivation of LDL oxidized lipids by assay. This method is one of many ways of measuring oxidative stress, enzymatic and non-enzymatic mechanisms []. And yet an inverse and it can be applied in supplementation trials [In this context, correlation between BMI and years of study was demonstrated, although pequi oil did not significantly reduce the DDI of the total which corroborates the literature and means a higher BMI in people group, it did significantly reduce hs-CRP.
Montalvão et al. J Rheum Dis Treat 2016, 2:029 • Page 4 of 7 • Table 2: The effect of pequi oil compared to placebo in patients with SLE in several variables.
Δ (initial - final)
Difference between groups
Pequi oil
Placebo - Pequi oil
Total cholesterol SLEDAI: Systemic Lupus Erythematosus Disease Activity Index; BMI: Body Mass Index; WC: Waist Circumference; HC: Hip Circumference; W/H: Waist/hip ratio; AC: Arm Circumference; TS: Triceps Skinfold thickness; AMC: Arm Muscle Circumference; AST: Aspartate Transaminase; ALT: Alanine aminotransferase; GGT: Gamma- Glutamyl Transferase; hs-CRP: High-Sensitivity C-reactive protein (hs-CRP); HDL: High-Density Lipoprotein; LDL: Low Density Lipoprotein; VLDL: Very Low Density Lipoprotein; *p-value with statistical significance. Values expressed as mean ± standard least squares error.
First, this non-reduction of DDI after treatment runs contrary to would have been observed beyond CRP reduction after treatment. the previous study with athletes of both genders who daily took 400 A possible explanation for this finding, which is not balanced in the mg of pequi oil capsule for 14 consecutive days. These athletes showed current crossover study, was the inclusion of patients with SLEDAI decreased lipid peroxidation tested by TBARS, besides reduced DDI < 10; in other words, there were patients with high disease activity. by comet assay. A reduction in muscle damage based on plasma An average level (3 mg/L) of CRP was recorded before beginning evaluation of AST and ALT was also detected, the latter especially in the use of the capsules, and the minimum (0.9 mg/L) and maximum women []. (15 mg/L) and standard deviation (3.2 mg/L) values are within the This same study found a significant drop in TC and LDL in the group ]  to measure low and ]. In contrast to this finding, there medium CRP.
was no significant reduction of TC, LDL, AST and ALT in the current High serum levels of hs-CRP are induced by various inflammatory crossover study. These controversial results, despite the similarity in conditions besides atherosclerosis. Thus, hs-CRP is not only a the daily dose of pequi oil and higher total dose (60 days), might be systemic inflammatory marker but also a local pro-atherosclerotic explained by different methods of oil extraction in the two studies. factor. Once a high level of hs-CRP is established, there is an In athletes, the extraction used the organic solvent chloroform, increased cardiovascular risk [A recent study even suggests that while the current study was by cold mechanical extraction. It has hs-CRP is a surrogate marker for cardiovascular risk in SLE patients, been shown that the extract has a higher mechanical peroxide but this must be viewed with care because their values fluctuate with content, demonstrating the greater vulnerability and lower content disease activity and infections [Atherosclerosis is a well-known of carotenoids when compared to organic extracts []. Moreover, the prevalence of and mortality from the storage time of the capsules with pequi oil was much higher in ], the current study than in athletes, which may have contributed to a and so these individuals have a greatly increased cardiovascular risk further deterioration of carotenoids. Another factor that may have compared to the general population [ contributed to the reduction of this antioxidant was sterilization by of the current study gain importance in clinical practice because radiation for the capsules used in the present study.
they show a significant reduction in an inflammatory marker and Secondly, even with the differences between the extraction predictor of atherosclerosis using antioxidant therapy.
methods of pequi oil, there was a significant reduction in hs-CRP in At the same time, no connection between hs-CRP and the various this work after pequi oil treatment, a result that confirms the previous qualitative and quantitative variables described here was noted, in study with athletes [in this aspect and also other studies evaluating contrast to the literature, which found an average increase in hs- the antioxidant intervention in inflammation by measuring hs- CRP in SLE patients with higher BMI and among those that were less CRP [correlation between ROS and CRP has educated, had lower family income and higher disease activity ]. been confirmed in asymptomatic individuals [and also in some ] showed the highest correlation SLE patients []. However,  it seems that the interrelationship between inflammation-mediated CRP and certain with hs-CRP among all variables. Another study demonstrated that forms of oxidative stress depended on the methods used. Moreover, both pre-obese and obese people in the general American population it has been found that the CRP did not induce forms of DNA damage, were more likely to have high levels of CRP than the normal weight single strand breaks and double strand breaks, but it was noted that controls []. Perhaps this same relationship was not detected in the prolonged exposure to CRP could have caused these types of damage current study, due to small sample size.
]. This may explain the significantly reduced CRP values of the Despite having performed a sophisticated clinical trial patients in our research after treatment with pequi oil, but not enough (randomized double-blind crossover study), the current study has to reflect a reduction in damage caused by single and double strand some limitations. There is no assurance that the patients properly breaks in DNA. Perhaps if the patients had had a higher initial value ingested the capsules as directed, 1 capsule (400 mg of pequi oil) of CRP or if the treatment time were longer, a reduction in the DDI per day for 60 consecutive days. Another important factor was Montalvão et al. J Rheum Dis Treat 2016, 2:029 • Page 5 of 7 • the difficulty for some patients to access the Clinical Laboratory at 16.
HUB. Ideally, the collection of blood and urine and anthropometric measurements were to take place on the 61st day after treatment or 17.
placebo. However, due to this limited access, sometimes the collection was carried out after completion of the therapy using capsules. Moreover, the extraction method used in this work was inferior to 18.
that used in a previous study, which may have affected the results. The peculiar and specific characteristics of the sample prevent the 19.
extrapolation of results to other populations of patients with SLE.
Although pequi oil did not significantly reduce the DNA damage index, it effectively reduced hs-CRP levels in these patients, indicating reduced inflammation with the use of antioxidant supplementation. This is important in clinical practice, in showing a significant 22.
reduction in an inflammatory marker that may predict atherosclerosis. Furthermore, the practice of physical activity and the use of vitamin 23.
D in patients with SLE could have an independent antioxidant effect.
The authors gratefully acknowledge the patients who participated in this research; University Hospital of Brasília, Farmacotécnica 25.
and Sabin Institute/Sabin Laboratories for technical support; and the National Council for Technological and Scientific Development (CNPq) for financial support.
2. Robbins S, Cotran R, Kumar V (2000) Patologia estrutural e funcional. 5a Edição. Rio de Janeiro: Guanabara Koogan 1277. 33. Blackburn GL, Thornton PA (1979) Nutritional assessment of the hospitalized patient. Medical Clinics of North America, Philadelphia 14: 1102-1108. Montalvão et al. J Rheum Dis Treat 2016, 2:029 • Page 6 of 7 • Montalvão et al. J Rheum Dis Treat 2016, 2:029 • Page 7 of 7 •


Advances in understanding and treatment of feline inappropriate elimination

Advances in Understanding and Treatment of FelineInappropriate Elimination Meghan E. Herron, DVM, DACVB Feline inappropriate elimination is the number one behavioral reason for relinquishment of cats to shelters andhas historically been the most commonly reported feline problem addressed by behavior professionals. Veter-inarians are hence challenged to uncover the underlying motivation for this behavior so that an accuratediagnosis can be made and an effective treatment plan implemented. Before a behavioral diagnosis can bemade, underlying medical disease must be addressed, making a comprehensive physical evaluation imperative.After all medical issues have been addressed, a behavior diagnoses list is made based on detailed historicalinformation obtained from the cat owner. A distinction is first established between marking and inappropriatetoileting, according to elimination postures described by the owner and the social relevance of the sites ofinappropriate eliminations. Next, inadequacies of the litter box management are identified and subsequentaversions and preferences, including litter box aversion, substrate aversion, location aversion, substrate pref-erence, and location preference, can be diagnosed. The practitioner should be cognizant of the fact that anxietyfrom the environment and social conflict may play a major role in both marking and inappropriate toiletingbehaviors. Once both the medical and behavioral diagnoses are established, a treatment plan catered to theindividual cat, owner, and household environment can be formulated. This should include acceptable forms ofmarking when indicated, appropriate litter box management and hygiene, reduction of environmental stres-sors, including resolution of social conflict in multicat households, proper treatment and restricted access tosoiled areas, pheromone application, and, when indicated, anxiolytic drug therapy.© 2010 Elsevier Inc. All rights reserved.

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