Continuous Production of Highly Tuned Silk/Calcium-Based Composites: Exploring New Pathways for Skin Regeneration.

Calcium plays an important role in barrier function repair and skin homeostasis. In particular, calcium phosphates (CaPs) are well established materials for biomedical engineering due to their biocompatibility. To generate biomaterials with a more complete set of biological properties, previously discarded silk sericin (SS) has been recovered and used as a template to grow CaPs. Crucial characteristics for skin applications, such as antibacterial activity, can be further enhanced by doping CaPs with cerium (Ce) ions. The effectiveness of cell attachment and growth on the materials highly depends on their morphology, particle size distribution, and chemical composition. These characteristics can be tailored through the application of oscillatory flow technology, which provides precise mixing control of the reaction medium. Thus, in the present work, CaP/SS and CaP/SS/Ce particles were fabricated for the first time using a modular oscillatory flow plate reactor (MOFPR) in a continuous mode. Furthermore, the biological behavior of both these composites and of previously produced pure CaPs was assessed using human dermal fibroblasts (HDFs). It was demonstrated that both CaP based with plate-shaped nanoparticles and CaP-SS-based composites significantly improved cell viability and proliferation over time. The results obtained represent a first step towards the reinvention of CaPs for skin engineering.

Low frataxin mRNA expression is associated with inflammation and oxidative stress in patients with type 2 diabetes.

BACKGROUND: The mitochondrial protein frataxin is involved in iron metabolism, as well as regulation of oxidative stress. To elucidate the association of frataxin with the pathophysiology of diabetes, we evaluated the mRNA levels of frataxin in leukocytes of patients with type 2 diabetes (T2D). In addition, we investigated the relation between frataxin mRNA levels, inflammatory cytokines, and oxidative stress biomarkers. METHODS: A study including 150 subjects (115 patients with T2D and 35 healthy subjects) was performed to evaluate the frataxin mRNA levels in leukocytes. We assessed the relation between frataxin and interleukin (IL)-6, IL-1, tumour necrosis factor-alpha (TNF-α), total oxidation status (TOS), total antioxidant capacity (TAC), and serum iron. RESULTS: The frataxin mRNA levels in the T2D group were significantly lower than those in healthy subjects. It was also demonstrated that T2D patients with frataxin mRNA levels in the lowest quartile had significantly elevated levels of serum iron, TOS, and inflammatory cytokines, such as TNF-α, IL-1, and IL-6, while TAC levels were significantly lower in this quartile when compared with the upper quartile. CONCLUSIONS: Our findings showed that T2D patients with low frataxin mRNA levels showed a high degree of inflammation and oxidative stress. It is speculated that frataxin deficiency in T2D patients can contribute to the imbalance in mitochondrial iron homeostasis leading to the acceleration of oxidative stress and inflammation.

MnSOD Ala16Val polymorphism in cognitive dysfunction in patients with epilepsy: A relationship with oxidative and inflammatory markers.

OBJECTIVE: The objective of the study was to evaluate the neurocognitive profile and its relation with Ala16ValMnSOD polymorphism in epilepsy and if these clinical parameters are linked to oxidative stress and inflammatory markers. METHODS: Patients with epilepsy (n = 31) and healthy subjects (n = 42) were recruited. A neuropsychological evaluation was performed in both groups through a battery of cognitive tests. Oxidative stress, inflammatory markers, apoptotic factors, and deoxyribonucleic acid (DNA) damage were measured in blood samples. RESULTS: Statistical analyses showed the association of MnSOD Ala16Val polymorphism with cognitive impairment, including praxis, perception, attention, language, executive functions, long-term semantic memory, short-term visual memory, and total memory in patients with epilepsy and Valine-Valine (VV) genotype compared with the control group. Compared with the controls and patients with epilepsy, Alanine-Alanine (AA), and Alanine-Valine (AV) genotype, the patients with epilepsy and VV genotype exhibited higher levels of tumor necrosis factor alpha (TNF-α), interleukin 1ß (IL-1ß), interleukin 6 (IL-6), activation of caspases 1 and 3 (CASP-1 and -3), and DNA damage. Our findings also showed higher carbonyl protein and thiobarbituric acid reactive substances (TBARS) levels as well as an increased superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities in patients with epilepsy and VV genotype. CONCLUSION: This study supports the evidence of a distinct neuropsychological profile in patients with epilepsy, especially those with the VV genotype. Furthermore, our results suggest that oxidative and inflammatory pathways may be associated with genetic polymorphism and cognitive dysfunction in patients with epilepsy.

Association between Urinary Levels of Interleukin-6, Interleukin-10 and Tumor Necrosis Factor-Alpha with Glomerular and Tubular Damage Indicators in Patients with Type 2 Diabetes.

BACKGROUND: This study investigated the association between urinary levels of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) with estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (uACR), and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in patients with type 2 diabetes (T2D). METHODS: Urinary concentrations of IL-6, IL-10, TNF-α, ACR, and NGAL were measured in 121 patients with T2D. RESULTS: Urinary IL-6 and TNF-α increased 45.5% and 49.4% in the highest uACR quartile compared to lowest quartile. Urinary IL-10 levels decreased 40.9% in the highest uACR quartile compared to the lowest quartile. Urinary IL-6 and TNF-α were 75.3% and 81.6%, higher in the highest uNGAL quartile compared to the lowest quartile. Urinary IL-10 concentration was 69.8% lower in patients from the highest uNGAL quartile compared to lowest quartile. CONCLUSIONS: Urinary IL-6, IL-10, and TNF-α were associated with indicators of glomerular and tubular injuries in patients with T2D.

Depressive, inflammatory, and metabolic factors associated with cognitive impairment in patients with epilepsy.

PURPOSE: The purpose of this study was to examine the cognitive function and depressive traits most frequently associated with the clinical assessment of patients with epilepsy and if these clinical parameters are linked to glycolipid levels and inflammatory and apoptotic markers. METHODS: Patients with epilepsy (n = 32) and healthy subjects (n = 41) were recruited to participate in this study. Neuropsychological evaluation was performed in both groups through a battery of cognitive tests. Inflammatory markers, apoptotic factors, and deoxyribonucleic acid (DNA) damage were measured in blood samples. Additionally, the metabolic markers total cholesterol (CHO), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), and glucose (GLU) levels were analyzed. RESULTS: Statistical analyses showed that patients with epilepsy presented decreased scores in memory, attention, language, and executive function tests compared with the control group. Analysis revealed that there was negative correlation in epilepsy for seizure duration vs. oral language (R = -0.4484, p < 0.05) and seizure duration vs. problem solving (executive functions) (R = -0.3995, p < 0.05). This was also observed when comparing depression with temporal-spatial orientation (TSO) (R = -0.39, p < 0.05). Furthermore, we observed a higher depression score in patients with epilepsy than in the healthy ones. Statistical analyses showed higher acetylcholinesterase (AChE) (p < 0.05), interleukin 1ß (IL-1ß, p < 0.001), and tumor necrosis factor-alpha (TNF-α) (p < 0.001) levels compared with those in the control group. Moreover, patients with epilepsy had significantly higher serum levels of caspase 3 (CASP 3) (p < 0.001) and Picogreen (p < 0.001) compared with the control subjects. Regarding the metabolic markers, higher glycolipid levels were observed in the patients with epilepsy (CHO < 0.05*, LDL < 0.0001*, TG < 0.05*, GLU p < 0.05). High-density lipoprotein levels were not significant. The patients with epilepsy had significant correlation when comparing total language with TNF-α (R = -0.4, p < 0.05), praxes with CASP 3 (R = -0.52, p < 0.01), total CHO with total language (R = -0.48, p < 0.05), TG with semantic memory (R = -0.54, p < 0.05), TG with prospective memory (R = -0.2165, p < 0.02), TG with total memory (R = -0.53, p < 0.02), and GLU with total attention (R = -0.62, p < 0.002). CONCLUSION: This study supports the evidence of a distinct neuropsychological profile between patients with epilepsy and healthy subjects. Furthermore, our findings suggest that inflammatory pathway, glycolipid profile, and depressive factors may be associated with cognitive dysfunction in patients with epilepsy.

Tactile stimulation during different developmental periods modifies hippocampal BDNF and GR, affecting memory and behavior in adult rats.

Recent studies have shown that tactile stimulation (TS) in pups is able to prevent and/or minimize fear, anxiety behaviors, and addiction to psychostimulant drugs in adult rats. In these studies, animals have been exposed to handling from postnatal day (PND) 1-21. This study was designed to precisely establish which period of preweaning development has a greater influence of TS on neuronal development. After birth, male pups were exposed to TS from PND1-7, PND8-14, and PND15-21. In adulthood, the different periods of postnatal TS were assessed through behavioral, biochemical, and molecular assessments. Animals that received TS from PND8-14 showed lower anxiety-like symptoms, as observed by decreased anxiety index in elevated plus maze. This same TS period was able to improve rats' working memory by increasing the percentage of alternation rate in Y-maze, and induce better ability to cope with stressful situations, as showed in the defensive burying test by a reduced time of burying behavior. On the other hand, animals receiving TS in the first week of life showed longest cumulative burying time, which is directly related to increased anxiety-like behavior. Moreover, TS from PND8-14 showed lower corticosterone levels and better oxidative status, as observed by decreased lipid peroxidation and increased catalase activity in the hippocampus. Brain-derived neurotrophic factor (BDNF) immunocontent was increased in the hippocampus of animals receiving TS from PND8-14, while glucocorticoid receptors immunocontent was decreased in both TS1-7 and TS15-21 , but not TS8-14 . To the best of our knowledge, this study is the first to show TS can be more efficient if applied over a focused period of neonatal development (PND8-14) and this beneficial influence can be reflected on reduced emotionality and increased ability to address stressful situations in adulthood. © 2016 Wiley Periodicals, Inc.

Anti-inflammatory effect of geranium nanoemulsion macrophages induced with soluble protein of Candida albicans.

Pelargonium graveolens is a member of the Geraniaceae family and has been used in folk medicine in many countries because of its anti-inflammatory activity. No studies have yet been reported to evaluate the anti-inflammatory activity of a nanoemulsion containing geranium oil (GO) model in macrophages. In this study the anti-inflammatory effect of Geranium nanoemulsion (NEG) macrophages induced with soluble proteins of Candida albicans was investigated. GO presented citronellol (17.74%) and geraniol (14.43%) as main constituents. The characterization in NEG was demonstrated, showing the particle size of 164 ± 3.5 nm, PDI of 0.12 ± 0.006 and zeta potential -10 mV ± 1.7. The MIC obtained for NEG and GO were 3.64 µg ml-1 and 1.82 µg ml-1, respectively. The viability of the macrophages treated with NEG and GO concentrations (1/2 x, 1x and 2x MIC) was evaluated. There was a significant reduction of viability and the MTT assay was not confirmed after the LDH assay. Anti-inflammatory activity was evaluated by determining nitric oxide (NO), cytokines (interleukin IL-1, IL-6 and IL-10), tumor necrosis factor-α (TNF) and the expression levels gene of interleukin (IL-2), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). The apoptosis inhibition capacity was assessed by determination of INFγ, caspase 3 and caspase 8. The results indicated that there was a significant increase of NO in the levels after treatment with NEG and significantly reduced levels after treatment with GO. The cytokines (IL-1, IL-6, IL-10, and TNF) were evaluated and NEG (½ x, 1x MIC) decreased IL-1 levels by 1.25-1.37 times, respectively. The NEG did not decrease IL-6 levels and a significant increase was observed for IL-10. GO significantly decreased IL-6 and IL-10 levels. There was a significant decrease in IL-2 and COX-2 levels and increased levels of iNOs. The levels of IFNγ and caspase-3 after treatment with NEG decreased indicating an anti-inflammatory effect and can inhibit apoptosis. Finally, the levels of caspase-8 do not change. Thus, pretreatment with NEG induced an anti-inflammatory effect against soluble proteins of C. albicans model macrophages.

Melaleuca alternifolia essential oil prevents alterations to purinergic enzymes and ameliorates the innate immune response in silver catfish infected with Aeromonas hydrophila.

Aeromonas hydrophila infection represents a major impediment to the development of aquaculture, leading to important economic losses. Over the last few years, different methods have been used to counteract and minimize the negative effects of this infection, such as the use of Melaleuca alternifolia essential oil, popularly known as tea tree oil (TTO), that possess a bactericide action against A. hydrophila. The purinergic system develops an important role in the inflammatory response, principally due to involvement of adenosine triphosphate (ATP) in the inflammatory process, as well as by the anti-inflammatory properties of adenosine (Ado), a molecule that is controlled by NTPDase, 5'-nucleotidase and adenosine deaminase (ADA) enzymes. Thus, the aim of this study was to investigate the involvement of purinergic enzymes in the pathogenesis of A. hydrophila infection, and whether the purinergic pathway and innate immune response are involved in the protective effects of TTO in silver catfish (Rhamdia quelen) experimentally infected with A. hydrophila. Our results revealed that A. hydrophila infection increased seric NTPDase and 5'-nucleotidase activity, while ADA activity decreased. Also, the seric levels of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ) increased in the infected fish, while the seric level of anti-inflammatory interleukin-10 (IL-10) decreased. Treatment with TTO was able to prevent the impairment of purinergic enzymes and improve the innate immune response through the modulation of cytokine response during A. hydrophila infection. In summary, prophylactic therapy with TTO can be considered an important approach to improve the immune response and consequently avoid the inflammatory process in fish infected with A. hydrophila.

Cholinergic enzymes and inflammatory markers in rats infected by Sporothrix schenckii.

The aim of this study was to evaluate the cholinesterase activity in serum, whole blood, and lymphocytes, as well as to verify its relation to immune response in rats experimentally infected by Sporothrix schenckii. For this study, 63 Wistar rats (Rattus norvegicus), male, adult were divided into three groups: the negative control group (GC: n = 21), the group infected subcutaneously (GSC: n = 21), and the group infected intraperitoneally (GIP: n = 21). The groups were divided into subgroups and the following variables were evaluated at 15, 30, and 40 days post-infection (PI): acetylcholinesterase (AChE) activity in lymphocytes and whole blood, butyrylcholinesterase (BChE) activity in serum, cytokines levels (IL-1, IL-6, TNFα, and INF-γ), immunoglobulins levels (IgA, IgG, IgM, and IgE), and protein profile by electrophoresis. Both infected groups showed increased levels of inflammatory parameters (P < 0.05) in tissue and inflammatory infiltrates. The activities of AChE in lymphocytes and BChE in serum increased (P < 0.05) significantly in animals from the GSC group on day 40 PI compared to the GC group. Regarding the GIP, there was a marked increase in the AChE activity in lymphocytes on days 30 and 40 PI, and in whole blood on days 15, 30, and 40 PI compared to GC. Furthermore, IL-10, an anti-inflammatory cytokine, was also present in high levels during chronic systemic S. schenckii infections in animals. Therefore, it is concluded that cholinesterase has an important modulatory role in the immune response during granulomatous infection by S. schenckii.

Short- and long-term metabolic responses to diets with different protein:carbohydrate ratios in Senegalese sole (Solea senegalensis, Kaup 1858).

Four isolipidic and isoenergetic diets with different protein:carbohydrate (CH) contents (48:38, 52:34, 56:30, 60:26) were fed to juvenile Senegalese sole (22·01 (sem 0·01) g) during 104 d. Oral glucose tolerance tests were performed at the beginning (4 d) and at the end (104 d) of the experiment to assess the effect of the dietary treatment on glucose tolerance. Samples of blood, liver and muscle of all dietary groups were also obtained at the initial and final phases of the trial at different postprandial times (0, 1, 5 and 10 h after feeding) in order to analyse glucose and NEFA in plasma, and metabolites and enzyme activities involved in glycogen metabolism, glycolysis, gluconeogenesis and lipogenesis pathways in liver and muscle. The results obtained in this study suggest a good glucose tolerance in Senegalese sole. This species tolerated important amounts of CH in the diet without showing any deleterious signs in terms of growth or any metabolic disorders. After 104 d of feeding diets with an important amount of CH (48:38 and 52:34), the control of glycaemia was maintained and even postprandial glucose levels in plasma were (in general) lower than at the beginning of the experiment. This reasonable tolerance to glucose is also reflected by an increased use of glucose through glycolysis in liver (indicated by glucokinase activity), and the absence of changes in lipogenic potential in the same tissue (indicated by ATP citrate lyase activity). No clear changes were induced in the muscle by the dietary treatments.

Stroke and Transient Ischemic Attack in Takayasu's Arteritis: A Systematic Review and Meta-analysis.

BACKGROUND: Cerebrovascular disease is one of the possible consequences of Takayasu's arteritis (TA). However, little is known about the prevalence of stroke/transient ischemic attack (TIA) or its related clinical features among these patients. We have performed a systematic review and meta-analysis to estimate the rate and risk factors of stroke/TIA in TA as well as to explore associations with poorer outcomes. METHODS: MEDLINE and Embase were searched (October 2014) for observational studies of any design reporting prevalence rates of stroke/TIA among TA patients. Study selection, data collection, and quality assessment were done independently. Studies' results were pooled through random-effect meta-analysis. Heterogeneity was assessed with the I(2) test. RESULTS: Twenty-one studies (16 studies were of cohort design) were included (n = 3269). The pooled stroke/TIA prevalence rate estimate was 15.8% (95% confidence interval [CI]: 10.7%-22.6%, I(2) = 94%). Sensitivity analysis, excluding 8 studies with poorer TA diagnostic criteria, yielded a similar estimate but without statistical heterogeneity (15.7%; 95% CI: 13.6%-18.1%, I(2) = 5.5%). Data were unavailable to explore possible associations between patients' characteristics and stroke/TIA prevalence. CONCLUSION: Our results document a high prevalence of stroke/TIA among TA patients. However, there is scarce information on the type of stroke, the characteristics of the affected individuals, and stroke-associated morbidity and mortality. Future studies should aim to further explore this disabling complication to find the best treatment and prevention strategies.

Swimming exercise and diphenyl diselenide-supplemented diet affect the serum levels of pro- and anti-inflammatory cytokines differently depending on the age of rats.

The increase in the inflammatory process is one of the main factors that contribute to aging. The aim of this study was to investigate the effects of a diphenyl diselenide (PhSe)2-supplemented diet (1p.p.m., 4weeks) and swimming exercise (3% of body weight, 20min per day, 4weeks) on the serum levels of cytokines in Wistar rats of different ages. The results demonstrated an increase in the levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNFα and INFγ) and a decrease in the levels of IL-10, an anti-inflammatory cytokine, with age. In middle-age rats, the swimming exercise and (PhSe)2-supplemented diet decreased serum levels of pro-inflammatory cytokines and increased the levels of IL-10. By contrast, in old rats the swimming exercise protocol increased the serum levels of pro-inflammatory cytokines and decreased the levels IL-10. Diet supplemented with (PhSe)2 did not alter the serum levels of cytokines in old rats. Middle-age and old rats subjected to swimming exercise and supplemented with (PhSe)2 in the diet had a decrease in the serum levels of pro-inflammatory cytokines and an increase in the levels of IL-10. This study demonstrated that swimming exercise and (PhSe)2-supplemented diet affect the serum levels of pro- and anti-inflammatory cytokines differently depending on the age of rats. (PhSe)2 supplemented in the diet had an anti-inflammatory effect, similar to that of induced by swimming exercise, in middle-age rats and reversed the pro-inflammatory effects of swimming exercise in old rats.

Effects of sulfamethoxazole-trimethoprim associated to resveratrol on its free form and complexed with 2-hydroxypropyl-ß-cyclodextrin on cytokines levels of mice infected by Toxoplasma gondii.

The aim of this study was to investigate the effects of resveratrol on its free form and complexed with 2-hydroxypropyl-ß-cyclodextrin (HPßCD) when associated with sulfamethoxazole-trimethoprim (ST) on cytokines levels of mice (n = 60) experimentally infected by Toxoplasma gondii. Groups A and E were used as controls (untreated): negative and positive, respectively. The onset of treatment started 20 days post-infection (PI), and it lasted for 10 consecutive days. ST was administered orally in doses of 0.5 mg kg(-1) for groups B and F, while 100 mg kg(-1) was the dose for resveratrol in its free form (groups C - G), inclusion complex (groups D and H), and on free and inclusion complex together (groups I - J). On day 31 PI, blood samples were collected in order to evaluate the cytokine profile. The mice that received drug combination (I and J) showed a significant (P < 0.05) reduction in the number of cysts in the brain compared to other infected groups (E - H). The results showed that mice from the Group E had increased (P < 0.001) levels of pro-inflammatory cytokines, while IL-10 levels were reduced when compared to the Group A. Additionally, there were increased levels of IL-4 and IFN-γ in animals of groups C and D, respectively (P < 0.05). Animals of the Group B showed reduced levels of IL-1, IL-4, IL-6, TNF-α, and IFN-γ (P < 0.05). Mice infected and treated (groups F - J) showed increased levels of pro-inflammatory cytokines along with a reduction of IL-10. Treatment with the combination of drugs (the Group J) led to a protective effect, i.e. reduction in pro-inflammatory cytokines. Therefore, resveratrol associated with ST was able to modulate seric cytokine profile and moderate the tissue inflammatory process caused by T. gondii infection, as well as to reduce parasite multiplication.

The antiatherogenic effect of bixin in hypercholesterolemic rabbits is associated to the improvement of lipid profile and to its antioxidant and anti-inflammatory effects.

Hypercholesterolemia and oxidative stress have been implicated in the pathophysiology of atherosclerosis and coronary artery disease. We investigated whether the carotenoid bixin (BIX) may reduce oxidative damage, inflammatory response, and the atherosclerotic lesion induced by hypercholesterolemia in rabbits. Rabbits received regular chow (control) or a hypercholesterolemic diet (0.5% cholesterol) alone or supplemented with BIX (10, 30 or 100 mg/kg body weight, b.w.) or simvastatin (15 mg/kg b.w.) for 60 days. Treatment with BIX or simvastatin reduced the atherosclerotic lesions in cholesterol-fed rabbits (up to 55 and 96% reduction, respectively). This protective effect of BIX was accompanied by decrease in the levels of tumor necrosis factor alpha by 15%, interleukin 6 by 19%, lipid peroxidation by 60%, non-high-density lipoprotein cholesterol (non-HDL-C) by 37%, and triglycerides by 41%. BIX increased by 160% the HDL-C levels and decreased by 67% the atherogenic index of hypercholesterolemic rabbits. In atherosclerotic rabbits, the non-protein thiol groups content and the activity of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and thioredoxin reductase were increased in the aortic tissue, whereas paraoxonase activity was reduced in the serum. All these changes were completely prevented by BIX or simvastatin treatment. These results demonstrate that BIX reduces the extent of atherosclerotic lesions and this effect was associated with the decrease in oxidative stress, inflammatory response, and improvement of dyslipidemia, which were most effectively controlled after treatment with 10-30 mg BIX/kg b.w. BIX consumption may, therefore, be an adjuvant to prevent atherosclerosis reducing risk factors for coronary diseases.

Improvement of blood inflammatory marker levels in patients with hypothyroidism under levothyroxine treatment.

BACKGROUND: There are several specific inflammatory and oxidative correlates among patients with hypothyroidism, but most studies are cross-sectional and do not evaluate the change in parameters during the treatment. The aim of this study was to investigate the effect of levothyroxine replacement therapy on biomarkers of oxidative stress (OS) and systemic inflammation in patients with hypothyroidism. METHODS: In this prospective open-label study, 17 patients with recently diagnosed primary hypothyroidism due to Hashimoto's thyroiditis who were not taking levothyroxine were included. The following parameters were measured before and at 6 and 12 months of levothyroxine treatment with an average dose of 1.5 to 1.7 µg/kg/day: thyroid-stimulating hormone (TSH), free thyroxine (FT4), high-sensitivity C-reactive protein (hs-CRP), interleukin 1 (IL-1), IL-6, IL-10, interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), thiobarbituric acid-reactive substances (TBARS), activity of aminolevulinic acid dehydratase (δ-ALA-D), nonprotein and total thiol (NP-SH and T-SH) groups, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). Generalized estimating equation (GEE) modeling was used to analyze the effects of LRT (at pre-treatment, 6 months and 12 months) on those variables. The hypothyroidism status (i.e., overt or subclinical hypothyroidism) was included as a confounder in all analyses. An additional GEE post hoc analysis was made to compare time points. RESULTS: There was a significant decrease in TSH over time (P < 0.0001), (initial levels were on average 32.4 µIU/mL and 10.5 µIU/mL at 12 months). There was a significant increase in FT4 (P < 0.0001) (initial levels were on average 0,8 ng/dL and 2.7 ng/dL at 12 months). There were significant changes in interleukin levels over time, with a significant increase in IL-10 (P < 0.0001) and significant decreases in IL-1 (P < 0.0001), IL-6 (P < 0.0001), INF-γ (P < 0.0001) and TNF-α (P < 0.0001). No significant difference in hs-CRP over time was observed (P < 0.284). There was a significant reduction in NP-SH (P < 0.0001). CONCLUSIONS: This study observed significant changes in the inflammatory profile in hypothyroid patients under treatment, with reduction of pro-inflammatory cytokines and elevation of anti-inflammatory cytokine. In these patients, a decrease in low-grade chronic inflammation may have clinical relevance due to the known connection between chronic inflammation, atherosclerosis and cardiovascular events.

Effect of zinc supplementation on E-ADA activity, seric zinc, and cytokines levels of Trypanosoma evansi infected Wistar rats.

The aim of this study was to evaluate the effect of zinc supplementation on the ecto-adenosine deaminase activity (E-ADA), zinc seric levels and cytokines (TNF-α, IL-1, IL-6, and IL -10) on rats experimentally infected by Trypanosoma evansi. Four groups with 10 rats each were used as negative controls (groups A and B), while the animals from the groups C and D were infected intraperitoneally with 0.1 mL of cryopreserved blood containing 1.4 × 10(4) of trypanosomes. Animals of groups B and D received two doses of Zinc (Zn) at 5 mg kg(-1), subcutaneously, on the 2nd and 7th day post-infection (PI). Blood samples were collected on days 5 (n = 5) and 15 PI (n = 5). Zn supplementation was able to increase the rat's longevity and to reduce their parasitemia. It was observed that seric Zn levels were increased on infected animals under Zn supplementation. Animals that were infected and supplemented with Zn showed changes in E-ADA activity and in cytokine levels (P < 0.05). Zn supplementation of healthy animals (Group B), increased the E-ADA activity, as well as reduced the concentration of cytokines. Infected animals from groups C and D showed increased levels of cytokines. Finally, we observed that Zn supplementation led to a modulation on cytokine's level in rats infected by T. evansi, as well as in E-ADA activity.

Moderate swimming exercise and caffeine supplementation reduce the levels of inflammatory cytokines without causing oxidative stress in tissues of middle-aged rats.

The levels of circulatory inflammatory markers, including interleukin (IL) IL-1ß, IL-6, tumor necrosis factor-α (TNF-α) and interferon (INF-γ), are known to increase associated to aging. Caffeine has been reported to produce many beneficial effects for health. Exercise is considered to be a safe medicine to attenuate inflammation and cellular senescence. The purpose of the present study was to investigate the effects of a moderate-intensity swimming exercise (3 % of body weight, 20 min per day, 4 weeks) and sub-chronic supplementation with caffeine (30 mg/kg, 4 weeks) on the serum cytokine levels in middle-aged (18 months) Wistar rats. The effects of swimming exercise and caffeine on oxidative stress in muscle and liver of middle-aged rats were also investigated. The two-way ANOVA of pro-inflammatory cytokine levels demonstrated a significant exercise x caffeine interaction for IL-1ß (F (1, 16) = 9.5772; p = 0.0069), IL-6 (F (1, 16) = 8.0463; p = 0.0119) and INF-γ (F (1, 16) = 15.078; p = 0.0013). The two-way ANOVA of TNF-α levels revealed a significant exercise × caffeine interaction (F (1, 16) = 9.6881; p = 0.00670). Swimming exercise and caffeine supplementation increased the ratio of reduced glutathione/oxidized glutathione in the rat liver and gastrocnemius muscle. Hepatic and renal markers of damage were not modified. In conclusion, a moderate-intensity swimming exercise protocol and caffeine supplementation induced positive adaptations in modulating cytokine levels without causing oxidative stress in muscle and liver of middle-aged rats.

Diphenyl diselenide and sodium selenite associated with chemotherapy in experimental toxoplasmosis: influence on oxidant/antioxidant biomarkers and cytokine modulation.

SUMMARY The aim of this study was to assess the effect of sulfamethoxazole/trimethoprim (ST) supplemented with diphenyl diselenide and sodium selenite in experimental toxoplasmosis, on oxidant/antioxidant biomarkers and cytokine levels. Eighty-four BALB/c mice were divided in seven groups: group A (negative control), and groups B to G (infected). Blood and liver samples were collected on days 4 and 20 post infection (p.i.). Levels of thiobarbituric acid (TBA) reactive substances and advanced oxidation protein products (AOPP) were assessed in liver samples. Both biomarkers were significantly increased in infected groups on day 4 p.i., while they were reduced on day 20 p.i., compared with group A. Glutathione reductase (GR) activity significantly (P<0·01) increased on day 4 p.i., in group G, compared with group A. INF-γ was significantly increased (P<0·001) in both periods, day 4 (groups B, C, F and G) and 20 p.i. (groups C, F and G). IL-10 significantly reduced (P<0·001) on day 4 p.i. in group B; however, in the same period, it was increased (P<0·001) in groups C and G, compared with group A. On day 20 p.i., IL-10 increased (P<0·001) in groups F and G. Therefore, our results highlighted that these forms of selenium, associated with the chemotherapy, were able to reduce lipid peroxidation and protein oxidation, providing a beneficial immunological balance between the production of pro- and anti-inflammatory cytokines.

Atherosclerotic process in taxi drivers occupationally exposed to air pollution and co-morbidities.

Consistent evidence has indicated that the exposure to environmental air pollution increases the risk of cardiovascular disease. This study aimed to evaluate the possible effects of occupational exposure to air pollution, especially to polycyclic aromatic hydrocarbons (PAHs), and the influence of co-morbidities on the atherosclerotic process and inflammation. For that, biomarkers of exposure such as 1-hydroxypyrene urinary, oxidative damage and markers of cardiovascular risk were determined in plasma, serum and blood. In addition, inflammation models such as carotid intima-media thickness and serum inflammatory cytokines were analyzed in 58 taxi drivers with and without co-morbidity. The results demonstrated that considering only taxi drivers without co-morbidities, 15% presented carotid intima-media thickness above reference values. For the first time it has been demonstrated that urinary 1-hydroxypyrene levels were associated with carotid intima-media thickness and with serum homocysteine levels. The multiple linear regression analysis showed that several factors may contribute to the increased carotid intima-media thickness, among which age, interleukin-6, fibrinogen and exposure to PAHs stand out. In summary, our results suggest that chronic occupational exposure to atmospheric pollution could be an additional contributor to the atherogenesis process, leading to impaired vascular health. Moreover, carotid intima-media thickness, serum homocysteine levels, fibrinogen and the total cholesterol/HDL-c ratio could be suggested as preventive measures to monitor drivers' health.