Int J Tuberc Lung Dis

BackgroundTherapeutic effects of antiretroviral therapy (ART) in patients with multidrug resistant tuberculosis (MDR-TB) and HIV infection have not been established.ObjectiveThe objective of this study was to assess therapeutic outcomes of ART integration with MDR-TB treatment.DesignA subgroup of MDR-TB patients from the SAPiT study, a randomized controlled trial, conducted in an out-patient clinic in Durban, South Africa from 2008\u20132012MethodsClinical outcomes at 18 months were compared in patients randomized to receive ART within 12 weeks of standard first-line tuberculosis treatment initiation with those who commenced ART after completing tuberculosis treatment.ResultsMycobacterium tuberculosis drug susceptibility was available in 489 (76%) of 642 SAPiT patients; 23 had MDR-TB, 14 in the integrated treatment arm and 9 in the sequential treatment arm. At 18 months, the mortality rate was 11.9/100 person-years (95% confidence interval (CI): 1.4\u201342.8) in the combined integrated treatment arm and 56.0/100 person-years (95%CI: 18.2\u2013130.8) in the sequential treatment arm, (Hazard Ratio adjusted for baseline CD4 count and whether MDR-TB treatment was initiated: 0.14; 95% CI: 0.02\u20130.94; P=0.04).ConclusionDespite the small sample size, the 86% reduction in mortality due to early initiation of ART in MDR-TB patients was statistically significant.D43TW00231/TW/FIC NIH HHS/United StatesD43 TW000231/TW/FIC NIH HHS/United States5U26PS001350/PS/NCHHSTP CDC HHS/United StatesU19 AI051794/AI/NIAID NIH HHS/United StatesU2G PS001350/PS/NCHHSTP CDC HHS/United StatesPEPFAR/United States2016-02-29T00:00:00Z24429305PMC47700138583vault:1580

Effects of two-months balanced diet in metabolically healthy obesity : lipid correlations with gender and BMI-related differences

Background: Nowadays no researches has been performed on fatty acid profile (FA) and desaturase activity in metabolically healthy obesity (MHO). The aim of this study was to assessed gender and BMI-related difference in FA, estimated desaturase activities and the efficacy on metabolic changes produced by 2-months well-balance diet in MHO subjects. Methods: In 103 MHO subjects (30/73 M/F; age:42.2 \ub1 9.5) FA, estimated desaturase activity, body composition (by DXA), Body Mass Index (BMI), lipid profile, adipokines (leptin, adiponectin, grelin, glucagon-like peptide-1), insulin resistence (by Homestasis metabolic assessment), C-reactive proteine, Atherogenic index of plasma (AIP) and Body Shape Index (ABSI) have been assessed. Gender and BMI related difference have been evaluated and the efficacy produced by 2-months well-balance diet has been considered. Results: At baseline, obese subjects, compared to overweight, show a significantly higher oleic (p <0.050), monounsaturated fatty acids (p <0.040), C18:0 delta-9 desaturase activity (D9D) (p <0.040) and lower linoleic acid (p <0.020), polyunsaturated fatty acids (p <0.020) and n-6 LCPUFA (p <0.010). Concerning gender-related difference, women show a significantly higher arachidonic acid (p <0.001), polyunsaturated fatty acids (p <0.001), n-6 LCPUFA (p <0.002), and lower monounsaturated fatty acids (p <0.001), D6D activity (p <0.030), C18:0 D9D (0.000) and C16:0 D9D (p <0.030). The 2-months diet was associated with a significantly increase in arachidonic acid (p = 0.007), eicosapentaenoic acid (p = 0.030), docosahexaenoic acid (p <0.001), long chain omega 3 polyunsaturated fatty acids (n-3 LCPUFA) (p <0.001), delta-5 desaturase activity (D5D) (p = 0.002), glucagon like peptide-1 (p <0.001) and a significant decrease in palmitoleic acid (p = <0.030), n-6/n-3 LCPUFA (p <0.001), insulin resistance (p = 0.006), leptin (p = 0.006), adiponectin (p <0.001), grelin (p = 0.030), CRP (p = 0.004), BMI (p <0.001) and android fat mass (p <0.001). Conclusions: The balanced diet intervention was effective in improving metabolic indices

Characterization of Antioxidant Potential of Seaweed Extracts for Enrichment of Convenience Food

In recent years, there has been a growing interest in natural antioxidants as replacements of synthetic compounds because of increased safety concerns and worldwide trend toward the usage of natural additives in foods. One of the richest sources of natural antioxidants, nowadays largely studied for their potential to decrease the risk of diseases and to improve oxidative stability of food products, are edible brown seaweeds. Nevertheless, their antioxidant mechanisms are slightly evaluated and discussed. The aims of this study were to suggest possible mechanism(s) of Fucus vesiculosus antioxidant action and to assess its bioactivity during the production of enriched rye snacks. Chemical and cell-based assays indicate that the efficient preventive antioxidant action of Fucus vesiculosus extracts is likely due to not only the high polyphenol content, but also their good Fe2+-chelating ability. Moreover, the data collected during the production of Fucus vesiculosus-enriched rye snacks show that this seaweed can increase, in appreciable measure, the antioxidant potential of enriched convenience cereals. This information can be used to design functional foods enriched in natural antioxidant ingredients in order to improve the health of targeted consumers

Characterization of chenopodin isoforms from quinoa seeds and assessment of their potential anti-inflammatory activity in Caco-2 cells

Several food-derived molecules, including proteins and peptides, can show bioactivities toward the promotion of well-being and disease prevention in humans. There is still a lack of information about the potential effects on immune and inflammatory responses in mammalian cells following the ingestion of seed storage proteins. This study, for the first time, describes the potential immunomodulation capacity of chenopodin, the major protein component of quinoa seeds. After characterizing the molecular features of the purified protein, we were able to separate two different forms of chenopodin, indicated as LcC (Low charge Chenopodin, 30% of total chenopodin) and HcC (High charge Chenopodin, 70% of total chenopodin). The biological effects of LcC and HcC were investigated by measuring NF-\u3baB activation and IL-8 expression studies in undifferentiated Caco-2 cells. Inflammation was elicited using IL-1\u3b2. The results indicate that LcC and HcC show potential anti-inflammatory activities in an intestinal cell model, and that the proteins can act differently, depending on their structural features. Furthermore, the molecular mechanisms of action and the structural/functional relationships of the protein at the basis of the observed bioactivity were investigated using in silico analyses and structural predictions

&#969;-3 Long Chain Polyunsaturated Fatty Acids as Sensitizing Agents and Multidrug Resistance Revertants in Cancer Therapy

Chemotherapy efficacy is strictly limited by the resistance of cancer cells. The \u3c9-3 long chain polyunsaturated fatty acids (\u3c9-3 LCPUFAs) are considered chemosensitizing agents and revertants of multidrug resistance by pleiotropic, but not still well elucidated, mechanisms. Nowadays, it is accepted that alteration in gene expression, modulation of cellular proliferation and differentiation, induction of apoptosis, generation of reactive oxygen species, and lipid peroxidation are involved in \u3c9-3 LCPUFA chemosensitizing effects. A crucial mechanism in the control of cell drug uptake and efflux is related to \u3c9-3 LCPUFA influence on membrane lipid composition. The incorporation of docosahexaenoic acid in the lipid rafts produces significant changes in their physical-chemical properties affecting content and functions of transmembrane proteins, such as growth factors, receptors and ATP-binding cassette transporters. Of note, \u3c9-3 LCPUFAs often alter the lipid compositions more in chemoresistant cells than in chemosensitive cells, suggesting a potential adjuvant role in the treatment of drug resistant cancers

Space flight effects on antioxidant molecules in dry tardigrades : the TARDIKISS experiment

The TARDIKISS (Tardigrades in Space) experiment was part of the Biokon in Space (BIOKIS) payload, a set of multidisciplinary experiments performed during the DAMA (Dark Matter) mission organized by Italian Space Agency and Italian Air Force in 2011. This mission supported the execution of experiments in short duration (16 days) taking the advantage of the microgravity environment on board of the Space Shuttle Endeavour (its last mission STS-134) docked to the International Space Station. TARDIKISS was composed of three sample sets: one flight sample and two ground control samples. These samples provided the biological material used to test as space stressors, including microgravity, affected animal survivability, life cycle, DNA integrity, and pathways of molecules working as antioxidants. In this paper we compared the molecular pathways of some antioxidant molecules, thiobarbituric acid reactive substances, and fatty acid composition between flight and control samples in two tardigrade species, namely, Paramacrobiotus richtersi and Ramazzottius oberhaeuseri. In both species, the activities of ROS scavenging enzymes, the total content of glutathione, and the fatty acids composition between flight and control samples showed few significant differences. TARDIKISS experiment, together with a previous space experiment (TARSE), further confirms that both desiccated and hydrated tardigrades represent useful animal tool for space research

Chemical-Physical Changes in Cell Membrane Microdomains of Breast Cancer Cells After Omega-3 PUFA Incorporation

Epidemiologic and experimental studies suggest that dietary fatty acids influence the development and progression of breast cancer. However, no clear data are present in literature that could demonstrate how n\ua0-\ua03 PUFA can interfere with breast cancer growth. It is suggested that these fatty acids might change the structure of cell membrane, especially of lipid rafts. During this study we treated MCF-7 and MDA-MB-231 cells with AA, EPA, and DHA to assess if they are incorporated in lipid raft phospholipids and are able to change chemical and physical properties of these structures. Our data demonstrate that PUFA and their metabolites are inserted with different yield in cell membrane microdomains and are able to alter fatty acid composition without decreasing the total percentage of saturated fatty acids that characterize these structures. In particular in MDA-MB-231 cells, that displays the highest content of Chol and saturated fatty acids, we observed the lowest incorporation of DHA, probably for sterical reasons; nevertheless DHA was able to decrease Chol and SM content. Moreover, PUFA are incorporated in breast cancer lipid rafts with different specificity for the phospholipid moiety, in particular PUFA are incorporated in PI, PS, and PC phospholipids that may be relevant to the formation of PUFA metabolites (prostaglandins, prostacyclins, leukotrienes, resolvines, and protectines) of phospholipids deriving second messengers and signal transduction activation. The bio-physical changes after n\ua0-\ua03 PUFA incubation have also been highlighted by atomic force microscopy. In particular, for both cell lines the DHA treatment produced a decrease of the lipid rafts in the order of about 20-30\ua0%. It is worth noticing that after DHA incorporation lipid rafts exhibit two different height ranges. In fact, some lipid rafts have a higher height of 6-6.5\ua0nm. In conclusion n\ua0-\ua03 PUFA are able to modify lipid raft biochemical and biophysical features leading to decrease of breast cancer cell proliferation probably through different mechanisms related to acyl chain length and unsaturation. While EPA may contribute to cell apoptosis mainly through decrease of AA concentration in lipid raft phospholipids, DHA may change the biophysical properties of lipid rafts decreasing the content of cholesterol and probably the distribution of key proteins

Heterogeneous and self-organizing mineralization of bone matrix promoted by hydroxyapatite nanoparticles

The mineralization process is crucial to the load-bearing characteristics of the bone extracellular matrix. In this work, we have studied the spatiotemporal dynamics of mineral deposition by human bone marrow mesenchymal stem cells differentiating toward osteoblasts promoted by the presence of exogenous hydroxyapatite nanoparticles. At molecular level, the added nanoparticles positively modulated the expression of bone-specific markers and enhanced calcified matrix deposition during osteogenic differentiation. The nucleation, growth and spatial arrangement of newly deposited hydroxyapatite nanocrystals have been evaluated using Scanning Micro X-Ray Diffraction and Scanning Micro X-Ray Fluorescence. As leading results, we have found the emergence of a complex scenario where the spatial organization and temporal evolution of the process exhibit a heterogeneous and self-organizing dynamics. At the same time the possibility to control the differentiation kinetic through the addition of synthetic nanoparticles, paves the way to empower the generation of more structured bone scaffolds in tissue engineering and to design new drugs in regenerative medicine

Fatty Acid Profile and Antioxidant Status Fingerprint in Sarcopenic Elderly Patients : Role of Diet and Exercise

Plasma fatty acids (FAs) and oxidant status contribute to the etiology of sarcopenia in the elderly concurring to age-related muscle loss and elderly frailty through several mechanisms including changes in FA composition within the sarcolemma, promotion of chronic low-grade inflammation, and insulin resistance. The aim of this study was to determine the FA profile and pro-antioxidant status in sarcopenic frail elderly patients enrolled in a nutritional and physical activity program and to evaluate their correlation with clinical markers. Moreover, the possible changes, produced after a short-term clinical protocol, were evaluated. Plasma and erythrocyte FA composition and pro-antioxidant status were analyzed in sarcopenic elderly subjects recruited for the randomized clinical study and treated with a placebo or dietary supplement, a personalized diet, and standardized physical activity. Subjects were tested before and after 30 days of treatment. Pearson correlations between biochemical parameters and patients' characteristics at recruitment indicate interesting features of sarcopenic status such as negative correlation among the plasma FA profile, age, and physical characteristics. Physical activity and dietetic program alone for 30 days induced a decrease of saturated FA concentration with a significant increase of dihomo-gamma-linolenic acid. Supplementation plus physical activity induced a significant decrease of linoleic acid, omega-6 polyunsaturated FAs, and an increase of stearic and oleic acid concentration. Moreover, glutathione reductase activity, which is an indicator of antioxidant status, significantly increased in erythrocytes. Changes over time between groups indicate significant differences for saturated FAs, which suggest that the amino acid supplementation restores FA levels that are consumed during physical activity. A relationship between FA and clinical/metabolic status revealed unique correlations and a specific metabolic and lipidomic fingerprint in sarcopenic elderly. The results indicate the positive beneficial role of supplementation and physical activity on plasma FA status and the antioxidant system as a co-adjuvant approach in sarcopenic, frail, elderly patients