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Background and objective Curcumin, one of an established curcuminoid substances extracted from Curcuma longa , has been used as a photosensitizer (PS) in photodynamic therapy (PDT). Curcuminoid substances has been reported to have benefits in treating dental chronic infection and inflammation diseases, such as chronic periodontitis. The purpose of this study was to find the optimum concentration of Curcuma longa ( CL ) extract, containing all curcuminoid substances, and the power density of blue light (BL) in photodynamic therapy against periodontally pathogenic bacteria, A. actinomycetemcomitans . Methods Antibacterial activity of various concentrations of CL extract against A. actinomycetemcomitans was determined. Exponentially growing bacteria were combined with 2-fold dilution of CL extract solution ranging from 25 to 0.098 μg/ml. Co-culture bacteria treated with 0.12% chlorhexidine (CHX) served as the positive control. The effect of photostimulation with light emitting diode (LED) 420–480 nm at 16.8 J/cm 2 for 1 min on the selected concentration of CL extract was examined. Bacteria viability was determined by plate counting technique. In addition, production of free radicals was tested by electron spin resonance spectroscope (ESR) with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Results The antibacterial activity of CL extract was dose dependent. Without BL, 25 μg/ml CL extract showed 6.03 ± 0.39 log 10 A. actinomycetemcomitans . Interestingly, the combination of BL and 0.78 μg/ml CL extract solution showed complete absence of A. actinomycetemcomitans . Peak signal intensity of hydroxyl radical production was also detected with the combination of BL and CL. Conclusions CL extract not only had antimicrobial activity but also could be used as an effective PS when stimulated with BL in PDT. The optimal antibacterial effect of CL extract with BL was equal to the standard oral disinfectant, 0.12% CHX. [ABSTRACT FROM AUTHOR]

Renal glomerular and tubular dysfunctions have been reported with high prevalence in β-thalassemia. Iron toxicity is implicated in the kidney damage, which may be reversed by iron chelation therapy. To mimic heavy iron overload and evaluate the efficacy of iron chelators in the patients, iron dextran (180 mg iron/mouse) was intraperitoneally (i.p.) injected in heterozygous β-globin knockout mice ( muβth−3/+ , BKO) and wild type mice (C57BL/6J, WT) over a period of 2 weeks, followed by daily i.p. injection of deferoxamine (DFO) or deferiprone (L1) for 1 week. In BKO mice, iron preferentially accumulated in the proximal tubule with a grading score of 0–1 and increased to grade 3 after iron loading. In contrast, iron mainly deposited in the glomerulus and interstitial space in iron overloaded WT mice. Increased levels of kidney lipid peroxidation, glomerular and medullar damage and fibrosis in iron overloaded mice were reversed by treatment with iron chelators. L1 showed higher efficacy than DFO in reduction of glomerular iron, which was supported by a significantly decreased the amount of glomerular damage. Notably, DFO and L1 demonstrated a distinct pattern of iron distribution in the proximal tubule of BKO mice. In conclusion, chelation therapy has beneficial effects in iron-overloaded kidneys. However, the defect of kidney iron metabolism in thalassemia may be a determining factor of the treatment outcome in individual patients. [ABSTRACT FROM AUTHOR]

Abstract: The liver and heart are the major target organs for iron accumulation and iron toxicity in β-thalassemia. To mimic the phenomenon of heavy iron overload resulting from repeated blood transfusions, a total of 180mg of iron dextran was intraperitoneally injected into C57BL/6J mice (WT) and heterozygous β-globin knockout mice (muβth-3/+, BKO). The effects of deferiprone and deferoxamine in this model were investigated. The iron was distributed homogenously throughout the 4 liver lobes (left, caudate, right and median) and was present in hepatocytes, Kupffer cells and the sinusoidal space. Iron accumulation in phagocytic macrophages, recruitment of hepatic lymphocytes and nucleus membrane degeneration were observed as a result of iron overload in the WT and BKO mice. However, the expansion of hepatic extramedullary hematopoiesis was observed only in the BKO mice with iron overload. In the heart, the iron accumulated in the cardiac interstitium and myocytes, and moderate hypertrophy of the myocardial fibers and cardiac myocyte degeneration were observed. Although the total liver iron was not significantly altered by iron chelation therapy, image analysis demonstrated a difference in the efficacies of two iron chelators. The major site of chelation was the extracellular compartment, but treatment with deferiprone also resulted in intracellular iron chelation. Interestingly, iron chelators reversed the pathological changes resulting from iron overload in WT and BKO mice despite being used for only a short treatment period. We suggest that some of these effects may be secondary to the anti-inflammatory activity of the chelators. [Copyright &y& Elsevier]

Abstract: The large and recent migrations of the main vector of the Chikungunya virus, Aedes albopictus, raise questions about the epidemiological impact of possible microevolutionary changes in new territories. Quantitative traits are suitable to detect such changes as induced by environmental adaptations, local competition and founder effects. Using landmark-based geometric morphometrics, we compared the size and shape of 22 populations (1572 females) of Ae. albopictus. The collection sites covered five countries around the world, with special emphasis on Asia, which is assumed to be the origin of the vector. Some collections came from places where an important epidemic outbreak of Chikungunya has recently occurred. Quantitative comparisons were based on 18 anatomical landmarks on the wing. To contrast geographic and possible interspecific shape variation, close species were introduced in the sample, namely five Aedes riversi and nine Ae. flavopictus from Japan. The three species had similar size, but they were clearly separated by shape. Within Ae. albopictus, there was general agreement on size variation with the available climatic data. Shape variation was less related to climatic data than to either geography or a known itinerary of past territorial expansion. Thus, two main clusters were distinguished by wing shape variation: the first one composed of the Southeast Asian sample, the second one grouping Japan, Florida, Hawaii and the Reunion Island samples. The Southeast Asian countries, assumed to be at the origin of the geographic expansion of the mosquito, had similar wings and constituted a distinct group where localities clustered into northern and southern localities. Contrasting with this homogeneous group, very distant localities such as United States (US) and Japan shared a common shape pattern. The US Ae. albopictus samples (Hawaii and Florida) were indeed very similar to the Japanese samples, with Florida behaving exactly like a northern Japanese locality, close to Tokyo and Yokohama. Shape proximity among these distant areas could be explained by a common and relatively recent ancestor, as generally suggested in the literature. The three Reunion Island samples conformed a group external to the Southeast Asian countries, loosely connected to the remaining localities. Thus, areas where recent epidemics took place, the Reunion Island and the southernmost localities of Thailand, did not cluster together, but represented separate groups. In sum, the size of the wing was apparently under the influence of climatic factors, while its shape could contribute information on species and geographic differences. Apparent departures from expectations based on geography were explained by known past and present migratory routes. These patterns of shape variation were compatible with genetic drift, suggesting microevolutionary changes probably induced by the expansion of the Ae. albopictus mosquito. [Copyright &y& Elsevier]

The oxidative status of twenty-three β-thalassemia/hemoglobin E patients was evaluated after administration of 75 mg/kg deferiprone (GPO- L -ONE®) divided into 3 doses daily for 12 months. Serum ferritin was significantly decreased; the median value at the initial and final assessments was 2842 and 1719 ng/mL, respectively. Progressive improvement with significant changes in antioxidant enzyme activity, including plasma paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH), and in antioxidant enzymes in red blood cells (glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD)) were observed at 3–6 months of treatment. The levels of total GSH in red blood cells were significantly increased at the end of the study. Improved red blood cell membrane integrity was also demonstrated using the EPR spin labeling technique. Membrane fluidity at the surface and hydrophobic regions of the red blood cell membrane was significantly changed after 12 months of treatment. In addition, a significant increase in hemoglobin content was observed (6.6 ± 0.7 and 7.5 ± 1.3 g/dL at the initial assessment and at 6 months, respectively). Correlations were observed between hemoglobin content, membrane fluidity and antioxidant enzymes in red blood cells. The antioxidant activity of deferiprone may partly be explained by progressive reduction of redox active iron that catalyzes free radical reactions, as demonstrated by the EPR spin trapping technique. In conclusion, iron chelation therapy with deferiprone notably improved the oxidative status in thalassemia, consequently reducing the risk of oxidative-related complications. Furthermore, the improvement in red blood cell quality may improve the anemia situation in patients. • Redox-active iron was promptly decreased without presenting negative iron balance. • Restored plasma PON1 but decreased PAF-AH activity may reduce cardiovascular risk. • Red cell lipid fluidity in hydrophilic and hydrophobic regions were improved. • Pro-oxidant activity of deferiprone was not observed. [ABSTRACT FROM AUTHOR]

Iron overload results in lipid peroxidation (LPO) and the oxidative modification of circulating lipoproteins, which contributes to cardiovascular complications in patients with β-thalassemia. Investigating LPO may provide opportunities for the development of novel therapeutic strategies; however, the chemical pathways underlying iron overload-induced LPO in β-thalassemia lipoproteins remain unclear. In this study, we identified various species of lipid radicals (L•), the key mediators of LPO, and oxidized cholesteryl esters (oxCE) derived from the in vitro oxidation of major core lipids, cholesteryl linoleate (CE18:2) and cholesteryl arachidonate (CE20:4); the levels of these radical products in low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were measured and compared between β-thalassemia patients and healthy subjects by using a specific fluorescent probe for L• with a liquid chromatography-tandem mass spectrometric method. Our results demonstrated that iron overload substantially decreased the levels of CE18:2 and CE20:4 substrates and α-tocopherol, resulting in higher levels of full-length and short-chain truncated L• and oxCE products. In particular, CE epoxyallyl radicals (•CE-O) were observed in the lipoproteins of β-thalassemia, revealing the pathological roles of iron overload in the progression of LPO. In addition, we found that intermission for two weeks of iron chelators can increase the production of these oxidized products; therefore, suggesting the beneficial effects of iron chelators in preventing LPO progression. In conclusion, our findings partly revealed the primary chemical pathway by which the LPO of circulating lipoproteins is influenced by iron overload and affected by iron chelation therapy. Moreover, we found that •CE + O shows potential as a sensitive biomarker for monitoring LPO in individuals with β-thalassemia. [Display omitted] • Iron overload results in the production of various lipid radicals and oxidized cholesteryl esters species in lipoproteins. • Short-term intermission of iron chelators significantly increases the level of iron-dependent lipid peroxidation products. • CE epoxyallyl radicals (•CE-O) show potential as new biomarkers for monitoring lipid peroxidation in β-thalassemia. [ABSTRACT FROM AUTHOR]

• 2–5 μM guaiazulene + red laser 4−8 J/cm2 generated a high amount of singlet oxygen. • 2–5 μM guaiazulene + red laser 4−8 J/cm2 did not affect cell viability. • 2–5 μM guaiazulene + red laser 4−8 J/cm2 effectively decreased RANTES and PGE 2. Photodynamic therapy improves oral mucositis treatment. The reactive oxygen species (ROS) generated from this reaction could contribute to an anti-inflammatory effect by suppressing inflammatory cells. To evaluate the anti-inflammatory effect of photodynamic therapy using guaiazulene and a red laser in peripheral blood mononuclear cells (PBMCs). Guaiazulene solutions (1, 2, 5, 25, 35, and 100 μM in 99.8 % methanol) were irradiated with red laser light (625 nm, 146.2 mW/cm2) in continuous mode at 0, 4, and 8 J/cm2 in black 96-well plates. ROS were measured using spin trapping technique with electron spin resonance (ESR) spectroscopy and fluorescence. The two highest concentrations were tested using cell viability (PrestoBlue®) and anti-inflammation (RANTES and PGE 2 ELISA) assay kits. Kruskal-Wallis and Dunn Bonferroni tests were used for statistical analyses with significant differences at p-value < 0.05. Guaiazulene solutions between 2 and 5 μM exposed to red laser light at 4−8 J/cm2 generated significantly more singlet oxygen compared to the no guaiazulene group (p < 0.01) and reduced RANTES and PGE 2 levels in TNF-α-inflamed peripheral blood mononuclear cells without affecting cell viability. Photodynamic activation of guaiazulene generated singlet oxygen and suppressed inflammatory markers in PBMCs. [ABSTRACT FROM AUTHOR]

Abstract: In spite of the adult body size variability of Aedes aegypti (Linnaeus) and its likely association with life history and vectorial capacity, the causes of size variation itself have been only partially identified. In particular, possible important factors such as climatic variation have not received much attention. The objective of this 2-year study was to describe from field collections the relationship of Ae. aegypti metric properties with available climatic data. The study took place in a dengue hyperendemic area of Thailand. Fourth instar larvae (L4) and pupae were collected from the same breeding places allowing the comparisons between seven successive collections, four in 2007 and three in 2008. Climatic data were relative humidity (RH) and temperature (T). They were considered for the periods covering either the pre-imaginal development or, assuming heritability of size, the previous generation. The pre-imaginal period was further subdivided into embryonic and larval phases of development. Size was estimated by traditional and geometric techniques, the latter based on 18 landmarks collected at the intersections of veins also allowing estimation of shape. The shape variation of the wing followed similar patterns as for size and was shown to be a passive allometric change. No significant correlation of size or shape could be disclosed with T. In contrast, significant correlation with RH was found during two periods of examination: (i) the period affecting the generation previous to the time of collection, suggesting possible selective mechanisms on genitors, and (ii) the one occurring during pre-imaginal development. The subdivision of the latter into embryonic and larval phases allowed to evidence a possible selecting effect on embryonic development. The selection would act through the resistance to water loss which is known to depend on the relative surface of the cuticle. In conclusion, our data highlight the importance of the emerged period of Ae. aegypti eggs as a critical time for the size of future adults, and point to the relative humidity as the likely selecting factor. [Copyright &y& Elsevier]

Abstract: The present study was designed to investigate the hypolipidemic effects and antioxidant effects of Hibiscus sabdariffa L. (roselle) with regard to protection of LDL oxidation in vivo and ex vivo in rats made hypercholesterolemic by continuous cholesterol feeding. Administering the dried calyx extracts of roselle at doses of 500 and 1000mg/kg together with continuous cholesterol feeding to hypercholesterolemic rats for 6 weeks significantly decreased serum cholesterol level by 22% and 26%, respectively (p <0.001); serum triglycerides level by 33% and 28%, respectively (p <0.05); serum LDL level by 22% and 32%, respectively (p <0.05). However, serum HDL level was not affected. LDL was extracted from plasma of the hypercholesterolemic rats and the effects of the dried calyx extracts of roselle on the oxidation of LDL in vivo and ex vivo were examined. Six-week treatment with 250, 500 and 1000mg/kg of the extracts significantly decreased thiobarbituric acid reactive substances (TBARs) formation (p <0.05) while the formation of conjugated dienes during the oxidation of LDL induced by CuSO4 was reduced, but not significantly different. These lines of evidence suggest that the aqueous extracts from the dried calyx of roselle possess both antioxidant effects against LDL oxidation and hypolipidemic effects in vivo. However, its mechanism(s) of action remains to be elucidated. [Copyright &y& Elsevier]

Brain iron overload is chronic and slow progressing and plays an important role in the pathogenesis of neurodegenerative disorders. Magnetic resonance imaging (MRI) is a useful noninvasive tool for determining liver iron content, but it has not been proven to be adequate for evaluating brain iron overload. We evaluated the usefulness of MRI-derived parameters to determine brain iron concentration in β-thalassemic mice and the effects of the membrane permeable iron chelator, deferiprone. Sixteen β-thalassemic mice underwent 1.5 T MRI of the brain that included a multiecho T2*-weighted sequence. Brain T2* values ranged from 28 to 31 ms for thalassemic mice. For the iron overloaded thalassemic mice, brain T2* values decreased, ranging from 8 to 12 ms, which correlated with the iron overload status of the animals. In addition, brain T2* values increased in the group with the treatment of deferiprone, ranging from 18 to 24 ms. Our results may be useful to understand brain pathology in iron overload. Moreover, data could lead to an earlier diagnosis, assist in following disease progression, and demonstrate the benefits of iron chelation therapy. [ABSTRACT FROM AUTHOR]

Graphical abstract Sources of pictures: https://www.greenville.k12.sc.us/hughes/main.asp?titleid=electronic , https://www.glacvcd.org/portfolio-item/aedes-aegypti-yellow-fever-mosquito/ , http://health.wusf.usf.edu/post/finding-zika-mosquitoes-could-help-control-virus-fiu-professor-says#stream/0. Highlights • We assessed the foraging, host-attacking and copulation activities of Aedes aegypti exposed to electronic music. • Music entertainment resulted in delayed response time and reduced visitation to host. • Females entertained with music attacked hosts much later than their non-entertained peers. • Blood feeding activity had low occurrence when music was played. • Adults entertained with music copulated far less than their peers under music-off condition. Abstract Sound and its reception are crucial for reproduction, survival, and population maintenance of many animals. In insects, low-frequency vibrations facilitate sexual interactions, whereas noise disrupts the perception of signals from conspecifics and hosts. Despite evidence that mosquitoes respond to sound frequencies beyond fundamental ranges, including songs, and that males and females need to struggle to harmonize their flight tones, the behavioral impacts of music as control targets remain unexplored. In this study, we examined the effects of electronic music (Scary Monsters and Nice Sprites by Skrillex) on foraging, host attack, and sexual activities of the dengue vector Aedes aegypti. Adults were presented with two sound environments (music-off or music-on). Discrepancies in visitation, blood feeding, and copulation patterns were compared between environments with and without music. Ae. aegypti females maintained in the music-off environment initiated host visits earlier than those in the music-on environment. They visited the host significantly less often in the music-on than the music-off condition. Females exposed to music attacked hosts much later than their non-exposed peers. The occurrence of blood feeding activity was lower when music was being played. Adults exposed to music copulated far less often than their counterparts kept in an environment where there was no music. In addition to providing insight into the auditory sensitivity of Ae. aegypti to sound, our results indicated the vulnerability of its key vectorial capacity traits to electronic music. The observation that such music can delay host attack, reduce blood feeding, and disrupt mating provides new avenues for the development of music-based personal protective and control measures against Aedes -borne diseases. [ABSTRACT FROM AUTHOR]

Food location by mosquitoes is mediated by resource-derived olfactory and visual signals. Smell sensation is intermittent and dependent on the environment, whereas visual signals are continual and precede olfactory cues. Success of mosquito bait technology, where olfactory cues are used for attraction, is being impeded by reduced attractiveness. Despite proof that mosquitoes respond to colored objects, including those mimicking floral shape, and that they can discriminate among flowers, the impacts of artificial flowers on foraging remain unexplored. Using artificial flowers with sugar rewards, we examined the foraging responses of Aedes aegypti to various colors in equal choice bioassays. Starved adults were exposed to single flowers with petals of a given color (Single Blue Flowers [SBFs]; Single Red Flowers [SRFs]; Single Yellow Flowers [SYFs]; Single Pink Flowers [SPIFs]; and Single Purple Flowers [SPFs]) and two others with white petals (SWFs). Discrepancies in response time, visitation, feeding, and resting of both sexes were compared between colored flowers and SWFs. Ae. aegypti exhibited shorter response times to colored flowers compared to SWFs, but this behavior was mostly seen for SBFs or SYFs in females, and SRFs, SYFs, SPIFs, or SPFs in males. When provided an option to land on colored flowers and SWFs, female visitation occurred at high rates on SBFs, SRFs, SYFs, SPIFs, and SPFs; for males, this preference for colored flowers was seen to a lesser degree on SBF and SPIFs. Both sexes exhibited preference for colored flowers as sugar sources, but with different patterns: SPIFs, SRFs, SYFs, and SPFs for females; SYFs, SPFs, SPIFs and SRFs for males. Females preferentially rested on colored flowers when in competition with SWFs, but this preference was more pronounced for SPFs, SRFs, and SBFs. Males exhibited an increased preference for SRFs, SPFs, and SYFs as resting sites. Our results indicated the attraction of Ae. aegypti to rewarding artificial flowers, in some cases in ways similar to live flowering plants. The discovery that both male and female Ae. aegypti can feed on nectar mimics held by artificial flowers opens new avenues for improving sugar bait technology and for developing new attract-and-kill devices. [ABSTRACT FROM AUTHOR]

In dengue vector control, attempts to minimize or replace the use of pesticides have mostly involved use of predators, but success has been severely impeded by difficulties associated with financial and environmental costs, predator mass production, and persistence in target habitats. Visual deterrents have been used successfully to control animal pests, in some cases in an effort to replace pesticide use. Despite evidence that visual signals are crucial in site choice for egg deposition by dengue vectors, and that female mosquitoes respond to artificial predation, the role of predator intimidation as it affects the oviposition behavior of dengue vectors remains largely unexplored. Here, we examined the oviposition responses of Aedes aegypti exposed to various mosquito predator pictures. Gravid females were presented with equal opportunities to oviposit in two cups with predator images [ Toxorhynchites splendens —TXI, Goldfish ( Carassius auratus )—small (SFI) and large (LFI) and Tx. splendens + Goldfish—TXFI] and two others without pictures. Differences in egg deposition were examined between sites with and without these images. When given a chance to oviposit in cups with and without TXI, Ae. aegypti females were similarly attracted to both sites. When provided an opportunity to oviposit in cups displaying pictures of fish (SFI or LFI) and blank cups, egg deposition rates were much lower in the fish picture sites. Females showed a preference for blank cups over TXFI for egg deposition. They also equally avoided cups with pictures of fish, regardless of the size of the picture. Our results indicate that the presence of images of goldfish and their association with Tx. larvae significantly reduced egg deposition by Ae. aegypti , and this was not the case with the predatory larvae alone. The observations that the images of natural predators can repel gravid females of a dengue vector provide novel possibilities to develop effective and inexpensive alternative tools to harmful insecticides. [ABSTRACT FROM AUTHOR]

Oxidized low density lipoprotein (Ox-LDL) is implicated in a variety of oxidative diseases. To clarify the mechanisms involved and facilitate the investigation of therapeutics, we previously developed a detection method for lipid-derived radicals using the fluorescent probe 2,2,6-trimethyl-6-pentyl-4-(4-nitrobenzo[1,2,5]oxadiazol-7-ylamino)piperidine-1-oxyl (NBD-Pen). In this study, NBD-Pen was used to detect lipid-derived radicals in Ox-LDL from in vitro and in vivo samples using an iron overloaded mouse model. By following the timeline of lipid radical generation using this method, the iron overloaded mice could be successfully treated with the antioxidant Trolox, resulting in successful lowering of the plasma lipid peroxidation, aspartate transaminase and alanine transaminase levels. Furthermore, using a combination therapy of the chelating agent deferoxamine (DFX) and Trolox, liver injury and oxidative stress markers were also reduced in iron overloaded mice. The NBD-Pen method is highly sensitive as well as selective and is suitable for targeting minimally modified LDL compared with other existing methods. [ABSTRACT FROM AUTHOR]

In nature, adult mosquitoes typically utilize nectar as their main energy source, but they can switch to other as yet unidentified sugary fluids. Contemporary lifestyles, with their associated unwillingness to consume leftovers and improper disposal of waste, have resulted in the disposal of huge amounts of waste into the environment. Such refuse often contains unfinished food items, many of which contain sugar and some of which can collect water from rain and generate juices. Despite evidence that mosquitoes can feed on sugar-rich suspensions, semi-liquids, and decaying fruits, which can be abundant in garbage sites, the impacts of sweet waste fluids on dengue vectors are unknown. Here, we investigated the effects of extracts from some familiar sweet home waste items on key components of vectorial capacity of Aedes aegypti . Adult mosquitoes were fed one of five diets in this study: water (WAT); sucrose (SUG); bakery product (remnant of chocolate cake, BAK); dairy product (yogurt, YOG); and fruit (banana (BAN). Differences in survival, response time to host, and egg production were examined between groups. For both males and females, maintenance on BAK extract resulted in marked survival levels that were similar to those seen with SUG. Sweet waste extracts provided better substrates for survival compared to water, but this superiority was mostly seen with BAK. Females maintained on BAK, YOG, and BAN exhibited shorter response times to a host compared to their counterparts maintained on SUG. The levels of egg production were equivalent in waste extract- and SUG-fed females. The findings presented here illustrate the potential of sweet waste-derived fluids to contribute to the vectorial capacity of dengue vectors and suggest the necessity of readdressing the issue of waste disposal, especially that of unfinished sweet foods. Such approaches can be particularly relevant in dengue endemic areas where rainfall is frequent and waste collection infrequent. [ABSTRACT FROM AUTHOR]

Vascular complications in β-thalassemia are associated with oxidative modification of lipoproteins under high oxidative stress. The lipid components of lipoproteins are oxidized via lipid peroxidation and produce lipid radicals (L•) as the key initial intermediates. Modification of lipid components, therefore, might result in alterations in the rate and products of lipid peroxidation. In this study, the kinetics of L• formation during the 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH)- and hemin-induced oxidation of low-density and high-density lipoproteins (LDL and HDL) from β-thalassemia patients and healthy volunteers were investigated using a specific and sensitive fluorescence probe for L•. Kinetic parameters, including initial lag time, propagation rate and total L• production, were calculated by monitoring a fluorescence-active NBD-Pen-L• adduct. Oxidation of thalassemia lipoproteins exhibited a significantly shorter lag time but a slower propagation rate of L• formation when compared with healthy lipoproteins. LDL showed higher resistance to oxidation during the initiation phase but higher L• formation than HDL. Our results indicated that the levels of α-tocopherol determined the initial lag time, whereas the levels of core lipids and cholesteryl esters, especially cholesteryl linoleate (CL), determined the propagation rate and total L• production. The difference in potency of AAPH and hemin supported that hemin preferentially targeted core lipids. Moreover, analysis of 13-hydroxyoctadecadienoic acid cholesteryl ester (13-HODE-CE)/CE ratio indicated that thalassemia lipoproteins have higher susceptibility to oxidation than healthy lipoproteins. In conclusion, our findings suggested that CL and α-tocopherol were implicated in the susceptibility of lipoproteins to lipid peroxidation in physiological and pathological conditions of β-thalassemia. [Display omitted] • A fluorescence probe, NBD-Pen, sensitively monitored lipid radical (L•) formation in lipoproteins. Kinetic profiles and the amount of L• depended on the target site of lipoprotein oxidation. • Kinetic profiles of L• formation demonstrated that contents of cholesteryl linoleate and α-tocopherol determine the susceptibility of lipid oxidation in β-thalassemia lipoproteins. • Contents of α-tocopherol negatively correlated with the initial lag time, while cholesteryl linoleate level positively correlated with the propagation rate and the amount of L•. [ABSTRACT FROM AUTHOR]

Abstract: Ya-Ba, a combination of the two potent psychostimulants methamphetamine (METH) and caffeine (CAF), is commonly used by drug abusers in Thailand and neighboring countries. While the neurotoxic effects of METH are well documented, the toxicity of this combination is mostly unknown. This study aimed to elucidate the effects of this particular drug combination using both in vitro and in vivo models. We found that combined treatment of METH and CAF at individually non-toxic concentrations significantly decreased viability of human neuroblastoma SK-N-SH cells. The reduction in cell survival was accompanied by an increase in reactive oxygen species (ROS) formation and the Bax/Bcl-2 ratio. In vivo data showed that combined administration of METH and CAF increased the mortality rate of rats, with an increase in the level of thiobarbituric acid reactive substances (TBARS), the indicator of oxidative stress, in striatal tissues. The results indicate that caffeine potentiates the toxic effects of methamphetamine, possibly via a mechanism involving an increase in dopamine release and excess ROS generation. [Copyright &y& Elsevier]

Abstract: Oxidative stress (OS) plays a pivotal role in the pathogenesis of Parkinson''s disease (PD). 6-Hydroxydopamine (6-OHDA) is a neurotoxin used to induce oxidative cell death of dopaminergic neurons in experimental models of PD. Curcumin I, or diferuloylmethane is a pure compound isolated from Curcuma longa Linn. that has been reported to have neuroprotective properties. The precise mechanism, however, remains unclear. This study aims to elucidate the mechanisms by which curcumin I exerts its effects, using 6-OHDA-induced neurotoxicity in the human dopaminergic cell line SH-SY5Y. In our experiments, pretreatment with curcumin I improved cell viability, and significantly reduced reactive oxygen species (ROS). Further investigations revealed a reduction of p53 phosphorylation and decrease of the Bax/Bcl-2 ratio, as measured by mRNA expression and protein level. Taken together, these findings indicate that curcumin I protects dopaminergic neurons from 6-OHDA-induced toxicity via the reduction of ROS production, and subsequent attenuation of p53 phosphorylation and reduction of the Bax/Bcl-2 ratio. [Copyright &y& Elsevier]

Abstract: Moringa oleifera is used in Thai traditional medicine as cardiotonic. Recent studies demonstrated its hypocholesterolaemic effect. However, to be clinically useful, more scientific data are needed. Aim of the Study: We investigated the antioxidant, hypolipidaemic and antiatherosclerotic activities of Moringa oleifera leaf extract. Materials and Methods: Scavenging activity of the extract on 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH), and the inhibitory effect on Cu2+-induced low-density lipoprotein (LDL) oxidation were determined in in vitro experiment. The effects of the extract on cholesterol levels, conjugated diene (CD) and thiobarbituric acid reactive substances (TBARS) and plaque formations in cholesterol-fed rabbits were investigated. Results: We found that in scavenging DPPH radicals the extract and Trolox® had IC50 of 78.15±0.92 and 2.14±0.12μg/ml, respectively. The extract significantly (P <0.05) prolonged the lag-time of CD formation and inhibited TBARS formation in both in vitro and ex vivo experiments in a dose-dependent manner. In hypercholesterol-fed rabbits, at 12 weeks of treatment, it significantly (P <0.05) lowered the cholesterol levels and reduced the atherosclerotic plaque formation to about 50 and 86%, respectively. These effects were at degrees comparable to those of simvastatin. Conclusions: The results indicate that this plant possesses antioxidant, hypolipidaemic and antiatherosclerotic activities and has therapeutic potential for the prevention of cardiovascular diseases. [Copyright &y& Elsevier]