Beneficial Protective Effects Research Articles

Abstract 17177: Crosstalk and Synergism Between Local Brain-derived and Exogenous 17β-Estradiol in Regulating Rapid, Pro-survival Signaling in the Hippocampus Following Global Cerebral Ischemia

Cardiac arrest-induced global cerebral ischemia (GCI) can lead to death of hippocampal CA1 neurons and cognitive impairment. Previous work has shown that the steroid hormone, 17β-estradiol (E2) is strongly neuroprotective against GCI, an effect that involves, in part, rapid signaling via the membrane estrogen receptor, GPR30. To gain greater insight into E2 actions, the current study examined: 1) whether GPR30 expression in the hippocampus changes after CGI, and 2) the role and potential crosstalk/synergism between local (brain-derived) and exogenous E2 in regulation of GPR30 and rapid prosurvival signaling after GCI. GCI was induced in adult ovariectomized female rats by a 4-vessel occlusion model (12-min occlusion). Vehicle or low diestrous levels of E2 were administered chronically by minipump beginning at the time of ovariectomy. The results showed that GPR30 expression in the hippocampal CA1 was unchanged at 3h, but significantly decreased at 1d and 3d after GCI. In contrast, aromatase expression showed an initial decrease at 3h, a rebound at 1day, and a robust elevation at 3 days after CGI. Administration of exogenous E2 increased both GPR30 and aromatase expression at 3h, 1d and 3d after GCI. Interestingly, central administration of the aromatase inhibitor, letrozole or aromatase antisense (AS) oligonucleotides abolished exogenous E2 enhancement of GPR30 and aromatase at 3d after GCI. Furthermore, letrozole and aromatase-AS treatment attenuated exogenous E2-induced phosphorylation/activation of prosurvival ERK1/2 and CREB following GCI, as well as exogenous E2-induced enhanced expression of BDNF, PSD95 and synaptophsin. As a whole, the results suggest that local-derived E2 may help mediate beneficial protective effects of exogenous E2 after GCI to enhance GPR30 expression, increase activation of ERK1/2-CREB-BDNF pro-survival signaling, and improve synaptic function.

CBLB502, an agonist of Toll-like receptor 5, has antioxidant and scavenging free radicals activities in vitro

The bacterial protein flagellin is the known agonist of Toll-like receptor 5 (TLR5). It has been reported that CBLB502, a novel agonist of TLR5 derived from Salmonella flagellin, could reduce radiation toxicity in mouse and primate models, protect mice from dermatitis and oral mucositis caused by radiation, inhibit acute renal ischemic failure, and inhibit the growth of A549 lung cancer cell. The property of CBLB502 is able to bind to TLR5 and activates NF-κB signaling. In this study, we investigated the antioxidant potential and free radicals scavenging properties of CBLB502 in vitro. Interestingly, we found that CBLB502 has a direct and distinct antioxidant capacity and can efficiently scavenge a variety of free radicals, including superoxide anion, hydroxyl radical, and ABTS cation (ABTS+). Through wave scanning and kinetic evaluation of scavenging ABTS+, we found that the ABTS+ scavenging process of CBLB502 is relatively slow, and the ABTS+ scavenging activity of CBLB502 has a consistently kinetics characteristics. In conclusion, our results suggested that CBLB502 has antioxidant and scavenging free radicals activities in vitro. It is implied that CBLB502 might partially promote the beneficial protective effect through its scavenging free radicals.

Beneficial protective effect of pramipexole on light-induced retinal damage in mice

We investigated the effects of pramipexole, a potent dopamine receptor D2/D3 agonist, on light-induced retinal damage in mice, H2O2-induced retinal pigment epithelium ARPE-19 cell injury in humans, and hydroxyl radical scavenging activity in a cell-free system. Pramipexole (0.1 and 1 mg/kg body weight) was orally administered to mice 1 h before light exposure (5000 lux, 2 h). Electrophysiological and morphologic studies were performed to evaluate the effects of the pramipexole on light-induced retinal damage in mice. Pramipexole significantly prevented the reduction of the a- and b-wave electroretinogram (ERG) amplitudes caused by light exposure in a dose-dependent manner. In parallel, damage to the inner and outer segments (IS/OS) of the photoreceptors, loss of photoreceptor nuclei, and the number of Tdt-mediated dUTP nick-end labeling (TUNEL)-positive cells in the outer nuclear layer (ONL) caused by light exposure were notably ameliorated by pramipexole. Additionally, pramipexole suppressed H2O2-induced ARPE-19 cell death in vitro in a concentration-dependent manner. The effect of pramipexole was significant at concentrations of 10−6 M or higher. Pramipexole also significantly prevented H2O2-induced activation of caspases-3/7 and the intracellular accumulation of reactive oxygen species (ROS) in a concentration-dependent manner ranging from 10−5 to 10−3 M. Furthermore, pramipexole increased the scavenging activity toward a hydroxyl radical generated from H2O2 in a Fenton reaction. Our results suggest that pramipexole protects against light-induced retinal damage as an antioxidant and that it may be a novel and effective therapy for retinal degenerative disorders, such as dry age-related macular degeneration.

Transglutaminase 2 and Anti Transglutaminase 2 Autoantibodies in Celiac Disease and Beyond: Anti- Transglutaminase 2 Autoantibodies: Friends or Enemies

Tissue transglutaminase is a multifunctional enzyme, exerting intra and extracellular, enzymatic and nonenzymatic, Ca2+ dependent and independent functions. Its specific autoantibody, the anti transglutaminase2 autoantibody is multifunctional, affecting many of the enzyme activities. Most of them are due to loss of function, the minority being gain of function of the enzyme. No beneficial protective effects, but only pathogenic ones, were assigned to those celiac disease associated anti TG2 autoantibodies. Taken together, celiac antibodies could collectively promote small bowel intestinal or extraintestinal damage. Yet, most of the transglutaminase2 autoantibody activities where explored in vitro and ex-vivo, very few in animal model but none in vivo, in human. The celiac disease serum contains numerous antibodies, IgA-transglutaminase2 is only one of them and up till now, its differential role in celiac disease induction and maintenance is far from being unraveled. Unraveling them might open some new therapeutic strategies for celiac disease.

Beneficial erythropoietic effects of recombinant human erythropoietin in very low-birth weight infants: A single-center randomized double-blinded placebo-controlled trial

Purpose: Due to appearing serious a complication following repeated blood products transfusion in premature neonates, beneficial protective effects of recombinant human erythropoietin (rhEpo) is being widely investigated. The present study evaluated the effectiveness of rhEpo in preventing anemia of prematurity by assessment of the changes in serum erythropoiesis parameters in very low birth weight (VLBW) neonates. Materials and Methods: In a single-center randomized, double-blinded, placebo-controlled trial, 60 premature infants with birth weight <1500g who were born between 24 and 31 weeks of gestation admitted to the neonatal intensive care unit of Fatemieh Hospital in Hamadan were enrolled. The study medication (rhEpo or placebo) was randomly assigned to each patient. The rhEpo (250 U rhEpo/kg body weight at birth, equal to 1 mL solution/kg birth weight) and placebo drug solutions were indistinguishable. The study drug was administered 3 times weekly for 3 weeks. Results: Monitoring hemoglobin, hematocrit and reticulocyte count showed no relevant deviation from baseline to the 2 nd week of the study. However, there was relevant difference for these parameters between investigated patients who received rhEpo and the patients who received placebo during the 3 rd week of the medication. 16 (53.3%) in the intervention group and 20 (66.7%) in the control group required blood transfusion with an insignificant difference. No serious side-effects were observed in either the rhEpo or placebo group. Conclusion: Our study suggested that rhEpo is an effective drug for improving erythropoiesis parameters after 3 weeks of administration in VLBW infants regardless its effect on the need for blood transfusions.

Renoprotective and antioxidant renal effects of cilnidipine in DOCA Salt -Treated Albino Rats

Aim: Cilnidipine is a dihydropyridine calcium channel blocker (CCB) that blocks both L-type and N- type channels at the smooth muscle in the artery and calcium channels at the presynaptic nerve terminal, respectively. It is dihydropyridine calcium antagonist that possesses a slow-onset, long-lasting vasodilating effect. The present study is designed to determine the effect of cilnidipine on creatinine clearance, thiobarbituric acid reactive substance, as an index of lipid peroxidation. Additionally, the level of superoxide dismutase enzyme in erythrocyte lysates and kidney catalase enzyme activitiy will be measured. Thirty-six albino rats are divided into 3 separate groups: rats of group 1 are control group, rats of group 2 are administered by deoxycorticosterone acetate (DOCA) salt sc twice/week + 1% NaCl for 2 weeks to be rendered hypertensive) and group 3 will receive 9 mg/kg cilnidipine for 3 weeks intragastrically after induction of hypertension by DOCA-salt as group 2. Results: DOCA-injected albino rats show marked reduction in creatinine clearance. Treatment with cilnidipine improves creatinine clearance compared to the non-treated hypertensive group 2. Additionally, it reduces thiobarbituric acid reactive substance, as an index of lipid peroxidation, with a significant increase in superoxide dismutase enzyme in erythrocyte lysates and kidney catalase enzyme activities. Conclusion: This study points to the possible beneficial renal protective effects of cilnidipine in hypertensive albino rats injected with DOCA for 2 weeks.

Potential Role of Carotenoids as Antioxidants in Human Health and Disease

Carotenoids constitute a ubiquitous group of isoprenoid pigments. They are very efficient physical quenchers of singlet oxygen and scavengers of other reactive oxygen species. Carotenoids can also act as chemical quenchers undergoing irreversible oxygenation. The molecular mechanisms underlying these reactions are still not fully understood, especially in the context of the anti- and pro-oxidant activity of carotenoids, which, although not synthesized by humans and animals, are also present in their blood and tissues, contributing to a number of biochemical processes. The antioxidant potential of carotenoids is of particular significance to human health, due to the fact that losing antioxidant-reactive oxygen species balance results in “oxidative stress”, a critical factor of the pathogenic processes of various chronic disorders. Data coming from epidemiological studies and clinical trials strongly support the observation that adequate carotenoid supplementation may significantly reduce the risk of several disorders mediated by reactive oxygen species. Here, we would like to highlight the beneficial (protective) effects of dietary carotenoid intake in exemplary widespread modern civilization diseases, i.e., cancer, cardiovascular or photosensitivity disorders, in the context of carotenoids’ unique antioxidative properties.

Oxidative stress: implications for the development of diabetic retinopathy and antioxidant therapeutic perspectives.

In recent decades, localized tissue oxidative stress has been implicated as a key component in the development of diabetic retinopathy (DR). Increasing evidence shows that oxidative stress caused by diabetes-induced metabolic abnormalities is the most common mechanism associated with the pathogenesis of DR for both type 1 and type 2 diabetes. Increase in intracellular reactive oxygen species (ROS) concentrations results in the activation of several mechanisms involved in the pathogenesis of DR. In particular, damage or dysfunction caused by oxidative stress still persists even after glycemia has been normalized. Despite considerable evidence showing the beneficial effects of antioxidants in preventing the development of retinopathy, results from large-scale clinical trials on classic antioxidants are somewhat ambiguous. Scavenging reactive radicals may not be the most ideal antioxidant strategy in DR. Advances in understanding the function of ROS in the development of DR can lead to the development of new therapeutic strategies based on the mechanisms of ROS generation and scavenging. Increasing amounts of data have demonstrated the promising prospect of antioxidant therapy and its beneficial effects in vision protection. Therefore, new strategies that utilize antioxidants as additive therapy should be implemented in the treatment of DR.

Effects of curcumin on changes of Egr-1mRNA, IL-1β and TNF-α in paraquat-induced acute lung injury in rats

Objective To observe the changes of early growth response factor-1 mRNA (Egr-1 mRNA),interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in rat with paraquat (PQ)-induced acute lung injury,and the potential protective effect of curcumin on this injury.Methods Adult male Sprague-Dauley (SD) rats were randomly (random number) divided into control,PQ-poisoning and curcumin-intervention groups.At 3 h,6 h,24 h,3 d,7 d after treatment,each group respectively further divided into 5 subgroups.Rats in PQ-poisoning group were intraperitoneally (IP) administered with PQ 15 mg/kg,and rats in cureumin-intervention group were administered with PQ 15 mg/kg IP at 15 min after curcumin 200 mg/kg IP.Rats in control group were given normal saline (NS) 1 mL IP instead.The expression of Egr-1 mRNA in lungs tissue were measured with Fluorescence real-time quantitative PCR device.The levels of IL-1β and TNF-α in bronchoalveolar lavage fluid (BALF) were measured with enzyme-hnked immunosorbent assay (ELISA).Pathological changes in lung were observed under light microscope.Experimental data were treated with single-factor analysis of variance and compared between groups with Bonferroni method.Results Compared with the control group,Egr-1 mRNA expression in lungs tissue and TNF-α level in BALF in PQ-poisoning group and curcumin-intervention group,IL-1β level in BALF in PQ-poisoning group increased significantly at 6 h,24 h,3 d,7 d after PQ exposure (P ＜ 0.05 or P ＜ 0.01),and IL-1β level in BALF increased significantly at 24 h after PQ exposure in curcuminintervention group (P ＜ 0.05).Compared with the PQ-poisoning group,Egr-1 mRNA expression in lungs tissue,TNF-α and IL-1 β level in BALF decreased significantly at 24 h,3 d,7 d after PQ exposure in curcumin-intervention group (P ＜ 0.05 or P ＜ 0.01).Pathological changes of lung tissue were more serious in PQ-poisoning group than those in curcumin-intervention group.Conclusions The up-regulated expression of Egr-1 mRNA increased releasing ofIL-1β and TNF-α,and initiating inflammation may be one of the mechanism of PQ-induced acute lung injury in rats.Curcumin may have beneficial protective effects on lung in this above described pathway of signaling. Key words: Paraquat ; Early growth response factor-1 mRNA ; Interleukin-1β ; Tumor necrosis factor-α; Lung injury; Curcumin; Poison; Rat

Protective value of Aloe vera extract against γ-irradiation-induced some biochemical disorders in rats

The current study was conducted to evaluate the modulating efficacy of prolonged administration of Aloe vera extract against γ-irradiation-induced oxidative stress in male rats. Aloe vera extract was orally administrated in a dose of 300 mg/kg body weight daily for 21 successive days before irradiation (5 Gy as an acute dose) and 7 days post exposure. The oxidative stress markers; malondialdehyde (MDA), reduced glutathione (GSH) and metallothionein (MT) were estimated in hepatic tissues. Levels of certain trace metals namely iron, copper and zinc were determined in blood, liver and intestinal tissues as well as in Aloe vera extract, in addition histological examination of liver tissues was investigated. Rats exposed to ionizing radiation had elevation in MDA, depletion in GSH and MT level, in addition to alterations in trace metal concentration in blood, liver and intestine. Photomicrograph showed abnormalities in hepatic tissues. Aloe vera extract administration pre- and post-γ-irradiation resulted in noticeable improvement in the studied antioxidant status of liver tissue; restored the control levels of Fe and Cu levels in liver and intestine as well as intestinal Zn. In conclusion, Aloe vera extract have a beneficial protective effect against radiation-induced oxidative stress.

Anti-influenza active and low toxic N-phenyl-substituted β-amidoamidines structurally related to natural antibiotic amidinomycin

A set of racemic N-phenyl-substituted β-amidoamidines hydrochlorides 4, which are structurally related to natural antiviral agent amidinomycin (1), was synthesized in four steps starting from methacryloyl anilide (5). In the final step of the synthetic route, an uncommon monoacylation of β-aminoamidine 8 at the less reactive β-phenylamino-group took place. To rationalize this result, a mechanism which involves initial acylation at the more active amidine-function followed by intramolecular acyl-group transfer to β-phenylamino-group was suggested. All three β-amidoamidines 4d–f bearing long linear aliphatic chain (from n-C8H17 to n-C12H25) revealed significant in vitro activity against influenza A virus (H3N2) and modest cytotoxicity. The in vitro antiviral potency of 4d,e is 6–20 times greater than that of commercial rimantadine with lower EC50 values and higher therapeutic index. The non-toxic in vivo compounds 4d–f showed a beneficial protective effect in influenza A (H3N2) infected mice.

Protective Effect of Alcoholic extract of Black Current in Male Reproductive System of Methionine Overload Rats

This study was undertaken to investigate the deleterious- effect of methionine overload on male reproductive system of adult male rats. It was also aim to studying the beneficial protective effect of alcoholic extract of black current. Eighteen adult male rats (175-200 gm) were used, animals were randomly divided into three groups (6/group) and were treated daily for 42 days as follows: 1-Group C (control); 2- group I(GI), the rats in this group were orally intubated by gavages needle DL-methionine (100 mg / Kg BW.) 3- animals in group II(GII) were administered orally alcoholic extract of black current (60 mg /Kg BW.) in addition to methionine. At the end of the experiment blood samples were collected for measuring serum testosterone (T) hormone and follicular stimulating hormone (FSH) concentrations. As well as histological section, for testis was taken for histopathological study the results revealed that oral intubation of 100mg /kg BW. of methionine for 42 days caused significant decrease - in serum testosterone (T) hormone and follicular stimulating hormone (FSH) concentrations in groups (GI and GII) comparing to control ,while oral intubation of alcoholic- extract of black current (GII) caused significant elevation in the concentration of these two hormones comparing to methionine treated group (GI). Furthermore, methionine intubation caused significant decrease in diameter and thickness of seminiferous tubules with cellular degeneration of Sertoli cells, while black current intubation caused significant increase in the previous criteria and regeneration of Sertoli cells. In conclusion, this study pointed to the deleterious effect of methionine overload and assures protective effect of alcoholic extract of black current on adult male rats reproductive system.

Supported liquid extraction in the quantitation of plasma enterolignans using isotope dilution GC/MS with application to flaxseed consumption in healthy adults

Dietary interventions involving foods that are enriched in lignans, such as flaxseed, are drawing attention due to their beneficial protective effects in various diseases and human conditions. Accurate quantitation of key lignan metabolites such as enterodiol (END) and enterolactone (ENL) is necessary in order to identify factors that may influence overall bioavailability. Here we describe the validation of a novel supported liquid extraction (SLE) method for isolation of plasma enterolignans, END and ENL, using 2H6-labeled isotopes with gas chromatography–mass spectrometry in micro selected ion storage (GC/MS-μSIS) mode. Following enzymatic hydrolysis and SLE extraction with 70:30 diethyl ether:ethyl acetate, enterolignans were rapidly separated within 8min. SLE in combination with GC/MS-μSIS gave high recoveries of 96.4% and 96.0% for END and ENL. Intra-assay precision ranged from 2.5 to 5.9% for both compounds whereas the inter-assay precision was 2.6–6.9%. SLE was also directly compared to liquid liquid extraction (LLE). Both techniques offered high precision and accuracy, however, SLE consistently enabled successful analyte extractions and derivatizations, unlike LLE, which had an ∼4% failure rate. SLE was also tested in a study where dietary milled flaxseed supplementation (30g/day for 1month) and enterolignan bioavailability was examined in a healthy, human population (n=10). Plasma total enterolignan levels significantly increased (P=0.002) at 4weeks relative to baseline. Average concentrations for END and ENL were 209nM and 304nM, respectively.

The protective effect of adipose-derived stem cells against liver injury by trophic molecules

BackgroundIn this study we investigated whether adipose-derived stem cells (ADSCs) had any beneficial protective effects on liver injury and regeneration in vivo. Moreover, we examined whether ADSCs protect hepatocytes via trophic molecules. Materials and methodsWe transplanted ADSCs into mice after 70% hepatectomy and ischemia-reperfusion, and observed liver injury and regeneration after reperfusion. We co-cultured hepatocytes with ADSCs using a Transwell system for 7 d and evaluated the viabilities of hepatocytes and the cytokine levels in the culture medium. Bevacizumab was used to confirm the effect of vascular endothelial growth factor (VEGF) on hepatocytes. ResultsADSCs improved serum liver function at 6 h after reperfusion in a nonlethal model and stimulated liver regeneration at 24 h after reperfusion in a lethal model. VEGF levels in the culture medium were increased by co-culture ADSCs with hepatocytes. ADSCs improved the viabilities of hepatocytes. The inhibited production of VEGF by bevacizumab did not affect the viability of hepatocytes. ConclusionsADSCs were able to ameliorate liver injury and stimulate liver regeneration in subsequent hepatectomy and ischemia-reperfusion–injured model mice. Furthermore, hepatocytes were protected by the trophic molecules of the ADSCs. However, such protective effects might be provided by mechanisms other than VEGF signaling.

Alpha-lipoic acid pre- and post-treatments provide protection against in vitro ischemia-reperfusion injury in cerebral endothelial cells via Akt/mTOR signaling

Alpha-lipoic acid (ALA) is an endogenous short-chain fatty acid that has beneficial protective effects against various vascular diseases. In this study, we sought to determine whether ALA could induce pre- or post-treatment protective effects against simulated ischemia and reperfusion-induced cerebral endothelial cell (CEC) injury by activating the Akt/mTOR pathway. CECs are currently considered to be an important target for ischemia therapy. Mouse brain endothelial cells (bEnd.3) and primary cultures of CECs were subjected to 6h of oxygen glucose deprivation (OGD) followed by 4h of simulated reperfusion, either alone or together with ALA administration before (pre-treatment) or immediately after (post-treatment) OGD. We found that pre-treatment administration of ALA reduced the OGD and simulated reperfusion-induced lactate dehydrogenase (LDH) release in bEnd.3 cells in a dose-dependent manner and that 1mM ALA pre- and post-treatments provided protection in both bEnd.3 cells and primary cultures of CECs. However, rapamycin, an mTOR inhibitor, was able to thoroughly abolish the protective effects of ALA. Western blotting showed that the ALA pre- and post-treatments up-regulated the phosphorylation of Akt, mTOR, S6K and 4E-BP1 in both bEnd.3 cells and primary cultures. However, after pre-treatment with rapamycin, the level of Akt phosphorylation was decreased in primary cultures of CECs but could still be restored by ALA, whereas the levels of mTOR, S6K and 4E-BP1 phosphorylation were significantly decreased and could not be restored. These results suggest that ALA pre- and post-treatments provide protective effects against simulated ischemia and reperfusion-induced CEC injury by promoting the Akt/mTOR pathway and that mTOR is required for ALA protection.

Editorial: Vitamin A as adjunct therapy for cerebral malaria: what is the evidence?

Severe malaria continues to cause significant morbidity and mortality in several settings in Africa despite the availability of efficacious and potent antimalarial drugs. This has led to an increased interest in adjunctive therapies that target the underlying pathophysiology of severe malaria as additional approaches to management that may further reduce morbidity and mortality. Several adjunctive therapies have been tested over the years including dexamethasone, exchange blood transfusion, N-acetylsysteine, anti-TNF, mannitol and levamisole. However despite numerous clinical trials, to date, effective adjunctive treatments have been elusive. Most trials have been underpowered and in a recent review many were found to have inadequate methodological quality. It is apparent therefore that different approaches to adjunctive therapy for severe malaria have been evaluated. One additional approach has been exploring the utilization of micronutrients in the management of malaria. Whereas micronutrients are well known to have antioxidant effects, their interaction with malaria is not well characterized. Their role for the treatment and prevention of malaria has however been a source of intrigue with studies reporting conflicting results on their impact. Zinc, vitamin A and E, carotenoids, vitamins B and C and folic acid have been reported to have modulatory effects on the pathogenesis of malaria1. Beneficial protective effects of vitamin A or zinc on malaria-related morbidity have been demonstrated in some settings2,3,4,5. In Burkina Faso, combined supplementation with vitamin A and zinc reduced the burden of clinical attacks of malaria in young children by 30%6. In contrast to these studies that have suggested potential protective effects of vitamin A or zinc supplementation, other studies have shown the reverse. A randomized, placebo-controlled trial in Burkina Faso of zinc supplementation failed to show a protective impact on malaria episodes7. In addition, a study done in 2006 found that iron and folic acid supplements instead increased malaria-related hospitalization and deaths by 12 per cent. In a more recent study in Tanzania, giving supplements containing iron, folic acid, copper and vitamins to about 600 children aged 6 months to 5 years with iron deficiency increased their likelihood of contracting malaria by 41 per cent8. These conflicting findings indicate that currently, there is no consensus on the exact impact of micronutrients on malaria treatment and prevention. In this issue of the African Health Sciences, Mwanga et al report results of a randomized controlled trial evaluating the effect of vitamin A adjunct therapy for cerebral malaria in children admitted to Mulago hospital9. As a leading cause of childhood mortality in sub-Saharan Africa, interventions to ameliorate mortality due to cerebral malaria are a public health priority. Vitamin A is an essential nutrient required for maintaining immune function, playing an important role in the regulation of cell-mediated immunity and in humoral antibody responses. Vitamin A has been shown to suppress growth of P.falciparum, scavenge free radicals, and exhibit synergistic action with quinine in parasite clearance10,10. Mwanga et al studied 142 children aged 6 months to 5 years, who were randomized to receive either Vitamin A or placebo and antimalarial treatment with intravenous quinine. The results show that whereas there were no significant differences in outcome measures between the two treatment arms, there was a trend towards earlier resolution of convulsions and lower mortality (8.1%) in children who received Vitamin A supplementation compared to 16.2% in the placebo. Whereas this difference in mortality did not reach statistical significance; it draws attention to the potential role of Vitamin A as adjunct therapy for cerebral malaria. Vitamin A is a particularly attractive option for this role as it is a relatively affordable, easy to administer and readily available intervention that could be appropriate for use in several malaria endemic countries. However, before any such recommendations are made, a sufficiently powered study with different dosing regimens are warranted to provide more conclusive evidence for the role Vitamin A could play as adjunct therapy. Furthermore reduction in severe malaria related mortality will also be achieved through embracing the use of intravenous artesunate as the preferred first line drug for the management of severe malaria. In several settings in sub-Saharan Africa, additional interventions will include improved health seeking behavior that will promote early treatment seeking, strengthening of referral systems, improved triage and emergency treatment approaches and finally better supportive care for hospitalized patients.

Aliskiren improves insulin resistance and ameliorates diabetic renal vascular complications in STZ-induced diabetic rats

Aliskiren, a direct renin inhibitor (DRI), has therapeutic effects in patients with hypertension and associated complications, but its potential mechanism in diabetic nephropathy is lacking. The effects of aliskiren in Streptozotocin (STZ)-induced renal complication in diabetic rats were investigated. Aliskiren treatment for eight weeks at the dose of 10 mg/kg/day, via osmotic mini-pump, induced improvement in blood glucose levels, systolic blood pressure (BP) and serum creatinine. Improvement of insulin resistance by aliskiren was confirmed by increased glucose translocation in liver and muscle and hence insulin levels. The treated group also showed improvement in glomerulosclerosis and tubulointerstitial injury. Aliskiren treatment also improved albumin levels in plasma, suppressed profibrotic and proinflammatory cytokine synthesis viz TNF-α and TGF-β and angiogenesis by a decrease in VEGF. In addition, the level of total proteins and GFR via cystatin c and beta-2microglobulin along with adiponectin and erythropoietin were also improved. These results suggest that the beneficial organ protective effect of aliskiren is mediated by improvement in insulin resistance as well as a direct anti-fibrotic effect in the target organ in STZ-induced diabetic rats with a slight effect on blood pressure. Aliskiren may be a useful therapeutic agent in the treatment of type 2 diabetes and diabetic nephropathy.

Discrimination of vicinal-diol-containing flavonoids and black teas by arrays of host–indicator ensembles

Tea has attracted attention the world over because of its purported beneficial protective effects against many kinds of diseases. Based on the ‘indicator displacement assay’ mechanism, we report a series of dynamic three-component sensing ensembles for the discrimination of vicinal-diol-containing flavonoids and black tea extracts. The sensing arrays constructed in this paper are capable of quick analyses of vicinal-diol-containing flavonoids and the differentiation of black teas.

Efecto hipoglicemiante del extracto acuoso de las hojas de Smallanthus sonchifolius (Yacón) en pacientes con diabetes mellitus tipo 2

El presente estudio se realizó con el objetivo de evaluar el efecto hipoglicemiante de las hojas de Smallanthus sonchifolius (yacón), en la forma de infusión (extracto acuoso), administrada a pacientes con diabetes mellitus tipo 2. Previa firma de su consentimiento informado, participaron 206 personas de 30 a 70 años de edad, hombres y mujeres: 105 con diagnostico de diabetes mellitus tipo 2 y 101 aparentemente sanas, como grupo control. Los pacientes diabéticos tipo 2 fueron personas que acuden al Servicio Académico Asistencial de Análisis Clínicos (SAAAC), al Gabinete de Atención Farmacéutica (GAF) de la Facultad de Farmacia y Bioquímica, al Club de diabéticos tipo 2 del Hospital Cayetano Heredia, y al Centro de Salud (CERIT) Raúl Patrucco Puig. De los 105 diabéticos tipo 2 que recibían tratamiento farmacológico 46 estaban metabólicamente controlados (Grupo A1) y 59 no (Grupo A2). Los sujetos aparentemente sanos fueron divididos en dos grupos: 60 sujetos normales (Grupo B1) y 41 sujetos sin diabetes mellitus tipo 2 con mal control metabólico (Grupo B2). A los Grupos A2 y B2 se les proporcionó bolsas filtrantes de hojas de yacón de 1 g cada una, para ser tomadas en infusión tres veces al día por 90 días. El Grupo A2 continuó recibiendo glibenclamida. A todos se les determinó en ayunas la concentración de glucosa, hemoglobina glicosilada (HbA1c) y fructosamina, antes y después del tratamiento. Al final del tratamiento, se encontró que, la administración de la infusión de hojas de yacón disminuyó los valores de: glucosa en 42,7 %, hemoglobina glicosilada en 21,7 % y fructosamina en 33,78 %, observándose una diferencia estadísticamente significativa con los valores basales. La eficacia de la combinación estudiada logra reducir las cifras de HbA1c en 4,5 % a los 30 días y 21,7 % a los 90 días. En conclusión, la infusión de hojas de Smallanthus sonchifolius (yacón), administrada a pacientes con diabetes mellitus tipo 2, tiene un efecto protector beneficioso sobre el control glucémico.

Dieta e aspectos nutricionais no lúpus eritematoso sistêmico

The authors reviewed the influence of nutritional factors on systemic lupus erythematosus (SLE) and discussed an alternative treatment option. The autoimmunity and inflammatory process of SLE are related to the presence of dyslipidemia, obesity, systemic arterial hypertension, and metabolic syndrome, which should be properly considered to decrease cardiovascular risk. A diet with moderate protein and energy content, but rich in vitamins, minerals (especially antioxidants), and mono/polyunsaturated fatty acids can promote a beneficial protective effect against tissue damage and suppression of inflammatory activity, in addition to helping the treatment of those comorbidities. Diet therapy is a promising approach and some recommendations may offer a better quality of life to patients with SLE.