Protective effect of anacardic acids from cashew (Anacardium occidentale) on ethanol-induced gastric damage in mice

Cashew nut-shell liquid and the contained anacardic acids (AAs) have been shown to possess antioxidant, lipoxygenase inhibitory, anti-Helicobacter pylori and antitumor properties. Despite these known effects, hitherto there were no published reports on their likely gastroprotective effects. The present study was designed to verify whether AAs afford gastroprotection against the ethanol-induced gastric damage and to examine the underlying mechanism(s). Gastric damage was induced by intragastric administration of 0.2 mL of ethanol (96%). Mice in groups were pretreated orally with AAs (10, 30 and 100 mg/kg), misoprostol (50 μg/kg), or vehicle (2% Tween 80 in saline, 10 mL/kg), 45 min before ethanol administration. They were sacrificed 30 min later, the stomachs excised, and the mucosal lesion area (mm²) measured by planimetry. Gastroprotection was assessed in relation to inhibition of gastric lesion area. To study the gastroprotective mechanism(s), its relations to capsaicin-sensitive fibers, endogenous prostaglandins, nitric oxide and ATP-sensitive potassium channels were analysed. Treatments effects on ethanol-associated oxidative stress markers GSH, MDA, catalase, SOD, and total nitrate/nitrite levels as an index of NO were measured in gastric tissue. Besides, the effects of AAs on gastric secretory volume and total acidity were analysed in 4-h pylorus-ligated rat. AAs afforded a dose-related gastroprotection against the ethanol damage and further prevented the ethanol-induced changes in the levels of GSH, MDA, catalase, SOD and nitrate/nitrite. However, they failed to modify the gastric secretion or the total acidity. It was observed that the gastroprotection by AAs was greatly reduced in animals pretreated with capsazepine, indomethacin, l-NAME or glibenclamide. These results suggest that AAs afford gastroprotection principally through an antioxidant mechanism. Other complementary mechanisms include the activation of capsaicin-sensitive gastric afferents, stimulation of endogenous prostaglandins and nitric oxide, and opening of K⁺_ATP channels. These combined effects are likely to be accompanied by an increase in gastric microcirculation.     

Floristics and environmental factors determining the geographic distribution of epiphytic bromeliads in the Brazilian Atlantic Rain Forest

We investigated how epiphytic species and subfamilies of Bromeliaceae change along the extent of the Atlantic Rain Forest, to answer the questions: (i) How do the epiphytic genera and subfamilies of Bromeliaceae change along the domain? (ii) How similar are the different regions of the Atlantic Rain Forest in relation to the epiphytic species of bromeliads? (iii) Which environmental variables are the most important factors in determining species composition along the domain? We found 114 species of Bromelioideae and 73 of Tillandsioideae. The predominance of Bromelioideae was unexpected, because they are not wind-dispersed as would be expected for most epiphytes. The smaller number of species of Tillandsioideae, and the high frequency of species of Vriesea with limited geographic distributions indicated that epiphytes with rather limited geographic distributions predominate in this domain. Species similarity was divided into one block of south–southeastern localities, and a second block of northeastern–southeastern localities. These results suggest that the distribution of epiphytic bromeliad species resembles that of the phorophyte trees, more than a previous pattern suggested for all epiphytes in the domain. Latitude, temperature and altitude were important factors affecting the species composition along the domain. In general, our results differ from those of other studies in Latin America, and we suggest that historical and evolutionary events generated these differences.     

Technetium-99m-labeled ceftizoxime loaded long-circulating and pH-sensitive liposomes used to identify osteomyelitis

Osteomyelitis is an infectious disease located in the bone or bone marrow. Long-circulating and pH-sensitive liposomes containing a technetium-99m-labeled antibiotic, ceftizoxime, (SpHL-(99m)Tc-CF) were developed to identify osteomyelitis foci. Biodistribution studies and scintigraphic images of bone infection or non infection-bearing rats that had been treated with these liposomes were performed. A high accumulation in infectious foci and high values in the target-non target ratio could be observed. These results indicate the potential of SpHL-(99m)Tc-CF as a potential agent for the diagnosis of bone infections.     

Citrate diminishes hypothalamic acetyl-CoA carboxylase phosphorylation and modulates satiety signals and hepatic mechanisms involved in glucose homeostasis in rats

The hypothalamic AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) pathway is known to play an important role in the control of food intake and energy expenditure. Here, we hypothesize that citrate, an intermediate metabolite, activates hypothalamic ACC and is involved in the control of energy mobilization. Initially, we showed that ICV citrate injection decreased food intake and diminished weight gain significantly when compared to control and pair-fed group results. In addition, we showed that intracerebroventricular (ICV) injection of citrate diminished (80% of control) the phosphorylation of ACC, an important AMPK substrate. Furthermore, citrate treatment inhibited (75% of control) hypothalamic AMPK phosphorylation during fasting. In addition to its central effect, ICV citrate injection led to low blood glucose levels during glucose tolerance test (GTT) and high glucose uptake during hyperglycemic-euglycemic clamp. Accordingly, liver glycogen content was higher in animals given citrate (ICV) than in the control group (23.3+/-2.5 vs. 2.7+/-0.5 microg mL(-1) mg(-1), respectively). Interestingly, liver AMPK phosphorylation was reduced (80%) by the citrate treatment. The pharmacological blockade of beta3-adrenergic receptor (SR 59230A) blocked the effect of ICV citrate and citrate plus insulin on liver AMPK phosphorylation. Consistently with these results, rats treated with citrate (ICV) presented improved insulin signal transduction in liver, skeletal muscle, and epididymal fat pad. Similar results were obtained by hypothalamic administration of ARA-A, a competitive inhibitor of AMPK. Our results suggest that the citrate produced by mitochondria may modulate ACC phosphorylation in the hypothalamus, controlling food intake and coordinating a multiorgan network that controls glucose homeostasis and energy uptake through the adrenergic system.     

UCP2 protects hypothalamic cells from TNF-alpha-induced damage

Uncoupling protein 2 (UCP2) is highly expressed in the hypothalamus; however, little is known about the functions it exerts in this part of the brain. Here, we hypothesized that UCP2 protects hypothalamic cells from oxidative and pro-apoptotic damage generated by inflammatory stimuli. Intracerebroventricular injection of tumor necrosis factor alpha (TNF-alpha)-induced an increase of UCP2 expression in the hypothalamus, which was accompanied by increased expression of markers of oxidative stress and pro-apoptotic proteins. The inhibition of UCP2 expression by an antisense oligonucleotide enhanced the damaging effects of TNF-alpha. Conversely, increasing the hypothalamic expression of UCP2 by cold exposure reversed most of the effects of the cytokine. Thus, UCP2 acts as a protective factor against cellular damage induced by an inflammatory stimulus in the hypothalamus.     

Statins and Antimicrobial Effects: Simvastatin as a Potential Drug against Staphylococcus aureus Biofilm

Statins are important lipid-lowering agents with other pleiotropic effects. Several studies have explored a possible protective effect of statins to reduce the morbidity and mortality of many infectious diseases. Staphylococcus aureus is one of the main pathogens implicated in nosocomial infections; its ability to form biofilms makes treatment difficult. The present study observed the MIC of atorvastatin, pravastatin and simvastatin against S. aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis. Simvastatin was the only agent with activity against clinical isolates and reference strains of methicilin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). Thus, the effects of simvastatin on the growth, viability and biofilm formation of S. aureus were tested. In addition, a possible synergistic effect between simvastatin and vancomycin was evaluated. Simvastatin’s MIC was 15.65 µg/mL for S. aureus 29213 and 31.25 µg/mL for the other strains of S. aureus. The effect of simvastatin was bactericidal at 4xMIC and bacteriostatic at the MIC concentration. No synergistic effect was found between simvastatin and vancomycin. However, the results obtained against S. aureus biofilms showed that, in addition to inhibiting adhesion and biofilm formation at concentrations from 1/16xMIC to 4xMIC, simvastatin was also able to act against mature biofilms, reducing cell viability and extra-polysaccharide production. In conclusion, simvastatin showed pronounced antimicrobial activity against S. aureus biofilms, reducing their formation and viability.     

Production of rhamnolipids in solid-state cultivation using a mixture of sugarcane bagasse and corn bran supplemented with glycerol and soybean oil

Rhamnolipid biosurfactants are attracting attention due to their low toxicity, high biodegradability, and good ecological acceptability. However, production in submerged culture is made difficult by severe foaming problems. Solid-state cultivation (SSC) is a promising alternative production method. In the current work, we report the optimization of rhamnolipid production by Pseudomonas aeruginosa UFPEDA 614 on a solid substrate containing sugarcane bagasse and corn bran. The best rhamnolipid production, 45 g/l of impregnating solution used, was obtained with a 50:50 (m/m) mixture of sugarcane bagasse and corn bran supplemented with an impregnating solution containing 6% (v/v) of each of glycerol and soybean oil. This level is comparable with those of previous studies undertaken in solid-state cultivation; the composition of the biosurfactant is similar, but our medium is cheaper. Our work therefore provides a suitable basis for future studies of the development of an SSC-based process for rhamnolipid production.     

Particle capture into the lung made simple?

Understanding the impact distribution of particles entering the human respiratory system is of primary importance as it concerns not only atmospheric pollutants or dusts of various kinds but also the efficiency of aerosol therapy and drug delivery. To model this process, current approaches consist of increasingly complex computations of the aerodynamics and particle capture phenomena, performed in geometries trying to mimic lungs in a more and more realistic manner for as many airway generations as possible. Their capture results from the complex interplay between the details of the aerodynamic streamlines and the particle drag mechanics in the resulting flow. In contrast, the present work proposes a major simplification valid for most airway generations at quiet breathing. Within this context, focusing on particle escape rather than capture reveals a simpler structure in the entire process. When gravity can be neglected, we show by computing the escape rates in various model geometries that, although still complicated, the escape process can be depicted as a multiplicative escape cascade in which each elementary step is associated with a single bifurcation. As a net result, understanding of the particle capture may not require computing particle deposition in the entire lung structure but can be abbreviated in some regions using our simpler approach of successive computations in single realistic bifurcations. Introducing gravity back into our model, we show that this multiplicative model can still be successfully applied on up to nine generations, depending on particle type and breathing conditions.     

The Dose-Dependent Antioxidant Effects of Physical Exercise in the Hippocampus of Mice

Exercise increases both the consumption of oxygen and the production of reactive species in biological tissues, and this is counterbalanced by antioxidant adaptations to regular physical training. When the intensity of exercise fluctuates between mild and moderate, it improves the status of reduction–oxidation balance in the brain and induces neuroplasticity. However, intense exercise can oxidize the brain and impair neurological function. The effect of the frequency of exercise, which is an important factor in physical training, is still unknown. The effect of periodic exercise on biomarkers of oxidative stress in the hippocampus of mice was evaluated in this study. Mice were made to run on a treadmill for 8 weeks, two, three, or five times per week, and their hippocampi and quadriceps femoris muscles were then dissected. Biomarkers of oxidative damage were negatively correlated with the frequency of exercise and mitochondrial muscular activity, while the sulfhydryl contents were positively correlated with exercise frequency. A logistic analysis revealed a dose-dependent effect of exercise on these biomarkers. In summary, these results suggested that manipulating the frequency of physical exercise could induce antioxidant-related adaptations in the hippocampi of adult mice.