Efficacy of surface hydrophobic agents in reducing water and chloride ion penetration in concrete

Hydrophobic agents are surface protection materials capable of increasing the angle of contact between the water and the concrete surface. For this reason, hydrophobic agents reduce water (in liquid form) penetration in concrete. Therefore, many European construction regulating agencies recommend this treatment in their maintenance policy. Nonetheless, there continues to be a gap in the understanding about which transport mechanisms of the concrete are modified by the hidrophobic agents. The aim of this study was to fill this gap in regards to reinforced concrete structures inserted in a marine environment. To this end, certain tests were used: Two involving permeability mechanism, one determining capillary absorption, and the last, a migration test used to estimate the chloride diffusion coefficient in saturated condition. Results indicated the efficacy of the hydrophobic agents in cases where capillary suction is the mechanism of water penetration (reduced by 2.12 and 7.0 times, depending of the product). However, when the transport mechanism is permeability this product is not advisable. Moreover, it was demonstrated that the chloride diffusion coefficient (in saturated condition) is reduced by the hydrophobic agents, however, the magnitude of this reduction is minor (reduced by 11% and 17%, depending on the product).

Cardiovascular Simulator Improvement: Pressure Versus Volume Loop Assessment

This article presents improvement on a physical cardiovascular simulator (PCS) system. Intraventricular pressure versus intraventricular volume (PxV) loop was obtained to evaluate performance of a pulsatile chamber mimicking the human left ventricle. PxV loop shows heart contractility and is normally used to evaluate heart performance. In many heart diseases, the stroke volume decreases because of low heart contractility. This pathological situation must be simulated by the PCS in order to evaluate the assistance provided by a ventricular assist device (VAD). The PCS system is automatically controlled by a computer and is an auxiliary tool for VAD control strategies development. This PCS system is according to a Windkessel model where lumped parameters are used for cardiovascular system analysis. Peripheral resistance, arteries compliance, and fluid inertance are simulated. The simulator has an actuator with a roller screw and brushless direct current motor, and the stroke volume is regulated by the actuator displacement. Internal pressure and volume measurements are monitored to obtain the PxV loop. Left chamber internal pressure is directly obtained by pressure transducer; however, internal volume has been obtained indirectly by using a linear variable differential transformer, which senses the diaphragm displacement. Correlations between the internal volume and diaphragm position are made. LabVIEW integrates these signals and shows the pressure versus internal volume loop. The results that have been obtained from the PCS system show PxV loops at different ventricle elastances, making possible the simulation of pathological situations. A preliminary test with a pulsatile VAD attached to PCS system was made.

Fungal pathogens as classical biological control agents against arthropods

Fungal entomopathogens have been used more frequently than other types of pathogens for classical biological control. Among 136 programs using different groups of arthropod pathogens, 49.3% have introduced fungal pathogens (including both the traditional fungi and microsporidia). The most commonly introduced species was Metarhizium anisopliae (Metschnikoff) Sorokin, with 13 introductions, followed by Entomophaga maimaiga Humber, Shimazu & Soper, which was released seven times. The majority of introduction programs have focused on controlling invasive species of insects or mites (70.7%) rather than on native hosts (29.4%). Almost half of the introductions of traditional fungi targeted species of Hemiptera and 75% of the microsporidia introduced have been introduced against lepidopteran species. The United States was the country where most introductions of fungi took place (n = 24). From 1993 to 2007, no arthropod pathogens were released in the US due to the rigorous regulatory structure, but in 2008 two species of microsporidia were introduced against the gypsy moth, Lymantria dispar (L.). Establishment of entomopathogenic fungi in programs introducing traditional fungi was 32.1% and establishment was 50.0% for programs introducing microsporidia. In some programs, releases have resulted in permanent successful establishment with no non-target effects. In summary, classical biological control using fungal entomopathogens can provide a successful and environmentally friendly avenue for controlling arthropod pests, including the increasing numbers of invasive non-native species.

Compatibility of Neoseiulus paspalivorus and Proctolaelaps bickleyi, candidate biocontrol agents of the coconut mite Aceria guerreronis: spatial niche use and intraguild predation

The eriophyid mite Aceria guerreronis occurs in most coconut growing regions of the world and causes enormous damage to coconut fruits. The concealed environment of the fruit perianth under which the mite resides renders its control extremely difficult. Recent studies suggest that biological control could mitigate the problems caused by this pest. Neoseiulus paspalivorus and Proctolaelaps bickleyi are two of the most frequently found predatory mites associated with A. guerreronis on coconut fruits. Regarding biological control, the former has an advantage in invading the tight areas under the coconut fruit perianth while the latter is more voracious on the pest mites and has a higher reproductive capacity. Based on the idea of the combined use/release of both predators on coconut fruits, we studied their compatibility in spatial niche use and intraguild predation (IGP). Spatial niche use on coconut fruits was examined on artificial arenas mimicking the area under the coconut fruit perianth and the open fruit surface. Both N. paspalivorus and P. bickleyi preferentially resided and oviposited inside the tight artificial chamber. Oviposition rate of P. bickleyi and residence time of N. paspalivorus inside the chamber were reduced in the presence of a conspecific female. Residence of N. paspalivorus inside the chamber was also influenced by the presence of P. bickleyi. Both N. paspalivorus and P. bickleyi preyed upon each other with relatively moderate IGP rates of adult females on larvae but neither species yielded nutritional benefits from IGP in terms of adult survival and oviposition. We discuss the relevance of our findings for a hypothetic combined use of both predators in biological control of A. guerreronis.

Influence of a probiotic soy product on fecal microbiota and its association with cardiovascular risk factors in an animal model

Background: Previous work showed that daily ingestion of an aqueous soy extract fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus 416, supplemented or not with isoflavones, reduced the total cholesterol and non-HDL-cholesterol levels, increased the high-density lipoprotein (HDL) concentration and inhibited the raising of autoantibody against oxidized low-density lipoprotein (ox-LDL Ab) and the development of atherosclerotic lesions. Objective: The aim of this study was to characterize the fecal microbiota in order to investigate the possible correlation between fecal microbiota, serum lipid parameters and atherosclerotic lesion development in rabbits with induced hypercholesterolemia, that ingested the aqueous soy extract fermented with Enterococcus faecium CRL 183 and Lactobacillus helveticus 416. Methods: The rabbits were randomly allocated to five experimental groups (n = 6): control (C), hypercholesterolemic (H), hypercholesterolemic plus unfermented soy product (HUF), hypercholesterolemic plus fermented soy product (HF) and hypercholesterolemic plus isoflavone-supplemented fermented soy product (HIF). Lipid parameters and microbiota composition were analyzed on days 0 and 60 of the treatment and the atherosclerotic lesions were quantified at the end of the experiment. The fecal microbiota was characterized by enumerating the Lactobacillus spp., Bifidobacterium spp., Enterococcus spp., Enterobacteria and Clostridium spp. populations. Results: After 60 days of the experiment, intake of the probiotic soy product was correlated with significant increases (P < 0.05) on Lactobacillus spp., Bifidobacterium spp. and Enterococcus spp. and a decrease in the Enterobacteria population. A strong correlation was observed between microbiota composition and lipid profile. Populations of Enterococcus spp., Lactobacillus spp. and Bifidobacterium spp. were negatively correlated with total cholesterol, non-HDL-cholesterol, autoantibodies against oxidized LDL (ox-LDL Ab) and lesion size. HDL-C levels were positively correlated with Lactobacillus spp., Bifidobacterium spp., and Enterococcus spp. populations. Conclusion: In conclusion, daily ingestion of the probiotic soy product, supplemented or not with isoflavones, may contribute to a beneficial balance of the fecal microbiota and this modulation is associated with an improved cholesterol profile and inhibition of atherosclerotic lesion development.

New antitumoral agents I: In vitro anticancer activity and in vivo acute toxicity of synthetic 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one and derivatives

This paper describes a new method for the preparation of 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one 1 and its derivatives 2-5. This set of synthetic compounds exhibited high antitumoral activities regarding in vitro screening against several human tumor cell lines as lung carcinoma NCI-460, melanoma UACC-62, breast MCF-7, colon HT-29, renal 786-O, ovarian OVCAR-03 and ovarian expressing the resistance phenotype for adriamycin NCI-ADR/ RES, prostate PC-3, and leukemia K-562. Compounds were also tested against murine tumor cell line B16F10 melanoma and lymphocytic leukemia L1210 as well as to their effect toward normal macrophages. Specific activity against colon cancer cells HT-29 was observed for all tested compounds and suggests further studies with models of colon cancer. Compounds 1, 2, and 4 showed significant cytotoxic activity with IC(50) values <= 2.3 mu M for all human cancer cell lines. Intraperitoneal acute administration of compound 1 and 2 showed very low toxicity rate. (C) 2010 Elsevier Ltd. All rights reserved.

3D-Pharmacophore mapping of thymidine-based inhibitors of TMPK as potential antituberculosis agents

Tuberculosis (TB) is the primary cause of mortality among infectious diseases. Mycobacterium tuberculosis monophosphate kinase (TMPKmt) is essential to DNA replication. Thus, this enzyme represents a promising target for developing new drugs against TB. In the present study, the receptor-independent, RI, 4D-QSAR method has been used to develop QSAR models and corresponding 3D-pharmacophores for a set of 81 thymidine analogues, and two corresponding subsets, reported as inhibitors of TMPKmt. The resulting optimized models are not only statistically significant with r (2) ranging from 0.83 to 0.92 and q (2) from 0.78 to 0.88, but also are robustly predictive based on test set predictions. The most and the least potent inhibitors in their respective postulated active conformations, derived from each of the models, were docked in the active site of the TMPKmt crystal structure. There is a solid consistency between the 3D-pharmacophore sites defined by the QSAR models and interactions with binding site residues. Moreover, the QSAR models provide insights regarding a probable mechanism of action of the analogues.

Molecular modeling studies and in vitro bioactivity evaluation of a set of novel 5-nitro-heterocyclic derivatives as anti-T. cruzi agents

In this study, in vitro anti-T. cruzi activity assays of nifuroxazide (NX) analogues, such as 5-nitro-2-furfuryliden and 5-nitro-2-theniliden derivatives, were performed. A molecular modeling approach was also carried out to relate the lipophilicity potential ( LP) property and biological activity data. The majority of the NX derivatives showed increased anti-T. cruzi activity in comparison to the reference drug, benznidazole (BZN). Additionally, the 5-nitro-2-furfuryliden derivatives presented better pharmacological profile than the 5-nitro-2-theniliden analogues. The LP maps and corresponding ClogP values indicate that there is an optimum lipophilicity value, which must be observed in the design of new potential anti-T. cruzi agents. (c) 2009 Elsevier Ltd. All rights reserved.

Topliss method in the optimization of salicylic acid derivatives as potential antimycobacterial agents

The Topliss method was used to guide a synthetic path in support of drug discovery efforts toward the identification of potent antimycobacterial agents. Salicylic acid and its derivatives, p-chloro, p-methoxy, and m-chlorosalicylic acid, exemplify a series of synthetic compounds whose minimum inhibitory concentrations for a strain of Mycobacterium were determined and compared to those of the reference drug, p-aminosalicylic acid. Several physicochemical descriptors (including Hammett`s sigma constant, ionization constant, dipole moment, Hansch constant, calculated partition coefficient, Sterimol-L and -B-4 and molecular volume) were considered to elucidate structure-activity relationships. Molecular electrostatic potential and molecular dipole moment maps were also calculated using the AM1 semi-empirical method. Among the new derivatives, m-chlorosalicylic acid showed the lowest minimum inhibitory concentration. The overall results suggest that both physicochemical properties and electronic features may influence the biological activity of this series of antimycobacterial agents and thus should be considered in designing new p-aminosalicylic acid analogs.

Piperamides and their derivatives as potential anti-trypanosomal agents

We describe herein an evaluation of the trypanocidal effect of eight piperamides (1-8) isolated from Piper tuberculatum bearing dihydropyridone, piperidine, and isobutyl moieties against epimastigote forms of Trypanosoma cruzi, the causative agent of Chagas` disease. Based on such results, three hydrogenated and two hydrolyzed derivatives (10-14) were prepared and evaluated as well. The dihydropyridone amides (1-3) displayed higher anti-trypanosomal activity. The (Z)-piplartine (1) showed higher activity with a 50% inhibition concentration (IC(50)) value of 10.5 mu M, almost four times more potent than the positive control, benznidazole (IC(50) = 42.7 mu M), and should be further evaluated as a suitable hit for the design of new antiprotozoal agents.

Alterations in growth and branching of Neurospora crassa caused by sub-inhibitory concentrations of antifungal agents

Six antifungal agents at subinhibitory concentrations were used for investigating their ability to affect the growth and branching in Neurospora crassa. Among the antifungals herein used, the azole agent ketoconazole at 0.5 mu g/ml inhibited radial growth more than fluconazole at 5.0 mu g/ml while amphotericin B at 0.05 mu g/ml was more effective than nystatin at 0.05 mu g/ml. Morphological alterations in hyphae were observed in the presence of griseofulvin, ketoconazole and terbinafine at the established concentrations. The antifungal agents were more effective on vegetative growth than on conidial germination. Terbinafine markedly reduced growth unit length (GU) by 54.89%, and caused mycelia to become hyperbranched. In all cases, there was a high correlation between hyphal length and number of tips (r > 0.9). All our results showed highly significant differences by ANOVA, (p < 0.001, alpha = 0.05). Considering that the hyphal tip is the main interface between the fungus and its environment/through which enzymes and toxins are secreted and nutrients absorbed, it would not be desirable to obtain a hyperbranched mycelia with inefficient doses of antifungal drugs.

Effects of Commonly Used Solubilizing Agents on a Model Nerve-Muscle Synapse

Solubility represents a limiting factor when testing new compounds in animal experiments, since solubilizing agents generally have pharmacological effects that can interfere with the studied substance. Vehicles are commonly used for solubilizing certain substances including apolar and polar extracts obtained from medicinal plants. In this study, fifteen vehicles were investigated on mice neuromuscular preparations. A known in vitro neuroblocker myotoxin from Bothrops jararacussu venom, bothropstoxin-I, was used as a pharmacological tool for testing the medicinal potential of apolar and polar extracts (hexane, dichloromethane, ethyl acetate and methanol) obtained from Casearia sylvestris Sw. leaves, which in turn were used for testing their solubility and concomitantly to produce no change on basal response of indirectly stimulated mouse phrenic nerve-diaphragm preparations. Taken together in vitro biological system and extracts solubility, our results showed that dimethyl sulphoxide and polyethylene glycol 400 were the better vehicles, and methanol extract solubilized on PEG 400 was the only one able to act against the paralysis induced by the myotoxin. Thus, this study points out to the relevant role that vehicles exhibit for extracting the potential pharmacological activity of plants in a given test system.

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial

Background: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage. Methods: This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution. Discussion: The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.

Chronic absence of baroreceptor inputs prevents training-induced cardiovascular adjustments in normotensive and spontaneously hypertensive rats

We investigate whether arterial baroreceptors mediate the training-induced blood pressure fall and resting bradycardia in hypertensive (SHR) and normotensive rats (WKY). Male SHR and WKY rats, submitted to sino-aortic denervation (SAD) or sham surgery (SHAM group), were allocated to training (T; 55% of maximal exercise capacity) or sedentary (S) protocols for 3 months. Rats were instrumented with arterial and venous catheters for haemodynamic measurements at rest (power spectral analysis) and baroreceptor testing. Kidney and skeletal muscles were processed for morphometric analysis of arterioles. Elevated mean arterial pressure (MAP) and heart rate (HR) in SHAM SHRS were accompanied by increased sympathetic variability and arteriolar wall/lumen ratio [+3.4-fold on low-frequency (LF) power and +70%, respectively, versus WKYS, P < 0.05]. Training caused significant HR (similar to 9% in WKY and SHR) and MAP reductions (-8% in the SHR), simultaneously with improvement of baroreceptor reflex control of HR (SHR and WKY), LF reduction (with a positive correlation between LF power and MAP levels in the SHR) and normalization of wall/lumen ratio of the skeletal muscle arterioles (SHR only). In contrast, SAD increased pressure variability in both strains of rats, causing reductions in MAP (-13%) and arteriolar wall/lumen ratio (-35%) only in the SHRS. Training effects were completely blocked by SAD in both strains; in addition, after SAD the resting MAP and HR and the wall/lumen ratio of skeletal muscle arterioles were higher in SHRT versus SHRS and similar to those of SHAM SHRS. The lack of training-induced effects in the chronic absence of baroreceptor inputs strongly suggests that baroreceptor signalling plays a decisive role in driving beneficial training-induced cardiovascular adjustments.

Rosuvastatin and Cardiovascular Events in Patients Undergoing Hemodialysis

Background Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved. Methods We conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events. Results After 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P = 0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P = 0.51). Conclusions In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number, NCT00240331.)