Will curcumin nanosystems be the next promising antiviral alternatives in COVID-19 treatment trials?

The COVID-19 has become of striking interest since the number of deaths is constantly rising all over the globe, and the search for an efficient treatment is more urgent. In light of this worrisome scenario, this opinion review aimed to discuss the current knowledge about the potential role of curcumin and its nanostructured systems on the SARS-CoV-2 targets. From this perspective, this work demonstrated that curcumin urges as a potential antiviral key for the treatment of SARS-CoV-2 based on its relation to the infection pathways. Moreover, the use of curcumin-loaded nanocarriers for increasing its bioavailability and therapeutic efficiency was highlighted. Additionally, the potential of the nanostructured systems by themselves and their synergic action with curcumin on molecular targets for viral infections have been explored. Finally, a viewpoint of the studies that need to be carried out to implant curcumin as a treatment for COVID-19 was addressed.

International high-risk clone of fluoroquinolone-resistant Escherichia coli O15:H1-D-ST393 in remote communities of Brazilian Amazon.

The global dissemination of multidrug-resistant Escherichia coli lineages belonging to high- risk clones poses a significant public health threat. Herein we report the identification and genomic profiling of two multidrug-resistant E. coli strains [BL-II-03(2) and BL-II-11(3)] belonging to the O15:H1-D-ST393 (clonal complex 31) worldwide spread clone, isolated from fecal samples of indigenous peoples belonging to two different ethnic groups of remote communities of Brazilian Amazon. Genomic analysis revealed genes and mutations conferring resistance to ß-lactams [blaTEM-1], aminoglycosides [aadA5, aph(3″)-Ib, aph(6)-Id], tetracyclines [tetB], sulfamethoxazole/trimethoprim [sul1, sul2, dfrA17], and fluoroquinolones [gyrA (D87N, S83L), parC (S80I, S57T), parE (L416F)]; and presence of IncQ1, IncFIA, and IncFIB(pB171) plasmids. On the other hand, phylogenomics of globally reported E. coli ST393 assigned E. coli strains BL-II-03(2) and BL-II-11(3) to a cluster comprising human isolates from Australia, Canada, China, Sweden, and United States of America. These results might provide valuable information for understanding dissemination of intercontinental multidrug-resistant clones in remote communities with low levels of antibiotic exposure.

Unveiling the Amphotericin B Degradation Pathway and Its Kinetics in Lipid-Based Solutions.

The purpose of this work was to determine the degradation pathway of Amphotericin B (AmB) and its kinetics in lipid-based solutions. Mixtures of AmB in lipophilic solvent media were stored under different conditions, such as surface area, temperature, light exposure, presence of antioxidants and other co-solutes. AmB was quantified by HPLC and UV-Vis spectrometry. Empirical models were proposed, and degradation rate constants were estimated by nonlinear regression. The HPLC method was precise and accurate with linearity from 4.45 to 52.0 nM. Surface area studies revealed that adsorption to glass did not affect AmB loss. Unsaturated oils and methanol better preserved AmB compared to medium chain-triglyceride. Temperature increased AmB loss in a nonlinear behavior and the presence of antioxidants reduced its degradation. Under dark conditions, autoxidation was the predominant degradation pathway of AmB in oil, which undergoes a complex degradation. Under light exposure, photo-oxidation accounted for AmB loss, which appeared to be of pseudo-first order. AmB oily samples should be preferably stored in glass vials protected from light with the addition of antioxidants. Furthermore, this work encourages further investigation in other media for future complex modeling and estimation of AmB degradation and kinetics in lipid-based formulations.

Use of Natural Products in Asthma Treatment.

Asthma, a disease classified as a chronic inflammatory disorder induced by airway inflammation, is triggered by a genetic predisposition or antigen sensitization. Drugs currently used as therapies present disadvantages such as high cost and side effects, which compromise the treatment compliance. Alternatively, traditional medicine has reported the use of natural products as alternative or complementary treatment. The aim of this review was to summarize the knowledge reported in the literature about the use of natural products for asthma treatment. The search strategy included scientific studies published between January 2006 and December 2017, using the keywords "asthma," "treatment," and "natural products." The inclusion criteria were as follows: (i) studies that aimed at elucidating the antiasthmatic activity of natural-based compounds or extracts using laboratory experiments (in vitro and/or in vivo); and (ii) studies that suggested the use of natural products in asthma treatment by elucidation of its chemical composition. Studies that (i) did not report experimental data and (ii) manuscripts in languages other than English were excluded. Based on the findings from the literature search, aspects related to asthma physiopathology, epidemiology, and conventional treatment were discussed. Then, several studies reporting the effectiveness of natural products in the asthma treatment were presented, highlighting plants as the main source. Moreover, natural products from animals and microorganisms were also discussed and their high potential in the antiasthmatic therapy was emphasized. This review highlighted the importance of natural products as an alternative and/or complementary treatment source for asthma treatment, since they present reduced side effects and comparable effectiveness as the drugs currently used on treatment protocols.

Bullfrog oil (Rana catesbeiana Shaw) induces apoptosis, in A2058 human melanoma cells by mitochondrial dysfunction triggered by oxidative stress.

Bullfrog oil, an animal oil extracted from the adipose tissue of Rana catesbeiana Shaw, showed promising cytotoxic activity against melanoma cells and, therefore, has the potential to become a pharmaceutical active compound. However, there is a lack of information regarding the pathways involved in its pharmacological activity. Thus, the aim of this study was to investigate and elucidate the cytotoxic effect of this oil against A2058 human melanoma cells. The cytotoxic potential was evaluated by the MTT assay, the cell cycle analysis and the cell death assay. In addition, the apoptotic potential was investigated by (i) the DNA fragmentation using propidium iodide staining analysis, (ii) the evaluation of mitochondrial membrane potential and (iii) the determination of intracellular Reactive Oxygen Species (ROS) level. The results showed that the bullfrog oil was able to promote a time-dependent cytotoxic effect, decreasing cell viability to 38% after 72 h of treatment without affecting the cell cycle. Additionally, the bullfrog oil induced the apoptosis in A2058 cells, increasing up to 50 ±â€¯13% of the intracellular ROS level, maintaining the DNA integrity and promoting an approximate decrease of 35 ±â€¯5% in the mitochondrial membrane potential. It can be concluded that the in vitro cytotoxic effect of the bullfrog oil in A2058 human melanoma cells is mediated by oxidative stress that induces mitochondrial dysfunction, triggering the apoptosis. These unprecedented results highlight the pharmacological potential of bullfrog oil and provide important information to support studies on the development of new pharmaceutical products for complementary and alternative treatments for melanoma.

Getting the Jump on the Development of Bullfrog Oil Microemulsions: a Nanocarrier for Amphotericin B Intended for Antifungal Treatment.

Amphotericin B (AmB), a potent antifungal drug, presents physicochemical characteristics that impair the development of suitable dosage forms. In order to overcome the AmB insolubility, several lipid carriers such as microemulsions have been developed. In this context, the bullfrog oil stands out as an eligible oily phase component, since its cholesterol composition may favor the AmB incorporation. Thus, the aim of this study was to develop a microemulsion based on bullfrog oil containing AmB. Moreover, its thermal stability, antifungal activity, and cytotoxicity in vitro were evaluated. The microemulsion formulation was produced using the pseudo-ternary phase diagram (PTPD) approach and the AmB was incorporated based on the pH variation technique. The antifungal activity was evaluated by determination of minimal inhibitory concentration (MIC) against different species of Candida spp. and Trichosporon asahii. The bullfrog oil microemulsion, stabilized with 16.8% of a surfactant blend, presented an average droplet size of 26.50 ± 0.14 nm and a polydispersity index of 0.167 ± 0.006. This system was able to entrap AmB up to 2 mg mL-1. The use of bullfrog oil as oily phase allowed an improvement of the thermal stability of the system. The MIC assay results revealed a growth inhibition for different strains of Candida spp. and were able to enhance the activity of AmB against T. asahii. The microemulsion was also able to reduce the AmB toxicity. Finally, the developed microemulsion showed to be a suitable system to incorporate AmB, improving the system's thermal stability, increasing the antifungal activity, and reducing the toxicity of this drug.

Monitoring structural features, biocompatibility and biological efficacy of gamma-irradiated methotrexate-loaded spray-dried microparticles.

In this study, biodegradable and biocompatible gamma irradiated poly-(dl-lactide-co-glycolide) (PLGA) spray-dried microparticles were prepared aiming to improve the efficacy of methotrexate (MTX). The experimental design included three formulations of microparticles containing distinct drug amount (9%, 18%, and 27% w/w) and three distinct gamma irradiation dose (15kGy, 25kGy, and 30kGy). The physicochemical and drug release properties of the microparticles supported their biocompatibility and biological efficacy studies in different cell lines. The irradiation induced slight changes in the spherical shape of the microparticles and the formation of free radicals was dependent on the drug loading. However, the amorphous character, particle size, drug loading, and drug release rate of the microparticles were preserved. The drug release data from all microparticles formulation were evaluated by using four drug kinetic models and by comparison of their similarity factor (f2). The gamma irradiation did not induce changes in the biocompatibility of PLGA microparticles and in the biological activity of the MTX-loaded microparticles. Finally, the spray-dried MTX-loaded PLGA microparticles enhanced the efficacy of the drug in the human cervical cancer cells (SiHa cell line). This study demonstrated the feasibility of the gamma irradiated spray dried PLGA microparticles for prolonged release of MTX, supporting a promising antitumor-drug delivery system for parenteral (subcutaneous) or pulmonary use.

Chemical Characterization and Antimicrobial Activity Evaluation of Natural Oil Nanostructured Emulsions.

The aim of this work was to investigate the antimicrobial activity of nanostructured emulsions based on copaiba (Copaifera langsdorffii) resin-oil, copaiba essential oil, and bullfrog (Rana catesbeiana Shaw) oil against fungi and bacteria related to skin diseases. Firstly, the essential oil was extracted from copaiba resin-oil and these oils, along with bullfrog oil, were characterized by gas chromatography combined with mass spectrometry (GC-MS). Secondly, nanostructured emulsion systems were produced and characterized. The antimicrobial susceptibility assay was performed, followed by the Minimum Inhibitory Concentration (MIC) determination, the bioautography assay, and the antibiofilm determination. Strains of the genera Staphylococcus, Pseudomonas, and Candida were used. The CG-MS analysis was able to identify the components of copaiba resin-oil, copaiba essential oil, and bullfrog oil. The MIC assay in association with the bioautography revealed that some esters of palmitic and oleic acids, a-curcumene, a-himachalene, isothujol, and α-fenchene--probably inhibited some strains. The nanostructured emulsions based on copaiba resin-oil and essential oil improved the antimicrobial activity of the pure oils, especially against Staphylococcus and Candida, resistant to azoles. The bullfrog oil nanostructured emulsion showed a lower antimicrobial effect when compared to the copaiba samples. However, bullfrog oil-based nanostructured emulsion showed a significant antibiofilm activity (p < 0.05). Given the significant antimicrobial and antibiofilm activities of the evaluated oils, it may be concluded that nanostructured emulsions based on copaiba and bullfrog oils are promising candidates for the treatment of infections and also may be used to incorporate other antimicrobial drugs.

Influence of the freeze-drying process on the physicochemical and biological properties of pre-heated amphotericin B micellar systems.

The moderate heat treatment of amphotericin B (AmB) in its micellar form (M-AmB) results in superaggregates (H-AmB) that present a substantially lower toxicity and similar activity. The aim of this work was to evaluate the H-AmB behavior after a freeze-drying process. H-AmB and M-AmB micelles were evaluated before and after freeze-drying concerning their physicochemical and biological properties by spectrophotometry and activity/toxicity assay, respectively. Four concentrations of M-AmB and H-AmB were studied aiming to correlate their aggregation state and the respective biological behavior: 50 mg L(-1), 5 mg L(-1), 0.5 mg L(-1), and 0.05 mg L(-1). Then, potassium leakage and hemoglobin leakage from red blood cells were used to evaluate the acute and chronic toxicity, respectively. The efficacy of M-AmB and H-AmB formulations was assessed by potassium leakage from Candida albicans and by the broth microdilution method. After heating, in addition to an evident turbidity, a slight blueshift from 327 to 323 nm was also observed at the concentrations of 50 and 5 mg L(-1) for H-AmB. Additionally, an increase in the absorbance at 323 nm at the concentration of 0.5 mg L(-1) was detected. Concerning the toxicity, H-AmB caused significantly lower hemoglobin leakage than M-AmB. These results were observed for H-AmB before and after freeze-drying. However, there was no difference between H-AmB and M-AmB concerning their activity. Accordingly, the freeze-drying cycle did not show any influence on the behavior of heated formulations, highlighting the suitability of such a method to produce a new AmB product with a long shelf life and with both greater efficiency and less toxicity.

Development of oil-in-water microemulsions for the oral delivery of amphotericin B.

Amphotericin B (AmB) is a very efficient drug against serious diseases such as leishmaniasis and systemic fungal infections. However, its oral bioavailability is limited due to its poor solubility in water. Nevertheless, it is marketed as high-cost lipid parenteral formulations that may induce serious infusion-related side effects. In this study, oil-in-water (O/W) microemulsions (MEs) were developed and characterized with a view to their use as solubility enhancers and oral delivery systems for AmB. Therefore, different nonionic surfactants from the Tween(®) and Span(®) series were tested for their solubilization capacity in combination with several oils. Based on pseudoternary phase diagrams, AmB-loaded MEs with mean droplet sizes about 120 nm were successfully produced. They were able to improve the drug solubility up to 1000-fold. Rheological studies showed the MEs to be low-viscosity formulations with Newtonian behavior. Circular dichroism and absorption spectra revealed that part of the AmB in the MEs was aggregated as an AmB reservoir carrier. Cytotoxicity studies revealed limited toxicity to macrophage-like cells that may allow the formulations to be considered as suitable carriers for AmB.

B-type natriuretic peptide in the evaluation and management of dyspnoea in primary care.

OBJECTIVES: The rapid and accurate diagnosis of heart failure in primary care is a major unmet clinical need. We evaluated the additional use of B-type natriuretic peptide (BNP) levels. DESIGN: A randomized controlled trial. SETTING: Twenty-nine primary care physicians in Switzerland and Germany coordinated by the University Hospital Basel, Switzerland. SUBJECTS: A total of 323 consecutive patients presenting with dyspnoea. INTERVENTIONS: Assignment in a 1 : 1 ratio to a diagnostic strategy including point-of-care measurement of BNP (n = 163) or standard assessment without BNP (n = 160). The total medical cost at 3 months was the primary end-point. Secondary end-points were diagnostic certainty, time to appropriate therapy, functional capacity, hospitalization and mortality. The final diagnosis was adjudicated by a physician blinded to the BNP levels. RESULTS: Heart failure was the final diagnosis in 34% of patients. The number of hospitalizations, functional status and total medical cost at 3 months [median $1655, interquartile range (IQR), 850-3331 vs. $1541, IQR 859-2827; P = 0.68] were similar in both groups. BNP increased diagnostic certainty as defined by the need for further diagnostic work-up (33% vs. 45%; P = 0.02) and accelerated the initiation of the appropriate treatment (13 days vs. 25 days; P = 0.01). The area under the receiver-operating characteristics curve for BNP to identify heart failure was 0.87 (95% confidence interval, 0.81-0.93). CONCLUSIONS: The use of BNP levels in primary care did not reduce total medical cost, but improved some of the secondary end-points including diagnostic certainty and time to initiation of appropriate treatment.

Amphotericin B microemulsion reduces toxicity and maintains the efficacy as an antifungal product.

Amphotericin B remains the drug of choice for the treatment of most of the systemic fungal infections in immunodeficient patients. Because of the high incidence of adverse drug reactions the clinical use of Amphotericin B is rather limited. To reduce its toxicity new drug delivery systems has been suggested. Nevertheless, these carriers present several technological drawbacks that impair the development of a marketable product. The aim of this work was to develop an Amphotericin B microemulsion in order to increase its efficacy and decrease its toxicity compared to Fungizon, the widely know inexpensive micellar system of Amphotericin B. Amphotericin B loaded microemulsion showed an average size close to 300 nm by photon correlation spectroscopy. In the UV spectrum, the observation of the monomeric peak at 405 nm, which was independent of the sample dilution, revealed that the Amphotericin B molecules were strongly and individually bound to the microemulsion droplets. The new microemulsion formulation had the same efficacy than Fungizon against C. albicans. Concerning toxicity, Amphotericin B loaded microemulsion showed lower toxicity against human red blood cells compared to the commercial product. Taken together, these results suggested that microemulsion is an eligible drug carrier for Amphotericin B or other water insoluble molecules, and it has potential applications to targeting fungal cells. Additionally, a novel formulation of Amphotericin B-loaded microemulsion was prepared by a straightforward and fast procedure.

Sensitive cardiac troponin in the diagnosis and risk stratification of acute heart failure.

BACKGROUND: The aim of our study was to investigate the diagnostic and prognostic value of a sensitive cardiac troponin I (s-cTnI) assay in patients with acute heart failure (AHF). METHODS: Sensitive cardiac troponin I was measured in 667 consecutive patients at presentation to the emergency department with acute dyspnoea. Three s-cTnI strata were predefined: below the limit of detection (<0.01 µg L(-1) , undetectable), detectable but still within the normal range (0.01-0.027 µg L(-1) ) and increased (≥0.028 µg L(-1) , ≥99th percentile). The final diagnosis was adjudicated by two independent cardiologists blinded to the s-cTnI levels. Median follow-up in patients with AHF was 371 days. RESULTS: Levels of s-cTnI were higher in patients with AHF (n = 377, 57%) compared to patients with noncardiac causes of acute dyspnoea (median 0.02 vs. <0.01 µg L(-1) , P < 0.001). In patients with AHF, in-hospital mortality increased with increasing s-cTnI in the three strata (2%, 5% and 14%, P < 0.001). One-year mortality also increased with increasing s-cTnI (21%, 33% and 47%, P < 0.001). s-cTnI remained an independent predictor of 1-year mortality [adjusted odds ratio 1.03 for each increase of 0.1 µg L(-1) , 95% confidence interval (CI) 1.02-1.05, P < 0.001] after adjustment for other risk factors including B-type natriuretic peptide. The net reclassification improvement was 68% (P < 0.001), and absolute integrated discrimination improvement was 0.18 (P < 0.001). The diagnostic accuracy of s-cTnI for the diagnosis of AHF as quantified by the area under the receiver operating characteristic curve was 0.78 (95% CI, 0.75-0.82). CONCLUSIONS: Sensitive cardiac troponin I is a strong predictor of short- and long-term prognosis in AHF that helps to reclassify patients in terms of mortality risk. Detectable levels of s-cTnI, even within the normal range, are independently associated with mortality.

PROCAM-, FRAMINGHAM-, SCORE- and SMART-risk score for predicting cardiovascular morbidity and mortality in patients with overt atherosclerosis.

BACKGROUND: The predictive value of PROCAM, FRAMINGHAM, SCORE and SMART-score to estimate the cardiovascular risk in patients with overt atherosclerosis had never been assessed. PATIENTS AND METHODS: 96 consecutive patients with clinically evident atherosclerosis (coronary, cerebrovascular, peripheral artery and renovascular disease) were enrolled in this preliminary observational study. At baseline, medical history and blood chemistry were obtained. Sonographic measurement of the intima-media thickness (IMT) in the common carotid artery was performed and risk estimations according to the above listed risk scores were calculated. During a 6 year follow-up the occurrence of cardiovascular death, acute coronary syndrome and stroke was assessed. RESULTS: Mean (±SD) risk-scores were 10.9±2.5, range 6-17 (SMART); 18.9±18.2%; range 0.2-94.1% (PROCAM); 21.4±13.1%, range 4-56% (FRAMINGHAM); and 4.8±3.9%, range 0.4-15.3% (SCORE). Mean IMT was 0.84±0.14 mm, range 0.51-1.20 mm. All scores correlate significantly with each other (r>0.321; p<0.01), but only SMART-score correlated significantly with baseline IMT(r=0.372; p<0.001). Within the median follow-up of 73 months, a cardiovascular endpoint was observed in 36 (42%) patients. The AUC (95% confidence interval) for SMART-risk-score predicting a cardiovascular event was 0.67 (0.54-0.77; p<0.02); for PROCAM 0.60 (0.47-0.73; p=n.s.); for FRAMINGHAM 0.56 (0.43-0.69; p=n.s.); and for SCORE 0.60 (0.46-0.73; p=n.s.). Cox regression analysis showed a relative risk for a cardiovascular event per additional SMART score point of 1.15 (95% CI 1.01-1.30 p=0.03). CONCLUSIONS: PROCAM-, FRAMINGHAM- and SCORE-risk score seem to be barely useful in a secondary prevention setting. In patients with overt atherosclerosis, the cardiovascular risk seems to be better assessed by means of the SMART score.

Interleukin family member ST2 and mortality in acute dyspnoea.

OBJECTIVES: The study objective was to investigate the prognostic utility and patient-specific characteristics of ST2 (suppression of tumorigenicity 2), assessed with a novel sensitive assay. BACKGROUND: Suppression of tumorigenicity 2 signalling has been shown to be associated with death in cardiac and pulmonary diseases. DESIGN/SUBJECTS: In an international multicentre cohort design, we prospectively enrolled 1091 patients presenting with acute dyspnoea to the emergency department (ED). ST2 was measured in a blinded fashion using a novel assay and compared to B-type natriuretic peptide (BNP) and NT-proBNP. The primary end-point was mortality within 30 days and 1 year. The prognostic value of ST2 was evaluated in comparison and in addition to BNP and NT-proBNP. RESULTS: Suppression of tumorigenicity 2 concentrations was higher amongst decedents than among survivors (median 85 vs. 43 U mL⁻¹, P < 0.001) and also higher in patients with impaired left ventricular ejection fraction (LVEF) when compared with preserved LVEF (P < 0.001). In receiver operator characteristics analysis, the area under the curve (AUC) for ST2, BNP and NT-proBNP to predict 30-day and 1-year mortality were 0.76, 0.63 and 0.71, and 0.72, 0.71 and 0.73, respectively. The combinations of ST2 with BNP or NT-proBNP improved prediction of mortality provided by BNP or NT-proBNP alone. After multivariable adjustment, ST2 values above the median (50 U mL⁻¹) significantly predicted 1-year mortality (HR 2.3, P < 0.001). CONCLUSION: In patients presenting to the ED with acute dyspnoea, ST2 is a strong and independent predictor of 30-day and 1-year mortality and might improve risk stratification already provided by BNP or NT-proBNP.

Use of B-type natriuretic peptide to predict blood pressure improvement after percutaneous revascularisation for renal artery stenosis.

OBJECTIVES: The purpose of this study was to evaluate the utility of B-type natriuretic peptide (BNP) to predict blood pressure (BP) response in patients with renal artery stenosis (RAS) after renal angioplasty and stenting (PTRA). METHODS: In 120 patients with RAS and hypertension referred for PTRA, 24-h ambulatory BP recordings were obtained before and 6 months after intervention. BNP was measured before, 1 day and 6 months after PTRA. RESULTS: BP improved in 54% of patients. Median BNP levels pre-intervention were 97 pg ml(-1) (interquartile range (IQR) 35-250) and decreased significantly within 1 day of PTRA to 62 pg ml(-1) (IQR 24-182) (p < 0.001), remaining at 75 pg ml(-1) (IQR 31-190) at 6 months. The area under the receiver operating curve for pre-intervention BNP to predict BP improvement was 0.57 (95% confidence interval (CI) 0.46-0.67). Pre-intervention BNP >50 pg ml(-1) was seen in 79% of patients with BP improvement compared with 56% in patients without improvement (p = 0.01). In a multivariate logistic regression analysis, BNP >50 pg ml(-1) was significantly associated with BP improvement (odds ratio (OR) 4.0, 95% CI 1.2-13.2). CONCLUSIONS: BNP levels are elevated in patients with RAS and decrease after revascularisation. Although BNP does not seem useful as a continuous variable, pre-interventional BNP >50 pg ml(-1) may be helpful to identify patients in whom PTRA will improve BP.

Impact of a high-dose nitrate strategy on cardiac stress in acute heart failure: a pilot study.

BACKGROUND: Intravenous nitrate therapy has been shown to improve short-term outcome of acute heart failure patients treated in the intensive care unit. The potential of a noninvasive high-dose nitrate strategy in the Emergency Department and the general ward remains unknown. METHODS: A total of 128 consecutive acute heart failure patients were either treated with standard therapy or high-dose sublingual and transdermal nitrates on top of standard of care treatment. Cardiac recovery, quantified by B-type natriuretic peptide (BNP) levels during the first 48 h, was the primary endpoint. Secondary endpoints ascertained the safety of the nitrate therapy. RESULTS: The high nitrate group received higher doses of nitrates during the first 48 h compared to the standard therapy group [82.4 mg (46.2-120.6) vs. 20 mg (10-30) respectively, P < 0.001]. The amount of diuretics given in both groups was similar. BNP levels decreased in all patients (P < 0.0001). However, the BNP decrease was larger in the high-dose nitrate group (P < 0.0001). The larger decrease in BNP in the high-dose nitrate group was already apparent 12 h after the initiation of treatment. After 48 h BNP values decreased by an average of 29 +/- 4.9% in the high-dose nitrate strategy group compared to 15 +/- 5.4% during standard therapy. There was a strong trend towards fewer ICU admissions in the high-dose nitrate group [high-dose nitrates: 2 cases (4%) vs. standard therapy: 9 cases (13%); P = 0.06]. During the study period, no intergroup changes were observed in blood pressure, RIFLE classes of acute kidney injury or troponin T. In-hospital and 90-day outcome was similar amongst the two groups. CONCLUSIONS: A noninvasive high-dose nitrate strategy on top of standard therapy is safe and notably accelerates cardiac recovery in patients observed on the general ward.

Adolescents: contraceptive knowledge and use, a Brazilian study.

The purpose of this study was to identify the knowledge and use of contraceptive methods by female adolescent students. The study was cross-sectional and quantitative, using a semi-structured questionnaire that was administered to 12- to 19-year-old female students in Maceió, Brazil. A representative and randomized sample was calculated, taking into account the number of hospital admissions for curettage. This study was approved by the Human Research Ethics Committee, and Epi Info software was used for data and result evaluation using the mean and chi-square statistical test. Our results show that the majority of students know of some contraceptive methods (95.5%), with the barrier/hormonal methods being the most mentioned (72.4%). Abortion and aborting drugs were inaccurately described as contraceptives, and 37.9% of the sexually active girls did not make use of any method. The barrier methods were the most used (35.85%). A significant association was found in the total sample (2,592) between pregnancy and the use of any contraceptive method. This association was not found, however, in the group having an active sexual life (559). The study points to a knowledge of contraceptive methods, especially by teenagers who have already been pregnant, but contraceptives were not adequately used. The low use of chemical methods of contraception brings the risk of pregnancy. Since abortion and aborting drugs were incorrectly cited as contraceptive methods, this implies a nonpreventive attitude towards pregnancy.

Development of superparamagnetic microparticles for biotechnological purposes.

Aqueous suspensions containing magnetic microparticles have been increasingly used in biosciences and biotechnology. This work describes an experimental procedure to produce superparamagnetic microparticles. The particles were prepared based on the coprecipitation of iron salts in alkaline medium. Afterwards, characterization was performed. Characterization data demonstrated that magnetite was the dominant phase in the analyzed sample, and 50% of them were in the size range of 0.5-5 microm. The results suggest that the experimental protocol provided a simple synthesis route to produce superparamagnetic microparticles. Such properties may be very useful for biotechnological purposes.

Influence of a lipophilic drug on the stability of emulsions: an important approach on the development of lipidic carriers.

The aim of this work was to investigate the influence of a lipophilic drug, Ibuprofen, on the stability of o/w emulsions. Five formulations were prepared by the phase inversion temperature (PIT) method, and Ibuprofen was incorporated into their oil phase. Emulsion stability was evaluated by short- and long-term studies. Concerning the former, stability under centrifugation showed an improved profile for Ibuprofen-loaded emulsions. The latter confirmed such findings. In conclusion, a rather resistant interfacial film may take place when Ibuprofen was incorporated into the emulsions. Therefore, the critical hydrophilic-lipophilic-balance (HLB) of o/w emulsions can be affected by a lipophilic drug into their oil phase. Such approach is of great importance on the development of lipid carriers for therapeutic drug targeting.