Pharmacokinetic aspects of Tert-Butylaminoethyl disulfide, an experimental drug against schistosomiasis in mice

A preliminary study of the pharmacokinetic parameters of t-Butylaminoethyl disulfide was performed after administration of two different single doses (35 and 300 mg/kg) of either the cold or labelled drug. Plasma or blood samples were treated with dithiothreitol, perchloric acid, and, after filtration, submitted to further purification with anionic resein. In the final step, the drug was retained on a cationic resin column, eluted with NaCl 1M and detected according to the method of Ellman (1958). Alternatively, radioactive drug was detected by liquid scintillation counting. The results corresponding to the smaller dose of total drug suggested a pharmacokinetic behavior related to a one open compartment model with the following parameters: area under the intravenous curve (AUC i.v.):671 ± 14; AUC oral: 150 ± 40 µg.min. ml [raised to the power of -1]; elimination rate constant: 0.071 min [raised to the power of -1]; biological half life: 9.8 min; distribution volume: 0.74 ml/g. For the higher dose, the results seemed to obey a more complex undertermined model. Combining the results, the occurence of a dose-dependent pharmacokinetic behavior is suggested, the drug being rapidly absorbed and rapidly eliminated; the elimination process being related mainly to metabolization. The drug seems to be more toxic when administered I.V. because by this route it escapes first pass metabolism, while being quickly distributed to tissues. The maximum tolerated blood level seems to be around 16 µg/ml.

Pharmacokinetic profile of tert-butylaminoethanethiol

A preliminary study of the pharmacokinetic parameters of t-Butylaminoethanethiol (TBAESH) was performed after administration of a single dose (35 mg/kg) either orally or intravenously. Plasma or blood samples were treated with dithiothreitol, perchloric acid and, after filtration, submitted to further purification with anionic resin. In the final step the drug was retained on a cationic resin column, eluted with NaCl lM and detected according to the method of Ellman (1958). The results suggested a pharmacokinetic behavior related to a one open compartment model with the following values for the total drug: area under the intravenous curve (AUC i.v.): 443(+ ou -) 24.0; AUC oral: 85.5(+ ou -) 14.5 ug min.ml(elevado a -1); elimination rate constant: 0.069(+ ou -) 0.0055 min(elevado a -1), biological half-life: 10.0(+ ou -) 0.80 min; distribution volume 1.15(+ ou -) 0.15 ml/g; biodisponibility: 0.19(+ ou -) 0.02. From a pharmacokinetic standpoint, TBAESH seems to have no advantage over the analogous disulfide compound.

Assessment of soil properties by organic matter and EM-microorganism incorporation

Properties of a claim loam soil, collected in Aranjuez (Madrid) and enriched with organic matter and microorganisms, were evaluated under controlled temperature and moisture conditions, over a period of three months. The following treatments were carried out: soil (control); soil + 50 t ha-1 of animal manure (E50); soil + 50 t ha-1 of animal manure + 30 L ha-1 of effective microorganisms (E50EM); soil + 30 t ha-1 of the combination of various green crop residues and weeds (RC30) and soil + 30 t ha-1 of the combination of various green crop residues and weeds + 30 L ha-1 of effective microorganisms (RC30EM). Soil samples were taken before and after incubation and their physical, chemical, and microbiological parameters analyzed. Significant increase was observed in the production of exopolysaccharides and basic phosphatase and esterase enzyme activities in the treatments E50EM and RC30EM, in correlation with the humification of organic matter, water retention at field capacity, and the cationic exchange capacity (CEC) of the same treatments. The conclusion was drawn that the incorporation of a mixture of effective microorganisms (EM) intensified the biological soil activity and improved physical and chemical soil properties, contributing to a quick humification of fresh organic matter. These findings were illustrated by the microbiological activities of exopolysaccharides and by alkaline phosphatase and esterase enzymes, which can be used as early and integrated soil health indicators.

Determinação espectrofotométrica de alumínio em concentrados salinos utilizados em hemodiálise empregando pré-concentração em fluxo

An automatic flow injection procedure for spectrophotometric aluminium determination in purified water and solutions containing high salts concentrations used for hemodyalisis treatment was developed. The method was base on reaction of Al3+ with cianine eriochrome R (ECR) after preconcentration using the AG50W-X8 cationic-exchange resin. Elution was carried out using a 1 % (m/v) calcium chloride solution. The manifold comprised an automatic proporcional injector controlled by a computer equipped with an eletronic interface and software written in QuicBASIC 4.5 with facilities to control the injector and perform data acquisition. Samples with concentration ranging from 4.96 to 19.90 µg L-1 Al were analyzed and recoveries between 88 and 113% were obtained by using the standard addition method. Other profitable analytical characteristics such as a relative standard deviation 1.3 % (n = 10) for a typical sample 14.5 µg L-1 Al, a linear response ranging up to 60.0 µg L-1Al, and a sampling throughput of 10 determinations per hour were achieved. A detection limit of 4.2 µg L-1 Al was estimated as suggested by IUPAC.

Recuperação de cádmio de baterias níquel-cádmio via extração seletiva com tributilfosfato (TBP)

This work describes a recovery process of cadmium from spent nickel-cadmium batteries by a new hydrometallurgical route based on the selective extraction in hydrochloric acid medium with tributylphosphate (TBP), alone or dissolved in kerosene. The best results were obtained when TBP concentration was at least 75 vol%. Nickel extraction was negligible under these conditions. It was isolated after processing the rafinate through an anionic ion-exchange column. Final wastes generated are basically sodium chloride solutions, with no turbidity, color or heavy metals present in significant amounts.

Rota hidrometalúrgica de recuperação de molibdênio, cobalto, níquel e alumínio de catalisadores gastos de hidrotratamento em meio ácido

This work describes a hydrometallurgical route for processing spent commercial catalysts (CoMo and NiMo/Al2O3). Samples were preoxidized (500 ºC, 5 h) in order to eliminate coke and other volatile species present. The calcined solid was dissolved in concentrated H2SO4 and water (1:1 vol/vol) at 90 ºC; the insoluble matter was separated from the solution. Molybdenum was recovered by solvent extraction using tertiary amines at pH around 1.8. Cobalt (or nickel) was separated by addition of aqueous ammonium oxalate at the above pH. Phosphorus was removed by passing the liquid through a strong anion exchange column. Aluminum was recovered by neutralizing the solution with NaOH. The route presented in this work generates less final aqueous wastes because it is not necessary to use alkaline medium during the metal recovery steps.

Outlining precision boundaries among areas with different variability standards using magnetic susceptibility and geomorphic surfaces

There is an increasing demand for detailed maps that represent in a simplified way the knowledge of the variability of a particular area or region maps. The objective was to outline precision boundaries among areas with different accuracy variability standards using magnetic susceptibility and geomorphic surfaces. The study was conducted in an area of 110 ha, which identified three compartment landscapes based on the geomorphic surfaces model. To determinate pH, organic matter, phosphorus, potassium and magnesium, the total sand and clay, 514 soil samples were collected at depths of 0-0.20 m and 0.60-0.80 m. The sum of base, cationic exchange capacity and base saturation were calculated and the magnetic susceptibility was evaluated in the laboratory using a system based on a balance of analytical precision method. Geomorphic surfaces identification allowed setting specific management areas (locations with maximum homogeneity of soil attributes). The map of spatial variability of magnetic susceptibility can be used to validate the precise boundaries among geomorphic surfaces identified in the field and infer the variability of clay content and soil base saturation.

Purification and characterization of a phytoalexin elicitor from spores of the saprobe Mucor ramosissimus

Plants accumulate antimicrobial compounds (phytoalexins) in response to a wide variety of microorganisms. Mucor ramosissimus Samutsevitsch is a saprobe capable of inducing phytoalexin production in soybean cotyledons and in the leaves of tropical Rubiaceae on whose surface it has been found. In the present study, the elicitor from M. ramosissimus was partially purified and the activity compared to that of a glucan elicitor isolated from Phytophthora sojae. Optimal isolation of the elicitor (based on fungal growth, yield of spores and elicitor activity) was achieved by autoclaving spores obtained from nine day-old cultures of the fungus. The elicitor was precipitated with ethanol and purified by chromatography on an anion exchange column, which retained the elicitor, and a Concanavalin A-affinity matrix, to which the elicitor did not bind. The purification resulted in a considerable increase (six-fold) in the specific activity of the elicitor. Neutral sugar composition, analyzed by HPLC, revealed the predominance of mannose, followed by glucose and galactose, whereas colorimetric quantification showed the presence of uronic acids. GC-MS analysis of the elicitor revealed the predominance of glucuronic acid and mannose. These results suggest that fragments of mucoran-type polysaccharides are the phytoalexin elicitors present in the spores of the saprobe M. ramosissimus. Our results also indicate for the first time that soybean cotyledon tissues can recognize fragments of glucuronic-acid heteropolymers as phytoalexin elicitors.

A single-step purification of bothropstoxin-1

Bothrops venoms are complex mixtures of components with a wide range of biological activities. Among these substances, myotoxins have been investigated by several groups. Bothropstoxin-1 (Bthtx-1) is a phospholipase A2-like basic myotoxin from Bothrops jararacussu. The purification of this component involves two chromatographic steps. Although providing a pure material, the association of these two steps is time consuming and a single-step method using high performance chromatography media would be useful. In the present study, we describe a single-step purification method for Bthtx-1. Bothrops jararacussu venom was dissolved in 1 ml buffer. After centrifugation, the supernatant was injected into a Resource-S cation exchange column connected to an FPLC system and eluted with a linear salt gradient. The complete procedure took 20 min, representing a considerable time gain when compared to a previously described method (Homsi-Brandenburgo MI et al. (1988) Toxicon, 26: 615-627). Bthtx-1 purity and identity, assessed by SDS-PAGE and N-terminal sequencing, resulted in a single band with a molecular mass of about 14 kDa and the expected sequence of the first 5 residues, S-L-F-E-L. Although the amount of protein purified after each run is lower than in the previously described method, we believe that this method may be useful for small-scale purifications.

Fumonisin B1 and ochratoxin A in beers made in Brazil

Samples of beer made in Brazil were analyzed for the presence of fumonisin B1 (FB1) and ochratoxin A (OTA). FB1 was searched for in 58 beer samples from 30 plants located in nine states. The samples were concentrated and cleaned up with strong ion exchange column, derivatized with OPA and analyzed by HPLC with fluorescence detection. The limit of detection was 0.26 ng.mL-1 and the average recovery was 98%. Twenty-five samples contained FB1 ranging from 1 to 40 ng.mL-1. Beer (123 samples) from 36 plants located in 5 states were analyzed for OTA by means of immunoaffinity column cleanup followed by liquid chromatography associated with fluorescence. The detection limit was 0.1 ng.mL-1 and the average recovery was 92%. Five samples contained OTA in concentrations from 1 to 18 ng.mL-1. The results indicate that FB1 and OTA contamination in Brazilian beer is not geographically limited and that beer does not contribute significantly to FB1 intake by consumers. In the case of regular high ingestion, beer could contribute sizably to OTA, intake although still below the maximum considered tolerable for the toxin.

STOCK EXCHANGE LISTING INDUCES SOPHISTICATION OF CAPITAL BUDGETING

This article compares capital budgeting techniques employed in listed and unlisted companies in Brazil. We surveyed the Chief Financial Officers (CFOs) of 398 listed companies and 300 large unlisted companies, and based on 91 respondents, the results suggest that the CFOs of listed companies tend to use less simplistic methods more often, for example: NPV and CAPM, and that CFOs of unlisted companies are less likely to estimate the cost of equity, despite being large companies. These findings indicate that stock exchange listing may require greater sophistication of the capital budgeting process.

Experimental ophitoxemia produced by the opisthoglyphous lora snake (Philodryas olfersii) venom

Several colubrid snakes produce venomous oral secretions. In this work, the venom collected from Venezuelan opisthoglyphous (rear-fanged) Philodryas olfersii snake was studied. Different proteins were present in its venom and they were characterized by 20% SDS-PAGE protein electrophoresis. The secretion exhibited proteolytic (gelatinase) activity, which was partially purified on a chromatography ionic exchange mono Q2 column. Additionally, the haemorrhagic activity of Philodryas olfersii venom on chicken embryos, mouse skin and peritoneum was demonstrated. Neurotoxic symptoms were demonstrated in mice inoculated with Philodryas olfersii venom. In conclusion, Philodryas olfersii venom showed proteolytic, haemorrhagic, and neurotoxic activities, thus increasing the interest in the high toxic action of Philodryas venom.

Gas exchange during exercise in different evolutional stages of chronic Chagas' heart disease

OBJECTIVE: To compare gas exchange at rest and during exercise in patients with chronic Chagas' heart disease grouped according to the Los Andes clinical/hemodynamic classification. METHODS: We studied 15 healthy volunteers and 52 patients grouped according to the Los Andes clinical/hemodynamic classification as follows: 17 patients in group IA (normal electrocardiogram/echocardiogram), 9 patients in group IB (normal electrocardiogram and abnormal echocardiogram), 14 patients in group II (abnormal electrocardiogram/echocardiogram, without congestive heart failure), and 12 patients in group III (abnormal electrocardiogram/echocardiogram with congestive heart failure). The following variables were analyzed: oxygen consumption (V O2), carbon dioxide production (V CO2), gas exchange rate (R), inspiratory current volume (V IC), expiratory current volume (V EC), respiratory frequency, minute volume (V E), heart rate (HR), maximum load, O2 pulse, and ventilatory anaerobic threshold (AT). RESULTS: When compared with the healthy group, patients in groups II and III showed significant changes in the following variables: V O2peak, V CO2peak, V ICpeak, V ECpeak, E, HR, and maximum load. Group IA showed significantly better results for these same variables as compared with group III. CONCLUSION: The functional capacity of patients in the initial phase of chronic Chagas' heart disease is higher than that of patients in an advanced phase and shows a decrease that follows the loss in cardiac-hemodynamic performance.