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.

Datação radiocarbônica de sítios arqueológicos do tipo sambaqui pela técnica de absorção de CO2: uma alternativa à síntese benzênica

The sambaquis are archaeological sites with remains of pre-historical Brazilian civilizations. They look like small hills containing different kinds of shells, animal and fish bones, small artifacts and even human skeletons. Since the sambaqui sites in the Rio de Janeiro state are younger than 6000 years, the applicability of CO2 absorption on Carbo-Sorb® and 14C determination by counting on a low background liquid scintillation counter was tested. The International Atomic Energy Agency standard reference material IAEA-C2 was used in order to standardize the method. Nine sambaqui samples from five different archaeological sites found in the Rio de Janeiro state were analyzed and 14C ages between 2100 and 3600 years BP were observed. The same samples were sent to the 14C Laboratory of the Centro de Energia Nuclear na Agricultura (CENA/USP) where similar results were obtained.

Glyphosate translocation in hairy fleabane (Conyza bonariensis) biotypes

The objective of this work was to evaluate the translocation of glyphosate in C. bonariensis plants resistant and susceptible to that herbicide. The 14C-glyphosate was mixed with commercial gyhphosate (800 g ha-1) and applied on the center of the adaxial face of a third node leaf, using a micro syringe, and adding 10 µL of a solution with specific activity of 1,400 Bq, 45 days after plant emergence. The concentration of the glyphosate translocated in the plant was evaluated at time intervals of 6, 12, 36 and 72 hours after being applied on the application leaf, stem, roots and leaves. Ten hours after treatment application, the distribution of the product in the application leaf, divided into base, center and apex, was also evaluated by measuring the radiation emitted by 14C-glyphosate in a liquid scintillation spectrometer. Greater glyphosate retention was observed in the resistant biotype leaf, approximately 90% of the total absorbed up to 72 hours. In the susceptible biotype, this value was close to 70% in the same period. Susceptible biotype leaves, stem and roots showed greater concentration of glyphosate, indicating greater translocation efficiency in this biotype. In the resistant biotype, the herbicide accumulated in greater quantity at the apex and center of the application leaf, while in the susceptible biotype greater accumulation was observed at the base and center leaf. Thus, it can be stated that the resistance mechanism is related to the differential translocation of this herbicide in the biotypes.

Sorption and desorption of Suflafenacil in two soils in the state of São Paulo with different physical and chemical attributes

A study was conducted to evaluate the sorption and desorption of 14C herbicide saflufenacil (pyrimidinedione) in two soils in the State of São Paulo, classified as Red Yellow Latosol with clayey texture (LVA-1) and medium texture (LVA-2), using the batch method through isotherms. The soils were air dried and sieved a 2 mm mesh. The radioactivity was determined by liquid scintillation spectrometry in acclimatized room (25 ± 2 °C). Sorption isotherms were conducted for 5 concentrations of saflufenacil (5.0; 2.5; 1.0; 0.5 and 0.05 μg mL-1) and the results were adjusted to the Freundlich equation, thus obtaining the parameters of sorption followed by two extractions with 0.01 M CaCl2 to determine desorption parameters similarly to sorption. The results showed that saflufenacil sorption was low for both soils studied, being greater for the LVA with higher organic matter content. The desorption coefficients were greater than their sorption coefficients, suggesting the occurrence of hysteresis. The sorption and desorption isotherms (classified as type C isotherms), hysteresis and the t-test between the angular coefficient of the respective isotherms showed that both the sorption and desorption occur with equal intensity.

Shikimate accumulation, glyphosate absorption and translocation in horseweed biotypes

In Brazil, few research works on mechanisms of weed resistance to glyphosate have been conducted so far. Therefore, this research aimed to study analytical procedures determining the relation between the concentration of plant shikimate after glyphosate application and the plant resistance to this herbicide; and evaluate the glyphosate absorption and translocation into two resistant ® and susceptible (S) horseweed biotypes to glyphosate. Horseweed plants with nine true leaves received glyphosate (720 g a.e. ha-1), and 2, 3, 4, 7 and 10 days after application (DAA) the concentration of shikimic acid was measured by HPLC. In another experiment, plants were treated with radiolabeled glyphosate (14C) (1.456 MBq mmol-1 specific activity) and radioactivity was measured 4, 8, 24, 48 and 72 hours after treatment (HAT) by liquid scintillation spectrometry. The shikimate concentration in plants increased 16,351.14 and 7,892.25 mg kg-1 of dry weight, for R and S plants respectively, at seven DAA. Therefore, the procedure for quantification of shikimic acid was suitable for R and S plants differentiation to glyphosate, indicating that the R population is actually resistant to glyphosate. On average, 98% of glyphosate applied was absorbed by the studied biotypes, at 72 HAT. Around 68% of the absorbed radioactivity remained on the biotypes leaves treated, the S biotype showing the highest translocation. Therefore, the R biotype resistance mechanism studied is associated to the differential translocation.

Retinol-induced changes in the phosphorylation levels of histones and high mobility group proteins from Sertoli cells

Chromatin proteins play a role in the organization and functions of DNA. Covalent modifications of nuclear proteins modulate their interactions with DNA sequences and are probably one of the multiple factors involved in the process of switch on/off transcriptionally active regions of DNA. Histones and high mobility group proteins (HMG) are subject to many covalent modifications that may modulate their capacity to bind to DNA. We investigated the changes induced in the phosphorylation pattern of cultured Wistar rat Sertoli cell histones and high mobility group protein subfamilies exposed to 7 µM retinol for up to 48 h. In each experiment, 6 h before the end of the retinol treatment each culture flask received 370 KBq/ml [32P]-phosphate. The histone and HMGs were isolated as previously described [Moreira et al. Medical Science Research (1994) 22: 783-784]. The total protein obtained by either method was quantified and electrophoresed as described by Spiker [Analytical Biochemistry (1980) 108: 263-265]. The gels were stained with Coomassie brilliant blue R-250 and the stained bands were cut and dissolved in 0.5 ml 30% H2O2 at 60oC for 12 h. The vials were chilled and 5.0 ml scintillation liquid was added. The radioactivity in each vial was determined with a liquid scintillation counter. Retinol treatment significantly changed the pattern of each subfamily of histone and high mobility group proteins.

The influence of fasting/refeeding on the lipoprotein lipase activity of adipose tissue and muscle

Lipoprotein lipase activity in adipose tissue and muscle is modulated by changes in the pattern of food intake. We have measured total lipoprotein lipase activity in adipose tissue and muscle of male Wistar rats (N = 6-10), weighing 200-250 g (~12 weeks), during the refeeding/fasting state following 24 h of fasting. Lipoprotein lipase activity in tissue homogenates was evaluated using a [³H]-triolein-containing substrate, and released [³H]-free fatty acids were extracted and quantified by liquid scintillation. Adipose tissue lipoprotein lipase activity did not completely recover within 2 h of refeeding (60% of refed ad libitum values). Cardiac lipoprotein lipase activity remained increased even 2 h after refeeding (100% of refed ad libitum values), whereas no significant changes were observed in the soleus and diaphragm muscles. Adipose tissue lipoprotein lipase activities were consistently higher than the highest skeletal muscle or heart values. It is therefore likely that adipose tissue, rather than muscle makes the major contribution to triacylglycerol clearance. There was concomitant relatively high lipoprotein lipase activity in both adipose tissue and cardiac muscle during the first few hours of refeeding, therefore cardiac muscle may contribute significantly to triacylglycerol clearance during this period. The results suggest that during fasting, increased lipoprotein lipase activity provides a complementary source of free fatty acids from circulating triacylglycerol, allowing the heart to maintain its continuous, high-energy expenditure.

Comparison of the efficacy of biodegradable and non-biodegradable scintillation liquids on the counting of tritium- and [14C]-labeled compounds

The widespread use of ³H and 14C in research has generated a large volume of waste mixed with scintillation liquid, requiring an effective control and appropriate storage of liquid radioactive waste. In the present study, we compared the efficacy of three commercially available scintillation liquids, Optiphase HiSafe 3, Ultima-Gold™ AB (biodegradable) and Insta-Gel-XF (non-biodegradable), in terms of [14C]-glucose and [³H]-thymidine counting efficiency. We also analyzed the effect of the relative amount of water (1.6 to 50%), radioisotope concentration (0.1 to 100 nCi/ml), pH (2 to 10) and color of the solutions (samples containing 0.1 to 1.0 mg/ml of Trypan blue) on the counting efficiency in the presence of these scintillation liquids. There were few significant differences in the efficiency of 14C and ³H counting obtained with biodegradable or non-biodegradable scintillation liquids. However, there was an 83 and 94% reduction in the efficiency of 14C and ³H counting, respectively, in samples colored with 1 mg/ml Trypan blue, but not with 0.1 mg/ml, independent of the scintillation liquid used. Considering the low cost of biodegradable scintillation cocktails and their efficacy, these results show that traditional hazardous scintillation fluids may be replaced with the new safe biodegradable fluids without impairment of ³H and 14C counting efficiency. The use of biodegradable scintillation cocktails minimizes both human and environmental exposure to hazardous solvents. In addition, some biodegradable scintillation liquids can be 40% less expensive than the traditional hazardous cocktails.

Uniformity of liquid distribution in the canopy of the bean plant, using the spectrophotometric analysis

Fungal diseases are important factors limiting common bean yield. White mold is one of the main diseases caused by soil pathogens. The objective of this study was to quantify the distribution of a fungicide solution sprayed into the canopy of bean plants by spectrophotometry, using a boom sprayer with and without air assistance. The experiment was arranged in a 2 x 2 x 2 factorial (two types of nozzles, two application rates, and air assistance on and off) randomized block design with four replications. Air assistance influenced the deposition of solution on the bean plant and yield increased significantly with the increased rate of application and air assistance in the boom sprayer.

Sugar content in liquid oral medicines for children

The most sold and/or prescribed liquid oral medicines for children in Tubarão, Southern Brazil, were assessed. Their sugar concentration was tested and compared to those in their directions for use. All pharmacies and pediatricians working in the city were visited by a previously trained interviewer. Pre-tested questionnaires were applied in order to assess the most sold pediatric as well as the most prescribed pediatric liquid oral medicines. Three samples of each medicine were analyzed by Lane-Eynon general volumetric method. Among the 14 most sold/prescribed medicines only four did not have sugar contents (analgesic, cortisone, and syrups). Sugar concentration ranged from 8.59 g/100 g of drug (SD=0.29 g/100 g) to 67.0 g/100 g of drug (SD=6.07 g/100 g). Only 50.0% of the total medicines that presented sugar in their ingredients showed this information in their directions.

Comparative evaluation of adverse effects in the use of powder trivalent antivenom and liquid antivenoms in Bothrops snake bites

INTRODUCTION: Snake bite, a problem in public health, generally occurs where there is no electric power. METHODS: A comparative clinical study was conducted with 102 victims of Bothrops snake bite, from the state of Amazonas, Brazil; 58 victims were treated with liofilizated trivalent antivenom serum (SATL) and 44 victims treated with liquid bivalent and monovalent antivenom serum (SAMBL). RESULTS: 17% (10/58) of patients presented adverse effects with the SATL and 25% (11/44) with the SAMBL. CONCLUSIONS: There was no statistic difference in number of adverse effects between the two types of snake bite antivenom.

Vancomycin monitoring in term newborns: comparison of peak and trough serum concentrations determined by high performance liquid chromatography and fluorescence polarization immunoassay

INTRODUCTION: Peak and trough serum concentrations of vancomycin were determined in term newborn infants with confirmed or suspected Staphylococcus sp sepsis by high performance liquid chromatography and flourescence polarization immunoassay. OBJECTIVE: To statistically compare the results of the high performance liquid chromatography and flourescence polarization immunoassay techniques for measuring serum vancomycin concentrations. METHODS: Eighteen peak and 20 trough serum samples were assayed for vancomycin concentrations using high performance liquid chromatography and flourescence polarization immunoassay from October 1995 to October 1997. RESULTS: The linear correlation coefficients for high performance liquid chromatography and flourescence polarization immunoassay were 0.27 (peak, P = 0.110) and 0.26 (trough, P = 0.1045) respectively, which were not statistically significant. CONCLUSION: There was wide variation in serum vancomycin concentrations determined by high performance liquid chromatography as compared with those determined by flourescence polarization immunoassay. There was no recognizable pattern in the variability; in an apparently random fashion, the high performance liquid chromatography measurement was sometimes substantially higher than the flourescence polarization immunoassay measurement, and at other times it was substantially lower.

Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats

Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

Liquid nitrogen cryopreservation of Bracoccidioides brasiliensis in Fava's Netto medium

The aplicability of Fava's Netto medium in the liquid nitrogen cryopreservation technique of Paracoccidioides brasiliensis cells was demonstrated.