3-[4-(1H-Indol-3-yl)-1,3-thiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines,Nortopsentin Analogues with Antiproliferative Activity

A new series of nortopsentin analogues, in which the imidazole ring of the natural product was replaced by thiazole and the indole unit bound to position 2 of the thiazole ring was substituted by a 7-azaindole moiety, was efficiently synthesized. Two of the new nortopsentin analogues showed good antiproliferative effect against the totality of the NCI full panel of human tumor cell lines (~60) having GI₅₀ values ranging from low micromolar to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, investigated on human hepatoma HepG2 cells, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and mitochondrial dysfunction. Moreover, the compounds induced a concentration-dependent accumulation of cells in the subG0/G1phase, while confined viable cells in G2/M phase.     

Occurrence of Lipophilic Marine Toxins in Shellfish from Galicia (NW of Spain) and Synergies among Them

Lipophilic marine toxins pose a serious threat for consumers and an enormous economic problem for shellfish producers. Synergistic interaction among toxins may play an important role in the toxicity of shellfish and consequently in human intoxications. In order to study the toxic profile of molluscs, sampled during toxic episodes occurring in different locations in Galicia in 2014, shellfish were analyzed by liquid chromatography tandem mass spectrometry (LC–MS/MS), the official method for the detection of lipophilic toxins. The performance of this procedure was demonstrated to be fit for purpose and was validated in house following European guidelines. The vast majority of toxins present in shellfish belonged to the okadaic acid (OA) group and some samples from a particular area contained yessotoxin (YTX). Since these toxins occur very often with other lipophilic toxins, we evaluated the potential interactions among them. A human neuroblastoma cell line was used to study the possible synergies of OA with other lipophilic toxins. Results show that combination of OA with dinophysistoxin 2 (DTX2) or YTX enhances the toxicity triggered by OA, decreasing cell viability and cell proliferation, depending on the toxin concentration and incubation time. The effects of other lipophilic toxins as 13-desmethyl Spirolide C were also evaluated in vitro.     

Biofilm formation in bacterial pathogens of veterinary importance

Bacterial biofilms are structured communities of bacterial cells enclosed in a self-produced polymer matrix that is attached to a surface. Biofilms protect and allow bacteria to survive and thrive in hostile environments. Bacteria within biofilms can withstand host immune responses, and are much less susceptible to antibiotics and disinfectants when compared with their planktonic counterparts. The ability to form biofilms is now considered a universal attribute of micro-organisms. Diseases associated with biofilms require novel methods for their prevention, diagnosis and treatment; this is largely due to the properties of biofilms. Surprisingly, biofilm formation by bacterial pathogens of veterinary importance has received relatively little attention. Here, we review the current knowledge of bacterial biofilms as well as studies performed on animal pathogens.     

Cadaverine production by Azospirillum brasilense and its possible role in plant growth promotion and osmotic stress mitigation

Polyamines are considered as plant growth regulating compounds; among them, cadaverine has been correlated with root growth promotion or osmotic stress mitigation in some plant species. The purpose of this study was to evaluate the capacity of bacterial Azospirillum brasilense Az39 strain to produce cadaverine in chemically defined medium and inoculated plants, and to correlate this capacity with root growth promotion or osmotic stress mitigation in hydroponics conditions. To evaluate cadaverine production in chemically defined medium A. brasilense Az39 was cultivated aerobically at 30 °C and 80 rpm in NFb medium or NFb-l supplemented with the precursor l-lysine. To evaluate the bacterial cadaverine production and growth promotion in plants, rice (Oryza sativa L.) cv. El Paso 144 seedlings were inoculated and hydroponically cultured under optimal conditions in growth chamber. In both, cadaverine was identified and quantified by dansyl-derivative method using a fluorescence-HPLC system, and lysine decarboxylase (LDC) activity was determined by ¹⁴CO₂ production in a closed tube system fed with [¹⁴C]-lysine. To evaluate the possible role of bacterial cadaverine in osmotic stress conditions, abscisic acid (ABA) production was analyzed in rice seedlings hydroponically cultured under 0 (no stress), ?0.47 (stress) or ?0.82 (severe stress) MPa osmotic potential generated by mannitol, with the addition of 1 nM or 1 μM cadaverine or A. brasilense Az39 inoculation. Our results indicate that A. brasilense Az39 promoted root growth and helped mitigate osmotic stress in rice seedlings, due in part to cadaverine production.     

Efficacy of Fe(o,o-EDDHA) and Fe(o,p-EDDHA) isomers in supplying Fe to strategy I plants differs in nutrient solution and calcareous soil

The FeEDDHA [iron(3+) ethylenediamine di(o-hydroxyphenylacetic) acid] is one of the most efficient iron chelates employed in the correction of iron clorosis in calcareous soils. FeEDDHA presents different positional isomers: the ortho-ortho (o,o), the ortho-para (o,p), and the para-para (p,p). Of these isomers, the p,p cannot chelate Fe in soil solution in a wide range of pH values, while both o,o and o,p can. The objective of this work was to compare the efficiency of both isomers (o,o and o,p) to provide Fe to two Strategy I plants (tomato and peach) in nutrient solution (pH approximately 6.0), as well as in calcareous soil (pH approximately 8.4; CALCIXEREPT). For this, chelates of both o,o-EDDHA and o,p-EDDHA with 57Fe (a nonradioactive isotope of Fe) were used, where the 57Fe acts as a tracer. The results obtained showed that the o,o isomer is capable of providing sufficient Fe to plants in both nutrient solution and calcareous soil. However, the o,p isomer is capable of providing sufficient Fe to plants in nutrient solution but not in calcareous soil.     

Effect of the photoperiod on the larval development,body growth and muscle cellularity of shi drum (Umbrina cirrosa L.)

Shi drum (Umbrina cirrosa L.) larvae were maintained under three photoperiod regimes: a natural photoperiod regime (16L:8D), continuous light (24L) and equal durations of light and dark (12L:12D) from the end of the vitelline phase to the end of the metamorphosis. Muscle and body parameters were studied at hatching and at 4, 10, 14, 39 and 55 days post hatching (dph). During the vitelline phase, the total body length growth was scarce, whereas the muscle grew significantly, being the hypertrophy of the main mechanism involved. Both the total body length and the hypertrophy were significantly greater at 16L:8D than in the rest of photoperiod regimes. At 10 and 14 dph, the greatest body length was reached at 16L:8D, followed by the 24L group, showing the 12L:12D group the lowest values. At 14 dph, the hypertrophy and hyperplasia were also higher at 16L:8D than in the rest of groups. At 39 dph, the highest values of body length were reached in both 16L:8D and 12L:12D regimes, this latter group reaching the highest values of hypertrophy, thus showing a compensatory growth when comparing with the previous stages. The end of the metamorphosis took place at 50–55 dph in all the groups, with 2.7–3.1 cm of body length (P > 0.05). At this stage, the transverse area of the white muscle was similar among the groups, but the greatest hypertrophy was reached at 16L:8D, whereas the highest hyperplasia was reached at 24L.     

Pharmacokinetics of tulathromycin in fetal sheep and pregnant ewes

Macrolides are important antimicrobials frequently used in human and veterinary medicine in the treatment of pregnant women and pregnant livestock. They may be useful for the control of infectious ovine abortion, which has economic, animal health, and human health impacts. In this study, catheters were surgically placed in the fetal vasculature and amnion of pregnant ewes at 115 (±2) days of gestation. Ewes were given a single dose of 2.5 mg/kg tulathromycin subcutaneously, and drug concentrations were determined in fetal plasma, maternal plasma, and amniotic fluid at 4, 8, 12, 24, 36, 48, 72, 144, and 288 hr after drug administration. Pharmacokinetic parameters in maternal plasma were estimated using noncompartmental analysis and were similar to those previously reported in nonpregnant ewes. Tulathromycin was present in fetal plasma and amniotic fluid, indicating therapeutic potential for use against organisms in these compartments, though concentrations were lower than those in maternal plasma. Time‐course of drug concentrations in the fetus was quite different than that in the ewe, with plasma concentrations reaching a plateau at 4 hr and remaining at this concentration for the remainder of the sampling period (288 hr), raising questions about how tulathromycin may be transported into or metabolized and eliminated by the fetus.     

Profiles of sex steroids, fecundity and spawning of a migratory characiform fish from the Paraguay–Paraná basin: a comparative study in a three-river system

This study investigated for the first time the reproductive biology of Prochilodus lineatus in a system of rivers in southeastern Brasil, relating it to the role of tributary rivers in the reproductive success of this important commercial fish in the Upper Paraná River basin, where a cascade of hydroelectric dams were deployed. Specimens were caught bimonthly in three river sites: (S1) Grande River, downstream from the Porto Colômbia dam; (S2) Pardo River; and (S3) Mogi Guaçu River. Sex steroid plasma levels, fecundity, follicular atresia, oocyte diameter and gonadosomatic index (GSI) were compared among sites. In S1, fish exhibited changes in the reproductive parameters: lower GSI, oocyte diameter and fecundity and higher follicular atresia index, when compared to S2 and S3. Frequency of maturing fish was higher in S3 and spawning was only registered in S3. In sites S2 and S3, plasma concentrations of testosterone and 17β-estradiol in females and testosterone in males showed wide variations following gonadal maturation. Fish from S1 showed few significant variations in sex steroid concentrations throughout the gonadal cycle. These results indicate that P. lineatus does not reproduce in Grande River (S1), but probably uses the Pardo River (S2) as a migratory route towards the Mogi Guaçu River (S3) where they complete gonadal maturation and spawning. Our findings contribute for understanding the reproductive biology of P. lineatus and to highlight the importance of tributaries in impounded rivers as a favourable environment for migration and spawning of fish.