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Adhesion between solid materials is caused by intermolecular forces that only take place if the adhering surfaces are at nanoscale contact (NSC) (i.e., 0.1-0.4 nm. To study adhesion, NSC can be evaluated with Förster Resonance Energy Transfer (FRET). FRET uses the interaction of compatible fluorescence molecules to measure the nanometer distance between bonded surfaces. For this, each surface is labeled with one fluorescence dye, named the Donor or Acceptor. If these molecules are in NSC, a nonradiative Donor-Acceptor energy transfer will occur and can be detected using FRET spectroscopy. Here, for the first time, we introduce an innovative concept of a FRET-based NSC measurement employing dye-nanolayer films prepared by a physical vapor deposition (PVD). The dye nanolayers were prepared by PVD from the vaporization of the Donor and Acceptor molecules separately. The selected molecules, 7-Amino-4-methyl-cumarin (C120) and 5(6)-Carboxy-2',7'-dichlor-fluorescein (CDCF), present high quantum yields (QY, QY D = 0.91 and QY A = 0.64) and a low FRET distance range of 0.6-2.2 nm, adequate for the study of NSC. The produced dye-nanolayer films exhibit a uniform dye distribution (verified by atomic force microscopy) and suitable fluorescence intensities. To validate the NSC measurements, FRET spectroscopy experiments were performed with bonded dye-nanolayer films prepared under different loads (from 1.5 to 140 bar), thus creating different degrees of NSC. The results show an increase in FRET intensity ( R 2 = 0.95) with the respective adhesion energy between the films, which is directly related to the degree of NSC. Hence, this work establishes FRET as an experimental technique for the measurement of NSC, and its relation to surface adhesion. Additionally, thanks to the FRET dye-nanolayer approach, the method can be employed on arbitrary surfaces. Essentially, any sufficiently transparent substrate can be functionalized with FRET compatible dyes to evaluate NSC, which represents a breakthrough in contact mechanics investigations of soft and hard solid materials., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: There is no consensus on the ideal strategy to treat posttransplant focal segmental glomerulosclerosis. The multiple-target therapy, which consisted of high-dose intravenous cyclosporine, prednisone, and plasmapheresis, showed favorable results., Methods: This single-center, prospective study sought to evaluate the multiple-target therapy in an independent cohort of patients., Results: Thirteen patients with posttransplant focal segmental glomerulosclerosis received multiple-target therapy. Complete remission was achieved in 2 patients (15.4%), and partial remission in another 2 patients (15.4%). Four patients (30.7%) did not show remission, and 5 patients (38%) lost the graft because of posttransplant focal segmental glomerulosclerosis during the 12-mo follow-up. Premature discontinuation of treatment occurred in 10 patients (77%), all associated with infectious adverse events. Cytomegalovirus was the most common complication, and preemptive therapy was used instead of prophylaxis., Conclusions: In this cohort of patients, the efficacy of the multiple-target therapy was poor and limited by the high incidence of infectious adverse events., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Hypothesis: Interfacial adhesion caused by intermolecular forces only occur between surfaces at nano-scale contact (NSC), i.e., 0.1-0.4 nm and can be evaluated using Forster resonance energy transfer spectroscopy (FRET). For this, a suitable pair of fluorescent dyes must be selected, which spectroscopic properties will determine the FRET system performance. Here, we present a brand-new FRET dye system specifically designed to measure NSC in the distance range relevant for van-der-Waals and hydrogen bonding, i.e., below 1 nm., Experiments: We propose the FRET pair: 7-Amino-4-methyl-cumarin (C120) and 5(6)-Carboxy-2',7'-dichlor-fluorescein (CDCF) with high quantum yield (QY, QY C120  = 0.91 and QY CDCF  = 0.64) and a distance detection range of 0.6-2.2 nm (0.1 mM). Adhered-thin films with increasing NSC degrees are produced with ascending pressure from 1.5 to 150 bar. To validate the proposed FRET measurement, we are correlating the bonded films interfacial adhesion (separation energy) to the measured FRET intensity, indicating its degree of NSC., Findings: We find that the proposed dyes are producing the desired FRET signal in adhered-thin films, for an interaction range of 0.6-2.2 nm, with high sensitivity due to the dye's high quantum yields. The increasing adhesion in these films is only caused by its increase in NSC. We find that the adhesion strength, measured as the separation energy between the films, is correlated to the measured FRET signal. Hence, the introduced FRET system is accurately able to measure the degree of NSC between soft surfaces., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The effects of ROM manipulation on muscle strength and hypertrophy response remain understudied in long-term interventions. Thus, we compared the changes in strength and regional muscle hypertrophy after training in protocols with different ranges of motion (ROM) in the seated dumbbell preacher curl exercise using a within-participant experimental design., Design and Methods: Nineteen young women had one arm randomly assigned to train in the initial ROM (INITIAL ROM : 0°-68°; 0° = extended elbow) while the contralateral arm trained in the final ROM (FINAL ROM : 68°-135°), three times per week over an eight-week study period. Pre- and post-training assessments included one repetition maximum (1RM) testing in the full ROM (0°-135°), and measurement of biceps brachii cross-sectional area (CSA) at 50% and 70% of humerus length. Paired t -tests were used to compare regional CSA changes between groups, the sum of CSA changes at 50% and 70% (CSA summed ), and the strength response between the training protocols., Results: The INITIAL ROM protocol displayed a greater CSA increase than FINAL ROM protocol at 70% of biceps length ( p = 0.001). Alternatively, we observed similar increases between the protocols for CSA at 50% ( p = 0.311) and for CSA summed ( p = 0.111). Moreover, the INITIAL ROM protocol displayed a greater 1RM increase than FINAL ROM ( p < 0.001)., Conclusions: We conclude that training in the initial angles of elbow flexion exercise promotes greater distal hypertrophy of the biceps brachii muscle in untrained young women. Moreover, the INITIAL ROM condition promotes a greater dynamic strength increase when tested at a full ROM compared to the FINAL ROM .

The adult zebrafish heart has a high capacity for regeneration following injury. However, the composition of the regenerative niche has remained largely elusive. Here, we dissected the diversity of activated cell states in the regenerating zebrafish heart based on single-cell transcriptomics and spatiotemporal analysis. We observed the emergence of several transient cell states with fibroblast characteristics following injury, and we outlined the proregenerative function of collagen-12-expressing fibroblasts. To understand the cascade of events leading to heart regeneration, we determined the origin of these cell states by high-throughput lineage tracing. We found that activated fibroblasts were derived from two separate sources: the epicardium and the endocardium. Mechanistically, we determined Wnt signalling as a regulator of the endocardial fibroblast response. In summary, our work identifies specialized activated fibroblast cell states that contribute to heart regeneration, thereby opening up possible approaches to modulating the regenerative capacity of the vertebrate heart., (© 2022. The Author(s).)

The study compared changes in strength and regional muscle hypertrophy between different ranges of motion (ROM) in the knee extension exercise. Forty-five untrained women were randomized to either a control group or to perform the exercise in one of the following 4 groups (0°=extended knee): Full ROM (FULL ROM : 100°-30° of knee flexion); Initial Partial ROM (INITIAL ROM : 100°-65°); Final Partial ROM (FINAL ROM : 65°-30°); Varied ROM (VAR ROM : daily alternation between the ROM of INITIAL ROM and FINAL ROM ). Pre- and post-training assessments included one repetition maximum (1RM) testing in the ROM corresponding to the initial, final and full ROM, and measurement of cross-sectional areas of the rectus femoris and vastus lateralis muscles at 40%, 50%, 60% and 70% of femur length in regard to regional muscle hypertrophy. Results showed that the INITIAL ROM group presented a greater relative increase than all groups at 70%, and at 50% and 60% the increases were greater than FINAL ROM , FULL ROM , and non-training control (CON) groups. Moreover, FINAL ROM group presented similar changes compared to the CON group at 60% and 70%. In regard to 1RM, FINAL ROM and INITIAL ROM groups presented greater relative increases at the ROM trained, and no group showed greater increases than VAR ROM or INITIAL ROM , regardless the ROM tested. In conclusion, partial ROM training in the initial phase of the knee extension exercise promoted greater relative hypertrophy in certain muscle regions than training in other ROM configurations, and no group promoted a greater 1RM increase than VAR ROM group, which showed similar 1RM increases in the different ROMs tested.

Polymer-liposome complexes (PLCs) can be efficiently applied for the treatment and/or diagnosis of several types of diseases, such as cancerous, dermatological, neurological, ophthalmic and orthopedic. In this work, temperature-/pH-sensitive PLC-based systems for controlled release were developed and characterized. The selected hydrophilic polymeric setup consists of copolymers of Pluronic ® -poly(acrylic acid) (PLU-PAA) and Pluronic ® -poly( N , N -dimethylaminoethyl methacrylate) (PLU-PD) synthesized by atom transfer radical polymerization (ATRP). The copolymers were incorporated into liposomes formulated from soybean lecithin, with different copolymer/phospholipid ratios (2.5, 5 and 10%). PLCs were characterized by evaluating their particle size, polydispersity, surface charge, capacity of release and encapsulation efficiency. Their cytotoxic potential was assessed by determining the viability of human epithelial cells exposed to them. The results showed that the incorporation of the synthesized copolymers positively contributed to the stabilization of the liposomes. The main accomplishments of this work were the innovative synthesis of PLU-PD and PLU-PAA by ATRP, and the liposome stabilization by their incorporation. The formulated PLCs exhibited relevant characteristics, notably stimuli-responsive attributes upon slight changes in pH and/or temperature, with proven absence of cellular toxicity, which could be of interest for the treatment or diagnosis of all diseases that cause some particular pH/temperature change in the target area.

Adhesion is caused by molecular interactions that only take place if the surfaces are in nanoscale contact (NSC); i.e., the distance between the surfaces is in the range of 0.1-0.4 nm. However, there are several difficulties measuring the NSC between surfaces, mainly because regions that appear to be in full contact at low magnification may show no NSC when observed at higher magnifications. Thus, the measurement area of NSC is very small with imaging techniques, and an experimental technique to evaluate NSC for large contact areas has not been available thus far. Here, we are proposing Förster resonance energy transfer (FRET) spectroscopy/microscopy for this purpose. We demonstrate that NSC in a distance range of 1-10 nm can be evaluated. Our experiments reveal that, for thin films pressed under different loads, NSC increases with the applied pressure, resulting in a higher FRET signal and a corresponding increase in adhesion force/energy when separating the films. Furthermore, we show that local variations in molecular contact can be visualized with FRET microscopy. Thus, we are introducing a spectroscopic technique for quantification (FRET spectroscopy) and imaging (FRET microscopy) of NSC between surfaces, demonstrated here for the application of surface adhesion. This could be of interest for all fields where adhesion or nanoscale surface contact are playing a role, for example, soft matter, biological materials, and polymers, but also engineering applications, like tribology, adhesives, and sealants.

Iron deficiency is the most common nutritional deficit worldwide. The goal of this work was to obtain iron-pectin beads by ionic gelation and evaluate their physiological behavior to support their potential application in the food industry. The beads were firstly analyzed by scanning electronic microscopy, and then physical-chemically characterized by performing swelling, thermogravimetric, porosimetry, Mössbauer spectroscopy and X-ray fluorescence analyses, as well as by determining the particle size. Then, physiological assays were carried out by exposing the beads to simulated gastric and intestinal environments, and determining the iron absorption and transepithelial transport into Caco-2/TC7 cells. Iron-pectin beads were spherical (diameter 1-2 mm), with high density (1.29 g/mL) and porosity (93.28%) at low pressure, indicating their high permeability even when exposed to low pressure. Swelling in simulated intestinal medium (pH 8) was higher than in simulated gastric medium. The source of iron [FeSO 4 (control) or iron-pectin beads] did not have any significant effect on the mineral absorption. Regarding transport, the iron added to the apical pole of Caco-2/TC7 monolayers was recovered in the basal compartment, and this was proportional with the exposure time. After 4 h of incubation, the transport of iron arising from the beads was significantly higher than that of the iron from the control (FeSO 4 ). For this reason, iron-pectin beads appear as an interesting system to overcome the low efficiency of iron transport, being a potential strategy to enrich food products with iron, without altering the sensory properties., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Liposomes are exceptional carriers for therapeutic drug delivery. However, they generally suffer from poor cell penetration, low half-life in bloodstream and loss of functionality during storage. To overcome these problems some strategies can be applied, such as functionalization with polymers and the use of protective molecules during dehydration processes. This work reports a complete study about the stability, including freeze-drying in the presence of trehalose, storage and internalization into HEp-2 cells, of stable formulations of pH sensitive polymer-liposome complexes (PLC) composed of soybean lecithin and crosslinked/non-crosslinked poly(acrylic acid) with a cholesterol end-group (CHO-PAA). The results showed that the average hydrodynamic particle size of the complexes persisted unaffected for approximately 75 days after freeze-drying in the presence of 10% w/v trehalose. The efficiency of calcein encapsulation and release profiles in physiologic conditions exhibited no significant alterations when stored for 0 and 1 month, and for 2 and 3 months of storage the calcein release increased with time. The stored complexes were efficiently uptaken into HEp-2-cells, as determined by confocal microscopy. In all cases, the percentage of viable cells was above 90%, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, indicating no potential toxicity. Finally, transepithelial transport assays demonstrated that both fresh and 2 months-stored complexes could transport their calcein content through HEp-2 monolayers over time., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The development of polymer-liposome complexes (PLCs), in particular for biomedical applications, has grown significantly in the last decades. The importance of these studies comes from the emerging need in finding intelligent controlled release systems, more predictable, effective and selective, for applications in several areas, such as treatment and/or diagnosis of cancer, neurological, dermatological, ophthalmic and orthopedic diseases, gene therapy, cosmetic treatments, and food engineering. This work reports the development and characterization of a pH sensitive system for controlled release based on PLCs. The selected hydrophilic polymer was poly(acrylic acid) (PAA) synthesized by atom transfer radical polymerization (ATRP) with a cholesterol (CHO) end-group to improve the anchoring of the polymer into the lipid bilayer. The polymer was incorporated into liposomes formulated from soybean lecithin and stearylamine, with different stearylamine/phospholipid and polymer/phospholipid ratios (5, 10 and 20%). The developed PLCs were characterized in terms of particle size, polydispersity, zeta potential, release profiles, and encapsulation efficiency. Cell viability studies were performed to assess the cytotoxic potential of PLCs. The results showed that the liposomal formulation with 5% of stearylamine and 10% of polymer positively contribute to the stabilization of the complexes. Afterwards, the carboxylic acid groups of the polymer present at the surface of the liposomes were crosslinked and the same parameters analyzed. The crosslinked complexes showed to be more stable at physiologic conditions. In addition, the release profiles at different pHs (2-12) revealed that the obtained complexes released all their content at acidic conditions. In summary, the main accomplishments of this work are: (i) innovative synthesis of cholesterol-poly(acrylic acid) (CHO-PAA) by ATRP; (ii) stabilization of the liposomal formulation by incorporation of stearylamine and CHO-PAA; (iii) new approach for CHO-PAA crosslinking, resulting in more stable PLCs at physiological conditions; (iv) destabilization of PLCs upon slight changes of pH, showing their pH sensitivity; and (v) the PLCs do not exhibit cellular toxicity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The origin, affinity and paleoecology of macrofossils of soft-bodied organisms of the terminal Ediacaran Period have been highly debated. Previous discoveries in South America are restricted to small shelly metazoans of the Nama Assemblage. Here we report for the first time the occurrence of discoidal structures from the Upper Ediacaran Cerro Negro Formation, La Providencia Group, Argentina. Specimens are preserved in tabular sandstones with microbially-induced sedimentary structures. Flute marks and linear scours at the base of the sandstone layers indicate deposition under high energy, episodic flows. Stratigraphic, sedimentologic, petrographic and taphonomic analyses indicate that the origin of these structures is not related to abiotic process. Preservational and morphological features, as invagination and the presence of radial grooves, indicate that they resemble typical morphs of the Aspidella plexus. The large number of small-sized individuals and the wide range of size classes with skewed distribution suggest that they lived in high-density communities. The presence of Aspidella in the Cerro Negro Formation would represent the first reliable record of Ediacaran soft-bodied organisms in South America. It also supports the paleogeographic scenario of the Clymene Ocean, in which a shallow sea covered part of the southwest Gondwana at the end of the Ediacaran.

Background: Zebrafish are able to regenerate many of its tissues and organs after damage. In amphibians this process is regulated by nerve fibres present at the site of injury, which have been proposed to release factors into the amputated limbs/fins, promoting and sustaining the proliferation of blastemal cells. Although some candidate factors have been proposed to mediate the nerve dependency of regeneration, the molecular mechanisms involved in this process remain unclear., Results: We have used zebrafish as a model system to address the role of nerve fibres in fin regeneration. We have developed a protocol for pectoral fin denervation followed by amputation and analysed the regenerative process under this experimental conditions. Upon denervation fins were able to close the wound and form a wound epidermis, but could not establish a functional apical epithelial cap, with a posterior failure of blastema formation and outgrowth, and the accumulation of several defects. The expression patterns of genes known to be key players during fin regeneration were altered upon denervation, suggesting that nerves can contribute to the regulation of the Fgf, Wnt and Shh pathways during zebrafish fin regeneration., Conclusions: Our results demonstrate that proper innervation of the zebrafish pectoral fin is essential for a successful regenerative process, and establish this organism as a useful model to understand the molecular and cellular mechanisms of nerve dependence, during vertebrate regeneration.

Phenotypic change in response to variation in environmental cues has been widely documented in fish. Transitions in social dominance, in particular, have been shown to induce a rapid switch in reproductive phenotypes in many species. However, this effect has been mainly studied in adults and focused on behavioural transitions. The way social cues constraint the phenotypic development of juveniles remains poorly studied in fish. We tested the importance of social dominance and density in the phenotypic development of juveniles of the peacock blenny Salaria pavo. This species shows sequential male alternative reproductive tactics. In the first breeding season males can reproduce as nest-holders or as parasitic males (female-mimicking), or postpone reproduction; from the following season afterwards all males reproduce as nest-holders. Parasitic males have relatively larger testes that lack a testicular gland, present in the testes of nest-holders. The testicular gland is the main source of androgens in the testes and accordingly nest-holders have higher circulating androgen levels. In addition, exogenous androgen administration to parasitic males promotes the development of secondary sexual characters (SSC) only present in nest-holders such as a head crest and an anal gland. We raised juveniles under a high or low-density treatment and monitored social interactions for 1 month. No significant effect of density on the development of juvenile males was detected. However, within each replicate, the relative body size of juvenile males at the beginning of the experiment determined their dominance status, with dominant males developing towards the nest-holder morphotype. Dominant males engaged in more nest defence behaviour, showed larger testicular glands, had higher levels of 11-ketotestosterone (11-KT) and testosterone (T) and developed more SSC, as compared to subordinate males. However, these effects of social dominance were moderated by body condition as only dominant males in good body condition developed SSC. The effect of social dominance and of the area of the testicular gland on the development of SSC was mediated by 11-KT and on the expression of nest defence behaviour by T. Interestingly, in spite of the higher androgen levels and more pronounced morphologic development of SSC in dominant individuals, gonadal development was independent of social dominance and most fish still had underdeveloped testis at the end of the experiment. In conclusion, social dominance promoted the development of the testicular gland, an increase in circulating androgen levels and the development of SSC, but did not promote testicular development. This suggests a dissociation of mechanisms underlying sexual maturation and the expression of male reproductive traits. This dissociation seems to be the key for the occurrence of female-mimicking males in this species, which are sexually mature despite lacking the SSC typical of nest-holders., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are common syndromes that affect both clinical and surgical patients. This study describes the effects of a potent and specific N-methyl-d-aspartate receptor antagonist (MK-801) against oxidative stress in acute lung injury induced by intratracheal lipopolysaccharide (LPS) injection. This study was performed using male Wistar rats weighing 200-250g. Rats were randomly divided into four groups: control with isotonic saline instillation (n=6); LPS (100μg/100g of body weight) treated with saline (n=6); LPS treated with MK-801 (0.3mg/kg, intraperitoneally; n=6); LPS treated with MK-801 (0.3mg/kg, intratracheally; n=6). Twelve hours after the LPS instillation, rats were anesthetized and a bronchoalveolar lavage (BAL) was performed in order to determine the alveolar-capillary membrane alterations and the inflammatory infiltrate level. Blood and lung samples were isolated and assayed for oxidative stress variables and histopathologic analysis. The use of MK-801 decreased bronchoalveolar lavage fluid protein, LDH activity and inflammatory cells. Indeed, the treatment with MK-801 significantly attenuated lung oxidative damage and histopathologic alterations after LPS instillation. Our data provide the first experimental demonstration that MK-801 decreases oxidative stress and limits inflammatory response and alveolar disarray in lipopolysaccharide-induced acute lung injury., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The following study aimed to evaluate, in vitro and in vivo, the anti-inflammatory effect of Ulomoides dermestoides, a beetle commonly used as a remedy for a variety of diseases including respiratory disorders and asthma. We used an acute inflammation model of injury, injection of carrageenan into the pleural cavity of rats. The rats were treated intraperitoneally with the aqueous extract of U. dermestoides 8 and 16 mg/kg. The exudate volume, protein concentration, polymorphonuclear leukocytes (PMNs) and total leukocyte were measured. The peripheral blood mononuclear cells (PBMCs) were isolated from the blood of healthy subjects and we investigated the immunomodulatory and cytotoxic effect of aqueous extract of U. dermestoides. In conclusion, in vitro we observed a non-cytotoxic effect and antiproliferative activity on the dose of 12.5 mg/dL. In vivo, this paper clarifies the great clinical relevance of the aqueous extract of U. dermestoides in elucidating its role as an anti-inflammatory agent.

Sepsis is a systemic response to an infection that leads to a generalized inflammatory reaction. There is an intimate relationship between procoagulant and proinflammatory activities, and coagulation abnormalities are common in septic patients. Pharmaceutical studies have focused to the development of substances that act on coagulation abnormalities and on the link between coagulation and inflammation. Fructose-1,6-bisphosphate (FBP) is a high-energy glycolitic metabolite that in the past two decades has been shown therapeutic effects in great number of pathological situations, including sepsis. The aims of this study were to assess the effects of FBP on platelet aggregation in vitro and ex vivo in healthy and septic rats and evaluate the use of FBP as a treatment for thrombocytopenia and coagulation abnormalities in abdominal sepsis in rat. FBP inhibited platelet aggregation (P < 0.001) in vitro in healthy rats from the smallest dose tested, 2.5 mM, in a dose-dependent manner. The mean effective dose calculated was 10.6 mM. The highest dose tested, 40 mM, completely inhibited platelet aggregation (P < 0.001) induced by ADP. Platelet aggregation in plasma from septic rats was inhibited only with higher doses of FBP, starting from 20 mM (P < 0.001). The calculated mean effective dose was 19.3 mM. Ex vivo platelet aggregation in septic rats was significantly lower (P < 0.05) than healthy rats and the treatment with FBP, at the dose of 2 g/kg, diminished the platelet aggregation at the extension of 27% (P < 0.001), suggesting that FBP is a potent platelet aggregation inhibitor in vivo. Moreover, treatment with FBP 2 g/kg prevented thrombocytopenia (P < 0.001), prolongation of prothrombin and partial thromboplastin time (P < 0.001), but not fibrinogen, in septic rats. The most important findings in this study are that FBP is a potent platelet aggregation inhibitor, in vitro and ex vivo. It presents protective effects on coagulation abnormalities, which can represent a treatment against DIC. The mechanisms for these effects remain under investigation.

Objectives: In the present study we assessed the inflammatory potential of venom obtained from caterpillar genus Dirphia in an acute model of lung injury., Material and Methods: Injection of extract from the bristles of Dirphia sp. (EBD) into the pleural cavity of rats elicited an acute inflammation response characterized by fluid accumulation which contained a large number of polymorphonuclear neutrophils (PMNs)., Results: The results show that EBD induces an inflammatory response, with a significant increase in PMNs, exudate and nitric oxide within 4 h after a 0.04 mg/kg dose. The administration of anti-inflammatory drugs (fructose-1,6-bisphosphate, dexamethasone, rofecoxib, sodium diclofenac and pyrilamine) significantly reduced the inflammatory effect of EBD., Conclusions: EBD causes an inflammatory reaction in the pleural cavity of rats involving a variety of inflammatory mediators, its action mechanism probably involving cellular injury and the exacerbated induction of cytokines and nitric oxide.

Fructose-1,6-bisphosphate (FBP) is a bisphosphorilated sugar with a protective action against events that lead to cellular damage. The toxicity of the drug was assessed when administered intravenously in Wistar rats in doses of between 250 and 4000 mg/kg. Ionic calcium, total calcium, inorganic serum phosphate and the electrocardiographic profile of these animals were assessed. The lethal dose (LD(50)) was established by means of PROBIT processing. There was no reduction in the levels of total calcium, with the administration of increased doses of FBP, although there was a significant reduction in the levels of ionic calcium in those groups that received 250 mg/kg and over. The serum phosphate showed a significant statistical increase in those groups that received 750 mg/kg and over. The LD(50) obtained in 24 h was 1068 mg/kg. Though it was not possible to elucidate the toxic mechanism of FBP, the electrocardiogram (ECG) showed that all the rats died of cardiac arrest.

The occurrence of subfossil material in bottom sediments of Couve Island, Ubatuba region, São Paulo State, is confirmed. The analyzed material consists of a bivalve shell that was dated by the electron spin resonance technique. By the additive irradiation method an archaeological absorbed dose of (25 +/- 5) Gy was obtained and calibration with other dating works in the same area allows the inference of an age of (25 +/- 5) x 10(2) years. The importance of this finding and its paleoecological implications could contribute to elucidating the nature of short-term environmental changes in the Brazilian coastline during the Holocene, as well as becoming an important tool to the understanding of the distribution and biological aspects of the bivalve fauna.