Effects of Bisphenol A on ion channels: Experimental evidence and molecular mechanisms

Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) produced in huge quantities in the manufacture of polycarbonate plastics and epoxy resins. It is present in most humans in developed countries, acting as a xenoestrogen and it is considered an environmental risk factor associated to several diseases. Among the whole array of identified mechanisms by which BPA can interfere with physiological processes in living organisms, changes on ion channel activity is one of the most poorly understood. There is still little evidence about BPA regulation of ion channel expression and function. However, this information is key to understand how BPA disrupts excitable and non-excitable cells, including neurons, endocrine cells and muscle cells. This report is the result of a comprehensive literature review on the effects of BPA on ion channels. We conclude that there is evidence to say that these important molecules may be key end-points for EDCs acting as xenoestrogens. However, more research on channel-mediated BPA effects is needed. Particularly, mechanistic studies to unravel the pathophysiological actions of BPA on ion channels at environmentally relevant doses.

An easy grammar of natural and experimental philosophy : for the use of schools /

Mode of access: Internet.

Prostanoids as friends, not foes: Further evidence from the interference by cycloxygenase-inhibitory drugs when inducing tolerance to experimental arthritigens in rats

Pharmacologists have generally been prejudiced against prostanoids, uncritically accepting their suppression as desirable therapy, especially for ‘quick-fix’ analgesia. This myopic perception for a long time ignored (a) the essentiality of prostanoid precursors in nutrition, (b) the physiological protective functions of natural prostaglandins (PGs) (vasculature, stomach, kidney), (c) resolution of inflammation after the expression of COX-2 and (d) increasing therapeutic use of either synthetic PGs (for erectile dysfunction, opthalmic disorders, inducing parturition, etc) or their natural precursors, e.g., ω3-rich polyunsaturated oils, to treat arthritis. Experimental studies in rats have indicated that prostaglandins (E series) are (i) useful, perhaps auto-regulators of established immunoreactivity and (ii) able to amplify (or even induce) anti-inflammatory activity with other agents. Furthermore, anti-prostanoid therapy (APT) can be arthritigenic!!, interfering with the acquisition of tolerance to some arthritigens. For patients with rheumatoid arthritis this additional side-effect of APT, barely recognised to date, may actually perpetuate their arthritis by impairing prostanoid-mediated remission processes. Hopefully, recent adverse publicity about COX-2 inhibitory drugs might stimulate serious re-assessment of some traditional anti-inflammatory therapies with low APT activity for the management of both acute pain (non-addictive cannabinoids, celery seed, etc.) and chronic inflammation, e.g., Lyprinol® (a mussel lipid extract).

Transglutaminase inhibition reduces fibrosis and preserves function in experimental chronic kidney disease

Progressive tissue fibrosis is involved in debilitating diseases that affect organs including the lungs, liver, heart, skin, and kidneys. Recent evidence suggests that tissue transglutaminase, an enzyme that crosslinks proteins, may be involved in tissue fibrosis by crosslinking and stabilizing the extracellular matrix or by recruiting and activating the large latent transforming growth factor (TGF)-β1 complex. We treated rats that had undergone 5/6-nephrectomy with two different irreversible inhibitors of transglutaminase and found that both prevented a decline in kidney function and reduced the development of glomerulosclerosis and tubulointerstitial fibrosis by up to 77% and 92%, respectively. Treatment reduced the accumulation of collagen I and collagen III, with the primary mechanism of action being direct interference with the crosslinking of extracellular matrix rather than altered regulation of TGFβ1. We conclude that inhibition of transglutaminase offers a potential therapeutic option for chronic kidney disease and other conditions that result from tissue fibrosis. Copyright © 2007 by the American Society of Nephrology.

Condensation versus air density change as a major cause of airflow: experimental evidence, link to data files and videos

The dominant model of atmospheric circulation posits that hot air rises, creating horizontal winds. A second major driver has recently been proposed by Makarieva and Gorshkov in their biotic pump theory (BPT), which suggests that evapotranspiration from natural closed-canopy forests causes intense condensation, and hence winds from ocean to land. Critics of the BPT argue that air movement to fill the partial vacuum caused by condensation is always isotropic, and therefore causes no net air movement (Bunyard, 2015, hdl:11232/397). This paper explores the physics of water condensation under mild atmospheric conditions, within a purpose-designed square-section 4.8 m-tall closed-system structure. Two enclosed vertical columns are connected at top and bottom by two horizontal tunnels, around which 19.5 m**3 of atmospheric air can circulate freely, allowing rotary airflows in either direction. This air can be cooled and/or warmed by refrigeration pipes and a heating mat, and changes in airflow, temperature, humidity and barometric pressure measured in real time. The study investigates whether the "hot-air-rises" or an implosive condensation model can better explain the results of more than 100 experiments. The data show a highly significant correlation (R2 >0.96, p value <0.001) between observed airflows and partial pressure changes from condensation. While the kinetic energy of the refrigerated air falls short of that required in bringing about observed airflows by a factor of at least 30, less than a tenth of the potential kinetic energy from condensation is shown to be sufficient. The assumption that condensation of water vapour is always isotropic is therefore incorrect. Condensation can be anisotropic, and in the laboratory does cause sustained airflow.

Insufficient Evidence of Jatropha curcas L. Invasiveness: Experimental Observations in Burkina Faso, West Africa

Biofuel plants such as Jatropha curcas L. have potential to support the livelihoods of rural communities and contribute to sustainable rural development in Africa, if risks and uncertainties are minimized. Yet, recent papers have warned of the risk of biological invasions in such tropical regions as a consequence of the introduction of exotic biofuel crops. We investigated the seed dispersal risk and invasiveness potential of both J. curcas monoculture plantations and live fences into adjacent cultivated and uncultivated land use systems in Sissili province, Burkina Faso. Invasiveness potential was assessed through (i) detecting evidence of natural regeneration in perimeters around J. curcas plantations and live fences, (ii) assessing seed dispersal mechanisms, and (iii) assessing seedling establishment potential through in situ direct seed sowing. Spontaneous regeneration around the plantation perimeters of the three sites was very low. Individual seedling density around J. curcas live fences was less than 0.01 m⁻² in all sites. Seventy percent of the seedlings were found close to the live fence and most of them derived from the same year (96 %), which indicates low seed-bank longevity and seedling survival. J. curcas can be dispersed by small mammals and arthropods, particularly rodents and ants. In some sites, such as in Onliassan, high secondary seed dispersal by animals (up to 98 %) was recorded. There were highly significant differences in germination rates between seeds at the soil surface (11 %) and those buried artificially at 1–2-cm depth (64 %). In conclusion, we failed to find convincing evidence of the spreading of J. curcas or any significant impact on the surrounding environment.

THE ROLE OF RULES, EXAMPLES AND INDIVIDUAL DIFFERENCES IN THE ACQUISITION OF DECLARATIVE AND PROCEDURAL SECOND LANGUAGE KNOWLEDGE

The relevance of explicit instruction has been well documented in SLA research. Despite numerous positive findings, however, the issue continues to engage scholars worldwide. One issue that was largely neglected in previous empirical studies - and one that may be crucial for the effectiveness of explicit instruction - is the timing and integration of rules and practice. The present study investigated the extent to which grammar explanation (GE) before practice, grammar explanation during practice, and individual differences impact the acquisition of L2 declarative and procedural knowledge of two grammatical structures in Spanish. In this experiment, 128 English-speaking learners of Spanish were randomly assigned to four experimental treatments and completed comprehension-based task-essential practice for interpreting object-verb (OV) and ser/estar (SER) sentences in Spanish. Results confirmed the predicted importance of timing of GE: participants who received GE during practice were more likely to develop and retain their knowledge successfully. Results further revealed that the various combinations of rules and practice posed differential task demands on the learners and consequently drew on language aptitude and WM to a different extent. Since these correlations between individual differences and learning outcomes were the least observed in the conditions that received GE during practice, we argue that the suitable integration of rules and practice ameliorated task demands, reducing the burden on the learner, and accordingly mitigated the role of participants’ individual differences. Finally, some evidence also showed that the comprehension practice that participants received for the two structures was not sufficient for the formation of solid productive knowledge, but was more effective for the OV than for the SER construction.

Molecular And Morphological Evidence Reveals A New Species In The Phyllomedusa Hypochondrialis Group (hylidae, Phyllomedusinae) From The Atlantic Forest Of The Highlands Of Southern Brazil.

The taxonomic status of a disjunctive population of Phyllomedusa from southern Brazil was diagnosed using molecular, chromosomal, and morphological approaches, which resulted in the recognition of a new species of the P. hypochondrialis group. Here, we describe P. rustica sp. n. from the Atlantic Forest biome, found in natural highland grassland formations on a plateau in the south of Brazil. Phylogenetic inferences placed P. rustica sp. n. in a subclade that includes P. rhodei + all the highland species of the clade. Chromosomal morphology is conservative, supporting the inference of homologies among the karyotypes of the species of this genus. Phyllomedusa rustica is apparently restricted to its type-locality, and we discuss the potential impact on the strategies applied to the conservation of the natural grassland formations found within the Brazilian Atlantic Forest biome in southern Brazil. We suggest that conservation strategies should be modified to guarantee the preservation of this species.

Micrornas And Drought Responses In Sugarcane.

There is a growing demand for renewable energy, and sugarcane is a promising bioenergy crop. In Brazil, the largest sugarcane producer in the world, sugarcane plantations are expanding into areas where severe droughts are common. Recent evidence has highlighted the role of miRNAs in regulating drought responses in several species, including sugarcane. This review summarizes the data from miRNA expression profiles observed in a wide array of experimental conditions using different sugarcane cultivars that differ in their tolerance to drought. We uncovered a complex regulation of sugarcane miRNAs in response to drought and discussed these data with the miRNA profiles observed in other plant species. The predicted miRNA targets revealed different transcription factors, proteins involved in tolerance to oxidative stress, cell modification, as well as hormone signaling. Some of these proteins might regulate sugarcane responses to drought, such as reduction of internode growth and shoot branching and increased leaf senescence. A better understanding on the regulatory network from miRNAs and their targets under drought stress has a great potential to contribute to sugarcane improvement, either as molecular markers as well as by using biotechnological approaches.

Reduction Of Oxidative Damage And Inflammatory Response In The Diaphragm Muscle Of Mdx Mice Using Iron Chelator Deferoxamine.

Oxidative stress and inflammatory processes strongly contribute to pathogenesis in Duchenne muscular dystrophy (DMD). Based on evidence that excess iron may increase oxidative stress and contribute to the inflammatory response, we investigated whether deferoxamine (DFX), a potent iron chelating agent, reduces oxidative stress and inflammation in the diaphragm (DIA) muscle of mdx mice (an experimental model of DMD). Fourteen-day-old mdx mice received daily intraperitoneal injections of DFX at a dose of 150 mg/kg body weight, diluted in saline, for 14 days. C57BL/10 and control mdx mice received daily intraperitoneal injections of saline only, for 14 days. Grip strength was evaluated as a functional measure, and blood samples were collected for biochemical assessment of muscle fiber degeneration. In addition, the DIA muscle was removed and processed for histopathology and Western blotting analysis. In mdx mice, DFX reduced muscle damage and loss of muscle strength. DFX treatment also resulted in a significant reduction of dystrophic inflammatory processes, as indicated by decreases in the inflammatory area and in NF-κB levels. DFX significantly decreased oxidative damage, as shown by lower levels of 4-hydroxynonenal and a reduction in dihydroethidium staining in the DIA muscle of mdx mice. The results of the present study suggest that DFX may be useful in therapeutic strategies to ameliorate dystrophic muscle pathology, possibly via mechanisms involving oxidative and inflammatory pathways.

Behaviour of oligodendrocytes and Schwann cells in an experimental model of toxic demyelination of the central nervous system

Oligodendrocytes and Schwann cells are engaged in myelin production, maintenance and repairing respectively in the central nervous system (CNS) and the peripheral nervous system (PNS). Whereas oligodendrocytes act only within the CNS, Schwann cells are able to invade the CNS in order to make new myelin sheaths around demyelinated axons. Both cells have some limitations in their activities, i.e. oligodendrocytes are post-mitotic cells and Schwann cells only get into the CNS in the absence of astrocytes. Ethidium bromide (EB) is a gliotoxic chemical that when injected locally within the CNS, induce demyelination. In the EB model of demyelination, glial cells are destroyed early after intoxication and Schwann cells are free to approach the naked central axons. In normal Wistar rats, regeneration of lost myelin sheaths can be achieved as early as thirteen days after intoxication; in Wistar rats immunosuppressed with cyclophosphamide the process is delayed and in rats administered cyclosporine it may be accelerated. Aiming the enlightening of those complex processes, all events concerning the myelinating cells in an experimental model are herein presented and discussed.

Allelopathic evidence in Brachiaria decumbens and its potential to invade the Brazilian Cerrados

The aim of this study was to look for evidence of allelochemicals in B. decumbens, in parts of the plant from where they could easily be released to the environment. The germination inhibition of Phalaris canariensis, Lactuca sativa (standard species) and Melinis minutiflora, another invasive African grass, was tested using B. decumbens germinating seeds and aqueous leachates of the roots, green and senescent leaves, at 5, 10 and 20% w/v. Both the germinating seeds and the aqueous leachates of B. decumbens reduced the germination of the species tested; the effectiveness of the aqueous leachates increased according to concentration. Apparently, the competitive advantage of B. decumbens in the cerrados could be amplified via allelopathy.

Protector mechanisms of the association between gastroesophageal reflux disease and asthma: experimental study in rats

BACKGROUND: It is well known the association between gastroesophageal reflux disease and asthma. The hyperreactivity of the airways is a characteristic of an asthmatic. Many studies associate the increase of the airways reactivity with gastroesophageal reflux disease. AIM: In this study we have evaluated the effect of the intraluminal exposition to gastric juice of trachea on the reactivity to methacholine from rats submitted to a pulmonary allergic inflammation. METHODS: Group of rats were sensitized and challenged with ovalbumin. After 24 hours the animals were sacrificed, and their tracheae were removed to be cultured with gastric juice. The gastric juice was obtained from a donor rat. Subsequently the segments were placed into plastic plates with RPMI-1640 for incubation, under suitable atmosphere and time. After the period of incubation the segments were put into chambers for the analysis of the contractile response to methacholine. RESULTS: We observed reduction in the contractile response of trachea cultured with gastric juice from allergic rats. This result was confirmed by the pharmacological treatments with compound 48/80 and dissodium cromoglicate (mast cells blockade), L-NAME (nitric oxide inhibitor, NO), capsaicin (neuropeptides depletion) and indomethacin (ciclooxigenase inhibitor). CONCLUSIONS: Our results highlight to the existence of a complex interaction between pulmonary allergy and gastric juice in the airways. The involvement of the non-adrenergic non-cholinergic system, NO, prostanoids and mast cells are directly related to this interaction. We suggest that the reduced contractile response observed in vitro may represent a protector mechanism of the airways. Despite its presence in the human body it can not be observed due to the predominant effects of excitatory the non-adrenergic non-cholinergic system.

Effect of cyhalothrin on Ehrlich tumor growth and macrophage activity in mice

Cyhalothrin, a pyrethroid insecticide, induces stress-like symptoms, increases c-fos immunoreactivity in the paraventricular nucleus of the hypothalamus, and decreases innate immune responses in laboratory animals. Macrophages are key elements in cellular immune responses and operate at the tumor-host interface. This study investigated the relationship among cyhalothrin effects on Ehrlich tumor growth, serum corticosterone levels and peritoneal macrophage activity in mice. Three experiments were done with 10 experimental (single gavage administration of 3.0 mg/kg cyhalothrin daily for 7 days) and 10 control (single gavage administration of 1.0 mL/kg vehicle of cyhalothrin preparation daily for 7 days) isogenic BALB/c mice in each experiment. Cyhalothrin i) increased Ehrlich ascitic tumor growth after ip administration of 5.0 x 106 tumor cells, i.e., ascitic fluid volume (control = 1.97 ± 0.39 mL and experimental = 2.71 ± 0.92 mL; P < 0.05), concentration of tumor cells/mL in the ascitic fluid (control = 111.95 ± 16.73 x 106 and experimental = 144.60 ± 33.18 x 106; P < 0.05), and total number of tumor cells in the ascitic fluid (control = 226.91 ± 43.22 x 106 and experimental = 349.40 ± 106.38 x 106; P < 0.05); ii) increased serum corticosterone levels (control = 200.0 ± 48.3 ng/mL and experimental = 420.0 ± 75.5 ng/mL; P < 0.05), and iii) decreased the intensity of macrophage phagocytosis (control = 132.3 ± 19.7 and experimental = 116.2 ± 4.6; P < 0.05) and oxidative burst (control = 173.7 ± 40.8 and experimental= 99.58 ± 41.7; P < 0.05) in vitro in the presence of Staphylococcus aureus. These data provide evidence that cyhalothrin simultaneously alters host resistance to Ehrlich tumor growth, hypothalamic-pituitary-adrenocortical (HPA) axis function, and peritoneal macrophage activity. The results are discussed in terms of data suggesting a link between stress, HPA axis activation and resistance to tumor growth.