Proton Exchange Membranes from Sulfonated Lignin Nanocomposites for Redox Flow Battery Applications.

Redox flow batteries (RFBs) are increasingly being considered for a wide range of energy storage applications, and such devices rely on proton exchange membranes (PEMs) to function. PEMs are high-cost, petroleum-derived polymers that often possess limited durability, variable electrochemical performance, and are linked to discharge of perfluorinated compounds. Alternative PEMs that utilize biobased materials, including lignin and sulfonated lignin (SL), low-cost byproducts of the wood pulping process, have struggled to balance electrochemical performance with dimensional stability. Herein, SL nanoparticles are demonstrated for use as a nature-derived, ion-conducting PEM material. SL nanoparticles (NanoSLs) can be synthesized for increased surface area, uniformity, and miscibility compared with macrosized lignin, improving proton conductivity. After addition of polyvinyl alcohol (PVOH) as a structural backbone, membranes with the highest NanoSL concentration demonstrated an ion exchange capacity of 1.26 meq g-1, above that of the commercial PEM Nafion 112 (0.98 meq g-1), along with a conductivity of 80.4 mS cm-1 in situ, above that of many biocomposite PEMs, and a coulombic efficiency (CE), energy efficiency (EE) and voltage efficiency (VE) of 91%, 68% and 78%, respectively at 20 mA cm-2. These nanocomposite PEMs demonstrate the potential for valorization of forest biomass waste streams for high value clean energy applications.

Trailing-edge far-field noise and noise source characterization in high inflow turbulence conditions.

Airframe noise currently is a bottle neck in various applications, e.g., wind energy, maritime applications, and aircraft. Airframe noise is significantly increased by the presence of inflow turbulence. High inflow turbulence influences the boundary layer and wall-pressure fluctuations close to the trailing edge of airfoils. In this research, measurements of boundary layer and wall-pressure fluctuations near the trailing edge of an airfoil are conducted to investigate how the inflow turbulence affects the trailing-edge noise generation mechanism. Far-field noise measurements of additional three airfoils are shown to understand the role of the airfoil geometry in the dominant noise source for the cases of inflow turbulence and to generalize the observed increase in trailing-edge noise. Inflow turbulence leads to an increase in both the wall-pressure spectrum and spanwise correlation length. Trailing-edge noise increases due to the inflow turbulence in the entire frequency range at least 2 dB up to more than 15 dB for all the cases. The contribution of leading- and trailing-edge noise to the total noise varies with the airfoil geometry and inflow velocity, with the trailing-edge noise dominating in a larger frequency range for the thickest airfoil and for lower velocities.

Neonatal exposure to aluminum chloride predisposes adult and senile gerbils to the prostatic hyperplasia.

Several pollutants can alter neonatal prostatic development predisposing this gland to diseases. The toxicity and endocrine disrupting potential of aluminum has been reported in many organs, but little is known about its effects on the prostate. This study aimed to evaluate the effects that aluminum neonatal exposure can cause in the male ventral prostate and in the female prostate of adult and senile gerbils. Male and female pups were treated orally with aluminum chloride (10 mg/kg) from the 1st to the 14th day life. After treatment, the animals were aged until they reached 90 days or 1 year of life. The prostate glands were dissected out and submitted to morphological, immunohistochemical and ultrastructural analyses. Ventral prostates of adult males showed moderate hyperplasia and increased epithelial proliferation not associated with androgen receptor (AR) deregulation. On the other hand, senile males showed intense prostatic hyperplasia, and increased cell proliferation and epithelial AR regulation. Additionally, at both ages, there was a reduction in the prostate secretory function. The morphological changes observed in the female prostate were like those found in males. However, in adult females, prostatic hyperplasia was accompanied by a lower regulation of AR and estrogen receptor alpha, while in senile females, intense hyperplastic growth was associated with an increase in estrogen receptor alpha and a reduction in stromal AR. These results demonstrate that aluminum chloride neonatal exposure alters the hormonal regulation of the male and female prostate, inducing tissue damage that occurs in adulthood and intensifies during aging.

The first use of LC-MS/MS proteomic approach in the brown mussel Perna perna after bacterial challenge: Searching for key proteins on immune response.

The brown mussel Perna perna is a valuable fishing resource, primarily in tropical and subtropical coastal regions. Because of their filter-feeding habits, mussels are directly exposed to bacteria in the water column. Escherichia coli (EC) and Salmonella enterica (SE) inhabit human guts and reach the marine environment through anthropogenic sources, such as sewage. Vibrio parahaemolyticus (VP) is indigenous to coastal ecosystems but can be harmful to shellfish. In this study, we aimed to assess the protein profile of the hepatopancreas of P. perna mussel challenged by introduced - E. coli and S. enterica - and indigenous marine bacteria - V. parahaemolyticus. Bacterial-challenge groups were compared with non-injected (NC) and injected control (IC) - that consisted in mussels not challenged and mussels injected with sterile PBS-NaCl, respectively. Through LC-MS/MS proteomic analysis, 3805 proteins were found in the hepatopancreas of P. perna. From the total, 597 were significantly different among conditions. Mussels injected with VP presented 343 proteins downregulated compared with all the other conditions, suggesting that VP suppresses their immune response. Particularly, 31 altered proteins - upregulated or downregulated - for one or more challenge groups (EC, SE, and VP) compared with controls (NC and IC) are discussed in detail in the paper. For the three tested bacteria, significantly different proteins were found to perform critical roles in immune response at all levels, namely: recognition and signal transduction; transcription; RNA processing; translation and protein processing; secretion; and humoral effectors. This is the first shotgun proteomic study in P. perna mussel, therefore providing an overview of the protein profile of the mussel hepatopancreas, focused on the immune response against bacteria. Hence, it is possible to understand the immune-bacteria relationship at molecular levels better. This knowledge can support the development of strategies and tools to be applied to coastal marine resource management and contribute to the sustainability of coastal systems.

Inflow turbulence distortion for airfoil leading-edge noise prediction for large turbulence length scales for zero-mean loading.

Turbulence distortion due to airfoil finite thickness is an important but not fully understood phenomenon that affects the airfoil radiated noise, resulting in inaccurate noise predictions. This study discusses the turbulence distortion in the leading edge (LE) region of an airfoil aiming to obtain more accurate LE noise predictions. Wind tunnel experiments were performed for National Advisory Committee for Aeronautics (NACA) 0008 and NACA 0012 airfoils at zero angle of attack subjected to large turbulence length scales (between 10 and 43 times the airfoil LE radius) generated by a grid and a rod. Hot-wire and surface pressure measurements were performed in the LE region. Results show that the root mean square of the velocity fluctuations urms and the turbulence integral length scale Λf at the stagnation line decrease considerably as the LE is approached. Rod-airfoil radiated noise was measured and compared with Amiet's model. The predicted noise overestimates the LE noise for high frequencies. However, the prediction agrees well with measurements when the turbulence spectrum based on the rapid distortion theory is used in Amiet's model, with as inputs the urms and Λf values measured close to the LE. This work's main contribution is to demonstrate that more accurate noise predictions are obtained when the inputs to the model consider the turbulence distortion effects.

Anti-inflammatory and antinociceptive effects, and safety toxicological profile of a new paracetamol analog, LQFM291.

In the scope of a research program with the goal of developing treatments for inflammatory diseases, the pharmacological evaluation of LQFM291, designed by molecular hybridization from butylated hydroxytoluene and paracetamol, was described. The antioxidant profile of LQFM291 was evaluated by electrochemical measurement. Also, acute or repeated treatments with equimolar doses to paracetamol were used to evaluate the antinociceptive and/or anti-inflammatory activities of LQFM291 in animal models. The toxicologic potential of LQFM291 was also evaluated and compared to paracetamol through biochemical and histopathological analysis after the repeated treatment schedule. As a result of the acute treatment, paracetamol showed a similar antinociceptive effect in formalin test compared to LQFM291. Whereas, after the repeated treatment, when carrageenan-induced hyperalgesia and edema tests were performed, paracetamol showed a delayed antinociceptive and anti-inflammatory effect compared to LQFM291. Furthermore, as other advantages the LQFM291 showed a high redox capacity, a gastroprotective activity and a safety pharmacological profile without any liver or kidney damage. These effects can be related to the prevention of oxidative stress by reduction of protein and lipid peroxidation in gastric tissue, maintenance of glutathione levels in hepatic homogenate, and a systemic reduction of pro-inflammatory cytokine levels, which may characterize the LQFM291 as a more viable and effective alternative to relief pain and inflammatory signs in patients with chronic disorders.

Physical (in)activity, and its predictors, among Brazilian adolescents: a multilevel analysis.

BACKGROUND: Physical activity is a multifactorial trait, determined by both individual and environmental characteristics, it seems relevant to understand the determinants related to youth guidelines accomplishment. The present study aimed to verify the differences between the Brazilian federative units regarding to the prevalence of youth physical activity guidelines accomplishment and to investigate the determinants related to the inter-individual differences in this accomplishment. METHODS: Sample comes from the 2015 Brazilian National School Health Survey (PeNSE), comprising 99,570 adolescents (51,527 girls, 13-17y), enrolled in 3039 schools. Adolescents reported the time they spend in moderate-to-vigorous physical activity daily, and they were categorized as active or inactive, if the guidelines were achieved, or not, respectively, and multilevel statistical analyses were used, including both child and school-level variables. Multilevel Binomial model was computed in the SuperMix software. RESULTS: The majority of the adolescents did not comply with the physical activity guidelines daily, where Bahian children complied the least, while those from Amazonas, Tocantins, and Mato Grosso do Sul complied the most. Boys (OR: 2.305; 95%CI: 2.277-2.334), older adolescents (OR: 1.044; 95%CI: 1.036-1.051), and those who spent more time in active travelling to/from school (OR: 1.001; 95%CI: 1.001-1.001) complied more the physical activity guidelines. At the school level, adolescents from larger schools (OR: 0.957; 95%CI: 0.928-0.986) tended to comply less with the guidelines. CONCLUSION: Significant differences between Brazilian federative units in youth daily physical activity guidelines compliance were observed, highlighting the role of individual but also environmental constraints in the Brazilian adolescents' engagement in physical activity.

Female Prostate Development: Morphological Analysis of the Budding Dynamic.

The presence of the prostate in female mammals has long been known. However, pieces of information related to its development are still lacking. The aim of this study was to explore the budding dynamic during the initial prostate development in female gerbils. Pregnant females were timed, the fetuses were euthanized, and the urogenital sinus was dissected out between the embryonic days 20 and 24 (E20-E24 groups). Newborn pups (1-day-old; P1 group) underwent the same procedures. The female prostate development was based on epithelial buds which arose far from the paraurethral mesenchyme (PAM). The epithelial buds reached the PAM at prenatal day 24, crossing a small gap in the smooth muscle layer between the periurethral mesenchyme (PEM) and the PAM. Steroid nuclear receptors such as the androgen receptor and estrogen receptor alpha were localized in the PEM through the urethral wall, although some epithelial labeling was also present in the urogenital sinus epithelium (UGE). P63-positive cells were found only in the UGE, becoming restricted to the basal compartment after the 23rd prenatal day. The results showed that the gerbil female prostate exhibits a distinct budding pattern as compared to the male prostate development.

Subacute exposure to aluminum chloride causes prolonged morphological insults in the ventral male prostate and in the female prostate of adult gerbils.

Aluminum (Al) is a widespread metal in the environment, and is found in fresh or processed foods, household utensils, packaging, and medicines. In addition to its high toxicity, Al can also have estrogenic agonistic effects on target organs. Considering that the Al effects on the prostate are little known, the aim of this study was to evaluate the impact of aluminum chloride (AlCl3 ) subacute exposure on the morphophysiology of the male ventral prostate and the female prostate of adult gerbils. Furthermore, the glandular restoration capacity in face of the Al insults was evaluated in gerbils that were submitted to 30 days of recovery. Male and female gerbils were orally exposed to AlCl3 (10 mg/kg) for 30 consecutive days. The animals were euthanized 1 day (Al1D) or 30 days (Al30D) after the end of treatment. Prostates were dissected out and processed for structural, ultrastructural and immunohistochemical analyses. Male ventral prostates and female prostates of the Al1D group showed increased cell proliferation, glandular hyperplasia, increased secretory activity and greater androgen receptor immunoreactivity. In males, Al withdrawal (Al30D) allowed a partial recovery of the prostate, as the glandular secretory activity, and frequency of androgen receptor positive cells were similar to the control group. In females, the recuperation interval (Al30D) was not enough to restore the prostatic morphology, since the gland remained hyperplastic, proliferative, and with greater androgen and estrogen receptor immunoreactivity. These data alert to the importance of avoiding Al exposure, since this metal can have a harmful and prolonged action on the prostate.

Delirium in the intensive care unit: identifying difficulties in applying the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).

BACKGROUND: Delirium is an underdiagnosed condition and this may be related, among other causes, to the incorrect use of assessment tools due to lack of knowledge about cognitive assessment and lack of training of the care team. The aim of this study was to investigate the difficulties encountered by the nursing team in the application of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in patients on mechanical ventilation. METHODS: This is descriptive study with a qualitative approach in a private tertiary hospital located in northeast Brazil. Data collection took place from July 2018 to January 2019. We included 32 nurses and used face-to-face semi-structured interviews. The recorded data were analysed using content analysis. This study followed the recommendations of the Standards for Reporting Qualitative Research (SRQR). RESULTS: We identified three major categories: lack of knowledge of professionals, subdivided into deficit in academic formation, difficulty in the differential diagnosis of delirium and delusion, and lack of knowledge about the steps of the CAM-ICU; difficulty in patient cooperation; and lack of adequate training to apply the CAM-ICU. CONCLUSION: Nurses have a deficit in academic formation on delirium and need adequate training for the correct and frequent use of the CAM-ICU.

How does the brown mussel Perna perna respond to environmental pollution? A review on pollution biomarkers.

The brown mussel Perna perna (Linnaeus, 1758) is a valuable resource for aquaculture in tropical and subtropical coastal regions. It presents desirable characteristics for biomonitoring, including being sessile, widely distributed and abundant, and is a filter-feeder able to accumulate several classes of pollutants (e.g., metals, hydrocarbons, among others). Mussels' biological responses to pollution exposure can be measured as biomarkers, which include alterations ranging from molecular to physiological levels, to estimate the degree of environmental contamination and its effects on biota. This full review compiles two decades (2000-2020) of literature concerning biological effects on P. perna mussel caused by environmental pollutants (i.e., metals, hydrocarbons, and emerging pollutants), considering environmental and farm-based biomonitoring. Biochemical markers related to mussels' oxidative status were efficient for the biomonitoring of metals (i.e., antioxidant enzymes associated with oxidative damage in biomolecules). Genotoxicity and cytotoxicity indicators (i.e., comet, micronucleus, and neutral red assays) provided a depiction of hydrocarbon contamination. The neutral red assay gave a time-concentration cytotoxic response to a wide range of pollutants, including emerging pollutants (e.g., pharmaceuticals and biocides) and hydrocarbons. Perna perna hemocyte parameters provided a useful approach for biocide biomonitoring. This paper summarizes useful biomarkers from molecular to physiological levels in this mussel species used to identify and quantify the degree of coastal pollution. An integrated biomarker analysis may provide a way to overcome possible biomarker variations and assess multi-polluted sites. Nevertheless, it is necessary to investigate biomarker variations according to natural factors (e.g., season and gonad maturation stage) to standardize them for trustworthy biomonitoring.

Gamma-Decanolactone Alters the Expression of GluN2B, A1 Receptors, and COX-2 and Reduces DNA Damage in the PTZ-Induced Seizure Model After Subchronic Treatment in Mice.

Gamma-decanolactone (GD) has been shown to reduce epileptic behavior in different models, inflammatory decreasing, oxidative stress, and genotoxic parameters. This study assessed the GD effect on the pentylenetetrazole (PTZ) model after acute and subchronic treatment. We evaluated the expression of the inflammatory marker cyclooxygenase-2 (COX-2), GluN2B, a subunit of the NMDA glutamate receptor, adenosine A1 receptor, and GD genotoxicity and mutagenicity. Male and female mice were treated with GD (300 mg/kg) for 12 days. On the tenth day, they were tested in the Hot Plate test. On the thirteenth day, all animals received PTZ (90 mg/kg), and epileptic behavior PTZ-induced was observed for 30 min. Pregabalin (PGB) (30 mg/kg) was used as a positive control. Samples of the hippocampus and blood were collected for Western Blotting analyses and Comet Assay and bone marrow to the Micronucleus test. Only the acute treatment of GD reduced the seizure occurrence and increased the latency to the first stage 3 seizures. Males treated with GD for 12 days demonstrated a significant increase in the expression of the GluN2B receptor and a decrease in the COX-2 expression. Acute and subchronic treatment with GD and PGB reduced the DNA damage produced by PTZ in males and females. There is no increase in the micronucleus frequency in bone marrow after subchronic treatment. This study suggests that GD, after 12 days, could not reduce PTZ-induced seizures, but it has been shown to protect against DNA damage, reduce COX-2 and increase GluN2B expression.

Prenatal and pubertal exposure to 17α-ethinylestradiol cause morphological changes in the prostate of old gerbils.

This study evaluated such as exposure to ethinylestradiol during the prenatal (18th-22nd day) and pubertal (42nd-49th day) periods acts on the male ventral prostate and female prostate of 12-month old gerbils. We performed the analysis to serum hormone levels for estradiol and testosterone. The prostates were submitted to morphometric and immunohistochemical analyses. Exposure to ethinylestradiol during these developmental periods decreased the testosterone serum levels in males and increased the estradiol serum levels in females. Morphologically, prostate intraepithelial neoplasia and disorders in the arrangement of the fibrous components were observed in the prostate glands of both sexes of gerbil exposed to ethinylestradiol during development periods. In the male prostate, the ethinylestradiol promoted decreased in the frequency of positive epithelial cell for androgen receptor (AR) and increased the frequency of positive stromal cell for estrogen receptor α. However, in the female prostate, this synthetic estrogen caused AR upregulation and increased cell proliferation. This study shows that the exposure to ethinylestradiol during development phases alters the morphology and the hormonal signaling in the male and female prostates of old gerbils, confirming the action of ethinylestradiol as endocrine disruptor.

The number and periodicity of seizures induce cardiac remodeling and changes in micro-RNA expression in rats submitted to electric amygdala kindling model of epilepsy.

Generalized tonic-clonic seizures (GTCS) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Also, among the several mechanisms underlying SUDEP there is the cardiac dysfunction. So, we aimed to evaluate the impact of the number of seizures on heart function and morphology in rats with epilepsy. Rats were randomized into three groups: Sham (without epilepsy), 5 S, and 10 S groups, referred as rats with epilepsy with a total of 5 or 10 GTCS, respectively. Epilepsy was induced by electrical amygdala kindling. The ventricular function was analyzed by the Langendorff technique and challenged by ischemia/reperfusion protocol. Cardiac fibrosis and hypertrophy were analyzed by histology. We also analyzed cardiac metalloproteinases (MMP2 and MMP9), ERK 1/2 and phosphorylated ERK1/2 (P-ERK) by western blot; microRNA-21 and -320 by RT-PCR; and oxidative stress (TBARS, catalase activity and nitrite) by biochemical analysis. Only the 5S group presented decreased values of ventricular function at before ischemia/reperfusion (baseline): intraventricular systolic pressure, developed intraventricular pressure, positive and negative dP/dt. During ischemia/reperfusion protocol, the variation of the ventricular function did not differ among groups. Both 5S and 10S groups had increased cardiomyocyte hypertrophy and fibrosis compared to Sham, but in the 5S group, these alterations were higher than in the 10S group. The 5S group increased in microRNA-21 and decreased in microRNA-320 expression compared to Sham and the 10S group. The 10S group increased in MMP9 and decreased in P-ERK/ERK expression, and increased in nitrite content compared to both Sham and the 5S group. Therefore, seizures impair cardiac function and morphology, probably through microRNA modulation. The continuation of seizures seems to exert a preconditioning-like stimulus that fails to compensate the cardiac tissue alteration.

Cardioprotective effects of the proline-rich oligopeptide Bj-PRO-7a in spontaneously hypertensive rats.

The proline-rich oligopeptide from Bothrops jararaca snake venom, Bj-PRO-7a, promotes acute effects in blood pressure in hypertensive animals. However, the cardiac effects of this heptapeptide are completely unknown. Thus, we sought to evaluate whether the Bj-PRO-7a could protect against cardiac remodelling in spontaneously hypertensive rats (SHR). SHR were treated with Bj-PRO-7a (71 nmol/kg/day, s.c.) or saline for 28 days. Wistar rats were used as control. Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff plethysmography. Cardiomyocyte diameter and interstitial and perivascular fibrosis of the left ventricle (LV) were evaluated using Picrosirius staining. Immunofluorescence was used to detect collagen I and III. Fibroblast proliferation was assessed by immunohistochemistry to detect proliferating cell nuclear antigen (PCNA). Protein expression was assessed by western blot. The superoxide dismutase and catalase activities and the concentration of lipid peroxidation products were evaluated in the LV. The SBP and HR were not different between treated and non-treated SHR at the end of the treatment. However, Bj-PRO-7a attenuated the cardiomyocyte hypertrophy, deposition of interstitial and perivascular fibrosis and collagen I, and positive PCNA-labelled fibroblasts. This peptide also reduced the increased levels of TBARS, expression and activity of catalase, and activity of SOD in LV from SHR. Also, the Bj-PRO-7a increased the expression of metalloproteinases-2 in SHR hearts. These findings demonstrate that the Bj-PRO-7a reduced the pathological cardiac remodelling in a pressure-independent manner in hypertensive rats through mechanisms mediated by oxidative stress regulation.

Adolescent's movement behaviors and built environment: a latent class analysis.

BACKGROUND: Latent class analysis (LCA) is an alternative and innovative approach to verify the relation of the various combinations of the constructed environment and movement behavior (levels of physical activity, sedentary behavior, and sleep) characteristics. This study aimed to identify latent classes based on the characteristics of the neighborhood environment perceived by adolescents and their association with gender, socioeconomic status (SS), body composition and movement behaviors. METHODS: This cross-sectional study includes 309 Brazilian adolescents (14 to 16 years old, 57% female). The characteristics of the neighborhood environment perceived were analyzed by the Neighborhood Walkability for Youth Scale. Accelerometers were used for a week to evaluate the movement behaviors. Questionnaires assessed the screen times, total sitting time (TST), and sociodemographic characteristics. LCA was used for modeling the "Perceived Enviroment" variable, having been conducted in the poLCA (Polychromous Variable Latent Class Analysis) package of the R statistical software. RESULTS: Three classes were recognized: class 1, "Best Perceived Environment" with 23.03% of adolescents; class 2, "Moderate Perceived Environment", 63.33%; and class 3, "Worst Perceived Environment", 13.67%. Light physical activity (LPA), TST, and SS were associated with class prevalence. The adolescents with medium and low SS were, respectively, 3.42 (95% CI 1.62-7.21) and 4.18 (95% CI 1.66-10.50) more likely to belong to class 2, and those with low SS were 5.21 (95% CI 1.35-20.13) more likely to belong to class 3. Class 1 adolescents were associated with a lower chance (OR: 0.09, 95% CI 0.02-0.55) of involvement in 'adequate LPA time' compared to class 3. Class 1 adolescents were associated with a lower chance (OR: 0.31, 95% CI 0.12-0.79) of involvement in 'adequate TST' compared to class 2. There was a difference between the LPA and TST classes; class 3 presented a longer time in LPA than class 1; class 1 had higher TST than the other classes. CONCLUSION: The findings highlight the influence of neighborhood classes on adolescents' LPA and TST.

Developmental changes induced by exogenous testosterone during early phases of prostate organogenesis.

The aim of this study was to evaluate the impact of prenatal testosterone exposure on prostate development in male and female neonatal gerbils. Pregnant females were exposed to subcutaneous injections of testosterone cypionate (500 µg/animal) at gestational days 20 and 22. Male and female pups were then euthanized at postnatal day 1. Morphological analysis showed that females were severely affected by androgen exposure. We also observed that male and female urogenital sinus (UGS) responded differentially to testosterone treatment, demonstrating heterogeneous immunostaining for the androgen receptor (AR), estrogen receptor alpha (ERα), and proliferating cell nuclear antigen (PCNA). Smooth muscle α-actin (α-SMA) analysis showed that testosterone delays the myodifferentiation, allowing buds to reach the ectopic mesenchymes of the female UGS. Our data showed that abnormal testosterone exposure disrupted prostate organogenesis, altered the expression patterns of important markers, and demonstrated that female UGS was particularly influenced by androgen exposure during a critical window in the developmental period.

Aluminum exposure promotes histopathological and pro-oxidant damage to the prostate and gonads of male and female adult gerbils.

Since the industrial revolution, all living beings have become susceptible to numerous sources of aluminum (Al) exposure. In addition to causing proven toxicity in many organs and systems, Al can also have estrogenic activity when absorbed by the body. The reproductive organs are commonly affected by environmental pollutants with estrogenic activity, but little is known about the effects of Al on the prostate and gonads. Therefore, the aim of this study was to evaluate the effects of subchronic Al exposure on the prostate and gonads of male and female adult gerbils. After 30 days of oral exposure to aluminum chloride (10 mg/kg/day), the animals were euthanized and the organs processed for cytochemical, ultrastructural, and biochemical assays. Ventral male prostates exposed to Al became hyperplastic and showed signs of cell aging. In addition, the male prostate showed decreased catalase (CAT) and superoxide dismutase (SOD) activity. The female prostate was structurally more affected than the ventral male prostate, since it presented hyperplasia and punctual foci of inflammation and prostatic intraepithelial neoplasia. However, CAT and SOD activities did not change in this gland. In the testis, Al promoted immature germ cell detachment and degeneration, as well as reduced CAT activity. In the ovaries, Al caused reduction in folliculogenesis and decreased SOD activity. Together, these results indicate that Al is toxic to the prostate and gonads of adult gerbils and that continuous exposure to this metal can impair the fertility of individuals of both sexes.

Mechanisms involved in the antinociceptive and anti-inflammatory effects of a new triazole derivative: 5-[1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl]-1H-tetrazole (LQFM-096).

The aim of this study was to design, synthesize and evaluate the potential analgesic and anti-inflammatory effects of 5-[1-(4-fluorphenyl)-1H-1,2,3-triazol-4-yl]-1H-tetrazole-(LQFM-096: a new triazole compound) as well as to elucidate its possible mechanisms of action. The oral administration of LQFM-096 (10, 20 or 40 mg/kg) decreased the number of writhing in mice. At the dose of 20 mg/kg, LQFM-096 reduced the licking time at both neurogenic and inflammatory phases of the formalin test. Pretreatment with naloxone (3 mg/kg) and glibenclamide (3 mg/kg) attenuated the antinociceptive effect of LQFM-096 in the first phase of the formalin test. At the dose of 20 mg/kg, LQFM-096 also decreased the licking time in the acidified saline-induced and capsaicin-induced nociception. This effect was blocked by naloxone (3 mg/kg) pretreatment prior to the administration of LQFM-096. In addition, LQFM-096 inhibited hyperalgesia induced by carrageenan and PGE2. Naloxone (3 mg/kg) attenuated the effect of LQFM-096 through disinhibition of PGE2-induced hyperalgesia. The anti-inflammatory effect of LQFM-096 was demonstrated in carrageenan-induced oedema or pleurisy as well as CFA-induced arthritis. The hyperalgesia and cellular migration in CFA-induced arthritis were reduced significantly. Altogether, these findings suggest antinociceptive effect of LQFM-096 and implicate the modulation of ASICs/TRPV1 channels by opioid/KATP pathway. The anti-inflammatory effect of LQFM-096 was mediated by a reduction in oedema, leukocytes migration, TNF-α, PGE2 levels and myeloperoxidase activity.

Design, synthesis and pharmacological assessment of new pyrazole compounds.

AIMS: This study investigated the antinociceptive and anti-inflammatory effects of new pyrazole compounds LQFM011(5), LQFM043(6) and LQFM044(7) as well as the mechanisms of action and acute in vitro toxicity. MAIN METHODS: The antinociceptive activity was evaluated using the acetic acid-induced abdominal writhing test, formalin-induced pain test and the Randall-Selitto test. The anti-inflammatory activity was evaluated using models of paw oedema and pleurisy induced by carrageenan; cell migration, the levels of tumour necrosis factor α (TNF-α) and myeloperoxidase (MPO) enzyme activity were evaluated. In addition, the ability to inhibit phospholipase A2 (PLA2) in vitro and docking in PLA2 were used. Acute oral systemic toxicity in mice was evaluated through the neutral red uptake assay. KEY FINDINGS: The synthesised compounds (5-7), delivered via gavage (p.o.) at 70, 140 or 280 µmol/kg, decreased the number of writhings induced by acetic acid; the three compounds (280 µmol/kg p.o.) reduced the paw licking time in the first and second phase of the formalin test and decreased the nociceptive threshold variation in the Randall-Selitto test. Furthermore, this dose reduced oedema formation, leucocyte migration (specifically through reduction in polymorphonuclear cell movement) and increased mononuclear cells. MPO activity and the levels of pro-inflammatory cytokines TNF-α were decreased. Evaluation of PLA2 inhibition via the docking simulation revealed more interactions of LQFM043R(6) and LQFM044(7), data that corroborated the half-maximal inhibitory concentration (IC50) of PLA2 inhibition in vitro. Therefore, LQFM011(5), LQFM043(6) and LQFM044(7) were classified with the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) as category 4.