The carbon sink of secondary and degraded humid tropical forests.

The globally important carbon sink of intact, old-growth tropical humid forests is declining because of climate change, deforestation and degradation from fire and logging1-3. Recovering tropical secondary and degraded forests now cover about 10% of the tropical forest area4, but how much carbon they accumulate remains uncertain. Here we quantify the aboveground carbon (AGC) sink of recovering forests across three main continuous tropical humid regions: the Amazon, Borneo and Central Africa5,6. On the basis of satellite data products4,7, our analysis encompasses the heterogeneous spatial and temporal patterns of growth in degraded and secondary forests, influenced by key environmental and anthropogenic drivers. In the first 20 years of recovery, regrowth rates in Borneo were up to 45% and 58% higher than in Central Africa and the Amazon, respectively. This is due to variables such as temperature, water deficit and disturbance regimes. We find that regrowing degraded and secondary forests accumulated 107 Tg C year-1 (90-130 Tg C year-1) between 1984 and 2018, counterbalancing 26% (21-34%) of carbon emissions from humid tropical forest loss during the same period. Protecting old-growth forests is therefore a priority. Furthermore, we estimate that conserving recovering degraded and secondary forests can have a feasible future carbon sink potential of 53 Tg C year-1 (44-62 Tg C year-1) across the main tropical regions studied.

Strength Training Protects High-Fat-Fed Ovariectomized Mice against Insulin Resistance and Hepatic Steatosis.

Menopause is characterized by a reduction in sex hormones in women and is associated with metabolic changes, including fatty liver and insulin resistance. Lifestyle changes, including a balanced diet and physical exercise, are necessary to prevent these undesirable changes. Strength training (ST) has been widely used because of the muscle and metabolic benefits it provides. Our study aims to evaluate the effects of ST on hepatic steatosis and insulin resistance in ovariectomized mice fed a high-fat diet (HFD) divided into four groups as follows: simulated sedentary surgery (SHAM-SED), trained simulated surgery (SHAM-EXE), sedentary ovariectomy (OVX-SED), and trained ovariectomy (OVX-EXE). They were fed an HFD for 9 weeks. ST was performed thrice a week. ST efficiently reduced body weight and fat percentage and increased lean mass in OVX mice. Furthermore, ST reduced the accumulation of ectopic hepatic lipids, increased AMPK phosphorylation, and inhibited the de novo lipogenesis pathway. OVX-EXE mice also showed a better glycemic profile, associated with greater insulin sensitivity identified by the euglycemic-hyperinsulinemic clamp, and reduced markers of hepatic oxidative stress compared with sedentary animals. Our data support the idea that ST can be indicated as a non-pharmacological treatment approach to mitigate metabolic changes resulting from menopause.

Determination and Analysis of Thermodynamic Properties of Methyl Methylanthranilate Isomers.

The enthalpies of formation in the gaseous phase of methyl 3-methylanthranilate and methyl 5-methylanthranilate were determined from experimental measurements of the corresponding standard energies of combustion, obtained from combustion calorimetry, and the standard enthalpies of vaporization and sublimation, obtained from Calvet microcalorimetry and Knudsen mass-loss effusion. A computational study, using the G3(MP2)//B3LYP composite method, has also been performed for the calculation of the gas-phase standard enthalpies of formation of those two molecules at T = 298.15 K, as well as for the remaining isomers, methyl 4-methylanthranilate and methyl 6-methylanthranilate. The results have been used to evaluate and analyze the energetic effect of the methyl substituent in different positions of the ring.

Th17 cell-linked mechanisms mediate vascular dysfunction induced by testosterone in a mouse model of gender-affirming hormone therapy.

Clinical data point to adverse cardiovascular events elicited by testosterone replacement therapy. Testosterone is the main hormone used in gender-affirming hormone therapy (GAHT) by transmasculine people. However, the cardiovascular impact of testosterone in experimental models of GAHT remains unknown. Sex hormones modulate T-cell activation, and immune mechanisms contribute to cardiovascular risk. The present study evaluated whether testosterone negatively impacts female cardiovascular function by enhancing Th17 cell-linked effector mechanisms. Female (8 wk old) C57BL/6J mice received testosterone (48 mg/kg/wk) for 8 wk. Male mice were used for phenotypical comparisons. The hormone treatment in female mice increased circulating testosterone to levels observed in male mice. Testosterone increased lean body mass and body mass index, and decreased perigonadal fat mass, mimicking clinical findings. After 8 wk, testosterone decreased endothelium-dependent vasodilation and increased peripheral Th17 cells. After 24 wk, testosterone increased blood pressure in female mice. Ovariectomy did not intensify phenotypical or cardiovascular effects by testosterone. Female mice lacking T and B cells [Rag1 knockout (-/-)], as well as female mice lacking IL-17 receptor (IL-17Ra-/-), did not exhibit vascular dysfunction induced by testosterone. Testosterone impaired endothelium-dependent vasodilation in female mice lacking γδ T cells, similarly to the observed in wild-type female mice. Adoptive transfer of CD4+ T cells restored testosterone-induced vascular dysfunction in Rag1-/- female mice. Together, these data suggest that CD4+ T cells, most likely Th17 cells, are central to vascular dysfunction induced by testosterone in female mice, indicating that changes in immune-cell balance are important in the GAHT in transmasculine people.NEW & NOTEWORTHY Sex hormone-induced cardiovascular events are important undesirable effects in transgender people under GAHT. Studies addressing the cardiovascular impact of GAHT will certainly contribute to improve healthcare services offered to this population. Our study showing that vascular dysfunction, via Th17 cell-related mechanisms, precedes increased blood pressure induced by testosterone in a GAHT mouse model, reveals potential mechanisms involved in GAHT-related cardiovascular events and may provide new markers/targets for clinical practices in transmasculine people.

Soluble epoxide hydrolase inhibitor, TPPU, increases regulatory T cells pathway in an arthritis model.

Epoxyeicosatrienoic acids (EET) and related epoxy fatty acids (EpFA) are endogenous anti-inflammatory compounds, which are converted by the soluble epoxide hydrolase (sEH) to dihydroxylethersatrienoic acids (DHETs) with lessened biological effects. Inhibition of sEH is used as a strategy to increase EET levels leading to lower inflammation. Rheumatoid arthritis is a chronic autoimmune disease that leads to destruction of joint tissues. This pathogenesis involves a complex interplay between the immune system, and environmental factors. Here, we investigate the effects of inhibiting sEH with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) on a collagen-induced arthritis model. The treatment with TPPU ameliorates hyperalgesia, edema, and decreases the expression of important pro-inflammatory cytokines of Th1 and Th17 profiles, while increasing Treg cells. Considering the challenges to control RA, this study provides robust data supporting that inhibition of the sEH is a promising target to treat arthritis.

Metabolomic Evaluation of Chronic Periodontal Disease in Older Adults.

Periodontal disease is an infectious inflammatory disease related to the destruction of supporting tissues of the teeth, leading to a functional loss of the teeth. Inflammatory molecules present in the exudate are catalyzed and form different metabolites that can be identified and quantified. Thus, we evaluated the inflammatory exudate present in crevicular fluid to identify metabolic biological markers for diagnosing chronic periodontal disease in older adults. Research participants were selected from long-term institutions in Brazil. Participants were individuals aged 65 years or older, healthy, or with chronic periodontal disease. Gas chromatography/mass spectrometry was used to evaluate potential biomarkers in 120 crevicular fluid samples. We identified 969 metabolites in the individuals. Of these, 15 metabolites showed a variable importance with projection score > 1 and were associated with periodontal disease. Further analysis showed that among the 15 metabolites, two (5-aminovaleric acid and serine, 3TMS derivative) were found at higher concentrations in the crevicular fluid, indicating their potential diagnostic power for periodontal disease in older adults. Our findings indicated that some metabolites are present at high concentrations in the crevicular fluid in older adults with periodontal disease and can be used as biomarkers of periodontal disease.

Does Interrupting Prolonged Sitting With 10- or 20-Min Standing Attenuate Postprandial Glycemia and Blood Pressure in Middle-Aged and Older Adults With Type 2 Diabetes?

We carried out three types of 2-hr experimental sessions with middle-aged and older adults with Type 2 diabetes in order to examine the acute effect of interrupting prolonged sitting with varying periods of standing on postprandial glycemia and blood pressure (BP): (a) prolonged sitting after breakfast; (b) standing for 10 min, 30 min after breakfast; and (c) standing for 20 min, 30 min after breakfast. Glucose and BP were assessed before and after breakfast. A generalized linear model revealed no significant differences for the incremental area under the curve of glucose between standing for 10 min, 30 min after breakfast, versus prolonged sitting after breakfast (ß = -4.5 mg/dl/2 hr, 95% CI [-17.3, 8.4]) and standing for 20 min, 30 min after breakfast, versus prolonged sitting after breakfast (ß = 0.9 mg/dl/2 hr, 95% CI [-11.9, 13.7]). There was no difference in area under the curve of systolic and diastolic BP among the sessions. Interrupting prolonged sitting time with 10 or 20 min of standing 30 min after breakfast does not attenuate postprandial glycemia or BP in middle-aged and older adults with Type 2 diabetes.

The role of carotid bodies in the generation of active inspiratory and expiratory responses to exercise in rats.

NEW FINDINGS: What is the central question of this study? What is the carotid bodies' contribution to active inspiratory and expiratory response to exercise? What is the main finding and its importance? Removal of the carotid bodies reduced the active inspiratory and expiratory responses of diaphragm and abdominal internal oblique muscles, respectively, to high-intensity, but not to low-intensity, exercise in rats. Removal of the carotid bodies increased PaCO2 and decreased arterial pH in response to high-intensity exercise. The carotid bodies contribute to the inspiratory and expiratory adjustments to high-intensity exercise in rats. ABSTRACT: Exercise involves the interaction of several physiological processes, in which adjustments in pulmonary ventilation occur in response to increased O2 consumption, CO2 production and altered acid-base equilibrium. The peripheral chemoreceptors (carotid bodies; CBs) are sensitive to changes in the chemical composition of arterial blood, and their activation induces active inspiratory and expiratory responses. Herein, we tested the hypothesis that the CBs contribute to the active inspiratory and expiratory responses to exercise in rats. We performed electromyographic recordings of the diaphragm (DiaEMG ) and abdominal internal oblique (AbdEMG ) muscles in rats before and after bilateral removal of the CBs (CBX) during constant-load low-intensity and high-intensity progressive treadmill exercise. We also collected arterial blood samples for gaseous and pH analyses. Similar increases in DiaEMG frequency in both experimental conditions (before and after CBX) during low-intensity exercise were observed, without significant changes in the DiaEMG amplitude. During high-intensity exercise, lower responses of both DiaEMG frequency and DiaEMG amplitude were observed in rats after CBX. The AbdEMG phasic active expiratory response was not significant either before or after CBX during low-intensity exercise. However, CBX reduced the phasic active expiratory responses during high-intensity exercise. The blunted responses of inspiratory and expiratory adjustments to high-intensity exercise after CBX were associated with higher PaCO2 levels and lower arterial pH values. Our data show that in rats the CBs do not participate in the inspiratory and expiratory responses to low-intensity exercise, but are involved in the respiratory compensation against the metabolic acidosis induced by high-intensity exercise.

Heart failure developed after myocardial infarction does not affect gut microbiota composition in the rat.

There is a body of evidence that supports the notion that gut dysbiosis plays a role in the pathogenesis of cardiovascular diseases. Decreased cardiac function can reduce intestinal perfusion, resulting in morphological alterations, which may contribute to changes in the gut microbiota composition in patients with heart failure (HF). In this regard, a germane question is whether changes in gut microbiota composition are a cause or consequence of the cardiovascular disturbance. We tested the hypothesis that the development of HF, after myocardial infarction, would cause gut dysbiosis. Fecal samples were collected before and 6 wk after myocardial infarction or sham surgery. Gut microbiota were characterized by sequencing the bacterial 16S ribosomal DNA. The composition of bacterial communities in the fecal samples was evaluated by calculating three major ecological parameters: 1) the Chao 1 richness, 2) the Pielou evenness, and 3) the Shannon index. None of these indices was changed in either sham or HF rats. The Firmicutes/Bacteroidetes ratio was not altered in HF rats. The number of species in each phylum was also not different between sham and HF rats. ß-Diversity analysis showed that the composition of gut microbiota was not changed with the development of HF. Bacterial genera were grouped according to their major metabolic end-products (acetate, butyrate, and lactate), but no differences were observed in HF rats. Therefore, we conclude that HF induced by myocardial infarction does not affect gut microbiota composition, at least in rats, indicating that the dysbiosis observed in patients with HF may precede cardiovascular disturbance.NEW & NOTEWORTHY Our study demonstrated that, following myocardial infarction in rats, heart failure (HF) development did not affect the intestinal microbiota despite distinct differences reported in the gut microbiota of humans with HF. Our finding is consistent with the notion that dysbiosis observed in patients with HF may precede cardiovascular dysfunction and therefore offers potential for early diagnosis and treatment.

Sustainable biosurfactant produced by Serratia marcescens UCP 1549 and its suitability for agricultural and marine bioremediation applications.

BACKGROUND: Biosurfactants are surface-active agents produced by microorganisms that have higher efficiency and stability, lower toxicity and higher biocompatibility and biodegradability than chemical surfactants. Despite its properties and potential application in a wide range of environmental and industrial processes, biosurfactants are still not cost-competitive when compared to their synthetic counterparts. Cost effective technologies and renewable raw substrates as agro-industrial and regional waste from northeast of Brazil as cassava flour wastewater, supplemented with lactose and corn oil are mainly the chemically media for growing microorganism and in turn the production of the biosurfactant of quality. This study aimed to obtained biosurfactant by Serratia marcescens UCP 1549 containing cassava flour wastewater (CWW), by application of a full-factorial design, as sustainable practices in puts the production process in promising formulation medium. The characterization of the biomolecule was carried out, as well as the determination of its stability and toxicity for cabbage seeds. In addition, its ability to stimulate seed germination for agriculture application and oil spill bioremediation were investigated. RESULTS: Serratia marcescens showed higher reduction of surface tension (25.92 mN/m) in the new medium containing 0.2% lactose, 6% cassava flour wastewater and 5% corn waste oil, after 72 h of fermentation at 28 °C and 150 rpm. The substrate cassava flour wastewater showed a promising source of nutrients for biosurfactant production. The isolate biosurfactant exhibited a CMC of 1.5% (w/v) and showed an anionic and polymeric structure, confirmed by infrared spectra. The biomolecule demonstrated high stability under different temperatures, salinity and pH values and non-toxicity against to cabbage seeds. Thus, exploring biosurfactant their potential role in seeds germinations and the promotion and agricultural applications was investigated. In addition, the effectiveness of biosurfactant for removal burned motor oil adsorbed in sand was verified. CONCLUSIONS: The use of medium containing CWW not only reduces the cost of process of biosurfactant production, but also the environmental pollution due to the inappropriate disposal of this residue. This fact, added to the high stability and non-toxicity of the biosurfactant produced by S. marcescens UCP 1549, confirms its high environmental compatibility, make it a sustainable biocompound that can be replace chemical surfactants in diverse industries. In addition, the effectiveness of biosurfactant for stimulate seed germination and removing burned motor oil from sand, suggests its suitability for agriculture and bioremediation applications.

Persistent effects of fragmentation on tropical rainforest canopy structure after 20 yr of isolation.

Assessing the persistent impacts of fragmentation on aboveground structure of tropical forests is essential to understanding the consequences of land use change for carbon storage and other ecosystem functions. We investigated the influence of edge distance and fragment size on canopy structure, aboveground woody biomass (AGB), and AGB turnover in the Biological Dynamics of Forest Fragments Project (BDFFP) in central Amazon, Brazil, after 22+ yr of fragment isolation, by combining canopy variables collected with portable canopy profiling lidar and airborne laser scanning surveys with long-term forest inventories. Forest height decreased by 30% at edges of large fragments (>10 ha) and interiors of small fragments (<3 ha). In larger fragments, canopy height was reduced up to 40 m from edges. Leaf area density profiles differed near edges: the density of understory vegetation was higher and midstory vegetation lower, consistent with canopy reorganization via increased regeneration of pioneers following post-fragmentation mortality of large trees. However, canopy openness and leaf area index remained similar to control plots throughout fragments, while canopy spatial heterogeneity was generally lower at edges. AGB stocks and fluxes were positively related to canopy height and negatively related to spatial heterogeneity. Other forest structure variables typically used to assess the ecological impacts of fragmentation (basal area, density of individuals, and density of pioneer trees) were also related to lidar-derived canopy surface variables. Canopy reorganization through the replacement of edge-sensitive species by disturbance-tolerant ones may have mitigated the biomass loss effects due to fragmentation observed in the earlier years of BDFFP. Lidar technology offered novel insights and observational scales for analysis of the ecological impacts of fragmentation on forest structure and function, specifically aboveground biomass storage.

Molecular Electronics Including Temperature Effects Based on Dyes Pigments.

In this work we used the Density Functional Theory to study the thermodynamic properties from Brazilein (BZE) and Brazilin (BZI) molecules, main pigments responsible for the red color from Brazil wood. We did a comparison between the two dyes to then know which dye has better resistance to temperature (T ) and external electric field (E) values, aiming their potential to possible applications in solar cells, as excitons trainers. We have found that the BZE molecule becomes less stable after a temperature known as degradation temperature, and therefore enters oxidation state. However, BZE is more stable and more resistant to high temperatures. With respect to the applied external electric field, we find that BZE is more reactive to almost all the applied electric fields, thus more easily converted into energy in the form of electrical work.

Hypercapnia-induced active expiration increases in sleep and enhances ventilation in unanaesthetized rats.

KEY POINTS: Expiratory muscles (abdominal and thoracic) can be recruited when respiratory drive increases under conditions of increased respiratory demand such as hypercapnia. Studying hypercapnia-induced active expiration in unanaesthetized rats importantly contributes to the understanding of how the control system is integrated in vivo in freely moving animals. In unanaesthetized rats, hypercapnia-induced active expiration was not always recruited either in wakefulness or in sleep, suggesting that additional factors influence the recruitment of active expiration. The pattern of abdominal muscle recruitment varied in a state-dependent manner with active expiration being more predominant in the sleep state than in quiet wakefulness. Pulmonary ventilation was enhanced in periods with active expiration compared to periods without it. ABSTRACT: Expiration is passive at rest but becomes active through recruitment of abdominal muscles under increased respiratory drive. Hypercapnia-induced active expiration has not been well explored in unanaesthetized rats. We hypothesized that (i) CO2 -evoked active expiration is recruited in a state-dependent manner, i.e. differently in sleep or wakefulness, and (ii) recruitment of active expiration enhances ventilation, hence having an important functional role in meeting metabolic demand. To test these hypotheses, Wistar rats (280-330 g) were implanted with electrodes for EEG and electromyography EMG of the neck, diaphragm (DIA) and abdominal (ABD) muscles. Active expiratory events were considered as rhythmic ABDEMG activity interposed to DIAEMG . Animals were exposed to room air followed by hypercapnia (7% CO2 ) with EEG, EMG and ventilation ( V̇E ) recorded throughout the experimental protocol. No active expiration was observed during room air exposure. During hypercapnia, CO2 -evoked active expiration was predominantly recruited during non-rapid eye movement sleep. Its increased occurrence during sleep was evidenced by the decreased DIA-to-ADB ratio (1:1 ratio means that each DIA event is followed by an ABD event, indicating a high occurrence of ABD activity). Moreover, V̇E was also enhanced (P < 0.05) in periods with active expiration. V̇E had a positive correlation (P < 0.05) with the peak amplitude of ABDEMG activity. The data demonstrate strongly that hypercapnia-induced active expiration increases during sleep and provides an important functional role to support V̇E in conditions of increased respiratory demand.

Endoplasmic reticulum stress in the peripheral nervous system is a significant driver of neuropathic pain.

Despite intensive effort and resulting gains in understanding the mechanisms underlying neuropathic pain, limited success in therapeutic approaches have been attained. A recently identified, nonchannel, nonneurotransmitter therapeutic target for pain is the enzyme soluble epoxide hydrolase (sEH). The sEH degrades natural analgesic lipid mediators, epoxy fatty acids (EpFAs), therefore its inhibition stabilizes these bioactive mediators. Here we demonstrate the effects of EpFAs on diabetes induced neuropathic pain and define a previously unknown mechanism of pain, regulated by endoplasmic reticulum (ER) stress. The activation of ER stress is first quantified in the peripheral nervous system of type I diabetic rats. We demonstrate that both pain and markers of ER stress are reversed by a chemical chaperone. Next, we identify the EpFAs as upstream modulators of ER stress pathways. Chemical inducers of ER stress invariably lead to pain behavior that is reversed by a chemical chaperone and an inhibitor of sEH. The rapid occurrence of pain behavior with inducers, equally rapid reversal by blockers and natural incidence of ER stress in diabetic peripheral nervous system (PNS) argue for a major role of the ER stress pathways in regulating the excitability of the nociceptive system. Understanding the role of ER stress in generation and maintenance of pain opens routes to exploit this system for therapeutic purposes.

Type 1 Reaction in Patients With Leprosy Corresponds to a Decrease in Proresolving Lipid Mediators and an Increase in Proinflammatory Lipid Mediators.

Background: Type 1 reaction (T1R) is an acute T-helper type 1 (Th1) inflammatory episode in patients with leprosy. While immunological responses associated with T1R have been investigated, the corresponding metabolic responses that could contribute to T1R pathology have received little attention. Methods: Metabolomics-based analyses of sera from 7 patients with and 9 without T1R were conducted via liquid chromatography-mass spectrometry. Serum metabolites present at levels that significantly differed (P < .05) with a log2 fold change of ≥ 1.0 between patient groups were interrogated against known metabolic pathways. The structural identification of targeted metabolites was confirmed and abundance changes validated by mass spectrometry and enzyme-linked immunoassay. Results: Forty metabolic pathways were perturbed in patients with T1R, with 71 dysregulated metabolites mapping to pathways for lipid mediators of inflammation. Of note was an increase in the abundance of the proinflammatory leukotriene B4 (LTB4) and a corresponding decrease in the level of proresolving resolvin D1 (RvD1). Also, levels of prostaglandin D2 (PGD2) and lipoxin A4 (LXA4) in patients with T1R were significantly increased, while the level of prostaglandin E2 (PGE2) was decreased. Conclusions: The dysregulation of metabolic pathways leading to abundance shifts between proinflammatory and proresolving lipid mediators provides a link between metabolic and cellular immune responses that result in the Th1-mediated pathology of T1R.

Modeling and mapping basal area of Pinus taeda L. plantation using airborne LiDAR data.

Basal area (BA) is a good predictor of timber stand volume and forest growth. This study developed predictive models using field and airborne LiDAR (Light Detection and Ranging) data for estimation of basal area in Pinus taeda plantation in south Brazil. In the field, BA was collected from conventional forest inventory plots. Multiple linear regression models for predicting BA from LiDAR-derived metrics were developed and evaluated for predictive power and parsimony. The best model to predict BA from a family of six models was selected based on corrected Akaike Information Criterion (AICc) and assessed by the adjusted coefficient of determination (adj. R²) and root mean square error (RMSE). The best model revealed an adj. R²=0.93 and RMSE=7.74%. Leave one out cross-validation of the best regression model was also computed, and revealed an adj. R² and RMSE of 0.92 and 8.31%, respectively. This study showed that LiDAR-derived metrics can be used to predict BA in Pinus taeda plantations in south Brazil with high precision. We conclude that there is good potential to monitor growth in this type of plantations using airborne LiDAR. We hope that the promising results for BA modeling presented herein will stimulate to operate this technology in Brazil.

Potentially mobile of heavy metals on the surface sediments in tropical hyper-saline and positive estuaries.

Estuarine sediments represent important pools of trace metals, released from both anthropogenic and natural sources. Fluctuations in the water column physicochemical conditions, on the other hand, may transfer metals from solid to liquid compartment and resulting in contamination of the surrounding environment. The present research was carried out to evaluate the weakly bounded heavy metal levels in tropical hyper-saline and positive estuaries, in order to quantify its potentially availability. The monitoring includes five metals (Cd, Cr, Cu, Pb, Zn) and cover nine estuaries in Rio Grande do Norte state/Brazil, including four hypersaline and five true estuaries. 50 surface sediment samples were collected in each estuary. At the same time, organic matter concentrations were evaluated in order to help explaining possible local variations in heavy metal levels. Organic matter results (0.7% - 7.3%) suggest the positive Potengi estuary as the most critical environmental quality situation. On the other hand, according to heavy metals levels, both Conchas and Potengi estuaries registered the higher concentrations of Cr. The highest concentrations were observed in the hyper-saline estuaries, with the exception of the Zn. The present study revealed that the watershed occupation has significantly influenced the heavy metal concentrations in the estuaries.

Anti-Ulcer Efficacy of Soluble Epoxide Hydrolase Inhibitor TPPU on Diclofenac-Induced Intestinal Ulcers.

Proton pump inhibitors such as omeprazole (OME) reduce the severity of gastrointestinal (GI) ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs) but can also increase the chance of dysbiosis. The aim of this study was to test the hypothesis that preventive use of a soluble epoxide hydrolase inhibitor (sEHI) such as TPPU can decrease NSAID-induced ulcers by increasing anti-inflammatory epoxyeicosatrienoic acids (EETs). Dose- [10, 30, and 100 mg/kg, by mouth (PO)] and time-dependent (6 and 18 hours) ulcerative effects of diclofenac sodium (DCF, an NSAID) were studied in the small intestine of Swiss Webster mice. Dose-dependent effects of TPPU (0.001-0.1 mg/kg per day for 7 days, in drinking water) were evaluated in DCF-induced intestinal toxicity and compared with OME (20 mg/kg, PO). In addition, the effect of treatment was studied on levels of Hb in blood, EETs in plasma, inflammatory markers such as myeloperoxidase (MPO) in intestinal tissue homogenates, and tissue necrosis factor-α (TNF-α) in serum. DCF dose dependently induced ulcers that were associated with both a significant (P < 0.05) loss of Hb and an increase in the level of MPO and TNF-α, with severity of ulceration highest at 18 hours. Pretreatment with TPPU dose dependently prevented ulcer formation by DCF, increased the levels of epoxy fatty acids, including EETs, and TPPU's efficacy was comparable to OME. TPPU significantly (P < 0.05) reversed the effect of DCF on the level of Hb, MPO, and TNF-α Thus sEHI might be useful in the management of NSAID-induced ulcers.

Electrical stimulation of the aortic depressor nerve in conscious rats overcomes the attenuation of the baroreflex in chronic heart failure.

Chronic heart failure (CHF) is characterized by autonomic dysfunction combined with baroreflex attenuation. The hypotensive and bradycardic responses produced by electrical stimulation of the aortic depressor nerve (ADN) were examined in conscious CHF and control male Wistar rats (12-13 wk old). Furthermore, the role of parasympathetic and sympathetic nervous system in mediating the cardiovascular responses to baroreflex activation was evaluated by selective ß1-adrenergic and muscarinic receptor antagonists. CHF was induced by myocardial infarction. After 6 wk, the subjects were implanted with electrodes for ADN stimulation. Twenty-four hours later, electrical stimulation of the ADN was applied for 20 s using five different frequencies (5, 15, 30, 60, and 90 Hz), while the arterial pressure was recorded by a catheter implanted into the femoral artery. Electrical stimulation of the ADN elicited progressive and similar hypotensive and bradycardic responses in control (n = 12) and CHF (n = 11) rats, while the hypotensive response was not affected by methylatropine. Nevertheless, the reflex bradycardia was attenuated by methylatropine in control, but not in CHF rats. Atenolol did not affect the hypotensive or bradycardic response in either group. The ADN function was examined under anesthesia through electroneurographic recordings. The arterial pressure-ADN activity relationship was attenuated in CHF rats. In conclusion, despite the attenuation of baroreceptor function in CHF rats, the electrical stimulation of the ADN elicited a stimulus-dependent hypotension and bradycardia of similar magnitude as observed in control rats. Therefore, electrical activation of the aortic baroreflex overcomes both the attenuation of parasympathetic function and the sympathetic overdrive.

Variable ventilation improves pulmonary function and reduces lung damage without increasing bacterial translocation in a rat model of experimental pneumonia.

BACKGROUND: Variable ventilation has been shown to improve pulmonary function and reduce lung damage in different models of acute respiratory distress syndrome. Nevertheless, variable ventilation has not been tested during pneumonia. Theoretically, periodic increases in tidal volume (VT) and airway pressures might worsen the impairment of alveolar barrier function usually seen in pneumonia and could increase bacterial translocation into the bloodstream. We investigated the impact of variable ventilation on lung function and histologic damage, as well as markers of lung inflammation, epithelial and endothelial cell damage, and alveolar stress, and bacterial translocation in experimental pneumonia. METHODS: Thirty-two Wistar rats were randomly assigned to receive intratracheal of Pseudomonas aeruginosa (PA) or saline (SAL) (n = 16/group). After 24-h, animals were anesthetized and ventilated for 2 h with either conventional volume-controlled (VCV) or variable volume-controlled ventilation (VV), with mean VT = 6 mL/kg, PEEP = 5cmH2O, and FiO2 = 0.4. During VV, tidal volume varied randomly with a coefficient of variation of 30% and a Gaussian distribution. Additional animals assigned to receive either PA or SAL (n = 8/group) were not ventilated (NV) to serve as controls. RESULTS: In both SAL and PA, VV improved oxygenation and lung elastance compared to VCV. In SAL, VV decreased interleukin (IL)-6 expression compared to VCV (median [interquartile range]: 1.3 [0.3-2.3] vs. 5.3 [3.6-7.0]; p = 0.02) and increased surfactant protein-D expression compared to NV (2.5 [1.9-3.5] vs. 1.2 [0.8-1.2]; p = 0.0005). In PA, compared to VCV, VV reduced perivascular edema (2.5 [2.0-3.75] vs. 6.0 [4.5-6.0]; p < 0.0001), septum neutrophils (2.0 [1.0-4.0] vs. 5.0 [3.3-6.0]; p = 0.0008), necrotizing vasculitis (3.0 [2.0-5.5] vs. 6.0 [6.0-6.0]; p = 0.0003), and ultrastructural lung damage scores (16 [14-17] vs. 24 [14-27], p < 0.0001). Blood colony-forming-unit (CFU) counts were comparable (7 [0-28] vs. 6 [0-26], p = 0.77). Compared to NV, VCV, but not VV, increased expression amphiregulin, IL-6, and cytokine-induced neutrophil chemoattractant (CINC)-1 (2.1 [1.6-2.5] vs. 0.9 [0.7-1.2], p = 0.025; 12.3 [7.9-22.0] vs. 0.8 [0.6-1.9], p = 0.006; and 4.4 [2.9-5.6] vs. 0.9 [0.8-1.4], p = 0.003, respectively). Angiopoietin-2 expression was lower in VV compared to NV animals (0.5 [0.3-0.8] vs. 1.3 [1.0-1.5], p = 0.01). CONCLUSION: In this rat model of pneumonia, VV improved pulmonary function and reduced lung damage as compared to VCV, without increasing bacterial translocation.