No Evidence of Short-term Changes in Muscle Activity Elicited by Dry Needling in Chronic Unilateral Shoulder Pain Patients.

OBJECTIVE: The aim of the study was to assess short-term changes in shoulder muscle activity elicited by dry needling in chronic unilateral shoulder pain (USP) patients. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted, in which 30 volunteers with USP were recruited and randomly assigned to either real or sham dry needling conditions. Pain intensity scores, pressure pain threshold, glenohumeral internal rotation angles, and electromyographic activity during isotonic shoulder tasks (shoulder flexion and extension) were assessed before, immediately, and 72 hours after the intervention in the infraspinatus and deltoid muscles. RESULTS: A single application of real dry needling resulted in lower pain intensity scores and a larger range in glenohumeral internal rotation 72 hours after the intervention in comparison with sham dry needling. No differences in pressure pain threshold or muscle activity were observed due to the intervention. DISCUSSION: A single application of real dry needling resulted in clinically significant changes in the short term. No differences were detected in muscle activation in the infraspinatus or deltoid muscles. Complementary interventions and longer follow-up times may be required to observe changes in muscle activity.

Effects of rainfall and land use on nutrient responses in rivers in the Brazilian semiarid region.

This paper investigated whether rainfall promotes dilution or increase in nutrient concentrations and which land use indicators are the main predictors of nutrients in intermittent rivers in a large Brazilian semiarid region. The total phosphorus (TP) and total inorganic nitrogen (TIN) were monitored between 2013 and 2018 at 92 river water quality monitoring sites. The monthly rainfall (Rn) was obtained from 575 rain gauges. Pearson's correlation (R) between Rn and nutrient concentration was performed. The correlation patterns were also analysed based on land use data: urban area (%), agricultural field area (%), demographic density (inhabitants/km2), sewer system coverage (%), and reservoir density (reservoir/km2). Backward stepwise regression was performed to identify predictors of nutrient concentrations. The results revealed a marginal effect of rainfall on nutrients when the effects of urbanisation outweigh all other aspects. However, in regions with greater accumulated rainfall and lower reservoir density, the rainfall was related to a linear increase in nutrient concentrations (R > 0.8). Contrastingly, in the basins with less accumulated rainfall and greater inter-basin hydrological disconnection, there was a linear reduction in nutrient concentration (R < - 0.5). In the backward stepwise regression, sewer system coverage and Rn had the greatest influence for TP, and the urban area was the strongest predictor for TIN. Importantly, our results demonstrated that in semiarid rivers in densely populated regions, there is no single pattern of variability in nutrient concentration, on a wide scale of assessment. Therefore, adaptative and decentralised management can be more effective in improving water quality in these regions.

Vitamin D supplementation at different doses affects the vagal component of the baroreceptor reflex and the Bezold-Jarisch reflex in eutrophic rats.

Vitamin D has been used to prevent several diseases. The 1,25 (OH) 2D3, the active form of vitamin D (VitD), participates in calcium metabolism, and has direct action in various tissues as those of the cardiovascular system binding to the VitD receptor. We investigated whether the supplementation with different doses of VitD affect or not the resting mean arterial pressure (MAP) and heart rate (HR), heart rate variability (HRV), baroreceptor and Bezold-Jarisch reflexes in eutrophic rats. Adult male Wistar rats were randomly assigned in 4 groups (Control, VitD 15, 250, and 3,750 IU/day, n = 6/group). After 3 days of supplementation, MAP and HR recordings were performed in freely moving rats. Baseline (resting) MAP, HR, and HRV showed no difference in Control and VitD groups. Nevertheless, the index of the baroreceptor reflex showed that the bradycardic component of the baroreflex evoked by a pressor dose of phenylephrine (3 µg/kg of b.w.) in bolus injection had a significant increase in rats supplemented with VitD 15 IU/day for 3 days compared to Control animals. No difference was observed in the index of the baroreflex evaluated with phenylephrine in rats treated with VitD 250 and 3,750 IU/day for 3 days in comparison to the Control group. The index of the baroreceptor reflex evaluated with an intravenous bolus injection of a depressor dose of sodium nitroprusside (30 µg/kg of b.w.) showed that the tachycardic component of the baroreflex is not different comparing all groups supplemented with VitD and Control animals. Rats supplemented with VitD 15 IU/day presented exaggerated bradycardic responses to the intravenous injection of phenylbiguanide (PBG, 5 µg/kg of b.w.) compared to Control animals, despite the similar hypotension in both groups. Higher doses of supplementation of VitD (250 and 3,750 IU/day for 3 days) abolished the hypotension and bradycardia induced by PBG. The findings suggest that the supplementation with different doses of VitD (15, 250, and 3,750 IU/day) for 3 days did not affect the resting arterial pressure, heart rate and autonomic modulation on the heart in rats. Despite that, the supplementation with a low dose of VitD (15 IU/day for 3 days) improved the sensitivity of the bradycardic component of the baroreflex, whereas higher doses of supplementation with VitD (250 and 3,750 IU/day for 3 days) were unable to cause such effect. In addition, the Bezold-Jarisch reflex responses can be affected regardless the dose of VitD (15, 250 or 3,750 IU/day) supplementation for 3 days in rats.

Formation of phosphorus monoxide through the [Formula: see text] reaction.

Phosphorus is a key and vital element for a diverse set of important biological molecules, being indispensable for life as we know. A deeper comprehension of its role in astrochemistry and atmospheric chemistry may aid in finding answers to how this element became available on Earth. The PO molecule is one of the main reservoirs of phosphorus in the interstellar medium (ISM), and a better understanding of the mechanisms and rate coefficients for its formation in the ISM is important for modelling its abundances. In this work, we perform multireference configuration interaction calculations on the formation of PO via the [Formula: see text] reaction, analyzing its potential energy surface and rate coefficients for the global reaction on both doublet and quartet states. We also perform DFT (M06-2X) and CCSD(T) calculations, in order to compare the results. We found that the OPO system possesses a high multiconfigurational character, making DFT and CCSD methodologies not suitable for its potential energy landscape calculation. The rate coefficients have been calculated using the master equation system solver (MESS) package, and the results compared to recent experimental data. It is shown that the quartet state contributes for temperatures higher than 700K. The computed rate coefficient can be described by a modified Arrhenius equation [[Formula: see text]] with [Formula: see text], [Formula: see text] and [Formula: see text] K.

Assessment of phosphorus loading dynamics in a tropical reservoir with high seasonal water level changes.

Nutrient accumulation in man-made reservoirs has been documented worldwide. Therefore, quantifying phosphorus loading and understanding its temporal dynamics in reservoirs is mandatory for sustainable water management. In this study, the Vollenweider's complete-mix phosphorus budget model was adapted to account for high water level variations, which are a common feature in tropical reservoirs, and for internal phosphorus loads. First- and zero-order kinetics were adopted to simulate phosphorus settling and release from the sediment layer, respectively, considering variable area of phosphorus release according to the height of the anoxic layer. The modeling approach was applied for a 52-months period to a 31-years-old reservoir located in the semiarid region of Brazil with 7.7 hm3 storage capacity. The simulations were supported by hydrological, meteorological and water quality data, as well as analyses of phosphorus partitioning of the reservoir bed sediment. The external phosphorus load was estimated from a relationship adjusted between inflow and phosphorus concentration, revealing an u-shaped pattern. Sedimentary phosphorus linked to iron and aluminum (PFeAl) increased over time and along the reservoir. Such measurements were used to estimate the internal phosphorus load, i.e., the yield from the bed sediments to the water column. The adaptations proposed to the model's structure improved its capacity to simulate phosphorus concentration in the water column, from "not satisfactory" to "good". We estimate that the internal phosphorus load currently accounts for 44% of the total load. It prevailed during the wet period, when reservoir stratification and hypolimnetic hypoxia were more notable, resulting in higher phosphorus concentration in the water column due to the combined effects of internal and external loadings. However, if the reservoir were 70 years older, the internal load would reach 83% of the total and the reservoir would become a source instead of a sink of phosphorus.

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial.

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve.

BACKGROUND: The effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain. METHODS: In this randomized trial, we compared rivaroxaban (20 mg once daily) with dose-adjusted warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months. RESULTS: A total of 1005 patients were enrolled at 49 sites in Brazil. A primary-outcome event occurred at a mean of 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (difference calculated as restricted mean survival time, 7.4 days; 95% confidence interval [CI], -1.4 to 16.3; P<0.001 for noninferiority). Death from cardiovascular causes or thromboembolic events occurred in 17 patients (3.4%) in the rivaroxaban group and in 26 (5.1%) in the warfarin group (hazard ratio, 0.65; 95% CI, 0.35 to 1.20). The incidence of stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (hazard ratio, 0.25; 95% CI, 0.07 to 0.88). Major bleeding occurred in 7 patients (1.4%) in the rivaroxaban group and in 13 (2.6%) in the warfarin group (hazard ratio, 0.54; 95% CI, 0.21 to 1.35). The frequency of other serious adverse events was similar in the two groups. CONCLUSIONS: In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months. (Funded by PROADI-SUS and Bayer; RIVER ClinicalTrials.gov number, NCT02303795.).

Effects of 4-Week Diacutaneous Fibrolysis on Myalgia, Mouth Opening, and Level of Functional Severity in Women With Temporomandibular Disorders: A Randomized Controlled Trial.

OBJECTIVE: The purpose of this study was to assess the effects of 4-week protocol of diacutaneous fibrolysis (DF) compared with simulated DF (sham-DF) on myalgia and mouth opening. METHODS: In a sham randomized controlled trial, 34 women with temporomandibular disorders and myofascial pain were randomly divided as intervention group (IG) and sham-DF group (SG). The IG received 4 weeks of real DF, and the SG received sham. Pain was assessed through the visual analog scale and pressure pain thresholds (PPTs) on the temporomandibular joint (TMJ), and over the temporal and masseter muscles. The Mandibular Function Impairment Questionnaire was used to classify the participants regarding to the severity of the functional limitation related to TMD. RESULTS: Pain scores decreased for both groups, but the IG showed lower values at week 4, with between-group differences. Bilateral temporal PPT showed higher values at week 4, with between-group differences. The SG had lower PPTs but the IG had higher PPTs, both compared to baseline results. The time-by-group interaction and the frequency of participants above 40 mm of mouth opening showed a significant difference for the IG over time with higher results at the 4-week assessment compared to its own baseline. Both groups showed lower MFIQ scores from baseline to 4-week assessment. There was a lower frequency of a moderate level of severity for the IG. No differences were observed for TMJ or for the masseter muscles PPT. CONCLUSION: Improvements were observed for visual analog scale scores and PPTs on temporal muscles. There was a group-by-time interaction in the IG, suggesting a possible potential use of DF for mouth opening.

Acupuncture ameliorated vasomotor symptoms during menopausal transition: single-blind, placebo-controlled, randomized trial to test treatment efficacy.

OBJECTIVES: This study aimed to evaluate the effects of acupuncture on women with vasomotor symptoms during the menopausal transition with the aid of the Kupperman-Blatt Menopausal Index. METHOD: Crossover, single-blind, sham-controlled trial with 100 women randomly divided into two groups of 50 participants each: G1 and G2. During the first 24 weeks of treatment, the G1 women received acupuncture and the G2 women were given sham acupuncture. The crossover was then applied: the G1 participants were given sham acupuncture, and the G2 participants received acupuncture for 24 more weeks. RESULTS: The mean score of hot flashes of the group who first experienced acupuncture (G1) was statistically higher than that of the group that started with sham acupuncture (G2, P = 0.020). Also, both groups had similar mean scores in the middle of the study (both were receiving acupuncture). During the last 6 months of the study, after crossover, the values of G2 (acupuncture) were lower than those of G1 (sham acupuncture). CONCLUSIONS: Acupuncture treatment may mitigate hot flashes and other climacteric symptoms during the menopausal transition.

Video Summary:http://links.lww.com/MENO/A641.

Tamarind Trypsin Inhibitor in Chitosan-Whey Protein Nanoparticles Reduces Fasting Blood Glucose Levels without Compromising Insulinemia: A Preclinical Study.

In vivo studies show the benefits of the trypsin inhibitor isolated from tamarind (Tamarindusindica L.) (TTI) seeds in satiety and obesity. In the present study, TTI nanoencapsulation (ECW) was performed to potentialize the effect of TTI and allow a controlled release in the stomach. The impact on glycemia, insulin, and lipid profile was evaluated in Wistar rats overfed with a high glycemic index diet (HGLI). Characterization of the nanoparticles and in vitro stability in simulated gastrointestinal conditions, monitored by antitrypsin activity and HPLC, was performed. ECW and empty nanoparticles (CW) were administered by gavage, using 12.5 and 10.0 mg/kg, respectively. Both nanoformulations presented a spherical shape and smooth surface, with an average diameter of 117.4 nm (24.1) for ECW and 123.9 nm (11.3) for CW. ECW maintained the antitrypsin activity (95.5%) in the gastric phase, while TTI was completely hydrolyzed. In Wistar rats, the nanoformulations significantly reduced glycemia and HOMA IR, and ECW increased HDL-c compared to CW (p < 0.05).Pancreas histopathology of animals treated with ECW suggested an onset of tissue repair. Thenanoencapsulation provided TTI protection, gradual release in the desired condition, and improvement of biochemical parameters related to carbohydrate metabolism disorders,without compromising insulinemia.

Acute Caffeinated Coffee Consumption Does not Improve Time Trial Performance in an 800-m Run: A Randomized, Double-Blind, Crossover, Placebo-Controlled Study.

INTRODUCTION: Studies evaluating caffeinated coffee (CAF) can reveal ergogenic effects; however, studies on the effects of caffeinated coffee on running are scarce and controversial. AIM: To investigate the effects of CAF consumption compared to decaffeinated coffee (DEC) consumption on time trial performances in an 800-m run in overnight-fasting runners. METHODS: A randomly counterbalanced, double-blind, crossover, placebo-controlled study was conducted with 12 healthy adult males with experience in amateur endurance running. Participants conducted two trials on two different occasions, one day with either CAF or DEC, with a one-week washout. After arriving at the data collection site, participants consumed the soluble CAF (5.5 mg/kg of caffeine) or DEC and after 60 min the run was started. Before and after the 800-m race, blood pressure and lactate and glucose concentrations were measured. At the end of the run, the ratings of perceived exertion (RPE) scale was applied. RESULTS: The runners were light consumers of habitual caffeine, with an average ingestion of 91.3 mg (range 6⁻420 mg/day). Time trial performances did not change between trials (DEF: 2.38 + 0.10 vs. CAF: 2.39 + 0.09 min, p = 0.336), nor did the RPE (DEC: 16.5 + 2.68 vs. CAF: 17.0 + 2.66, p = 0.326). No difference between the trials was observed for glucose and lactate concentrations, or for systolic and diastolic blood pressure levels. CONCLUSION: CAF consumption failed to enhance the time trial performance of an 800-m run in overnight-fasting runners, when compared with DEC ingestion. In addition, no change was found in RPE, blood pressure levels, or blood glucose and lactate concentrations between the two trials.

Folate-targeted nanostructured lipid carriers for enhanced oral delivery of epigallocatechin-3-gallate.

The well-known pleiotropic health benefits of green tea are mainly attributed to epigallocatechin-3-gallate (EGCG), a polyphenolic compound from the group of catechins. EGCG's poor stability and intestinal permeability, however, can strongly impair its biological activities. In this work, EGCG-loaded nanostructured lipid carriers (NLC) functionalized with folic acid were optimized through a Box-Behnken design intended to provide an enhanced oral absorption and increased bioavailability of EGCG. Size, zeta potential and encapsulation efficiency (EE) of the produced spherical nanoparticles were evaluated. NLC were further characterized by Differential Scanning Calorimetry (DSC). An in vitro release study in simulated gastric and intestinal fluids was conducted and the storage stability of the nanoparticles was evaluated over a period of 8weeks. The overall results demonstrated the suitability of the developed formulation for the oral delivery of EGCG and its potential for applications in food industry.

Supplementation with a new trypsin inhibitor from peanut is associated with reduced fasting glucose, weight control, and increased plasma CCK secretion in an animal model.

Ingestion of peanuts may have a beneficial effect on weight control, possibly due to the satietogenic action of trypsin inhibitors. The aim of this study was to isolate a new trypsin inhibitor in a typical Brazilian peanut sweet (paçoca) and evaluate its effect in biochemical parameters, weight gain and food intake in male Wistar rats. The trypsin inhibitor in peanut paçoca (AHTI) was isolated. Experimental diets were prepared with AIN-93G supplemented with AHTI. Animals had their weight and food intake monitored. Animals were anesthetized, euthanized, and their bloods collected by cardiac puncture for dosage of cholecystokinin (CCK) and other biochemical parameters. Supplementation with AHTI significantly decreased fasting glucose, body weight gain, and food intake. These effects may be attributed to increased satiety, once supplemented animals showed no evidence of impaired nutritional status and also because AHTI increased CCK production. Thus, our results indicate that AHTI, besides reducing fasting glucose, can reduce weight gain via food intake reduction.

Control of crystallite and particle size in the synthesis of layered double hydroxides: Macromolecular insights and a complementary modeling tool.

Zinc-aluminum layered double hydroxides with nitrate intercalated (Zn(n)Al-NO3, n=Zn/Al) is an intermediate material for the intercalation of different functional molecules used in a wide range of industrial applications. The synthesis of Zn(2)Al-NO3 was investigated considering the time and temperature of hydrothermal treatment. By examining the crystallite size in two different directions, hydrodynamic particle size, morphology, crystal structure and chemical species in solution, it was possible to understand the crystallization and dissolution processes involved in the mechanisms of crystallite and particle growth. In addition, hydrogeochemical modeling rendered insights on the speciation of different metal cations in solution. Therefore, this tool can be a promising solution to model and optimize the synthesis of layered double hydroxide-based materials for industrial applications.

Smart electroconductive bioactive ceramics to promote in situ electrostimulation of bone.

Biomaterials can still be reinvented to become simple and universal bone regeneration solutions. Following this roadmap, conductive CNT-based "smart" materials accumulate exciting grafting qualities for tuning the in vitro cellular phenotype. Biphasic electrical stimulation of human osteoblastic cells was performed in vitro on either dielectric bioactive bone grafts or conductive CNT-reinforced composites. The efficiency of the electrical stimuli delivery, as well as the effect of stimulation on cellular functions were investigated. Conductive substrates boosted the local culture medium conductivity and the confinement of the exogenous electrical fields. Hence, bone cell proliferation, DNA content and mRNA expression were maximized on the conductive substrates yielding superior stimuli delivering efficiency over dielectric ones. These findings are suggestive that bioactive bone grafts with electrical conductivity are capable of high spatial and temporal control of bone cell stimulation.

[Impact of cocooning and maternal voice on the autonomic nervous system activity in the premature newborn infant]. / Impact du cocooning et de la voix humaine sur le système nerveux autonome (SNA) de l'enfant grand prématuré

INTRODUCTION: Discomfort, pain, and stress have an adverse impact on the psychomotor development in the premature newborn infant. Recent studies indicate that pain and stress are associated with a reduction of parasympathetic outflow. We hypothesized that cocooning associated with the human voice has a favorable impact on parasympathetic activity in the premature newborn infant. METHOD: We compared heart rate variability (HRV) before and after standardized cocooning phases associated with the human voice and carried out: 1) by the mother and 2) by a third person. HRV was assessed and expressed as an index reflecting the parasympathetic tone. RESULTS: Ten children were included (median gestational age, 33 weeks (30(+4)-33(+2))). We observed a higher HRV index after the period of cocooning associated with the human voice compared with the baseline measurement (P<0.05), whether the procedure was carried out by the mother or a third person. CONCLUSION: This study shows that cocooning associated with the human voice enhances HRV in the preterm newborn infant, indicating an increase in parasympathetic activity after cocooning associated with the human voice. However, the impact is similar whether the cocooning associated with the human voice is performed by the mother or a third person. This result suggests that cocooning associated with the human voice carried out either by the mother or a third person contributes to decreasing stress and discomfort in the premature newborn infant.

Antinociceptive effects of citronellal in formalin-, capsaicin-, and glutamate-induced orofacial nociception in rodents and its action on nerve excitability.

AIMS: To evaluate the antinociceptive effects of citronellal (CTL) on formalin-, capsaicin-, and glutamate-induced orofacial nociception in mice and to investigate whether such effects might involve a change in neural excitability. METHODS: Male mice were pretreated with CTL (50, 100, and 200 mg/kg, ip), morphine (5 mg/kg, ip), or vehicle (distilled water plus one drop of Tween 80 0.2%) before formalin (20 microL, 2%), capsaicin (20 microL, 2.5 microg) or glutamate (40 microL, 25 microM) injection into the right vibrissa. Sciatic nerve recordings were made using the single sucrose gap technique in rats. The data obtained were analyzed by ANOVA followed by Dunnett's test for the behavioral analyses and by the Student t test for CAP evaluation. RESULTS: Pretreatment with CTL was effective in reducing nociceptive face-rubbing behavior in both phases of the formalin test, which was also naloxone-sensitive. CTL produced significantly antinociceptive effect at all doses in the capsaicin- and glutamate- tests. Rota-rod testing indicated that such results were unlikely to be provoked by motor abnormality. Recordings using the single sucrose gap technique revealed that CTL (10 mM) could reduce the excitability of the isolated sciatic nerve through a diminution of the compound action potential amplitude by about 42.4% from control recordings. CONCLUSION: These results suggest that CTL might represent an important tool for management and/or treatment of orofacial pain.

Ciliary neurotrophic factor infused intracerebroventricularly shows reduced catabolic effects when linked to the TAT protein transduction domain.

Ciliary neurotrophic factor (CNTF) regulates the differentiation and survival of a wide spectrum of developing and adult neurons, including motor neuron loss after injury. We recently described a cell-penetrant recombinant human CNTF (rhCNTF) molecule, formed by fusion with the human immunodeficiency virus-1 transactivator of transcription (TAT) protein transduction domain (TAT-CNTF) that, upon subcutaneous administration, retains full neurotrophic activity without cytokine-like side-effects. Although the CNTF receptor is present in hypothalamic nuclei, which are involved in the control of energy, rhCNTF but not TAT-CNTF stimulates signal transducers and activators of transcription 3 phosphorylation in the rat hypothalamus after subcutaneous administration. This could be due limited TAT-CNTF distribution in the hypothalamus and/or altered intracellular signaling by the fusion protein. To explore these possibilities, we examined the effect of intracerebroventricular administration of TAT-CNTF in male adult rats. TAT-CNTF-induced weight loss, although the effect was smaller than that seen with either rhCNTF or leptin (which exerts CNTF-like effects via its receptor). In contrast to rhCNTF and leptin, TAT-CNTF neither induced morphological changes in adipose tissues nor increased uncoupling protein 1 expression in brown adipose tissue, a characteristic feature of rhCNTF and leptin. Acute intracerebroventricular administration of TAT-CNTF induced a less robust phosphorylation of signal transducers and activators of transcription 3 in the hypothalamus, compared with rhCNTF. The data show that fusion of a protein transduction domain may change rhCNTF CNS distribution, while further strengthening the utility of cell-penetrating peptide technology to neurotrophic factor biology beyond the neuroscience field.

Anti-inflammatory effects of Lafoensia pacari and ellagic acid in a murine model of asthma.

We have shown that the ethanolic extract of Lafoensia pacari inhibits eosinophilic inflammation induced by Toxocara canis infection, and that ellagic acid is the secondary metabolite responsible for the anti-eosinophilic activity seen in a model of beta-glucan peritonitis. In the present study, we investigated the preventive and curative effects of L. pacari extract and ellagic acid on allergic lung inflammation using a murine model of ovalbumin-induced asthma. In bronchoalveolar lavage fluid, preventive (22-day) treatment with L. pacari (200 mg/kg) and ellagic acid (10 mg/kg) inhibited neutrophil counts (by 75% and 57%) and eosinophil counts (by 78% and 68%). L. pacari reduced IL-4 and IL-13 levels (by 67% and 73%), whereas ellagic acid reduced IL-4, IL-5 and IL-13 (by 67%, 88% and 85%). To investigate curative anti-inflammatory effects, we treated mice daily with ellagic acid (0.1, 1, or 10 mg/kg), also treating selected mice with L. pacari (200 mg/kg) from day 18 to day 22. The highest ellagic acid dose reduced neutrophil and eosinophil numbers (by 59% and 82%), inhibited IL-4, IL-5, and IL-13 (by 62%, 61%, and 49%). Neither L. pacari nor ellagic acid suppressed ovalbumin-induced airway hyperresponsiveness or cysteinyl leukotriene synthesis in lung homogenates. In mice treated with ellagic acid (10 mg/kg) or L. pacari (200 mg/kg) at 10 min after the second ovalbumin challenge, eosinophil numbers were 53% and 69% lower, respectively. Cytokine levels were unaffected by this treatment. L. pacari and ellagic acid are effective eosinophilic inflammation suppressors, suggesting a potential for treating allergies.