Airflow restriction mask induces greater central fatigue after a non-exhaustive high-intensity interval exercise.

The airflow restriction mask (ARM) is a practical and inexpensive device for respiratory muscle training. Wearing an ARM has recently been combined with high-intensity interval exercise (HIIE), but its effect on neuromuscular fatigue is unknown. The present study investigated the effects of ARM wearing on neuromuscular fatigue after an HIIE session. Fourteen healthy men performed two HIIE sessions (4 × 4 min at 90% HRmax , 3 min recovery at 70% HRmax ) with or without an ARM. Neuromuscular fatigue was quantified via pre- to post-HIIE changes in maximal voluntary contraction (MVC), voluntary activation (VA, central fatigue), and potentialized evoked twitch force at 100, 10, and 1 Hz (peripheral fatigue). Blood pH and lactate were measured before and after the HIIE session, while HR, SpO2 , dyspnea, physical sensation of effort (P-RPE), and Task Effort and Awareness (TEA) were recorded every bout. The exercise-induced decrease in MVC was higher (p < 0.05) in the ARM (-28 ± 12%) than in the Control condition (-20 ± 11%). The VA decreased (p < 0.05) in the ARM (-11 ± 11%) but not in the control condition (-4 ± 5%, p > 0.05). Pre- to post-HIIE declines in evoked twitch at 100, 10, and 1 Hz were similar (p > 0.05) between ARM and control conditions (ARM: -18 ± 10, -43 ± 11 and -38 ± 12%; Control: -18 ± 14, -43 ± 12 and -37 ± 17%). When compared with the control, the HIIE bout wearing ARM was marked by higher heart rate, plasma lactate concentration, dyspnea, P-RPE and TEA, as well as lower SpO2 and blood pH. In conclusion, ARM increases perceptual and physiological stress during a HIIE, which may lead to a greater post-exercise central fatigue.

Maytenus ilicifolia Extract Increases Oxygen Uptake without Changes in Neuromuscular Fatigue Development during a High-Intensity Interval Exercise.

OBJECTIVE: We investigated the effects of acute ingestion of Maytenus ilicifolia extract on metabolic and cardiopulmonary responses during a high-intensity interval exercise (HIIE), and its consequence on neuromuscular fatigue. METHODS: Ten healthy men underwent a HIIE (4 x 4 min, 3 min recovery) one hour after ingesting 400 mg of Maytenus ilicifolia extract (MIE) or placebo. Oxygen uptake (V̇O2), dioxide carbon production (V̇CO2), ventilation (V̇E) and heart rate (HR) were measured throughout the HIIE. Maximal voluntary contraction (MVC), voluntary activation (VA), and evoked 1, 10 and 100 Hz force twitch were measured before supplementation (baseline), and before (pre-HIIE) and after the HIIE (post-HIIE). RESULTS: The V̇O2, V̇E, V̇E/V̇O2 ratio and HR increased progressively throughout the HIIE under both conditions (p < 0.05). MIE increased HR, however, at bouts 1 and 2 and mean V̇O2 during HIIE. The mean respiratory exchange ratio during recovery was also reduced with MIE (p < 0.05). MVC and evoked force at 1, 10 and 100 Hz declined similarly after HIIE, regardless of the condition (MIE: -18 ± 17%, -50 ± 15%, -61 ± 13% and -34 ± 10% vs. placebo: -19 ± 15%, -48 ± 16%, -58 ± 12 and -29 ± 11%, respectively, p < 0.05). There was no effect of exercise or MIE on VA (p > 0.05). CONCLUSION: MIE increases heart rate in the first bouts and mean oxygen uptake during HIIE without changes in neuromuscular fatigue development.

Antiviral Potential of Spondias mombin L. Leaves Extract Against Herpes Simplex Virus Type-1 Replication Using In Vitro and In Silico Approaches.

Spondias mobin leaves have been traditionally used for treating cold sores. The study investigated the mechanism of antiherpes action of S. mombin extract, fractions, and geraniin. Different concentrations of samples were used to evaluate the in vitro antiherpes activity (anti-HSV-1) in virucidal, post-infection, attachment, and penetration assays. The mechanism of action of geraniin was investigated considering the glycoproteins gB and gD of HSV-1 surface as potential molecular targets. Molecular docking simulations were carried out for both in order to determine the possible binding mode position of geraniin at the activity sites. The binding mode position was posteriorly optimized considering the flexibility of the glycoproteins. The chemical analysis of samples was performed by LC-MS and revealed the presence of 22 substances, which are hydrolysable tannins, O-glycosylated flavonoids, phenolic acids, and a carbohydrate. The extract, tannin-rich fraction and geraniin showed important in vitro virucidal activity through blocking viral attachment but showed no relevant inhibition of viral penetration. The in silico approaches demonstrated a high number of potential strong intermolecular interactions as hydrogen bonds between geraniin and the activity site of the glycoproteins, particularly the glycoprotein gB. In silico experiments indicated that geraniin is at least partially responsible for the anti-herpes activity through interaction with the viral surface glycoprotein gB, which is responsible for viral adsorption. These results highlight the therapeutic potential of S. mombin anti-herpes treatment and provides support for its traditional purposes. However, further studies are required to validate the antiviral activities in vivo, as well as efficacy in humans.

Monitoring structural features, biocompatibility and biological efficacy of gamma-irradiated methotrexate-loaded spray-dried microparticles.

In this study, biodegradable and biocompatible gamma irradiated poly-(dl-lactide-co-glycolide) (PLGA) spray-dried microparticles were prepared aiming to improve the efficacy of methotrexate (MTX). The experimental design included three formulations of microparticles containing distinct drug amount (9%, 18%, and 27% w/w) and three distinct gamma irradiation dose (15kGy, 25kGy, and 30kGy). The physicochemical and drug release properties of the microparticles supported their biocompatibility and biological efficacy studies in different cell lines. The irradiation induced slight changes in the spherical shape of the microparticles and the formation of free radicals was dependent on the drug loading. However, the amorphous character, particle size, drug loading, and drug release rate of the microparticles were preserved. The drug release data from all microparticles formulation were evaluated by using four drug kinetic models and by comparison of their similarity factor (f2). The gamma irradiation did not induce changes in the biocompatibility of PLGA microparticles and in the biological activity of the MTX-loaded microparticles. Finally, the spray-dried MTX-loaded PLGA microparticles enhanced the efficacy of the drug in the human cervical cancer cells (SiHa cell line). This study demonstrated the feasibility of the gamma irradiated spray dried PLGA microparticles for prolonged release of MTX, supporting a promising antitumor-drug delivery system for parenteral (subcutaneous) or pulmonary use.

Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading.

Previous studies reported low benznidazole (BNZ) loading in conventional emulsions due to the weak interaction of the drug with the most common oils used to produce foods or pharmaceuticals. In this study, we focused on how the type of surfactant, surfactant-to-oil ratio w/w (SOR) and oil-to-water ratio w/w (OWR) change the phase behavior of different lipid-based drug delivery systems (LBDDS) produced by emulsion phase inversion. The surfactant mixture composed of soy phosphatidylcholine and sodium oleate (1:7, w/w, hydrophilic lipophilic balance = 16) stabilized medium chain triglyceride in water. Ten formulations with the clear aspect or less turbid dispersions (five with the SOR ranging from 0.5 to 2.5 and five with the OWR from 0.06 to 0.4) were selected from the phase behavior diagram to assess structural features and drug-loading capacity. The rise in the SOR induced the formation of distinct lipid-based drug delivery systems (nanoemulsions and liquid crystal lamellar type) that were identified using rheological measurements and cross-polarized light microscopy images. Clear dispersions of small and narrow droplet-sized liquid-like nanoemulsions, Newtonian flow-type, were produced at SOR from 0.5 to 1.5 and OWR from 0.12 to 0.4, while clear liquid or gel-like liquid crystals were produced at SOR from 1.5 to 2.5. The BNZ loading was improved according to the composition and type of LBDDS produced, suggesting possible drug location among surfactant layers. The cell viability assays proved the biocompatibility for all of the prepared nanoemulsions at SOR less than 1.5 and liquid crystals at SOR less than 2.5, demonstrating their promising features for the oral or parenteral colloidal delivery systems containing benznidazole for Chagas disease treatment.

Spontaneous epidural hematoma due to cervico-thoracic angiolipoma.

Epidural angiolipomas are uncommon benign tumors of the spine. Their clinical presentation is usually a progressive spinal cord compression. We report the case of a 22-year-old patient who presented with an acute paraparesis and a spontaneous epidural hematoma, which revealed a epidural angiolipoma which extended from C7 to T3. The patient underwent a C7-T3 laminectomy, in emergency, with evacuation of the hematoma and extradural complete resection of a fibrous epidural tumor bleeding. The postoperative course was favorable with regression of neurological symptoms. Epidural angiolipomas can be revealed by spontaneous intratumoral hemorrhage without traumatism. The standard treatment is total removal by surgery.

Dengue in the State of Rio Grande do Norte, Brazil, 2010-2012.

OBJECTIVE: To present results of virological surveillance and epidemiological aspects of dengue in the State of Rio Grande do Norte, Brazil. METHODS: A total of 1581 cases, reported from 2010 to 2012 at various health centres in the state, were analysed by viral isolation and/or RT-PCR for viral detection and typing. To identify whether different genotypes were circulating in the state during this period, sequencing of the complete E gene for DENV (1485 bp in length) was performed directly from patient serum samples. RESULTS: All four serotypes of dengue virus circulated in Rio Grande do Norte, with the introduction of DENV-4 in the state in 2011. In 2012, DENV-4 represented 100% of positive confirmed cases. 53.97% of cases occurred in Natal. Case numbers peaked in April (21%) and May (23%). Genetic characterisation of circulating strains confirmed the circulation of genotypes V, south-east Asian/American and II, respectively, for DENV-1, DENV-2 and DENV-4. CONCLUSIONS: This work furthers a better understanding of dengue viruses in the State of Rio Grande do Norte. Strengthening control efforts in the region is important considering the impact of dengue.

Phase Transition in all-trans-ß-Carotene Crystal: Temperature-Dependent Raman Spectra.

In this study, we studied the stability of an all-trans-ß-carotene single crystal using Raman spectroscopy with line excitation at 632.8 nm, in the temperature range 20­300 K. The Raman spectra exhibit clear modifications in the spectral range of the lattice and internal vibrational modes. The temperature dependence of the most intense vibrational modes ν1 (1511 cm(­1)) and ν2 (1156 cm(­1)) that are related to the C═C and C­C stretching vibrations of the polyene chain, respectively, shows an upward shift on the Raman modes. This behavior is similar to that stated in the theoretical work of Wei-Long Liu et al. We conclude that the all-trans-ß-carotene crystal undergoes a temperature-induced phase transition at approximately 219 K. This transition is interpreted as a rotation experienced by ß-ring groups at each end of the all-trans-ß-carotene molecule around the dihedral angle. At low temperatures, the new molecular configuration affects the sliding plane of the space group C2h(5)(P2(1)/n), and the phase transition leads to an unchanged monoclinic structure; however, the original space group is possibly lowered to the space group C2. In the temperature range 200­220 K, the spectral ratio (S) of the integrated intensities of the spectral modes around the symmetric and asymmetric stretching wavenumbers of the methyl group (CH3) changes as a function of temperature in agreement with the phase transition. Furthermore, according to phase transition undergone by the all-trans-ß-carotene, the thermal results obtained by differential scanning calorimetry show an exothermic process that occurs near the transition temperature assigned by the Raman spectra.

Influence of the CCR-5/MIP-1 α axis in the pathogenesis of Rocio virus encephalitis in a mouse model.

Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in Brazil and its immunopathogenesis remains poorly understood. CC-chemokine receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory protein (MIP-1 α). Both molecules are associated with inflammatory cells migration during infections. In this study, we demonstrated the importance of the CCR5 and MIP-1 α, in the outcome of viral encephalitis of ROCV-infected mice. CCR5 and MIP-1 α knockout mice survived longer than wild-type (WT) ROCV-infected animals. In addition, knockout mice had reduced inflammation in the brain. Assessment of brain viral load showed mice virus detection five days post-infection in wild-type and CCR5-/- mice, while MIP-1 α-/- mice had lower viral loads seven days post-infection. Knockout mice required a higher lethal dose than wild-type mice as well. The CCR5/MIP-1 α axis may contribute to migration of infected cells to the brain and consequently affect the pathogenesis during ROCV infection.

Urinary matrix metalloproteinases-2/9 in healthy infants and haemangioma patients prior to and during propranolol therapy.

UNLABELLED: The mechanism of therapeutic success of propranolol for severe infantile haemangioma remains unclear. Propranolol was shown to modify matrix metalloproteinase (MMP) levels, which are associated with tumour pathogenesis. We hypothesized that urinary MMP2/9 is higher in patients with infantile haemangioma compared to healthy infants and that propranolol reduces MMP2/9 levels and thus leads to an involution of the haemangioma. In this case, MMP2/9 could be used as a marker of indicated therapy or therapeutic success. Urinary samples were taken before, 2 weeks after, and 2 months after the beginning of propranolol treatment in haemangioma patients and once in healthy controls. Activity of MMP2/9 was determined by commercially available activity kits. Urine of 22 haemangioma patients and 21 control subjects was obtained. Propranolol therapy had significant success in all patients. MMP2/9 was present in most samples, the younger the children the higher the MMP2 levels. Haemangioma patients showed lower levels of MMP2. The MMP2 levels were significantly higher after 2 weeks of propranolol than prior to therapy. There were no differences in MMP9 levels. CONCLUSIONS: Presence of MMP2/9 in the urine of infants <1 year can be explained by high rate of physiological tissue remodelling. Unexpectedly, MMP2 was lower in the urine of haemangioma patients and higher 2 weeks after propranolol treatment. Taking this and the diverse results in literature into account, the correlation between MMPs, proliferation, and regression of haemangiomas and propranolol remains unclear.

Spontaneous pneumomediastinum and subcutaneous emphysema in asthma exacerbation: The Macklin effect.

OBJECTIVE: We describe the clinical features of a 17-year-old girl with severe asthma exacerbations. On admission to the intensive care unit, she manifested expiratory dyspnea, cyanosis, and an unproductive cough. Her chest x-rays showed extensive pneumomediastinum (PM), mild subcutaneous emphysema at the right anterior triangle of the neck, and right upper-lobe atelectasis. Her PM resulted from the "Macklin effect," which involves a three-step process: overly distended alveolar rupture, air dissection along the bronchovascular sheaths, and air spreading into the mediastinum. METHODS: Treatment consisted of oxygen therapy, parenteral corticosteroids, and nebulized bronchodilators. RESULTS: She made a good recovery, and was discharged from the intensive care unit after 2 days. CONCLUSION: This case illustrates that conservative management strategies in this severe and unusual complication of asthma exacerbation can result in rapid and complete recovery. Nonetheless, every asthma exacerbation should be considered potentially life-threatening, and must be treated promptly and adequately.

Cerebellar effects after consumption of edible morels (Morchella conica, Morchella esculenta).

Morchella esculenta and Morchella conica are well known edible morels, which seldom induce clinical symptoms. We report six persons who developed cerebellar effects 6-12 hours after consumption of these mushrooms. The symptoms were self-limited and disappeared after one day.

[Adder bites in humans]. / Kreuzotterbisse beim Menschen.

In Germany the common viper (Vipera berus) and very seldom Vipera aspis are the only in freedom normally existing snakes. In general, bites by the common viper cause slight local symptoms, sometimes strong swellings of the extremities, but only rarely severe perilous general symptoms such as shock and angioneurotic edema. Mortal progresses despite of medical treatment are the exceptions. The most important therapeutic measure is the immobilization of the bitten extremity and the transport in a recumbent position to the next surgeon or clinic. The perilous shock and the angioneurotic edema often react on the administration of antihistaminica and corticosteroids, whereas the increase of the swelling of the extremity cannot be influenced by this treatment. The corresponding antisera have an advantageous and fast effect on all general symptoms and seem to favourably influence the swelling of the extremities. Because of the allergic reactions against the sera from horses, which do not occur seldom, in severe cases only Beritab--which is not yet admitted in Germany--with purified Fab-fragment antibodies from sheep should be used.

GLC determination of ethinamate and its hydroxy derivative in biological fluids.

A sensitive, specific GLC assay was developed for the determination of ethinamate in plasma and its major metabolite, trans-4-hydroxyethinamate, in urine. The assay uses a mass internal standard of dimethylethinamate. Ethinamate is extracted from alkalinized plasma with dichloromethane. Urine samples require beta-glucuronidase hydrolysis prior to extraction of hydroxyethinamate. The dichloromethane is removed by evaporation, and the compounds are measured by GLC using a flame-ionization detector. By using GLC-chemical-ionization mass spectrometry, the compounds measured were identified as the intact ethinamates. Plasma and urine data are presented from a bioavailability study to demonstrate the utility of this method. From these data, the ethinamate plasma half-life was calculated as 1.9 +/- 0.3 hr.

GLC determination of acetohexamide and hydroxyhexamide in biological fluids.

A sensitive and specific GLC assay was developed for acetohexamide and hydroxyhexamide, its major metabolite, in plasma and urine. The assay uses tolbutamide as a mass internal standard. Compounds are extracted from acidified plasma or urine with toluene, converted to methylated derivatives with dimethyl sulfate, and measured by GLC using a flame-ionization detector. With GLC-mass spectrometry, the compounds measured are the N-methylsulfonamides resulting from GLC pyrolysis. Plasma and urine data are presented from a bioavailability study to demonstrate the utility of this method.