Endogenous galectin-3 is required for skeletal muscle repair.

Skeletal muscle has the intrinsic ability to self-repair through a multifactorial process, but many aspects of its cellular and molecular mechanisms are not fully understood. There is increasing evidence that some members of the mammalian ß-galactoside-binding protein family (galectins) are involved in the muscular repair process (MRP), including galectin-3 (Gal-3). However, there are many questions about the role of this protein on muscle self-repair. Here, we demonstrate that endogenous Gal-3 is required for: (i) muscle repair in vivo by using a chloride-barium myolesion mouse model and (ii) mouse primary myoblasts myogenic programming. Injured muscle from Gal-3 knockout mice (GAL3KO) showed persistent inflammation associated with compromised muscle repair and the formation of fibrotic tissue on the lesion site. In GAL3KO mice, osteopontin expression remained high even after 7 and 14 d of the myolesion, while Myoblast differentiation transcription factor (MyoD) and myogenin had decreased their expression. In GAL3KO mouse primary myoblast cell culture, Paired Box 7 (Pax7) detection seems to sustain even when cells are stimulated to differentiation and MyoD expression is drastically reduced. The detection and temporal expression levels of these transcriptional factors appear to be altered in Gal-3-deficient myoblast. Gal-3 expression in wild-type mice for GAL3KO states, both in vivo and in vitro, in sarcoplasm/cytoplasm and myonuclei; as differentiation proceeds, Gal-3 expression is drastically reduced, and its location is confined to the sarcolemma/plasma cell membrane. We also observed a change in the temporal-spatial profile of Gal-3 expression and muscle transcription factors levels during the myolesion. Overall, these results demonstrate that endogenous Gal-3 is required for the skeletal muscle repair process.

Effects of barium graded doses on redox status, membrane bound ATPases and histomorphological aspect of the liver in adult rats.

Nowadays, liver diseases constitute a major health problem in the world. The objective of the present study was to elucidate the hepatotoxicity induced by barium chloride (BaCl2) administered at graded doses in order to evaluate redox state and membrane-bound ATPases in the liver of adult rats. Our results showed, after 21 days of treatment with barium at doses 67 150 and 300 ppm, an increase in hepatic biomarkers such as AST, ALT and GGT activities and in bilirubin and albumin levels. A significant increase in MDA, LOOHs, H2O2, AOPP and PCO levels in liver of treated rats with graded doses of BaCl2 was also observed suggesting the implication of oxidative stress with a significant relation between dose and response. Moreover, LDH activity increased in plasma and decreased in liver of all treated groups. Antioxidant activities of glutathione peroxidase and catalase decreased, especially with the highest dose of barium, indicating a failure of antioxidant system defense. Additionally, the activities of Na+K+-ATPase and Mg2+-ATPase significantly decreased in all treated groups. Our biochemical findings were supported by histological observations. These results highlight the subchronic hepatotoxicity of barium.

Preparation of BaTiO3/Cu2O and BaTiO3/Cu2O/Au Complexes: Their Photocatalytic and Antipathogenic Effect.

BaTiO3/Cu2O and BaTiO3/Cu2O/Au complexes were prepared from CuCl2, HAuCl4 solution, and BaTiO3 by the solution method. BaTiO3 particles were dispersed in a CuCl2 solution, and the BaTiO3/CuO complex was produced through crystallization of CuO onto the BaTiO3 surface by hydrolysis of CuCl2 in the first stage. After the reaction, CuO was reduced to Cu2O by treatment with glucose, thereby yielding the BaTiO3/Cu2O complex. The BaTiO3/Cu2O/Au complex was prepared by treating the BaTiO3/Cu2O particles with HAuCl4. Under visible light, the obtained BaTiO3/Cu2O0/Au complex showed higher photocatalytic activity than the Degussa P-25sample. In addition, the BaTiO3/Cu2O complex showed excellent antipathogenic effect.

Biomimetic piezoelectric nanomaterial-modified oral microrobots for targeted catalytic and immunotherapy of colorectal cancer.

Lactic acid (LA) accumulation in the tumor microenvironment poses notable challenges to effective tumor immunotherapy. Here, an intelligent tumor treatment microrobot based on the unique physiological structure and metabolic characteristics of Veillonella atypica (VA) is proposed by loading Staphylococcus aureus cell membrane-coating BaTiO3 nanocubes (SAM@BTO) on the surface of VA cells (VA-SAM@BTO) via click chemical reaction. Following oral administration, VA-SAM@BTO accurately targeted orthotopic colorectal cancer through inflammatory targeting of SAM and hypoxic targeting of VA. Under in vitro ultrasonic stimulation, BTO catalyzed two reduction reactions (O2 → •O2- and CO2 → CO) and three oxidation reactions (H2O → •OH, GSH → GSSG, and LA → PA) simultaneously, effectively inducing immunogenic death of tumor cells. BTO catalyzed the oxidative coupling of VA cells metabolized LA, effectively disrupting the immunosuppressive microenvironment, improving dendritic cell maturation and macrophage M1 polarization, and increasing effector T cell proportions while decreasing regulatory T cell numbers, which facilitates synergetic catalysis and immunotherapy.

Barium selenate supplementation and its effect on intramammary infection in pasture-based dairy cows.

A significant proportion of cattle receive inadequate dietary Se because of its low content in soils and pastures of various regions of the world. Several economically important diseases in dairy cows, such as mastitis, have been associated with Se deficiency. The objective of this study was to evaluate the effect of a single injection of a long-acting form of Se at drying off on the risk and incidence rate of new intramammary infections and on milk somatic cell count in the subsequent lactation in pasture-based dairy cows. Forty-nine Chilean Holstein-Friesian cows were fed a diet containing <0.05 mg of Se/kg of ration dry matter. During the dry period, cows were allocated to 1 of 2 groups, a supplemented (n=24) group treated with a single subcutaneous injection of barium selenate 2 mo before calving and a control group (n=25) that remained unsupplemented. Duplicate foremilk samples were aseptically collected within 6 d after calving and every 2 wk until drying-off for bacteriological culture. Milk samples were also collected monthly for somatic cell count evaluation. Blood samples were collected before treatment and at 30, 90, 180, and 270 d after treatment for analysis of blood glutathione peroxidase (GPx) activity. The activity of glutathione peroxidase was higher in supplemented cows 30 d after the injection until the end of the study. The risk and incidence rate of new intramammary infections was not affected by supplementation. A progressive increase in somatic cell count was observed throughout lactation, but there was no effect of supplementation. In conclusion, a one-time injection of barium selenate 2 mo before calving in these pasture-based dairy cows did not affect udder health in the subsequent lactation, indicating that Se basal intake was adequate for preventing subclinical mastitis in pasture-based cows in southern Chile.

Viscosity in infant dysphagia management: comparison of viscosity of thickened liquids used in assessment and thickened liquids used in treatment.

The purpose of this study was to investigate comparability of viscosity of liquids used in assessment and treatment of infants with dysphagia. Goals of this study were as follows: (1) Establish baseline viscosity values for (a) the commercial barium assessment liquids of varying thicknesses and (b) clinically typical infant formula thickened with varied thickeners. (2) Compare the baseline viscosities of the various liquids for correlation of values. We attempted to mimic real-world situations and recreate clinical assessment and treatment conditions. We also identified and made every effort to control typical clinical variables, e.g., mixer and mixing procedure, brand of product, and temperature of liquid. The method of measurement was based on rheologic principles and used a Brookfield Engineering LVDV II + Pro Cone/Plate Viscometer at spindle and speed combinations to maximize shear rates consistent with swallowing. Statistically, there was no comparability between barium and formula mixtures, regardless of thickener utilized. The implications of these findings and the need to develop a standardized means of thickening formula to a viscosity comparable to the assessment materials are discussed.

Patient dose during videofluoroscopy swallowing studies in a Hong Kong public hospital.

A videofluoroscopy swallowing study (VFSS) is a major tool in diagnosing swallowing disorders. Like all other medical examinations that involve irradiation, patient dosage is a major concern. Cerebrovascular accident (CVA) and nasopharyngeal carcinoma (NPC) have been two of the most common indicating pathologies for VFSS studies. The goals of this study were to determine the mean dose area product (DAP) value and fluoroscopic time for VFSS examinations in Tuen Mun Hospital, to compare the result with the dose reference level of other similar studies, and to document the results with respect to the various common indicating pathologies for VFSS (i.e., CVA, NPC). Three hundred ninety-eight VFSS exams were performed at our center in a 24-month period; the mean DAP was 2.42 +/- 2.04 Gy cm(2) for an effective dose of 0.31 +/- 0.26 mSv. The mean fluoroscopic time is 4.23 +/- 2.56 min. The P value of 0.0034 was obtained using the Kruskal-Wallis test to compare the DAP from various groups of indicating pathologies. It suggests that there are significant differences in dosage between CVA and NPC patients and the entire population. We conclude that the dose of radiation received by a patient undergoing a VFSS examination in our center was comparable to the international standard and that of other similar studies. We can also conclude that there is a significant difference in dosage between NPC and CVA patients and the overall population suggesting that the indicating pathologies for a VFSS have certain effects on the resulting irradiating dose delivered but more studies have to be done to explain such differences.

Prevention of clinical mastitis with barium selenate in dairy goats from a selenium-deficient area.

Mastitis is one of the most negative factors involved in the economy of dairy goat farms. The effect of selenium on mammary gland resistance to infectious diseases has been demonstrated. This work evaluates the efficacy of a slow-release Se salt (barium selenate) to reduce the incidence of clinical mastitis in goats reared on Se-deficient areas. Six hundred milking goats of the Malagueña breed, from 4 commercial dairy farms located in a Se-deficient area, were randomly allotted to 2 groups: treated group (given a subcutaneous injection of barium selenate at a dose of 1 mg of Se/kg of body weight 15 d before mating) and control group (no supplement). During the lactation the does were monitored to assess the occurrence of clinical mastitis by physical examination, California Mastitis Test performance, and microbiological study. The Se content of the ration consumed previously by the animals did not meet the requirements for dairy goats. The Se injection significantly increased glutathione peroxidase activity in the treated group and had evident beneficial effects in the subsequent lactation. The somatic cell count and the incidence of clinical mastitis were significantly lower in the treated group than in the control group. However, no significant differences were found for milk composition. Thus, in Se-deficient areas, the supplementation with Se of any source in programs for prevention of clinical mastitis and improvement of milk quality is strongly recommended.

Electrophysiologic effects of the IK1 inhibitor PA-6 are modulated by extracellular potassium in isolated guinea pig hearts.

The pentamidine analog PA-6 was developed as a specific inward rectifier potassium current (IK1) antagonist, because established inhibitors either lack specificity or have side effects that prohibit their use in vivo. We previously demonstrated that BaCl2, an established IK1 inhibitor, could prolong action potential duration (APD) and increase cardiac conduction velocity (CV). However, few studies have addressed whether targeted IK1 inhibition similarly affects ventricular electrophysiology. The aim of this study was to determine the effects of PA-6 on cardiac repolarization and conduction in Langendorff-perfused guinea pig hearts. PA-6 (200 nm) or vehicle was perfused into ex-vivo guinea pig hearts for 60 min. Hearts were optically mapped with di-4-ANEPPS to quantify CV and APD at 90% repolarization (APD90). Ventricular APD90 was significantly prolonged in hearts treated with PA-6 (115 ± 2% of baseline; P < 0.05), but not vehicle (105 ± 2% of baseline). PA-6 slightly, but significantly, increased transverse CV by 7%. PA-6 significantly prolonged APD90 during hypokalemia (2 mmol/L [K+]o), although to a lesser degree than observed at 4.56 mmol/L [K+]o In contrast, the effect of PA-6 on CV was more pronounced during hypokalemia, where transverse CV with PA-6 (24 ± 2 cm/sec) was significantly faster than with vehicle (13 ± 3 cm/sec, P < 0.05). These results show that under normokalemic conditions, PA-6 significantly prolonged APD90, whereas its effect on CV was modest. During hypokalemia, PA-6 prolonged APD90 to a lesser degree, but profoundly increased CV Thus, in intact guinea pig hearts, the electrophysiologic effects of the IK1 inhibitor, PA-6, are [K+]o-dependent.

Involvement of the MEK-ERK/p38-CREB/c-fos signaling pathway in Kir channel inhibition-induced rat retinal Müller cell gliosis.

Our previous studies have demonstrated that activation of group I metabotropic glutamate receptors downregulated Kir channels in chronic ocular hypertension (COH) rats, thus contributing to Müller cell gliosis, characterized by upregulated expression of glial fibrillary acidic protein (GFAP). In the present study, we explored possible signaling pathways linking Kir channel inhibition and GFAP upregulation. In normal retinas, intravitreal injection of BaCl2 significantly increased GFAP expression in Müller cells, which was eliminated by co-injecting mitogen-activated protein kinase (MAPK) inhibitor U0126. The protein levels of phosphorylated extracellular signal-regulated protein kinase1/2 (p-ERK1/2) and its upstream regulator, p-MEK, were significantly increased, while the levels of phosphorylated c-Jun N-terminal kinase (p-JNK) and p38 kinase (p-p38) remained unchanged. Furthermore, the protein levels of phosphorylated cAMP response element binding protein (p-CREB) and c-fos were also increased, which were blocked by co-injecting ERK inhibitor FR180204. In purified cultured rat Müller cells, BaCl2 treatment induced similar changes in these protein levels apart from p-p38 levels and the p-p38:p38 ratio showing significant upregulation. Moreover, intravitreal injection of U0126 eliminated the upregulated GFAP expression in COH retinas. Together, these results suggest that Kir channel inhibition-induced Müller cell gliosis is mediated by the MEK-ERK/p38-CREB/c-fos signaling pathway.

Cellular basis for electrocardiographic and arrhythmic manifestations of Andersen-Tawil syndrome (LQT7).

BACKGROUND: Andersen-Tawil syndrome, a skeletal muscle syndrome associated with periodic paralysis and long QT intervals on the ECG, has been linked to defects in KCNJ2, the gene encoding for the inward rectifier potassium channel (I(K1).) OBJECTIVES: The purpose of this study was to examine the cellular mechanisms underlying the ECG and arrhythmic manifestations of Andersen-Tawil syndrome. METHODS: To investigate the effects of KCNJ2 loss-of-function mutations responsible for Andersen-Tawil syndrome, we used barium chloride (BaCl(2)) to inhibit I(K1) in arterially perfused wedge preparation. Transmembrane action potentials (APs) were simultaneously recorded from endocardial, midmyocardial, and epicardial cells, together with a transmural ECG. RESULTS: BaCl(2) (1 to 30 microM) produced a concentration-dependent prolongation of the QT interval, secondary to a homogeneous prolongation of AP duration of the three cell types. QT interval was prolonged without an increase in transmural dispersion of repolarization (TDR). Low extracellular potassium (2.0 mM), isoproterenol (20-50 nM), and an abrupt increase in temperature (36 degrees C-39 degrees C) in the presence of 10 microM BaCl(2) did not significantly increase TDR but increased ectopic extrasystolic activity. Early afterdepolarizations were not observed under any condition. Spontaneous torsades de pointes arrhythmias were never observed, nor could they be induced with programmed electrical stimulation under any of the conditions studied. CONCLUSION: Our results provide an understanding of why QT prolongation associated with Andersen-Tawil syndrome is relatively benign in the clinic and provide further support for the hypothesis that the increase in TDR, rather than QT interval, is responsible for development of torsades de pointes.

The roles of the Na+/K+-ATPase, NKCC, and K+ channels in regulating local sweating and cutaneous blood flow during exercise in humans in vivo.

Na+/K+-ATPase has been shown to regulate the sweating and cutaneous vascular responses during exercise; however, similar studies have not been conducted to assess the roles of the Na-K-2Cl co-transporter (NKCC) and K+ channels. Additionally, it remains to be determined if these mechanisms underpinning the heat loss responses differ with exercise intensity. Eleven young (24 ± 4 years) males performed three 30-min semirecumbent cycling bouts at low (30% VO2peak), moderate (50% VO2peak), and high (70% VO2peak) intensity, respectively, each separated by 20-min recovery periods. Using intradermal microdialysis, four forearm skin sites were continuously perfused with either: (1) lactated Ringer solution (Control); (2) 6 mmol·L-1 ouabain (Na+/K+-ATPase inhibitor); (3) 10 mmol·L-1 bumetanide (NKCC inhibitor); or (4) 50 mmol·L-1 BaCl2 (nonspecific K+ channel inhibitor); sites at which we assessed local sweat rate (LSR) and cutaneous vascular conductance (CVC). Inhibition of Na+/K+-ATPase attenuated LSR compared to Control during the moderate and high-intensity exercise bouts (both P Ë‚ 0.01), whereas attenuations with NKCC and K+ channel inhibition were only apparent during the high-intensity exercise bout (both P ≤ 0.05). Na+/K+-ATPase inhibition augmented CVC during all exercise intensities (all P Ë‚ 0.01), whereas CVC was greater with NKCC inhibition during the low-intensity exercise only (P Ë‚ 0.01) and attenuated with K+ channel inhibition during the moderate and high-intensity exercise conditions (both P Ë‚ 0.01). We show that Na+/K+-ATPase, NKCC and K+ channels all contribute to the regulation of sweating and cutaneous blood flow but their influence is dependent on the intensity of dynamic exercise.

[Bioavailability and bone toxicity of barium chloride by chronic administration in rats]. / Biodisponibilité et toxicité osseuse du chlorure de baryum en administration chronique chez le rat.

Knowing long term total parenteral nutrition (TPN) can bring 12 micrograms/kg/day as barium contamination, we investigated the barium ability to give the same bone toxicity as observed in patients' underlying TPN. A preliminary study carried out on 21 rats allowed us to calculate the bioavailability of barium chloride (50%) with doses fixed at 1 mg/kg for the intravenous route and 10 mg/kg for the oral route. As it is very difficult to feed rats parenterally for more than 30 days, we decided to give barium chloride orally. Twenty rats received 48 micrograms/kg/day barium chloride during 4 months. The barium plasma and bone levels were not statistically different between the control group and the tested group. The femurs and tibias were removed for analysis, carried out by different fixation and coloration techniques. No anomalies could be detected in the treated group concerning main bone parameters that are disturbed in patients' underlying TPN.

Direct visualization of gastrointestinal tract with lanthanide-doped BaYbF5 upconversion nanoprobes.

Nanoparticulate contrast agents have attracted a great deal of attention along with the rapid development of modern medicine. Here, a binary contrast agent based on PAA modified BaYbF5:Tm nanoparticles for direct visualization of gastrointestinal (GI) tract has been designed and developed via a one-pot solvothermal route. By taking advantages of excellent colloidal stability, low cytotoxicity, and neglectable hemolysis of these well-designed nanoparticles, their feasibility as a multi-modal contrast agent for GI tract was intensively investigated. Significant enhancement of contrast efficacy relative to clinical barium meal and iodine-based contrast agent was evaluated via X-ray imaging and CT imaging in vivo. By doping Tm(3+) ions into these nanoprobes, in vivo NIR-NIR imaging was then demonstrated. Unlike some invasive imaging modalities, non-invasive imaging strategy including X-ray imaging, CT imaging, and UCL imaging for GI tract could extremely reduce the painlessness to patients, effectively facilitate imaging procedure, as well as rationality economize diagnostic time. Critical to clinical applications, long-term toxicity of our contrast agent was additionally investigated in detail, indicating their overall safety. Based on our results, PAA-BaYbF5:Tm nanoparticles were the excellent multi-modal contrast agent to integrate X-ray imaging, CT imaging, and UCL imaging for direct visualization of GI tract with low systemic toxicity.

Comparison of standardized bariums with varying rheological parameters on swallowing kinematics in males.

This study measured dose-response of a range of commercially available liquid barium materials designed for use in videofluoroscopic oropharyngeal swallowing assessments, particularly as they relate to the necessity of adding a thickening agent for swallow safety. A group of 25 adult males representing various medical diagnoses consented to participate, with 16 qualifying to complete a videofluoroscopic swallowing assessment with liquid barium materials of three viscosities (nectar: 300 cP, thin honey: 1,500 cP, thick honey: 3,000 cP). Outcome measures included airway invasion (Penetration-Aspiration score), postswallow residue, and patient preference. Penetration-Aspiration and residue scores did not significantly differ between thin honey and thick honey bariums. Significantly more severe airway invasion was observed with nectar boluses than with two levels of honey boluses (p < 0.001). Significantly more residue was observed in the oral cavity (p < 0.002) and valleculae (p < 0.001) with thin and thick honey bariums than with nectar barium. Thin honey was rated as "easy" or "average" to drink by 67% of subjects, compared with 54% for thick honey. This study supports the use of thin honey barium over thick honey barium during videofluoroscopic swallowing assessments because the two honey bariums were comparable in terms of airway protection and postswallow residue in the oropharynx and the thin honey was preferred by patients.

An outbreak of granulomatous peritonitis caused by injectable selenium in a flock of Merino sheep.

During meat inspection, unusual pigmented lesions were found in the abdomens of 411 sheep from a flock raised in the Northern Tablelands of New South Wales. In each affected sheep there were multiple discrete, soft, yellow homogeneous plaques beneath the parietal peritoneum and extending into marginating facial planes of the diaphragm and body wall. Microscopically, the lesions consisted of focal granulomatous peritonitis with intracellular acicular refractile golden-brown crystals. Energy dispersive X-ray spectroscopy revealed intralesional barium and selenium, two components of an injectable selenium compound administered to the sheep 6-8 months prior, which contains the yellow pigment, iron oxide. The mechanism of subperitoneal deposition of the compound could not be confirmed, but is presumed to have involved intraperitoneal injection of barium selenate. Meat inspectors and diagnosticians should consider barium selenate injection-site granulomas as a possible explanation for yellow pigmented lesions, especially in livestock from selenium-deficient areas. Animal care providers should be aware that incorrect administration of barium selenate can result in losses from condemnation or downgrading of meat product.

Depot injection of barium selenate for long-term prevention of selenium inadequacy in beef cattle.

In southern Australia, cattle at risk from selenium (Se) deficiency can be given an oral dose of supplements that are effective in maintaining adequate Se status for between 9 and 12 months. The present study was undertaken to assess the duration of the effect of parenteral barium selenate (BaSe) in raising the Se status of cattle at pasture in an area of marginal Se deficiency. The BaSe was given subcutaneously to Hereford heifers, using an 18-gauge needle. Cattle had regular blood sampling to assay Se, from 8 days before dosing to 1155 days afterwards. Results show that a single injection of BaSe was effective in elevating blood and plasma Se concentrations to normal values for at least 2 to 3 years, when given to beef cattle of low normal Se status. We suggest that a prophylactic dosage of 0.5 mg Se/kg body weight as BaSe should be given every 2 years to prevent Se inadequacy in beef cattle grazing pasture of marginal Se content.