Orally Ingested Self-Powered Stimulators for Targeted Gut-Brain Axis Electrostimulation to Treat Obesity and Metabolic Disorders.

Obesity is a significant health concern that often leads to metabolic dysfunction and chronic diseases. This study introduces a novel approach to combat obesity using orally ingested self-powered electrostimulators. These electrostimulators consist of piezoelectric BaTiO3 (BTO) particles conjugated with capsaicin (Cap) and aim to activate the vagus nerve. Upon ingestion by diet-induced obese (DIO) mice, the BTO@Cap particles specifically target and bind to Cap-sensitive sensory nerve endings in the gastric mucosa. In response to stomach peristalsis, these particles generate electrical signals. The signals travel via the gut-brain axis, ultimately influencing the hypothalamus. By enhancing satiety signals in the brain, this neuromodulatory intervention reduces food intake, promotes energy metabolism, and demonstrates minimal toxicity. Over a 3-week period of daily treatments, DIO mice treated with BTO@Cap particles show a significant reduction in body weight compared to control mice, while maintaining their general locomotor activity. Furthermore, this BTO@Cap particle-based treatment mitigates various metabolic alterations associated with obesity. Importantly, this noninvasive and easy-to-administer intervention holds potential for addressing other intracerebral neurological diseases.

Metabolism of barium in the human body after suicidal ingestion: A CARE-compliant case report.

RATIONALE: Thus far, barium poisoning has been seldom reported and the metabolism of barium in human body has not been explored. PATIENT CONCERNS: A 21-year-old young man was taken to the local hospital by "120 emergency medical services" after a suicidal attempt. About 100 mL of barium chloride solution with a concentration of 100 g/L was ingested, while the actual amount of ingested barium chloride solution was unclear because of immediate vomiting after the ingestion. DIAGNOSES: About 2 hours after the suicidal ingestion, the patient was presented with somnolence, the pulse rate was 67 beats per minute, the blood pressure was 158/92 mm Hg, but he exhibited no nausea or vomiting. About 3 hours after the ingestion, the blood concentration of potassium was 1.5 mmol/L. INTERVENTIONS: The patient received gastric lavage by magnesium sulfate solution, intravenous sodium thiosulfate, and potassium supplementation. Other symptomatic treatments were applied simultaneously. To investigate the metabolism of barium in the human body, we measured the concentration of barium in 9 groups of paired serum and urine samples sequentially collected from the patient. OUTCOMES: The patient was rescued successfully. LESSONS: The serum concentration of barium decreased rapidly in the first 24 hours. In this period, prompt and massive potassium supplementation and other symptomatic treatments are effective and recommended.

Membrane reactor based synthesis of biodiesel from Toona ciliata seed oil using barium oxide nano catalyst.

Membrane technology has been embraced as a feasible and promising substitute to the traditional technologies employed for biodiesel synthesis which are energy and time consuming. It needs less energy, has high stability, is environmentally friendly, and is simple to operate and control. Therefore, in our current study membrane technology was employed to synthesize biodiesel from Toona ciliate novel and non-edible seed oil. Since Toona ciliata has affluent oil content (33.8%) and is effortlessly and extensively available. In fact, we intended to scrutinize the effects of green synthesized barium oxide nanoparticles for one step transesterification of biodiesel production using membrane technology followed by characterization of prepared catalyst via innovative techniques. Optimal yield of biodiesel attained was 94% at 90 °C for 150 min with methanol to oil molar ratio of 9:1 and amount of about 0.39 wt %. Quantitative analysis of synthesized Toona ciliata oil biodiesel was carried out by advance techniques of Gas chromatography mass spectrometry (GC-MS), Fourier-transform infrared (FTIR) spectroscopy and Nuclear magnetic resonance (NMR) which authorize the synthesis of fatty acid methyl ester compounds using oil from Toona ciliata seeds. Values of Toona ciliata fuel properties for instance flash point (70°C), density (0.89 kg/m3), viscosity (5.25 mm2/s), cloud point (-8°C) and pour point (-11°C) met the specifications of international standards i. e American (ASTM D-6751), European (EN-14214) and China (GB/T 20,828). Subsequently, it is concluded that membrane technology is environmentally friendly and efficient technique for mass-production of sustainable biodiesel using green nano catalyst of barium oxide.

Biocompatibility and colorectal anti-cancer activity study of nanosized BaTiO3 coated spinel ferrites.

In the present work, different nanoparticles spinel ferrite series (MFe2O4, Co0.5M0.5Fe2O4; M = Co, Mn, Ni, Mg, Cu, or Zn) have been obtained via sonochemical approach. Then, sol-gel method was employed to design core-shell magnetoelectric nanocomposites by coating these nanoparticles with BaTiO3 (BTO). The structure and morphology of the prepared samples were examined by X-ray powder diffraction (XRD), scanning electron microscope (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), high-resolution transmission electron microscope (HR-TEM), and zeta potential. XRD analysis showed the presence of spinel ferrite and BTO phases without any trace of a secondary phase. Both phases crystallized in the cubic structure. SEM micrographs illustrated an agglomeration of spherical grains with nonuniformly diphase orientation and different degrees of agglomeration. Moreover, HR-TEM revealed interplanar d-spacing planes that are in good agreement with those of the spinel ferrite phase and BTO phase. These techniques along with EDX analyses confirmed the successful formation of the desired nanocomposites. Zeta potential was also investigated. The biological influence of (MFe2O4, CoMFe) MNPs and core-shell (MFe2O4@BTO, CoMFe@BTO) magnetoelectric nanocomposites were examined by MTT and DAPI assays. Post 48 h of treatments, the anticancer activity of MNPs and MENCs was investigated on human colorectal carcinoma cells (HCT-116) against the cytocompatibility of normal non-cancerous cells (HEK-293). It was established that MNPs possess anti-colon cancer capability while MENCs exhibited a recovery effect due to the presence of a protective biocompatible BTO layer. RBCs hemolytic effect of NPs has ranged from non- to low-hemolytic effect. This effect that could be attributed to the surface charge from zeta potential, also the CoMnFe possesses the stable and lowest zeta potential in comparison with CoFe2O4 and MnFe2O4 also to the protective effect of shell. These findings open up wide prospects for biomedical applications of MNPs as anticancer and MENCs as promising drug nanocarriers.

3-Aminopyrazolo[3,4-b]pyridine: Effective Precursor for Barium Hydroxide-Mediated Three Components Synthesis of New Mono- and Bis(pyrimidines) with Potential Cytotoxic Activity.

In this study, an efficient one-pot procedure for preparing a new series of pyrazolo[3,4-b]pyridine-fused pyrimidines was described. The target hybrids were developed through a three-component reaction of 3-amino-1H-pyrazolo[3,4-b]pyridine, benzaldehydes, and acetophenones (molar ratio 1 : 1 : 1). The best conditions for the previous reaction were 2.5 equivalents of barium hydroxide in DMF at 150 °C for 6 h. New bis(pyrimidines) were synthesized in high yields using a similar one-pot reaction protocol with some modifications. Thus, two equivalents of each of the appropriate acetophenones and 3-aminopyrazolopyridine were reacted with one equivalent of the appropriate bis(aldehydes). The reaction was carried out at 150 °C for 8 h using 4.5 equivalents of barium hydroxide in DMF. Repeating the previous reaction with the appropriate bis(acetyl) derivatives and benzaldehydes resulted in good yields of the target bis(pyrimidines). The in vitro cytotoxic activity of new pyrimidines against the MCF-7, HEPG2, and Caco2 cell lines was evaluated using the reference doxorubicin (IC50 values of 4.34-6.97 µM). Hybrid 6h had the best activity against Caco2 and MCF-7 cell lines, IC50 values of 12.62 and 14.50 µM, respectively. The IC50 values for hybrids 6c, 6e, and 6f against MCF-7 and Caco2 cell lines were 23.99-41.69 and 33.14-43.33 µM, respectively. Furthermore, hybrid 6e displayed IC50 value of 20.06 µM HEPG2 cell lines, while the hybrids 6c, 6f and 6h exhibited IC50 values ranging between 26.29-50.51 µM. Furthermore, hybrid 6e had an IC50 value of 20.06 µM for the HEPG2 cell lines, whereas hybrids 6c, 6f, and 6h had IC50 values ranging from 26.29 to 50.51 µM.

Protective Effects of 3,4-Seco-Lupane Triterpenes from Food Raw Materials of the Leaves of Eleutherococcus Senticosus and Eleutherococcus Sessiliflorus on Arrhythmia Induced by Barium Chloride.

As a traditional wild vegetable and food raw material, the leaves of Eleutherococcus senticosus and Eleutherococcus sessiliflorus are rich in 3,4-seco-lupane triterpenes, including chiisanoside (CSS), divaroside (DVS), sessiloside-A (SSA), and chiisanogenin (CSG). This study was conducted to evaluate the anti-arrhythmic effects of these 3,4-seco-lupane triterpenes. Evaluation of the cytotoxicity of compounds was performed by measuring cell viability and apoptosis with the CCK-8 assay. In vivo, arrhythmia was induced by rapid injection of BaCl2 via rat caudal vein. The occurrence time and duration of arrhythmias in rats were studied. The levels of SOD and MDA in serum, and Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase in myocardial homogenate were detected by ELISA. The histopathological changes of rats myocardial were observed by HE staining. Changes in the expression of PKA and related proteins were detected by Western blot. The 3,4-seco-lupane triterpenes interactions with protein kinase A were analyzed by molecular docking. In the present study, we found that 3,4-seco-lupane triterpenes exhibited powerful anti-arrhythmic activity, especially DVS completely relieved the ventricular arrhythmia induced by BaCl2 . This study suggests that the leaves of E. senticosus and E. sessiliflorus might be used as functional food materials to prevent arrhythmia, and DVS can potentially be further developed as an anti-arrhythmic drug.

Barium Titanate Nanoparticles Sensitise Treatment-Resistant Breast Cancer Cells to the Antitumor Action of Tumour-Treating Fields.

Although tumour-treating fields (TTFields) is a promising physical treatment modality based on disruption of dipole alignments and generation of dielectrophoretic forces during cytokinesis, not much is known about TTFields-responsive sensitisers. Here, we report a novel TTFields-responsive sensitiser, barium titanate nanoparticles (BTNPs), which exhibit cytocompatibility, with non-cytotoxic effects on breast cancer cells. BTNPs are characterised by high dielectric constant values and ferroelectric properties. Notably, we found that BTNPs sensitised TTFields-resistant breast cancer cells in response to TTFields. In addition, BTNPs accumulated in the cytoplasm of cancer cells in response to TTFields. Further, we showed that TTFields combined with BTNPs exhibited antitumor activity by modulating several cancer-related pathways in general, and the cell cycle-related apoptosis pathway in particular. Therefore, our data suggest that BTNPs increase the antitumor action of TTFields by an electric field-responsive cytosolic accumulation, establishing BTNP as a TTFields-responsive sensitiser.

In vitro evaluation of barium titanate nanoparticle/alginate 3D scaffold for osteogenic human stem cell differentiation.

Nanomaterials can mimic properties of extracellular matrix molecules, promising great potential for scaffold composition in tissue engineering. In the present study, we investigated whether barium titanate nanoparticles (BT NP) combined with alginate polymer would provide a new cytocompatible three-dimensional (3D) scaffold to induce osteogenic stem cell differentiation. In vitro cytocompatibility and osteogenic differentiation potential were investigated using human mesenchymal stem cells (MSC). Firstly, we studied the cell viability and oxidative stress by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) thiazolyl blue tetrazolium bromide (MTT) and superoxide dismutase (SOD) assays. Overall, neither pure BT NP or BT NP/alginate 3D scaffold induced cytotoxicity. The scanning electron and atomic force microscopy revealed that BT NP/alginate 3D scaffold produced exhibited highly interconnected pores and surface nanotopography that were favorable for MSC differentiation. Von Kossa staining showed mineralization nodules and MSCs morphology changed from spindle to cuboid shape after 21 d. Finally, BMP-2 and ALP mRNA were significantly upregulated on cells grown into the BT NP/alginate 3D scaffold. Thus, the BT NP/alginate 3D scaffold showed an osteogenic differentiation induction potential, without the addition of osteogenic supplements. These results indicate that the BT NP/alginate 3D scaffold provides a cytocompatible and bioactive microenvironment for osteogenic human MSC differentiation.

BaTiO3-core Au-shell nanoparticles for photothermal therapy and bimodal imaging.

We report sub-100 nm metal-shell (Au) dielectric-core (BaTiO3) nanoparticles with bimodal imaging abilities and enhanced photothermal effects. The nanoparticles efficiently absorb light in the near infrared range of the spectrum and convert it to heat to ablate tumors. Their BaTiO3 core, a highly ordered non-centrosymmetric material, can be imaged by second harmonic generation, and their Au shell generates two-photon luminescence. The intrinsic dual imaging capability allows investigating the distribution of the nanoparticles in relation to the tumor vasculature morphology during photothermal ablation. Our design enabled in vivo real-time tracking of the BT-Au-NPs and observation of their thermally-induced effect on tumor vessels. STATEMENT OF SIGNIFICANCE: Photothermal therapy induced by plasmonic nanoparticles has emerged as a promising approach to treating cancer. However, the study of the role of intratumoral nanoparticle distribution in mediating tumoricidal activity has been hampered by the lack of suitable imaging techniques. This work describes metal-shell (Au) dielectric-core (BaTiO3) nanoparticles (abbreviated as BT-Au-NP) for photothermal therapy and bimodal imaging. We demonstrated that sub-100 nm BT-Au-NP can efficiently absorb near infrared light and convert it to heat to ablate tumors. The intrinsic dual imaging capability allowed us to investigate the distribution of the nanoparticles in relation to the tumor vasculature morphology during photothermal ablation, enabling in vivo real-time tracking of the BT-Au-NPs and observation of their thermally-induced effect on tumor vessels.

Naringenin Regulates CFTR Activation and Expression in Airway Epithelial Cells.

BACKGROUND/AIMS: Sputum symptoms are commonly seen in the elderly. This study aimed to identify an efficacious expectorant treatment stratagem through evaluating the secretion-promoting activation and cystic fibrosis transmembrane conductance regulator (CFTR) expression of the bioactive herbal monomer naringenin. METHODS: Vectorial Cl- transport was determined by measuring short-circuit current (ISC) in rat airway epithelium. cAMP content was measured by ELISA in primary cultured epithelial cells and Calu-3 cells. CFTR expression in Calu-3 cells was determined by qPCR. RESULTS: Addition of naringenin to the basolateral side of the rat airway led to a concentration-dependent sustained increase in ISC. The current was suppressed when exposed to Cl--free solution or by bumetanide, BaCl2, and DPC but not by DIDS and IBMX. Forskolin-induced ISC increase and CFTRinh-172/MDL-12330A-induced ISC inhibition were not altered by naringenin. Intracellular cAMP content was significantly increased by naringenin. With lipopolysaccharide stimulation, CFTR expression was significantly reduced, and naringenin dose-dependently enhanced CFTR mRNA expression. CONCLUSION: These results demonstrate that naringenin has the ability to stimulate Cl- secretion, which is mediated by CFTR through a signaling pathway by increasing cAMP content. Moreover, naringenin can increase CFTR expression when organism CFTR expression is seriously hampered. Our data suggest a potentially effective treatment strategy for sputum.

Selenomethionine as a Safer Substitute for Barium Selenate in Long-Acting Injectable Se Supplements for Food-Producing Animals.

Nutritional supplementation with selenium (Se) can prevent Se deficiency in food-producing animals. Injection with slow-release formulations is a preferred method for free-range grazing sheep and cattle, and barium selenate (BaSeO4) provides optimal efficacy. This chemical can become a health risk to humans if the concentrated depot of an injection site is consumed, and consequently such use is recently banned in the EU. A possible replacement is selenomethionine (SeMet), a naturally occurring form of Se supplementation hitherto only administered orally. In four animal studies we found that injection with SeMet maintained nutritionally adequate concentrations of Se in blood and tissues of lambs for at least 191 days and in blood and milk of dairy cows for at least 95 days. Stereoisomer forms L- and DL-SeMet were functionally equivalent. This is the first demonstration that injectable SeMet can deliver efficacy similar to BaSeO4 but with less risk of undesirable residues in edible tissues.

Clinical Value of Contrast Enema Prior to Ileostomy Closure.

Purpose To determine the value of routine contrast enema of loop ileostomy before elective ileostomy closure regarding the influence on the clinical decision-making. Materials and Methods Retrospective analysis of contrast enemas at a tertiary care center between 2005 und 2011. Patients were divided into two groups: Group I with ileostomy reversal, group II without ileostomy closure. Patient-related parameters (underlying disease, operation method) and parameters based on the findings (stenosis, leakage of anastomosis, incontinence) were evaluated. Results Analyzing a total of 252 patients in 89 % (group I, n = 225) ileostomy closure was performed. In 15 % the radiologic report was the only diagnostic modality needed for therapy decision; in 36 % the contrast enema and one or more other diagnostic methods were decisive. In 36 % the radiological report of the contrast imaging was not relevant for decision at all. In 11 % (group II, n = 27) no ileostomy closure was performed. In this group in 11 % the radiological report of the contrast enema was the only decision factor for not performing the ileostomy reversal. In 26 % one or more examination was necessary. In 26 % the result of the contrast examination was not relevant. Conclusion The radiologic contrast imaging of loop ileostomy solely plays a minor role in complex surgical decision-making before planned reversal, but is important as first imaging method in detecting complications and often leads to additional examinations. Key points · Contrast enema of loop ileostomy before planned ileostomy closure is a frequently performed examination.. · There exist no general guidelines that give further recommendations on decision-making planning ileostomy closure.. · The radiologic contrast imaging of loop ileostomy solely plays a minor role in decision-making before planned reversal, but is important as first imaging method.. Citation Format · Goetz A, da Silva NP, Moser C et al. Clinical Value of Contrast Enema Prior to Ileostomy Closure. Fortschr Röntgenstr 2017; 189: 855 - 863.

CFTR-mediated anion secretion across intestinal epithelium-like Caco-2 monolayer under PTH stimulation is dependent on intermediate conductance K+ channels.

Parathyroid hormone (PTH), a pleiotropic hormone that maintains mineral homeostasis, is also essential for controlling pH balance and ion transport across renal and intestinal epithelia. Optimization of luminal pH is important for absorption of trace elements, e.g., calcium and phosphorus. We have previously demonstrated that PTH rapidly stimulated electrogenic [Formula: see text] secretion in intestinal epithelial-like Caco-2 monolayers, but the underlying cellular mechanism, contributions of other ions, particularly Cl- and K+, and long-lasting responses are not completely understood. Herein, PTH and forskolin were confirmed to induce anion secretion, which peaked within 1-3 min (early phase), followed by an abrupt decay and plateau that lasted for 60 min (late phase). In both early and late phases, apical membrane capacitance was increased with a decrease in basolateral capacitance after PTH or forskolin exposure. PTH also induced a transient increase in apical conductance with a long-lasting decrease in basolateral conductance. Anion secretion in both phases was reduced under [Formula: see text]-free and/or Cl--free conditions or after exposure to carbonic anhydrase inhibitor (acetazolamide), CFTR inhibitor (CFTRinh-172), Na+/H+ exchanger (NHE)-3 inhibitor (tenapanor), or K+ channel inhibitors (BaCl2, clotrimazole, and TRAM-34; basolateral side), the latter of which suggested that PTH action was dependent on basolateral K+ recycling. Furthermore, early- and late-phase responses to PTH were diminished by inhibitors of PI3K (wortmannin and LY-294002) and PKA (PKI 14-22). In conclusion, PTH requires NHE3 and basolateral K+ channels to induce [Formula: see text] and Cl- secretion, thus explaining how PTH regulated luminal pH balance and pH-dependent absorption of trace minerals.

Desulfurization: Critical step towards enhanced selenium removal from industrial effluents.

Selenium (Se) removal from synthetic solutions and from real Flue Gas Desulfurization (FGD) wastewater generated by a coal-fired power plant was studied for the first time using a commercial iron oxide impregnated strong base anion exchange resin, Purolite® FerrIX A33E. In synthetic solutions, the resin showed high affinity for selenate and selenite, while sulfate exhibited a strong competition for both oxyanions. The FGD wastewater investigated is a complex system that contains Se (∼1200 µg L-1), SO42- (∼1.1 g L-1), Cl- (∼9.5 g L-1), and Ca2+ (∼5 g L-1), alongside a broad spectrum of toxic trace metals including Cd, Cr, Hg, Ni, and Zn. The resin performed poorly against Se in the raw FGD wastewater and showed moderate to good removal of several trace elements such as Cd, Cr, Hg, and Zn. In FGD effluent, sulfate was identified as a powerful competing anion for Se, having high affinity for the exchange active sites of the resin. The desulfurization of the FGD effluent using BaCl2 led to the increase in Se removal from 3% (non-desulfurized effluent) to 80% (desulfurized effluent) by combined precipitation and ion exchange treatment. However, complete desulfurization using equimolar BaCl2 could not be achieved due to the presence of bicarbonate that acts as a sulfate competitor for barium. In addition to selenium and sulfate removal, several toxic metals were efficiently removed (Cd: 91%; Cr: 100%; Zn: 99%) by the combined (desulfurization and ion exchange) treatment.

Microwave-assisted synthesis, structure and anti-tumor activity of selenized Artemisia sphaerocephala polysaccharide.

In this work, selenylation of Artemisia sphaerocephala polysaccharide (SeASPMW) was studied by using H2SeO3/HNO3/BaCl2 reaction system in microwave field. SeASPMW exhibited the Se content range of 111-264µg/g with high yields (72.1-94.9%). 13C NMR results indicated that the weak C-6 substitution was occurred. The decrease (from 7.348×104g/mol to 1.736-4.667×104g/mol) in weight average molecular mass (MW) of SeASPMW was observed in size exclusion chromatography combined with multi angle laser light scattering (SEC-MALLS) analysis. SeASPMW exhibited a more rigid solution conformation which might be due to the degradation of polysaccharide chains in acidic reaction reagent. This was also supported by atomic force microscopy (AFM) result that SeASPMW showed short chains and island-like topography. In anti-tumor activity assays, SeASPMW6 exhibited the inhibition rates of 32.381% and 39.776% against human non-small cell lung cancer cell line (H1650) at the concentration of 100 and 200µg/mL, respectively. The relatively weak inhibition effect of SeASPMW was not related to cell apoptosis and cell cycle arrest, suggesting Se content might be a key factor to influence the anti-tumor activities of selenized polysaccharides in vitro.

Protective effects of dietary selenium and vitamin C in barium-induced cardiotoxicity.

Several metals including barium (Ba) known as environmental pollutants provoke deleterious effects on human health. The present work pertains to the potential ability of selenium (Se) and/or vitamin C, used as nutritional supplements, to alleviate the toxic effects induced by barium chloride (BaCl2) in the heart of adult rats. Animals were randomly divided into seven groups of six each: group 1, serving as negative controls, received distilled water; group 2 received in their drinking water BaCl2 (67 ppm); group 3 received both Ba and Se (sodium selenite 0.5 mg kg-1 of diet); group 4 received both Ba and vitamin C (200 mg kg-1 bodyweight) via force feeding; group 5 received Ba, Se, and vitamin C; and groups 6 and 7, serving as positive controls, received either Se or vitamin C for 21 days. The exposure of rats to BaCl2 caused cardiotoxicity as monitored by an increase in malondialdehyde, hydrogen peroxide, and advanced oxidation protein product levels, a decrease in Na+-K+ adenosine triphosphatase (ATPase), Mg2+ ATPase, and acetylcholinesterase activities and in antioxidant defense system (catalase, glutathione peroxidase, superoxide dismutase, glutathione, and nonprotein thiols). Plasma lactate dehydrogenase and creatine kinase activities, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels increased, while high-density lipoprotein-cholesterol level decreased. Coadministration of Se and/or vitamin C restored the parameters indicated above to near control values. The histopathological findings confirmed the biochemical results. Se and vitamin C may be a promising therapeutic strategy for Ba-induced heart injury.

Synthesis and Structure-Activity Relationships of a Series of Aporphine Derivatives with Antiarrhythmic Activities and Acute Toxicity.

Some aporphine alkaloids, such as crebanine, were found to present arrhythmic activity and also higher toxicity. A series of derivatives were synthesized by using three kinds of aporphine alkaloids (crebanine, isocorydine, and stephanine) as lead compounds. Chemical methods, including ring-opening reaction, bromination, methylation, acetylation, quaternization, and dehydrogenation, were adopted. Nineteen target derivatives were evaluated for their antiarrhythmic potential in the mouse model of ventricular fibrillation (VF), induced by CHCl3, and five of the derivatives were investigated further in the rat model of arrhythmia, induced by BaCl2. Meanwhile, preliminary structure-activity/toxicity relationship analyses were carried out. Significantly, N-acetamidesecocrebanine (1d), three bromo-substituted products of crebanine (2a, 2b, 2c), N-methylcrebanine (2d), and dehydrostephanine (4a) displayed antiarrhythmic effects in the CHCl3-induced model. Among them, 7.5 mg/kg of 2b was able to significantly reduce the incidence of VF induced by CHCl3 (p < 0.05), increase the number of rats that resumed sinus rhythm from arrhythmia, induced by BaCl2 (p < 0.01), and the number of rats that maintained sinus rhythm for more than 20 min (p < 0.01). Therefore, 2b showed remarkably higher antiarrhythmic activity and a lower toxicity (LD50 = 59.62 mg/kg, mice), simultaneously, indicating that 2b could be considered as a promising candidate in the treatment of arrhythmia. Structural-activity analysis suggested that variationsin antiarrhythmic efficacy and toxicity of aporphines were related to the C-1,C-2-methylenedioxy group on ring A, restricted ring B structural conformation, N-quaternization of ring B, levoduction of 6a in ring C, and the 8-, 9-, 10-methoxy groups on ring D on the skeleton.

The role of the defaecating pouchogram in the assessment of evacuation difficulty after restorative proctocolectomy and pouch-anal anastomosis.

AIM: Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) is the most frequently performed operation for intractable ulcerative colitis (UC) and for many patients with familial adenomatous polyposis (FAP). It can be complicated by a functional evacuation difficulty, which is not well understood. We aimed to evaluate the role of defaecating pouchography in an attempt to assess the mechanism of evacuation difficulty in pouch patients. METHOD: All RPC patients who had had a defaecating pouchogram for evacuation difficulty at one hospital between 2006 and 2014 were retrospectively reviewed. The findings and features were correlated with the symptoms. Demographic, clinical and radiological variables were analysed. RESULTS: Eighty-seven [55 (63%) female] patients aged 47.6 ± 12.5 years (mean standard ± SD) were identified. Thirty-five had a mechanical outlet obstruction and 52 had no identified mechanical cause to explain the evacuation difficulty. The mean age of these 52 [33 (63%) female] patients was 48.2 ± 13 years. Of these 52 patients, significantly more used anti-diarrhoeal medication (P = 0.029), complained of a high frequency of defaecation (P = 0.005), experienced a longer time to the initiation of defaecation (P = 0.049) and underwent pouchoscopy (P = 0.003). Biofeedback appeared to improve the symptoms in 7 of 16 patients with a nonmechanical defaecatory difficulty. The most common findings on defaecating pouchography included residual barium of more than 33% after an attempted evacuation (46%, n = 24), slow evacuation (35%, n = 18) and mucosal irregularity (33%, n = 17). Correlation between radiological features and symptoms showed a statistically significant relationship between straining, anal pain, incontinence and urgency with patterns of anismus or pelvic floor descent or weakness seen on the defaecating pouchogram. Symptoms of incomplete evacuation, difficulty in the initiation of defaecation, high defaecatory frequency and abdominal pain were not correlated with the radiological features of the pouchogram. CONCLUSION: Defaecating pouchography may be useful for identifying anismus and pelvic floor disorders in pouch patients who have symptoms of straining, anal pain or incontinence. In patients with a high frequency of defaecation and abdominal pain it does not provide clinically meaningful information. Patients who complain of straining, incontinence, anal pain or urgency and have anismus or pelvic floor disorders may benefit from behavioural therapy.

Protective effects of pomegranate peel against hematotoxicity, chromosomal aberrations, and genotoxicity induced by barium chloride in adult rats.

CONTEXT: Pomegranate peel (PP) has health benefits including antibacterial, antioxidant, anti-inflammatory, and antimutagenic properties. OBJECTIVE: This study investigated the biochemical composition and protective effects of PP against hematotoxicity and genotoxicity induced by barium chloride (BaCl2) in adult rats. MATERIALS AND METHODS: Adult Wistar rats were divided into four groups of six each: control, barium (67 ppm via drinking water), PP (5% via diet), and their combination during 21 d. Oxidative stress was determined by MDA, AOPP, and antioxidant status: CAT, GPx, GSH, Vit C. Osmotic fragility (OF), chromosomal aberrations (CAs), and micronucleus (MN) assays were also studied. RESULTS: PP showed a rich composition of antioxidant compounds. DPPH test found IC50 value= 5.3 µg/mL and a high polysaccharides content (315 ± 5 mg/g of extract). In vivo study showed a decrease in red blood cells (70%) and platelet counts (46%), hemoglobin content (8%), hematocrit percent (7%), and an 80% increase of white blood cells in Ba-treated rats. A reduction in antioxidant status: catalase, glutathione peroxidase activities, glutathione, and vitamin C levels by 31, 21, 28, and 29%, respectively, and an increase in MDA (46%) and AOPP levels (72%) were also observed compared with controls. BaCl2-treatment showed a significant increase in the frequencies of total chromosomal aberrations with abnormal metaphases and micronucleus in bone-marrow cells. Oxidative stress induced by BaCl2 might be the major cause for chromosomal abnormalities leading to DNA damage. DISCUSSION AND CONCLUSION: A decrease in hematotoxic and genotoxic effects induced by PP is due to its powerful antioxidant capacity.

Improvement of kidney redox states contributes to the beneficial effects of dietary pomegranate peel against barium chloride-induced nephrotoxicity in adult rats.

CONTEXT: Pomegranate (Punica granatum L., Punicaceae) is known to possess enormous antioxidant activity. OBJECTIVE: This study investigates the protective effects of pomegranate peel against barium-mediated renal damage. MATERIALS AND METHODS: Rats were exposed during 21 days either to barium (67 ppm), barium + pomegranate peel (5% of diet) or to only pomegranate peel (5% of diet). RESULTS: Exposure rats to barium provoked a significant increase in kidney malondialdehyde (MDA), advanced oxidation protein products (AOPP) and hydrogen peroxide (H2O2) levels. Creatinine, urea and uric acid levels in plasma and urine were also modified. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, non protein thiol (NPSH) and reduced glutathione (GSH) levels were decreased. Metallothionein (MT) production was increased and their genes expressions were up-regulated. All these changes were improved by dietary pomegranate peel. Moreover, the distorted histoarchitecture in kidney of barium group was alleviated by pomegranate peel. CONCLUSION: Our data showed, for the first time, the protective effects of pomegranate peel against barium-induced renal oxidative damage.