Toxins2015, 7(8), 2860-2871; doi:10.3390/toxins7082860 (registering DOI) - published 30 July 2015 Show/Hide Abstract
Abstract: Although intravesical injection of onabotulinumtoxinA (BoNT-A) has been proved promising in treating patients with interstitial cystitis/bladder pain syndrome (IC/BPS), what kind of patients that may benefit from this treatment remains unclear. This study investigated the predictors for a successful treatment outcome. Patients with IC/BPS who failed conventional treatments were enrolled to receive intravesical injection of 100 U of BoNT-A immediately followed by hydrodistention. Variables such as O’Leary-Sant symptom and problem indexes (ICSI and ICPI), pain visual analogue scale (VAS), functional bladder capacity (FBC), voiding diary, and urodynamic parameters were measured at baseline and six months after treatment. A global response assessment (GRA) ≥ 2 at six months was defined as successful. There were101 patients enrolled. Significant improvements were observed in mean ICSI, ICPI, OSS (ICSI + ICPI), pain VAS, FBC, frequency, nocturia and GRA at six months after BoNT-A injections (all p < 0.05). The successful rate at six months was 46/101 (45.54%). Multivariate logistic regression revealed the baseline ICSI (odds ratio = 0.770, 95% confidence interval = 0.601–0.989) was the only predictor for a treatment outcome. ICSI ≥ 12 was the most predictive cutoff value for a treatment failure, with a ROC area of 0.70 (sensitivity = 69.1%, specificity = 60.9%).
Abstract: Deoxynivalenol (DON, vomitoxin), a common trichothecene mycotoxin found in cereal foods, dysregulates immune function and maintenance of energy balance. The purpose of this study was to determine if sex differences are similarly evident in DON’s anorectic responses in mice. A bioassay for feed refusal, previously developed by our lab, was used to compare acute i.p. exposures of 1 and 5 mg/kg bw DON in C57BL6 mice. Greater anorectic responses were seen in male than female mice. Male mice had higher organ and plasma concentrations of DON upon acute exposure than their female counterparts. A significant increase in IL-6 plasma levels was also observed in males while cholecystokinin response was higher in females. When effects of sex on food intake and body weight changes were compared after subchronic dietary exposure to 1, 2.5, and 10 ppm DON, males were found again to be more sensitive. Demonstration of male predilection to DON-induced changes in food intake and weight gain might an important consideration in future risk assessment of DON and other trichothecenes.
Abstract: Amyotrophic lateral sclerosis (ALS) includes progressively degenerated motor neurons in the brainstem, motor cortex, and spinal cord. Recent reports demonstrate the dysfunction of multiple organs, including the lungs, spleen, and liver, in ALS animals and patients. Bee venom acupuncture (BVA) has been used for treating inflammatory diseases in Oriental Medicine. In a previous study, we demonstrated that BV prevented motor neuron death and increased anti-inflammation in the spinal cord of symptomatic hSOD1G93A transgenic mice. In this study, we examined whether BVA’s effects depend on acupuncture point (ST36) in the organs, including the liver, spleen and kidney, of hSOD1G93A transgenic mice. We found that BV treatment at ST36 reduces inflammation in the liver, spleen, and kidney compared with saline-treatment at ST36 and BV injected intraperitoneally in symptomatic hSOD1G93A transgenic mice. Those findings suggest that BV treatment combined with acupuncture stimulation is more effective at reducing inflammation and increasing immune responses compared with only BV treatment, at least in an ALS animal model.
Abstract: The natural phosphoprotein phosphatase inhibitor cantharidin, primarily used for topical treatment of warts, has later been shown to trigger tumor cell apoptosis and is thus considered for the treatment of malignancy. Similar to apoptosis of tumor cells, erythrocytes may undergo eryptosis, a suicidal cell death characterized by cell shrinkage and translocation of cell membrane phosphatidylserine to the erythrocyte surface. Signaling of eryptosis includes increase of cytosolic Ca2+-activity ([Ca2+]i), ceramide, oxidative stress and dysregulation of several kinases. Phosphatidylserine abundance at the erythrocyte surface was quantified utilizing annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ceramide from antibody binding, and reactive oxidant species (ROS) from 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence. A 48 h treatment of human erythrocytes with cantharidin significantly increased the percentage of annexin-V-binding cells (≥10 mg/mL), significantly decreased forward scatter (≥25 mg/mL), significantly increased [Ca2+]i (≥25 mg/mL), but did not significantly modify ceramide abundance or ROS. The up-regulation of annexin-V-binding following cantharidin treatment was not significantly blunted by removal of extracellular Ca2+ but was abolished by kinase inhibitor staurosporine (1 mM) and slightly decreased by p38 inhibitor skepinone (2 mM). Exposure of erythrocytes to cantharidin triggers suicidal erythrocyte death with erythrocyte shrinkage and erythrocyte membrane scrambling, an effect sensitive to kinase inhibitors staurosporine and skepinone.
Abstract: Consumption of feedstuffs contaminated with ergot alkaloids has a broad impact on many different physiological mechanisms that alters the homeostasis of livestock. This change in homeostasis causes an increased sensitivity in livestock to perturbations in the ambient environment, resulting in an increased sensitivity to such stressors. This ultimately results in large financial losses in the form of production losses to livestock producers around the world. This review will focus on the underlying physiological mechanisms that are affected by ergot alkaloids that lead to decreases in livestock production.
Abstract: This article reviews the diagnoses and treatment of temporomandibular disorders (TMD) and outlines of the role of botulinum toxin (BoNT) in the treatment of myofacial TMD. This manuscript includes a brief history of the use of BoNT in the treatment of pain, the mechanism of action of BoNT, and the techniques for injections, adverse effects and contraindications when using BoNT to treat mayofacial pain caused by TMD.