Clinico-toxinological characterization of the acute effects of the venom of the marine snail, Conus loroisii

The venom of the marine snail, Conus loroisii, was studied to assess its risk and lethal factors in regard of human welfare. The lethality of the crude venom (LD50-5.0 mg/kg via i.p.) in mice was associated with reduced motor activity, asphyxiation, followed by respiratory failure. The effects on vital tissues revealed vascular congestion and inflammatory cell infiltration around the portal triad of the liver, spongiosis of the brain, hemorrhages/congested blood vessels in lung and endothelial cells of the renal tubule. Repeated measures of hematological profiles indicated that the venom significantly reduced erythrocytes (P<0.001, GLM repeated measures), followed associated with depletion of hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and platelet count. Serum enzymes such as, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase and alkaline and acid phosphatases were altered significantly (P<0.05, Friedman test), which in turn confirmed the damage of vital organ tissues. Dual effect of the venom on the activity of mouse brain acetylcholinesterase stand for concentration specific, whereas maximal inhibition (60.41%, P<0.05, Wilcoxon signed rank test) in erythrocyte acetylcholinesterase did not show the dual activity observed in brain. The Ciphergen ProteinChip analysis of the envenomed serum further revealed that the venom causes changes in definite molecules involved in inflammatory process and ionic transport. In all, the venom of C. loroisii is potentially lethal to mammals, through its rapid action on the central and peripheral nervous systems by blocking neurotransmission with selective interference of ionic channels/receptors.     

The effects of botulinum neurotoxin A induced muscle paresis during a critical period upon muscle and spinal cord development in the rat

The second postnatal week is a critical period in rat motor development. The expansion of corticospinal innervation coincides with elimination of polyneuronal innervation of muscles, onset of quadrupedal locomotion and refinement of muscle afferent input to the ventral horn. Such developmental events are believed to be activity-dependent. In the present study, muscle afferent activity was temporarily reduced by injecting distal forelimb muscles with botulinum toxin A (BTX). Injections of toxin or saline were made unilaterally on postnatal day (P) 7 which in BTX-treated animals lead to a profound loss of movement in the affected limb over the next week before function returned. The neural tracer cholera toxin B (CTB) was injected into the extensor digitorum communis (EDC) at either P14 or P28. Allowing 3 days for tracer transport, the spinal cords were sectioned and immunostained for CTB and cJun. In separate experiments, behavioural testing of the forelimb was carried out between P35 and P49. Then, sections of EDC muscle were immunostained for slow myosin. An increased density of ventral horn muscle afferent boutons was observed at P17 in BTX-treated animals compared to controls, however, by P31, this difference was not significant. However, CTB labelling also revealed significantly increased motor axon terminals in the ventral Renshaw cell region in BTX-treated animals at P31, accompanied by raised expression of cJun in ipsilateral motoneurones. BTX-treated animals showed deficits in ladder walking, and their muscles contained a higher density and significantly more clustering of slow myosin expressing muscle fibres than controls. Temporary reduction in activity did not significantly alter muscle afferent development, but temporary blockade of neuromuscular junctions did affect both muscle and motor axon, in the longer term.     

Ketanserin and Granisetron Reduce Cholera Toxin-Induced Hypersecretion in Pig Jejunum

Hansen MB, Skadhauge E. Ketanserin and granisetron reduce cholera toxin-induced hypersecretion in pig jejunum. Scand J Gastroenterol 1994;29:908-915.

Background: Serotonin antagonists have been proven antisecretory in cholera toxin (CT)-induced hypersecretion in the small intestine of rodents. The pig small intestine is a good model for the human small intestine with regard to physiologic and pharmacologic processes. Methods: The antisecretory effect of intraluminally administered methysergide, renzapride, ketanserin, granisetron, and tropisetron on CT-induced hypersecretion was tested in isolated pig jejunal loops in vivo. Results: Methysergide, ketanserin. and granisetron reduced the hypersecretory effect of CT maximally by 25%, 80%, and 50%, respectively. Tropisetron enhanced whereas renzapride did not alter the CT response. Combination of ketanserin and granisetron gave a maximal inhibitory effect of about 85%. Surprisingly, renzapride, granisetron, and tropisetron each induced hypersecretion. Taking into account the hypersecretory effect of the antagonists, they all reduced this CT-elicited hypersecretion. Conclusions: Results suggest involvement of the 5-hydroxytryptamine-2 and 5-hydroxytryptamine-3 receptor subtypes as mediators in CT-induced hypersecretion in pig jejunum, and antidianheal therapeutic potentials of ketanserin and granisetron.     

Bovine lymphocytes express functional receptors for Escherichia coli Shiga toxin 1

Interactions of Shiga toxins (Stxs) and immune cells contribute to the pathogenesis of diseases due to Stx-producing Escherichia coli (STEC) infections in humans and facilitate the persistence of infection in asymptomatically infected cattle. Our recent findings that bovine B and T lymphocytes express Gb(3)/CD77, the human Stx-receptor, prompted us to determine whether the bovine homologue also mediates binding and internalization of Stx1. In fact, Stx1 holotoxin and recombinant B subunit (rStxB1) bound to stimulated bovine peripheral blood mononuclear cells, especially to those subpopulations (B cells, BoCD8(+) T cells) that are highly sensitive to Stx1. Competition and HPTLC-binding studies confirmed that Stx1 binds to bovine Gb(3), but different receptor isoforms with varying affinities for rStxB1 were expressed during the course of lymphocyte activation. At least one of these isoforms mediated toxin uptake. An anti-StxB1 mouse monoclonal antibody, used as a model for bovine serum antibodies specific for Stx1, modulated rather than generally prevented rStxB1 binding to and internalization by the receptors. The presence of functional Stx1-receptors on bovine lymphocytes explains the immunomodulatory effect of Stx1 observed in cattle at a molecular level. Furthermore, expression of such receptors by bovine but not human T cells enlightens the background for the differential outcome of STEC infections in cattle and man, i.e., persistent infection and development of disease, respectively.     

探析红斑狼疮使用GCS不同阶段的辨证施治

系统性红斑狼疮(systemic lupus erythematosus,SLE)是自身免疫机制介导的,以血清中出现多种自身抗体和多器官、多系统累及为主要临床特征的弥漫性结缔组织病。目前现代医学治疗SLE以糖皮质激素(Glucocorticoid,GCS)为主。中医认为,GCS性属纯阳,长期大量使用多致伤阴耗气。在SLE使用GCS的首始阶段,患者多为热毒炽盛证,以清热解毒为主要方法,阴虚内热者以滋阴清热为法,瘀热闭阻证则用祛瘀解毒法;撤减阶段,患者多为气阴两虚,治以益气养阴为主;GCS维持量阶段,患者多为脾肾阳虚,当从温肾补脾论治,同时,视血瘀、热毒之轻重,分别予以兼顾。SLE使用GCS各个治疗阶段,要根据SLE病机发展变化的不同,辨证选用不同中药同病异治,以期取得增效解毒的临床效果。     

Potential value of repeat stool testing for Clostridium difficile stool toxin using enzyme immunoassay?

Abstract

Objective:

The aim of this brief review is to summarize the literature as it relates to the potential value of repeat stool testing for Clostridium difficile (C. difficile) toxin using an enzyme immunoassay (EIA) for toxin A&B and also propose a potential newer algorithm for diagnosing C. difficile.     

Antinociceptive activity and pathway of the pallanalgesin isolated from venom of Agkistrodon halys (Pallas)

Abstract

Context: Venom of Agkstrodon halys (Pallas) is a traditional Chinese medicine for the control of severe pain, but its analgesic mechanism is not clear.

Objective: To isolate the analgesic fraction from the venom, evaluate the profile of its action on pain using preclinical nociceptive tests and determine the involvement of neurotransmitters in its action.

Materials and methods: Venom was separated with SPXL resin, and further purified by Superdex 75 and Superdex 30 resin. Its biochemical characteristics were analyzed including molecular weight (MW), isoelectric point (pI) and amino acid sequence. Animal pain models were applied including the hot plate test, acetic acid-induced writhing test, formalin test, Randall–Selitto pressure test, antagonistic test, spinalized rats test and intracerebral injection test. The endogenous neuropeptides leucine-enkephalin, β-endorphin and P substance were determined by HPLC in the tissues of brain and spinal cord.

Results: An analgesic protein named pallanalgesin (MW 16.6?kDa, pI 8.8) was obtained from the venom of A. halys. It had significant antinociceptive activity in different animal pain models of thermal, chemical and mechanical stimulation. It effects both central and peripheral nerve systems, and it is related to opiate receptors and monoamines rather than acetylcholine receptors. Pallanalgesin could modulate the levels of neuropeptides in the brain and spinal cord, which contributes to the recovery of nerve injury and pain control.

Conclusion: As a novel analgesic, pallanalgesin has been found to explain the function of the venom of A. halys on severe pain control in traditional uses, and can be used as a new analgesic in the future.     

Botulinum toxin A for the treatment of cervical dystonia

Idiopathic cervical dystonia (ICD) is the most common adult-onset focal dystonia. It is characterised by relatively sustained, involuntary contractions of neck muscles. Injections of botulinum toxin (BTX)-A are safe and effective for the treatment of ICD, and have substantially improved its treatment. BTX-A is manufactured by Allergan Pharmaceuticals in the US and Ireland, and is distributed as Botox^®. In Europe, BTX-A is manufactured and distributed by Ipsen Pharmaceuticals as Dysport^®. Success rates for BTX-A injections for ICD ranges 64 – 90%, with 76 – 93% of injected patients experiencing pain reduction. Side effects are generally mild and include dysphagia and neck weakness.