Venoms

Venoms of several animals have been used to study various physiopathologic processes, and also to offer
opportunity to design and develop new therapeutic drugs. We briefly review certain wasp venom components and their
biological effects, which may be potential sources of novel pharmacologically active compounds

Toxinology in Brazil developed specially during the 19th and 20th centuries. A very brief description of the main contributions made by pioneer toxinologists is presented here in an attempt to give an idea of the evolution of toxinology in our country, from its first steps until the XVI World Congress of the International Society on Toxinology, held in Recife, Brazil

Bufalin is the major component of Chan-Su (a traditional Chinese medicine, TCM) extracts from the venom of Bufo bufo gargarizan. In the present study, we investigated the pharmacological mechanisms of cell cycle arrest and autophagic cell death induced by bufalin in SK-HEP-1 human hepatocellular carcinoma cells in vitro. Bufalin inhibited cell survival by MTT assay and increased cell death by trypan blue exclusion assay in a concentration-dependent manner. In addition, bufalin induced G2/M phase arrest by reducing CDK1 activity. Bufalin triggered DNA fragmentation and apoptotic cell death in SK-HEP-1 cells by DNA gel electrophoresis, TUNEL and caspase-3 activity assay, while bufalin induced autophagic cell death by double-membrane vacuoles (transmission electron microscopy, TEM), acidic vesicular organelles (acridine orange staining) and cleavage of microtubule-associated protein 1 light chain 3 (LC3). Protein expression levels of cyclin A and B, CDK1, phospho-CDK1 (Thr161), Cdc25c,...

Nach Behandlung des Sartoriusmuskels von Rana temporaria mit Bu TX wurden die Endplattenpotentiale durch Tubocurarin und Atropin mit unveränderter Wirksamkeit blockiert. Bungarotoxin stabilisiert das Umkehrpotential der Endplatte, welches nachher durch eine Verminderung der äusseren Konzentration von K+ oder durch Atropin nicht mehr verändert werden kann.

Human envenomations by Heloderma species are a rare but clinically important medical problem. We report a case of an adult male bitten on the left hand by a 50-cm male, captive specimen of Heloderma suspectum (Gila monster). Immediate signs and symptoms included pain at the bite site radiating into the arm and axilla and swelling of the hand and forearm. Systemic complaints of nausea, diaphoresis, and dizziness (without a decrease in blood pressure) lasted approximately 1 hour, and laboratory studies were normal. The patient's course was uneventful except for persistent hyperesthesia, which eventually abated. Two types of helodermatid bites produce distinct clinical pictures. The chewing bite potentially causes more envenomation than the slashing bite. The venom contains a number of protein and nonprotein components including serotonin, a bradykinin-releasing substance, protease, hyaluronidase, helodermin, and gilatoxin. The clinical presentation of a helodermatid bite can inclu...

We have developed a unique long-acting drug-delivery system for the GLP-1 agonist exenatide. The peptide was covalently attached to Tetra-PEG hydrogel microspheres by a cleavable β-eliminative linker; upon s.c. injection, the exenatide is slowly released at a rate dictated by the linker. A second β-eliminative linker with a slower cleavage rate was incorporated in polymer crosslinks to trigger gel degradation after drug release. The uniform 40 micron microspheres were fabricated using a flow-focusing microfluidic device and in situ polymerization within droplets. The exenatide-laden microspheres were injected subcutaneously into the rat, and serum exenatide measured over a one-month period. Pharmacokinetic analysis showed a t1/2,β of released exenatide of about seven days which represents over a 300-fold half-life extension in the rat and exceeds the half-life of any currently approved long-acting GLP-1 agonist. Hydrogel-exenatide conjugates gave an excellent Level A in vitro-in viv...

Exenatide is the first glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes mellitus (T2DM). Exenatide lowers blood glucose through multiple mechanisms, including enhancement of glucose-dependent insulin secretion, suppression of excess glucagon secretion, reduction of food intake and slowing of gastric emptying. The current formulation of exenatide requires twice-daily dosing (exenatide BID), and an extended-release formulation of exenatide is now in development for use as a once-weekly injection (exenatide QW). The purpose of this report is to review the most current clinical data on the development of exenatide QW for the treatment of T2DM. In clinical trials, exenatide QW significantly improved glycemic control, resulted in patient weight loss, and was well tolerated in patients with T2DM. In a head-to-head clinical trial, exenatide QW caused greater improvements in glycemic control and was better tolerated than exenatide BID. Given the rapidly increasing prevalence of diabetes and obesity worldwide, exenatide QW is a promising development candidate for the treatment of T2DM.

Introduction Glucagon-like peptide-1 (GLP-1) is produced and secreted from L-cells, an open-type intestinal epithelial endocrine cell, following the entry of nutrients in the gut lumen. GLP-1 is a member of the incretin family and as such, upon its binding to the GLP-1 receptor expressed at the surface of pancreatic cells, potentiates glucosedependent insulin secretion from pancreatic islet 1 . Several studies have demonstrated that GLP-1 secretion and action are reduced in T2DM and Vilsbøll et al. demonstrated that infusion of GLP-1 at supraphysiological doses in T2DM patients restored insulin levels comparable to non-diabetic controls. 2-4 However, the rapid inactivation of native GLP-1 by the dipeptidyl Significant findings of the study: Treatment with GLP-1Ra was not associated with any modifications in the occurrence of bone fractures in type 2 diabetes mellitus.

Glucagon-like peptide-1 (GLP-1) has shown to influence the oxidative stress status in a number of in vitro, in vivo and clinical studies. Well-known effects of GLP-1 including better glycemic control, decreased food intake, increased insulin release and increased insulin sensitivity may indirectly contribute to this phenomenon, but glucose-independent effects on ROS level, production and antioxidant capacity have been suggested to also play a role. The potential 'antioxidant' activity of GLP-1 along with other proposed glucose-independent modes of action related to ameliorating redox imbalance remains a controversial topic but could hold a therapeutic potential against micro- and macrovascular diabetic complications. This review discusses the presently available knowledge from experimental and clinical studies on the effects of GLP-1 on oxidative stress in diabetes and diabetes-related complications.