Cholinoceptor Activation Subserving the Effects of Interferon Gamma on the Contractility of Rat Ileum

Recombinant rat interferon γ stimulated the contractility of isolated rat ileum at doses of 4–12 units/ml. Muscarinic cholinoceptors were involved, as treatment of the tissue with atropine prevented the contractile response of the ileum. Furthermore, interferon γ increased the affinity of carbachol for the cholinoceptors and did not change its maximum effect. Neurogenic pathways were also involved since pretreatment of ileum with hexamethonium, hemicholinium or tetrodotoxin impaired the contractile effect of interferon γ. In contrast to the action of exogenous carbachol, the effects of interferon γ are indirect. They appear to involve a G protein regulating phosphoinositide turnover and cytoskeletal structures since they could not be induced in ileum strips that were pretreated with pertussis toxin, phospholipase C inhibitors (2-nitro-carboxyphenyl, NN-diphenyl carbamate and neomycin), cytochalasine B or colchicine

Cytokine Combination Therapy with Erythropoietin and Granulocyte Colony Stimulating Factor in a Porcine Model of Acute Myocardial Infarction

PurposeErythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) have generated interest as novel therapies after myocardial infarction (MI), but the effect of combination therapy has not been studied in the large animal model. We investigated the impact of prolonged combination therapy with EPO and GCSF on cardiac function, infarct size, and vascular density after MI in a porcine model.MethodsMI was induced in pigs by a 90 min balloon occlusion of the left anterior descending coronary artery. 16 animals were treated with EPO+GCSF, or saline (control group). Cardiac function was assessed by echocardiography and pressure-volume measurements at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI.ResultsAt week 6, EPO+GCSF therapy stabilized left ventricular ejection fraction, (41 ± 1% vs. 33 ± 1%, p < 0.01) and improved diastolic function compared to the control group. Histopathology revealed increased areas of viable myocardium and vascular density in the EPO+GCSF therapy, compared to the control. Despite these encouraging results, in a historical analysis comparing combination therapy with monotherapy with EPO or GCSF, there were no significant additive benefits in the LVEF and volumes overtime using the combination therapy.ConclusionOur findings indicate that EPO+GCSF combination therapy promotes stabilization of cardiac function after acute MI. However, combination therapy does not seem to be superior to monotherapy with either EPO or GCSF

Perspectives on the Trypanosoma cruzi-host cell receptor interaction

Chagas disease is caused by the parasite Trypanosoma cruzi. The critical initial event is the interaction of the trypomastigote form of the parasite with host receptors. This review highlights recent observations concerning these interactions. Some of the key receptors considered are those for thromboxane, bradykinin, and for the nerve growth factor TrKA. Other important receptors such as galectin-3, thrombospondin, and laminin are also discussed. Investigation into the molecular biology and cell biology of host receptors for T. cruzi may provide novel therapeutic targets

Autoantibodies against Submandibular Gland Muscarinic Cholinoceptor Subtypes in Primary Sjögren Syndrome

Sjögren Syndrome (SS) is a chronic autoimmune disease characterized by parasympathetic exocrine gland dysfunction. Here, the involvement of submandibular gland muscarinic acetylcholine receptor (mAChR) M 4 subtype is proposed as an IgG target together with M 1 and M 3 mAChR subtypes. The Kd values were total membranes 0.20 ± 0.017 nM; acini membranes 0.33 ± 0.023 nM and duct membranes 0.22 ± 0.040 nM and Bmax values were total, 1038 ± 24, acini, 1359 ± 28 and ducts, 593 ± 30. The rank order of Bmax was: acini > total > ducts, indicating that acini express the highest number of binding sites. The specific mAChR antagonists (4-DAMP [M 3 ], tropicamide [M 4 ], pirenzepine [M 1 ]) and the corresponding synthetic peptides impaired IgG-mAChR subtype interactions. The specificity of these reactions was assessed by the corresponding affinity-purified anti peptide antibodies recognizing M 4 , M 3 and M 1 mAChR. These data concerning autoantibodies contribute to explain the pathogenesis of SS and also represent a new clinical marker for SS diagnosis