The vagal involvement in the antiarrhythmic and arrhythmogenic effects of prostaglandin F2 alpha on ouabain-induced cardiac arrhythmias in cats

The effects of prostaglandin F2 alpha (PGF2 alpha) on ouabain-induced cardiac arrhythmias were investigated in chloralose-anaesthetized cats. Bilateral vagotomy and atropine intervention were employed to elucidate the involvement of vagal neural influences. PGF2 alpha (2-16 micrograms/kg i.v. bolus) predominantly suppressed the ouabain-induced ventricular and supraventricular arrhythmias and less commonly aggravated them in vagi-intact cats. The antiarrhythmic effect of PGF2 alpha was considerably, but not statistically significantly, decreased while its arrhythmogenic effect was significantly (p less than 0.05) increased in atropine-pretreated group. In vagotomised group PGF2 alpha failed to abolish the arrhythmias but it aggravated them to a degree comparable to that observed in vagi-intact group. It is concluded that the PGF2 alpha exhibits both antiarrhythmic and arrhythmogenic properties and these are largely due to elicitation of two opposing neural reflexes - one being protective and another being deleterious to ouabain-induced arrhythmias.     

Annexin A2 Is a Molecular Target for TM601, a Peptide with Tumor-targeting and Anti-angiogenic Effects

TM601 is a synthetic form of chlorotoxin, a 36-amino acid peptide derived from the venom of the Israeli scorpion, Leirius quinquestriatus, initially found to specifically bind and inhibit the migration of glioma cells in culture. Subsequent studies demonstrated specific in vitro binding to additional tumor cell lines. Recently, we demonstrated that proliferating human vascular endothelial cells are the only normal cell line tested that exhibits specific binding to TM601. Here, we identify annexin A2 as a novel binding partner for TM601 in multiple human tumor cell lines and human umbilical vein endothelial cell (HUVEC). We demonstrate that the surface binding of TM601 to the pancreatic tumor cell line Panc-1 is dependent on the expression of annexin A2. Identification of annexin A2 as a binding partner for TM601 is also consistent with the anti-angiogenic effects of TM601. Annexin A2 functions in angiogenesis by binding to tissue plasminogen activator and regulating plasminogen activation on vascular endothelial cells. We demonstrate that in HUVECs, TM601 inhibits both vascular endothelial growth factor- and basic fibroblast growth factor-induced tissue plasminogen activator activation, which is required for activation of plasminogen to plasmin. Consistent with inhibition of cell surface protease activity, TM601 also inhibits platelet-derived growth factor-C induced trans-well migration of both HUVEC and U373-MG glioma cells.     

Pyrrolines as Prodrugs of γ-Aminobutyric Acid Analogues

Abstract: Δ'-Pyrroline, S-methyl-Δ'-pyrroline, and 5.5-dimethyl-Δ'-pyrroline have been identified as substances metabolized to γ-aminobutyric acid (GABA), 4-aminopentanoic acid (raethyl GABA), and 4-amino-4-methylpen-tanoic acid (dimethyl GABA), respectively. An enzyme system residing in the soluble fraction of rabbit liver catalyzes the conversion of Δ'-pyrroline to GABA and its lactam, 2-pyrrolidinone. Acetaldehyde, allopurinol, and cyanide inhibited the reaction. Incubation of deuterium-labeled Δ'-pyrroline with mouse brain homogenates produced deuterated GABA. Mouse liver 10,000 g supernatant and mouse brain homogenates converted S-methyl-Δ'-pyrroline to methyl GABA, and 5,5-dimethyl-Δ'-pyrroline to dimethyl GABA. Four hours after intraperitoneal injection of 5-methyl-Δ'-pyrroline (200 mg/kg), methyl GABA was detected in mouse brain (0.27 μ-mol/g). Dimethyl GABA (1.21 μmol/g) was determined in mouse brain 30 min after intraperitoneal administration of 5.5-dimethyl-Δ'-pyrroline (200 mg/kg). Neither methyl GABA nor dimethyl GABA penetrated into the central nervous system when administered in the periphery. The present studies suggest that pyrrolines may represent a chemical class of brain-penetrating precursors of pharmacologically active analogues of GABA.     

Plasmodium hermani: Experimental transmission by Culex salinarius and comparison with other susceptible Florida mosquitoes

Culex salinarius is susceptible to Plasmodium hermani, a malarial parasite of wild turkeys in Florida. The sporogonous cycle was completed and mosquitoes with infected salivary glands transmitted the parasite by bites. Transmission was also achieved by intraperitoneal and intravenous injections of whole body slurry. This is the third species found to be susceptible to turkey malaria in Florida. A comparison of C. salinarius with two other susceptible Florida mosquitoes, Culex nigripalpus and Wyeomyia vanduzeei, revealed that C. salinarius was more susceptible to P. hermani based on oocyst counts. C. nigripalpus has previously been demonstrated as an experimental and a natural vector of P. hermani, whereas W. vanduzeei has been designated as an experimental host only. In W. vanduzeei at least 30% of the oocysts were melanized (“black bodies”) and this mosquito did not transmit the parasite via bites. Additional detailed comparisons of comparative susceptibility and transmission potentials of these three species to turkey malaria, P. hermani, have been made.     

Studies on the neurosecretory system of Iphita limbata Stal.

Summary The present paper gives an account of some experiments upon the insect Iphita limbata Stal. (Hemiptera: Pyrrhocoridae). The experiments were carried out in order to find out whether in the adult animal there is a relationship between the activity of the neurosecretory cells and the water balance. Under varying conditions one group of the neurosecretory cells of the pars intercerebralis of the brain, the so called A-cells, show histological differences. It has been seen that under conditions stimulating hydration there is a marked retention of the stainable colloids in the cytoplasm of A cells. This retention probably indicates a relationship between the secretions of A cells and the water balance of the insect.The author is indebted to Mr. N. R. Prabhoo and Miss Maya Menon of this Department for a critical discussion of the paper.     

Liposomes with entrapped doxorubicin exhibit extended blood residence times

The blood residence time of liposomes with entrapped doxorubicin is shown to be significantly longer than for identically prepared empty liposomes. Liposomal doxorubicin systems with a drug-to-lipid ratio of 0.2 (w/w) were administered at a dose of 100 mg lipid/kg. Both doxorubicin and liposomal lipid were quantified in order to assess in vivo stability and blood residence times. For empty vesicles composed of phosphatidylcholine (PC)/cholesterol (55:45, mole ratio) and sized through filters of 100 nm pore size, 15-25% of the administered lipid dose was recovered in the blood 24 h after i.v. injection. The percentage of the dose retained in the circulation at 24 h increased 2-3-fold when the liposomes contain entrapped doxorubicin. For 100 nm distearoyl PC/chol liposomal doxorubicin systems, as much as 80% of the injected dose of lipid and drug remain within the blood compartment 24 h after i.v. administration.     

Inter-relationships among root cec,yield and mono- and divalent cations in coconut (Cocos nucifera L.)

Plant and Soil - A study was conducted on different yield groups of coconut palm (West Coast Tall) to investigate the relationships among root CEC, yield and mono- and divalent cations. The results...