Semi-quantitative scintigraphic follow-up studies of cerebral arteriovenous malformations after radiosurgical treatment

An evaluation of semi-quantitative 99Tcm-red blood cell scintigraphy (RBCS) was undertaken in patients with cerebral arteriovenous malformations (AVM) during follow-up after radiosurgical treatment. Twenty-seven patients were studied with an initial dynamic imaging sequence of 32 frames each lasting 2 s, planar images in four projections beginning 15 min post-injection and single photon emission tomography immediately following the planar imaging. A 2 ml cubital vein blood sample was imaged to obtain an extracorporeal equivalent of the intravascular activity. The counts within the AVM on a planar image were divided by the counts obtained from the image of the blood sample (corrected for the same acquisition time and radioactive decay). This value yielded the 'volume index' (VI), which was proportional to the volume of the AVM. The VI obtained from the first RBCS served as the initial reference value and was set at 100%. The VIs obtained from the follow-up investigations of the same patient in the same projection were expressed as the percentage of the initial VI. We found RBCS identified the AVM in all patients. The VIs obtained from the follow-up studies demonstrated a decrease in blood volume at different time intervals after radiosurgical treatment. RBCS provides a sensitive, relatively non-invasive, semi-quantitative method for measuring the relative volume and follow-up of the degree of obliteration of AVMs after radiosurgical treatment.     

Optimal discrete systems with pure delays

Necessary and sufficient conditions for the optimization of multivariable discrete systems containing pure delays in dynamics, in performance index, and in constraints are investigated. Using nonlinear programming, it is shown that a discrete maximum principle similar to the one derived by Pearson and Sridhar [1] is valid for a subclass of these problems, that is, systems with linear dynamics, convex inequality constraints, and convex performance index.     

Selective activation of group-II metabotropic glutamate receptors is protective against excitotoxic neuronal death

Aminopyrrolidine-2R,4R-dicarboxylated (2R,4R-APDC) has recently been introduced as a potent and highly selective agonist of metabotropic glutamate (mGlu) receptor subtypes mGlu2 and -3. In murine cortical cultures containing both neurons and astrocytes, 2R,4R-APDC attenuated the delayed neuronal degeneration induced by a 10-min pulse of N-methyl-D-aspartate (NMDA). 2R,4R-APDC was maximally neuroprotective in a range of concentrations (0.1-1 microM) comparable to that reported for the activation of mGlu2 or -3 receptors in heterologous expression systems. The action of 2R,4R-APDC was sensitive to the mGlu2/3 receptor antagonists, (2S)-alpha-ethylglutamate and (2S,1S',2S',3R')-2-(2'-carboxy-3'-phenylcyclopropyl)glycine. These results indicate that activation of mGlu2 and/or -3 receptors is sufficient per se to protect neurons against excitotoxic degeneration, and encourage the search for potent, selective and systemically active mGlu2/3 receptor agonists as neuroprotective drugs.     

Comparative efficacy of a single 400 mg dose of albendazole or mebendazole in the treatment of nematode infections in children

The relative efficacy of a single 400 mg dose of albendazole or mebendazole in the treatment of nematode infections was assessed in 2- to 9-year-old children living in two different Bolivian rural communities. Both agents were equally very effective (100% cure rate) in treating ascariasis. Albendazole was clearly more active than mebendazole against hookworm infections, both in terms of egg reduction rate (92.8% vs. 62.4%) and cure rate (81.8% vs. 17.2%). As far as trichuriasis is concerned, albendazole produced a higher egg reduction rate than mebendazole (45.7% vs 15%), but a lower cure rate (33.3% vs 60%). Both drugs were well tolerated.     

Immortalized hypothalamic neurons express metabotropic glutamate receptors positively coupled to cyclic AMP formation

We have characterized the expression pattern and pharmacological profile of activation of metabotropic glutamate receptors (mGluRs) in immortalized, gonadotropin releasing hormone (GnRH)-secreting GT1-7 cells, which represent a homogeneous cellular population of hypothalamic origin. These cells are known to respond to the mGluR agonist (1S,3R)-cyclopentanedicarboxylic acid (1S,3R-ACPD) with increased GnRH release. To establish which specific mGluR subtypes are expressed by GT1-7 cells, we used polyclonal antibodies raised against non-conserved regions of the carboxy-terminal domains of individual subtypes. The selectivity of these antibodies was tested in HEK 293 cells transiently transfected with each mGluR subtype. GT1-7 cells stained positively for the subtypes mGluR1a, -1b and -5 (belonging to group I mGluR2/3 (group II) and mGluR7 (group III). Agonists of group I mGluRs, including 1S,3R-ACPD, activated phosphoinositide hydrolysis in GT1-7 cells. This effect, however, was manifested only when cell density was low, and it disappeared when cells reached confluence. Stimulation of phosphoinositide hydrolysis could not therefore have been related to hormone secretion because 1S,3R-ACPD effectively released GnRH in confluent cultures. We then focused on group II and III mGluRs, which in transfected cells are negatively linked to adenylate cyclase activity. Unexpectedly, however, agonist which preferentially activate group II and III mGluRs increased both basal and forskolin-stimulated cAMP accumulation in GT1-7 cells. Stimulation of cAMP accumulation by mGluR agonists was not prevented by enzymatic depletion of endogenous adenosine, but was obliterated when cells were incubated with agonists of receptors positively coupled to adenylate cyclase, such as beta-adrenergic and prostaglandin E2 receptors. These results suggest that GT1-7 cells express a novel mGluR subtype positively coupled to adenylate cyclase, which shares the same transduction pathway of other classical receptors coupled with a Gs-type of GTP-binding protein.     

Metabotropic Glutamate Receptor Blockade Reduces Preservation Damage in Livers from Donors after Cardiac Death

We previously demonstrated that the blockade of mGluR5 by 2-methyl-6(phenylethynyl)pyridine (MPEP) reduces both cold and warm ischemia/reperfusion injury. Here we evaluated whether MPEP reduces the hepatic preservation injury in rat livers from cardiac-death-donors (DCDs). Livers from DCD rats were isolated after an in situ warm ischemia (30 min) and preserved for 22 h at 4 °C with UW solution. Next, 10 mg/Kg MPEP or vehicle were administered 30 min before the portal clamping and added to the UW solution (3 µM). LDH released during washout was quantified. Liver samples were collected for iNOS, eNOS, NO, TNF-α, ICAM-1, caspase-3 and caspase-9 protein expression and nuclear factor-erythroid-2-related factor-2 (Nrf2) gene analysis. Lower LDH levels were detected in control grafts versus DCD groups. An increase in eNOS and NO content occurred after MPEP treatment; iNOS and TNF-α content was unchanged. ICAM-1 expression was reduced in the MPEP-treated livers as well as the levels of caspase-3 and caspase-9. Nrf2, oxidative stress-sensitive gene, was recovered to control value by MPEP. These results suggest that MPEP can be used to reclaim DCD livers subjected to an additional period of cold ischemia during hypothermic storage. MPEP protects against apoptosis and increased eNOS, whose overexpression has been previously demonstrated to be protective in hepatic ischemia/reperfusion damage.