Parasitism of the horse chestnut leaf miner, Cameraria ohridellaDeschka and Dimic (Lep., Gracillariidae), in Serbia and Macedonia

A study concerning the parasitism of Cameraria ohridella, a pest of Aesculus hippocastanum invading Europe, has been carried out in Serbia and Macedonia in 1998 and 1999. From C. ohridella 14 species of parasitoids were reared, which are polyphagous and occur in the whole of Europe. Twelve of the species found belong to the Chalcidoidean family Eulophidae. The rates of parasitism at different sampling dates did not exceed 25%. The results, when compared with data from central Europe, showed that C. ohridella most certainly does not originate from Serbia or Macedonia – the regions in which C. ohridella was observed for the first time – as an indigenous leaf miner on A. hippocastanum.     

Parasitism of the horse chestnut leaf miner, Cameraria ohridella Deschka and Dimic (Lep., Gracillariidae), in Serbia and Macedonia

A study concerning the parasitism of Cameraria ohridella, a pest of Aesculus hippocastanum invading Europe, has been carried out in Serbia and Macedonia in 1998 and 1999. From C. ohridella 14 species of parasitoids were reared, which are polyphagous and occur in the whole of Europe. Twelve of the species found belong to the Chalcidoidean family Eulophidae. The rates of parasitism at different sampling dates did not exceed 25?%. The results, when compared with data from central Europe, showed that C. ohridella most certainly does not originate from Serbia or Macedonia – the regions in which C. ohridella was observed for the first time – as an indigenous leaf miner on A. hippocastanum.     

Development and validation of the maximal electro-shock seizure model in dogs

The development and validation of the maximal electro-shock (MES) model using phenobarbital (Pb) as the positive control is described. This approach builds on previous work in rodent model systems, and has been adapted to dogs as a tool for pharmaceutical dose selection. Dogs, like rodents, exhibit generalized convulsions which manifest as progressive clinical signs in a dose (electrical current) dependent fashion. At the limit (300 mA, 200 msec) animals underwent clonic-tonic convulsions consistent with complete generalized (Grand Mal) seizures with a grade 3 clinical score (CS) and a menace response time of 98.5 +/- 24.4 sec (n = 8). Pretreatment of animals with Pb at 3, 10, and 30 mg/kg, in a 4-by-4 complete block crossover design (Latin-Square), resulted in a dose-dependant reduction in CS and menace response time. Estimates of plasma Pb concentration taken prior to MES induction showed a similar dose-dependent reduction in CS and menace response time with concentration. Using a cumulative logistic regression model, a predicted 50% probability of a CS = 1 was approximately 11.4 mg/kg. In addition, plasma Pb concentrations predicted a 50% probability of a CS = 1 occurs at plasma Pb concentration of approximately 16.0 mug/mL. Combined these data suggest that MES is a useful model for evaluating generalized convulsions in canines and may provide a tool for dose selection of novel pharmaceutical compounds.     

Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo

Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions. Furthermore, blood-brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patroling to shielding of the injured site. Microglia thus are busy and vigilant housekeepers in the adult brain.     

Pharmacokinetics of gemcitabine and its primary metabolite in dogs after intravenous infusion

Gemcitabine is a relatively new chemotherapeutic compound used to treat a variety of cancers in dogs. Previous work presented in a companion paper explored the plasma kinetics of gemcitabine and its inactive metabolite, 2',2'-difluorodeoxyuridine (dFdU), in dogs after an intravenous bolus gemcitabine dose and demonstrated the saturation of intracellular dFdCTP (2',2'-difluorodeoxycytidine 5'-triphosphate) occurs in vitro with increasing extracellular gemcitabine exposure in canine melanoma cells. In this study, the plasma pharmacokinetics (PKs) of gemcitabine and dFdU are further explored after gemcitabine doses of 10, 30, and 60 mg/kg administered by intravenous infusion with a loading dose. Gemcitabine displayed linear PKs, while the kinetics of dFdU were not dose proportional. The overall clearance, volume of distribution at steady-state, and terminal elimination half-life (t(1/2)) for gemcitabine were 0.421 L/h.kg, 0.822 L/kg, and 1.49 h, respectively. Plasma concentrations of dFdU peaked at approximately 2 h postdosing and had a t(1/2) of 14.9 h.     

Pharmacokinetics and dose selection of a novel, long-acting transdermal fentanyl solution in healthy laboratory Beagles

A novel, transdermal fentanyl solution (TFS) was developed that delivers sustained concentrations of fentanyl for days following a single application. The pharmacokinetics following a single topical dose was examined. Eighteen adult Beagle dogs were divided into three groups of six dogs (3M, 3F). Each group was administered a single dose of 1.3 (25), 2.6 (50), or 5.2 mg/kg (100 μL/kg) of TFS. The dose was applied to the clipped, ventral abdominal skin using a 1-mL tuberculin syringe. Immediately following dosing, collars were placed on each dog through 72 h to prevent direct licking of the application site. Serial jugular venous blood samples were collected at 0 (predosing), 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 240, 336, 408, and 504 h after dosing and assayed for plasma fentanyl concentration. Fentanyl was rapidly detected following application with a mean absorption lag time (t(lag) ) of 0.333 h in the 1.3 mg/kg group and 0 in the other two groups. The mean C(max) increased with dose and were 2.28, 2.67, and 4.71 ng/mL in the 1.3, 2.6 and 5.2 mg/kg dose groups, respectively. Mean terminal half-lives were 53.7, 69.6, and 103 h in the 1.3, 2.6, and 5.2 mg/kg dose groups, respectively. The mean AUC(0-LLOQ) from lowest to highest dose groups were 157, 268, and 645 ng·h/mL and were dose proportional with a R(2) value of 0.9818. Adverse reactions were limited to the highest dose group and included sedation (four of six dogs) and decreased food and water intake (one dog). A dose of 2.6 mg/kg (50 μL/kg) is proposed for further development studies based on the lack of adverse events that were observed compared to the 5.2 mg/kg group and a more rapid onset of action and longer duration of action compared to the 1.3 mg/kg group.     

Parasitism of the horse chestnut leaf miner, Cameraria ohridellaDeschka and Dimic (Lep., Gracillariidae), in Serbia and Macedonia

A study concerning the parasitism of Cameraria ohridella, a pest of Aesculus hippocastanum invading Europe, has been carried out in Serbia and Macedonia in 1998 and 1999. From C. ohridella 14 species of parasitoids were reared, which are polyphagous and occur in the whole of Europe. Twelve of the species found belong to the Chalcidoidean family Eulophidae. The rates of parasitism at different sampling dates did not exceed 25%. The results, when compared with data from central Europe, showed that C. ohridella most certainly does not originate from Serbia or Macedonia – the regions in which C. ohridella was observed for the first time – as an indigenous leaf miner on A. hippocastanum.