Prefrontal cortex dysfunction and depression in atypical parkinsonian syndromes.

Depressive symptoms are common in patients with neurodegenerative disorders. Imaging studies suggest that a disruption of frontal-subcortical pathways may underlie depression associated with basal ganglia disease. This pilot study tested the hypothesis that frontal dysfunction contributes to depression associated with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Depressed patients with MSA (n = 11), PSP (n = 9), and age-matched controls (n = 25) underwent measures of cerebral glucose metabolism applying positron emission tomography with (18)F-fluorodeoxyglucose. Regional metabolism in the patient groups was compared to the normal subjects using the voxel-based statistical parametric mapping. Depressive symptom severity (Hamilton Depression Rating) and degree of locomotor disability (Hoehn & Yahr) were assessed in the patient groups. The association between prefrontal metabolism and the occurrence of depressive symptoms and the degree of locomotor disability was investigated. When compared to controls, MSA patients revealed significant metabolic decreases in bilateral frontal, parietal, and cerebellar cortex and in the left putamen. In PSP patients, significant hypometabolism was demonstrated in bilateral frontal cortex, right thalamus, and midbrain. Depression severity but not the patients' functional condition was significantly associated with dorsolateral prefrontal glucose metabolism in both patient groups. The findings of this pilot study support the hypothesis that depressive symptoms in MSA and PSP are associated with prefrontal dysfunction.     

Characterization of the major secreted zinc metalloprotease- dependent glycerophospholipid:cholesterol acyltransferase, PlaC, of Legionella pneumophila

Legionella pneumophila, an intracellular pathogen causing a severe pneumonia, possesses distinct lipolytic activities which have not been completely assigned to specific enzymes so far. We cloned and characterized a gene, plaC, encoding a protein with high homology to PlaA, the major secreted lysophospholipase A of L. pneumophila and to other hydrolytic enzymes belonging to the GDSL family. Here we show that L. pneumophila plaC mutants possessed reduced phospholipase A and lysophospholipase A activities and lacked glycerophospholipid:cholesterol acyltransferase activity in their culture supernatants. The mutants' reduced phospholipase A and acyltransferase activities were complemented by reintroduction of an intact copy of plaC. Additionally, plaC conferred increased lysophospholipase A and glycerophospholipid:cholesterol acytransferase activities to recombinant Escherichia coli. Furthermore, PlaC was shown to be another candidate exported by the L. pneumophila type II secretion system and was activated by a factor present in the bacterial culture supernatant dependent on the zinc metalloprotease. Finally, the role of plaC in intracellular infection of Acanthamoeba castellanii and U937 macrophages with L. pneumophila was assessed, and plaC was found to be dispensable. Thus, L. pneumophila possesses another secreted lipolytic enzyme, a protein with acyltransferase, phospholipase A, and lysophospholipase A activities. This enzyme is distinguished from the previously characterized phospholipases A and lysophospholipases A by its capacity not only to cleave fatty acids from lipids but to transfer them to cholesterol. Cholesterol is an important compound of eukaryotic membranes, and an acyltransferase might be a tool for host cell modification to fit the needs of the bacterium.     

Fertilization and early embryology: Effects of persistent chlorinated hydrocarbons on fertility and embryonic development in the rabbit

The commercial polychlorinated biphenyl (PCB) formulation Aroclor1260 (4 mg/kg body weight), technical grade dichlorodiphenyltrichloroethane(DDT; 3 mg) and Lindane (-hexachlorocyclohexane; 0.8 mg) wereadministered orally, either separately or in combination, tosexually mature female rabbits three times per week for 12–15weeks. Oviductal and uterine luminal fluid, cleavage stage embryos(day 1 post coitum), blastocysts (day 6), fetuses, exocoelicfluid and placentae (day 11) were analysed, firstly for chlorinatedhydrocarbon residues, and secondly for embryonic and fetal development.The doses applied were well tolerated by the treated animals.PCB and DDT accumulated in uterine secretions (day 6) but notin oviductal luminal fluid (day 1). Both chlorinated hydrocarbonswere found in preimplantation blastocysts. Residues in day 11fetuses were 16- (DDT) or 18-fold (PCB) higher than in day 6blastocysts. Significant amounts were also detected in placentaltissue and in exocoelic fluid. A specific accumulation of thehighly chlorinated biphenyl congener no. 180 was noted in fetuses,placentae and exocoelic fluid. The clear accumulation of thechlorinated hydrocarbon compounds in luminal fluid and embryonictissue is contrasted by rather weak effects on fertility. Nostatistically significant differences between treated animalsand controls were observed for fertilization rate and pre- andpost-implantation (up to day 11 post coitum) losses. However,in females exposed to PCB, a 20% higher loss of blastocystswas noticed, as compared with controls (P > 0.05). This effectwas shown on day 6 of embryonic development and may be due tothe embryotoxic activities of PCB.     

Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex

Weak transcranial direct current stimulation (tDCS) of the human motor cortex results in excitability shifts which occur during and after stimulation. These excitability shifts are polarity-specific with anodal tDCS enhancing excitability, and cathodal reducing it. To explore the origin of this excitability modulation in more detail, we measured the input–output curve and motor thresholds as global parameters of cortico-spinal excitability, and determined intracortical inhibition and facilitation, as well as facilitatory indirect wave (I-wave) interactions. Measurements were performed during short-term tDCS, which elicits no after-effects, and during other tDCS protocols which do elicit short- and long-lasting after-effects. Resting and active motor thresholds remained stable during and after tDCS. The slope of the input–output curve was increased by anodal tDCS and decreased by cathodal tDCS. Anodal tDCS of the primary motor cortex reduced intracortical inhibition and enhanced facilitation after tDCS but not during tDCS. Cathodal tDCS reduced facilitation during, and additionally increased inhibition after its administration. During tDCS, I-wave facilitation was not influenced but, for the after-effects, anodal tDCS increased I-wave facilitation, while cathodal tDCS had only minor effects. These results suggest that the effect of tDCS on cortico-spinal excitability during a short period of stimulation (which does not induce after-effects) primarily depends on subthreshold resting membrane potential changes, which are able to modulate the input-output curve, but not motor thresholds. In contrast, the after-effects of tDCS are due to shifts in intracortical inhibition and facilitation, and at least partly also to facilitatory I-wave interaction, which is controlled by synaptic activity.     

Examination of resistance of the lens capsule against the waterjet

BACKGROUND: Although cataract surgery is highly developed today, there are still problems such as secondary cataract. In polishing the posterior capsule lens, epithelial cells often remain, causing secondary cataracts. Additionally, there are the problems of tissue heating and endothelial cell loss during phacoemulsification by ultrasound. This could be another field for improvement of cataract surgery by using the waterjet. METHODS: After removing the cornea of freshly enucleated porcine bulbs, we used the water jet from 4 to 12 bar. The hit angel on the capsule varied between 45 degrees and 90 degrees. RESULTS: Rupture of the posterior capsule occurred at a mean of 8.5 bar using the jet at 45 degrees and a mean of 8.6 bar using the jet at 90 degrees. CONCLUSION: The waterjet pressure should not be over 4 bar during polishing of the posterior capsule.     

Pharmacokinetics of trofosfamide and its dechloroethylated metabolites

 To contribute to effective and safe outpatient treatment, we investigated the metabolism of trofosfamide (Trofo) after oral administration. We analyzed Trofo metabolism in 15 patients aged from 3 to 73 years who were treated with 150 or 250 mg/m² Trofo in combination with etoposide. Serum samples were collected with 13 patients after oral administration, and Trofo and its dechloroethylated metabolites were quantified by gas chromatography. Urine samples were collected from five patients and analyzed by same method. Ifosfamide (Ifo) was the main metabolite in serum and urine (AUC_Trofo:AUC_Ifo 1:13), whereas cyclophosphamide (Cyclo) was formed in smaller amounts (AUC_Ifo:AUC_Cyclo 18:1). Ifo and Cyclo were further oxidized in the chloroethyl side chains to form 2- and 3-dechloroethylifosfamide in varying quantities. The urinary excretion of Trofo and its dechloroethylated metabolites amounted to about 10% of the total dose. Our results confirm former in vitro observations about the metabolism of Trofo. The main side-chain metabolites Ifo and Cyclo can be further activated by oxidation and formation of their respective phosphoramide mustards. Hence, Trofo is an interesting agent for oral chemotherapy. Received 21 July 1996 / Accepted: 11 November 1996