Glutamate transporter 1-expressing glia in the rat substantia nigra—Morphometric analysis and relationships to synapses

Glial cells have a major role in protecting neurons against various forms of stress. Especially, astrocytes mediate the bulk of glutamate clearance in the brain via specific membrane transporters (GLAST and GLT1), thereby preventing the occurrence of excitotoxic events. Although glutamate-mediated mechanisms are thought to contribute to nigral dopaminergic neuron degeneration in Parkinson's disease, detailed information on the organization of glia in the substantia nigra is still lacking. The present study was performed to provide quantitative information on the organization of astroglia and on the relationships between astrocytes and excitatory synapses in the rat substantia nigra. Using immunolabeling of GLT1 and confocal imaging, we found that the substantia nigra was filled with a dense meshwork of immunoreactive astrocyte processes. Stereological analysis performed on electron microscope images revealed that the density of immunoreactive astrocyte plasma membranes was substantial, close to 1 μm²/μm³, in the substantia nigra neuropil, both in the pars compacta and the pars reticulata. Excitatory synapses had on average two thirds of their perimeters free from glia, a disposition that may favor transmitter spillover. The density of glutamatergic synapses, as quantified on confocal images by the simultaneous detection of bassoon and of vesicular glutamate transporter 1 or 2, was very low (0.01 and 0.025 per μm³ in the reticulata and compacta subdivisions, respectively). Thus the ratio of GLT1-expressing glial membrane surface to glutamatergic synapses was very high (40–100 μm²), suggesting an efficient regulation of extracellular glutamate concentrations.     

Cost-utility of lumbar decompression with or without fusion for patients with symptomatic degenerative lumbar spondylolisthesis

Background contextThe most common surgical treatment of symptomatic degenerative lumbar spondylolisthesis (DLS) is decompression and instrumented fusion. However, contemporary, midline-sparing, microdecompressive techniques have shown good results for selected patients with stable Grade 1 DLS. Growing concerns over the rising cost and rates of spinal fusion warrant both clinical and economic comparative effectiveness research in this common spinal diagnosis.PurposeTo determine the relative cost-utility of decompression with and without concomitant instrumented fusion for selected patients with DLS.Study design/settingComparative cost-effectiveness study.Patient sampleProbabilities and utilities were estimated from an observational cohort study and the current literature. Costing information was obtained from our institution (microcase costing data/patient) and the literature. Probabilities considered were perioperative and general mortality, probability of clinical improvement and clinical worsening, and reoperation.Outcome measuresThe primary outcome was the incremental cost/utility ratio (ICUR) expressed as the differential cost per relative gain in quality-adjusted life-year (QALY).MethodsA Markov model with 10-year follow-up was developed. The analyses were carried out from the hospital’s perspective. Sensitivity analysis was used to test the robustness of the model.ResultsThe cost-utility of decompression with fusion and decompression alone at 10 years postintervention was $3,281/QALY and $1,040/QALY, respectively. Compared with decompression alone, decompression plus instrumented fusion was associated with an improvement in quality of life at a cost of $185,878 per QALY in the base-case analysis. The ICUR was invariant to changes in clinical effectiveness of decompression alone, percentage of inpatient decompressions, and varying cost or QALY discounting rates. The ICUR was sensitive to change in QALY and cost structure changes.ConclusionsFor a select subgroup of patients with DLS (leg-dominant pain with a stable Grade 1 spondylolisthesis), decompression without fusion is significantly more cost effective than instrumented fusion and provides an opportunity for increased service delivery and/or cost savings for this growing population.     

Genetic deletion of melanin‐concentrating hormone neurons impairs hippocampal short‐term synaptic plasticity and hippocampal‐dependent forms of short‐term memory

The cognitive role of melanin‐concentrating hormone (MCH) neurons, a neuronal population located in the mammalian postero‐lateral hypothalamus sending projections to all cortical areas, remains poorly understood. Mainly activated during paradoxical sleep (PS), MCH neurons have been implicated in sleep regulation. The genetic deletion of the only known MCH receptor in rodent leads to an impairment of hippocampal dependent forms of memory and to an alteration of hippocampal long‐term synaptic plasticity. By using MCH/ataxin3 mice, a genetic model characterized by a selective deletion of MCH neurons in the adult, we investigated the role of MCH neurons in hippocampal synaptic plasticity and hippocampal‐dependent forms of memory. MCH/ataxin3 mice exhibited a deficit in the early part of both long‐term potentiation and depression in the CA1 area of the hippocampus. Post‐tetanic potentiation (PTP) was diminished while synaptic depression induced by repetitive stimulation was enhanced suggesting an alteration of pre‐synaptic forms of short‐term plasticity in these mice. Behaviorally, MCH/ataxin3 mice spent more time and showed a higher level of hesitation as compared to their controls in performing a short‐term memory T‐maze task, displayed retardation in acquiring a reference memory task in a Morris water maze, and showed a habituation deficit in an open field task. Deletion of MCH neurons could thus alter spatial short‐term memory by impairing short‐term plasticity in the hippocampus. Altogether, these findings could provide a cellular mechanism by which PS may facilitate memory encoding. Via MCH neuron activation, PS could prepare the day's learning by increasing and modulating short‐term synaptic plasticity in the hippocampus. © 2015 Wiley Periodicals, Inc.     

Dissipation Kinetics of Chlorantraniliprole in Soils of Sugarcane Ecosystem

Dissipation kinetics of chlorantraniliprole was studied in sandy loam soils of sugarcane ecosystem by adopting a rapid analytical method. The recovery of chlorantraniliprole was 91.67 % when extracted with ethyl acetate as against only 65.58 % in acetonitrile-based extraction. An additional cleanup step with primary secondary amine did not enhance the recovery significantly over the no-cleanup method. The ethyl acetate-based extraction followed by direct quantification in HPLC (High-performance liquid chromatography) without any cleanup facilitated rapid quantification of chlorantraniliprole residues. The LOQ (limit of quantification) of the method was 0.01 μg/g. The half-life of chlorantraniliprole was 6.50 and 6.81 days for the recommended and double the recommended doses, respectively.     

Single graft loss in dual renal transplant recipients: impact of graft placement on recipient outcomes

We aimed to assess the impact of graft placement in dual renal transplantation on the risk for single graft loss and to report recipient outcomes. Between 2004 and 2007, 55 dual renal transplants were performed at our institution. Allografts were placed bilaterally (one in each iliac fossa) in 42 patients and unilaterally (both in the same iliac fossa) in 14 patients. Nine recipients (16.4%) underwent explantation of a single graft as a consequence of vascular thrombosis designated as the SINGLE group, whereas 46 had two functional allografts (DUAL group). There was a higher rate of graft loss in case of unilateral placement (n = 5/14) compared with bilateral placement (n = 4/41) (35.7% vs. 9.8%, P = 0.035). One‐year glomerular filtration rate was significantly lower in the SINGLE group (29.4 ml/min/1.73 m² vs. 49.4 ml/min/1.73 m² in the DUAL group, P < 0.05). Significantly, none of the nine recipients of the SINGLE group returned to dialysis with a mean follow‐up of 34.1 months. Graft survival at 1 year was 100% and 97.9% in SINGLE and DUAL groups, respectively. Unilateral placement of both allografts is associated with an increased risk of single graft loss and therefore lower renal function at 1 year. However, this strategy is safe in selected indications.     

N-Acylated Derivatives of Sulfamethoxazole and Sulfafurazole Inhibit Intracellular Growth of Chlamydia trachomatis

Antibacterial compounds with novel modes of action are needed for management of bacterial infections. Here we describe a high-content screen of 9,800 compounds identifying acylated sulfonamides as novel growth inhibitors of the sexually transmitted pathogen Chlamydia trachomatis. The effect was bactericidal and distinct from that of sulfonamide antibiotics, as para-aminobenzoic acid did not reduce efficacy. Chemical inhibitors play an important role in Chlamydia research as probes of potential targets and as drug development starting points.