Paramagnetic macrocyclic complexes as contrast agents for MR imaging: proton nuclear relaxation rate enhancement in aqueous solution and in rat tissues

Paramagnetic macrocyclic chelates show promise as magnetic resonance (MR) imaging contrast agents due to stability and relaxivity comparable to those of DTPA-type chelates. For the three copper and manganese macrocyclic complexes studied in aqueous solution, T1 and T2 relaxivities ranged from 0.14 to 5.88 mM-1sec-1 at 6.25 MHz. In rats, the intravenous administration of 16 mumol/kg of Mn(cyclam) caused the liver T1 relaxation rate to double at 15 minutes after injection. T1 measurements by pulsed MR imaging and manganese analyses on excised tissue showed that both relaxation rate (1/T1) and manganese content of liver and kidney increase linearly with the dosage of Mn(cyclam). The linear relationship between 1/T1 and manganese content can be considered an "in tissue" relaxivity plot for the agent. The resulting relaxivity is 54 mM-1sec-1 in liver, compared with 3.1 mM-1sec-1 in aqueous solution. Although this work is preliminary, the implication for medical MR imaging applications is that macrocyclic contrast agents can be effective at approximately one-tenth the current typical dose used for gadolinium DTPA.     

Setting standards of performance expected in neurosurgery residency: A study on entrustable professional activities in competency-based medical education

BackgroundCompetency-based medical education requires evaluations of residents’ performances of tasks of the discipline (ie. entrustable professional activities (EPAs)). Using neurosurgical Faculty perspectives, this study investigated whether a sample of neurosurgical EPAs accurately reflected the expectations of general neurosurgical practice.MethodA questionnaire was sent to all Canadian neurosurgery Faculty using a SurveyMonkey® platform.ResultsThe proportion of respondents who believed the EPAs were representative of general neurosurgery competences varied significantly across all EPAs [47%–100%] (p < 0.0001). For 9/15 proposed EPAs, ≥75% agreed they were appropriate for general neurosurgery training and expected residents to attain the highest standard of performance. However, a range of 27–53% of the respondents felt the other six EPAs would be more appropriate for fellowship training and thus, require a lower standard of performance from graduating residents.ConclusionThe shift towards subspecialization in neurosurgery has implications for curriculum design, delivery and certification of graduating residents.     

Effects of Co‐composting of Municipal Solid Waste and Pigeon Pea Biochar on Heavy Metal Mobility in Soil and Translocation to Leafy Vegetable Spinach

Bulletin of Environmental Contamination and Toxicology - An experiment was conducted to study the effects of co-composted products of municipal solid waste (MSW) and pigeon pea biochar (PPB) on...     

pH-adjusted periocular anaesthesia for primary vitreoretinal surgery

PURPOSE: To evaluate the efficacy of pH-adjusted bupivacaine in conjunction with medial orbital periconal block (periocular anaesthesia). METHODS: Sixty consecutive patients undergoing primary vitreoretinal surgery were enrolled prospectively. RESULTS: Adequate anaesthesia and akinesia with no intraoperative supplementation was achieved in 53 eyes (88.3%). Factors influencing intraoperative supplementation were combined vitrectomy with scleral buckling (p = 0.005) and duration of surgery of more than 2 hours (p = 0.001). No ocular or systemic complication resulted. CONCLUSION: pH-adjusted periocular anaesthesia is safe and effective in patients undergoing primary vitreoretinal surgery.     

Subcommissural organ-Reissner's fiber complex of the teleost Clarias batrachus responds to GABA treatment

Subcommissural organ (SCO) is a highly specialized ependymal gland located in the roof of the third ventricle. The secretory products of the SCO, which condense to form Reissner's fiber (RF), were recently found to cross-react with the anti-calcitonin antibody. To understand the mechanisms regulating the formation of the RF and the possible function of these discrete structures, we studied the response of the SCO-RF complex to intracranially administered GABA, using immunocytochemical labeling with anti-calcitonin antibody. Although the SCO-RF complex of control fish was intensely immunostained, 1 h after GABA treatment, the ependymal cells revealed partial loss of immunoreactivity; the RF showed occasional loss of immunoreactivity with its diameter increased by about 56% of the control value. Following 2 h of GABA treatment, the SCO revealed dramatic loss of calcitonin-like immunoreactivity from the ependymal cells. The RF showed a dual response in this group, while in some segments the RF appeared conspicuously thick, elsewhere it appeared thin. The mean diameter was, however, not significantly different from the normal. Following 4 h of GABA treatment, while calcitonin-like immunoreactive material made its reappearance in the SCO, the RF diameter was uniformly reduced to about 35% of the control value. The responses by the RF as well as the SCO to intracranially administered GABA were blocked by pretreatment with bicuculline, a GABA(A) receptor antagonist. The results suggest that GABA, acting via GABA(A) receptors, may trigger the release of secretory material from the SCO and induce histomorphological changes in the RF indicative of discharge of stored material.     

Induction of neuronal death by alpha-synuclein

The molecular and cellular mechanisms underlying neuronal loss in neurodegenerative diseases are unclear. It is generally thought that aggregation of mutated, abnormally modified or abnormally folded proteins leads to the accumulation of extracellular, intracellular or intranuclear deposits that severely compromise cell physiology, leading to the death of the affected neurons. However, there is growing evidence that neuronal apoptosis in the absence of obvious pathological deposits could have a serious impact on the pathogenesis of neurodegenerative diseases. alpha-Synuclein has been implicated in aetiology and pathogenesis of certain neurodegenerative diseases, although the precise role of this protein in neurodegeneration is uncertain. The normal functions of alpha-synuclein and other members of the synuclein family in the development and function of the nervous system also remain elusive. Here we show that overexpression of wild-type and mutant forms of alpha-synuclein in cultured neurons, but not the closely related persyn (gamma-synuclein), causes apoptosis. These findings suggest that abnormalities of alpha-synuclein metabolism could lead to the neuronal loss occurring in certain forms of neurodegeneration before the formation of characteristic pathological lesions.     

Growth of asthmatic children is slower during than before treatment with inhaled glucocorticoids

Reports on the influence of inhaled glucocorticoids on growth have been controversial. We studied the growth of prepubertal asthmatic children prior to and during glucocorticoid therapy. We collected retrospectively the notes of 201 asthmatic children aged 1–11 years receiving inhaled beclomethasone dipropionate or budesonide. We calculated their height and height velocity standard deviation scores (HSDS and HVSDS, respectively) before the treatment and up to 5 years during the treatment and compared those with the growth of healthy peers. The dose of the medication was calculated and the severity of asthma was assessed. The asthmatic children grew similarly to their healthy peers before treatment with inhaled glucocorticoids: the mean HSDS was +0.02 and the mean HVSDS +0.01 for boys and -0.16 and +0.13 for girls, respectively. Growth retardation took place soon after the start of the treatment, the most profound decrease in the growth velocity (the change in the mean HVSDS from +0.05 to -0.88) occurring during the first year of treatment. The growth-retarding effect of inhaled glucocorticoids was not dose dependent. In the covariance analysis the increasing severity of asthma had a significant interaction with repeated measurements, showing more growth retardation along with more severe asthma, especially during long-term treatment. Asthma per se does not impair growth, but inhaled glucocorticoids may do so. Careful monitoring of the growth of all asthmatic children receiving inhaled glucocorticoids is necessary because the growth-retarding effect of the medication is not dose dependent. Individual sensitivity might explain the differences seen in the growth patterns of children receiving inhaled glucocorticoids.