Neurotransmitter-Mediated Changes in the Electrophysiological Properties of Pituicytes

Intracellular recordings were obtained from pituicytes in the neural lobe of the isolated rat pituitary. Like other glia, pituicytes lacked action potentials in response to depolarizing current injection, but they tended to have more positive resting membrane potentials and higher input resistances than astrocytes in other preparations. Dye-coupling typical of astrocytes was also demonstrated amongst pituicytes, and their morphologies were similar to those of pituicytes stained for glial fibrillary acidic protein. Action potentials, anode-break spikes or barium spikes were not observed in pituicytes, even under conditions that maximized the elicitation of Ca²⁺-dependent responses. This suggests that pituicytes either have no or a very low density of Ca²⁺ channels or Ca²⁺ currents that are too small to generate action potentials. Dynorphin A (1–13), a kappa-opioid agonist, produced long-lasting increases in pituicyte input resistance with no significant changes in resting membrane potential. Dynorphin's action was concentration-dependent and was blocked by the opioid antagonist naloxone. This is consistent with previous reports demonstrating kappa-opioid receptors on pituicytes in the neurohypophysis. The β-adrenergic agonist isoproterenol (100 μM) reversed the increases in pituicyte input resistance produced by opioid application, with no significant changes in resting membrane potential. The fact that pituicytes responded to neurotransmitters suggests a functional link between pituicytes and neurosecretory nerve fibres.     

Hydrophobic IgG-containing immune complexes in the plasma of autoimmune MRL/lpr mice, lactate dehydrogenase-elevating virus-infected mice, and pigs: association with transforming growth factor-beta and pH-dependent amplification

Persistent infection of mice with lactate dehydrogenase-elevating virus (LDV) is associated with polyclonal B cell activation, autoimmunity, and circulating hydrophobic IgG-containing immune complexes (ICs), which bind to the surfaces of uncoated ELISA plates in the presence of 0.05% Tween 20. We demonstrate here that hydrophobic IgG-containing ICs also appear naturally in the plasma of autoimmune MRL/lpr mice. These and the similar hydrophobic ICs of LDV-infected mice as well as pigs coincide on ELISA plate surfaces with TGF-beta, apparently in the form of an IgG-TGF-beta complex. Circulating hydrophobic IgG-containing ICs are also susceptible to considerable amplification in vitro by exposure to alkaline conditions. By this latter method, the fraction of in vivo hydrophobic IgG, relative to the maximum in vitro chemically inducible IgG, was found to be about 20% in the plasma of LDV-infected mice, 5% in normal mouse plasma, and less than about 2% in pig plasma. These results indicate the potential for both chemically induced and protein-binding contributions to the generation of hydrophobic IgG-containing molecules, and have implications for immunopathological mechanisms in autoimmunity and persistent virus infections.     

Reversible blockade of experience-dependent plasticity by calcineurin in mouse visual cortex

Numerous protein kinases have been implicated in visual cortex plasticity, but the role of serine/threonine protein phosphatases has not yet been established. Calcineurin, the only known Ca2+/calmodulin-activated protein phosphatase in the brain, has been identified as a molecular constraint on synaptic plasticity in the hippocampus and on memory. Using transgenic mice overexpressing calcineurin inducibly in forebrain neurons, we now provide evidence that calcineurin is also involved in ocular dominance plasticity. A transient increase in calcineurin activity is found to prevent the shift of responsiveness in the visual cortex following monocular deprivation, and this effect is reversible. These results imply that the balance between protein kinases and phosphatases is critical for visual cortex plasticity.     

Phototherapeutic keratoectomy (PTK) after keratoconjunctivitis epidemica

Background: Persistent and recurrent nummuli after epidemic keratokonjunktivitis (EKC) often lead to reduced visual acuity and increased glare. In spite of long-term topical steroid therapy nummuli often recur. We tried to treat persistent nummuli with phototherapeutic keratectomy (PTK). Patients: PTK with an excimer laser (193 nm) was performed in 13 eyes of 9 patients with nummuli. The nummuli were observed over 3–72 months (mean: 36 months). Preoperatively, the visual acuity was 0.1–0.9 (mean: 0.39 ± 0.22) and the brightness acuity test (BAT) was 0.05–0.5 (mean: 0.25 ± 0.15). Prior to PTK all eyes had been treated with local steroids several times for recurrent nummuli. Results: During the follow-up from 15 to 56 months (mean: 33 ± 11.5 ms), 11 eyes had an increase in visual acuity: 0.3–1.0 (mean: 0.63 ± 0.26). The reduction of glare was especially beneficial for the patients: 0.3–0,9 (mean: 0.55 ± 0.21). One patient had a recurrence of nummuli in both eyes 6 weeks after PTK. The subjective-induced spheric refractive change was − 2.5 D to + 2.0 D. The astigmatic error changed between − 2.0 D to + 1.5 D. Conclusion: PTK seems to be an effective method of treating persistent, recurrent nummuli after EKC. The low rate of recurrence of nummuli after PTK is remarkable.      

Contribution of platelet aggregation inhibitors in the prevention of complications of atherothrombosis

RECOGNIZED EFFICACY: Platelet antiaggregats have been used with success for more than twenty years in industrialized countries, participating in reducing the number of complications of atherothrombosis. New compounds have appeared on the market over the last 3 years. CLOPIDOGREL: Clopidogrel is a thienopyridine similar to ticlopidine but with less toxicity, particularly hematological toxicity. Compared with aspirin for secondary prevention of atherothrombotic events in high risk patients, clopidogrel provides a significant 8.7% (p < 0.043) reduction in the relative risk of severe complications: myocardial infarction, ischemic stroke, death due to vascular cause. The most remarkable benefit is obtained in patients with atheromatous arteriopathy of the lower limbs: 23.8% reduction in relative risk. STENT AFTER ANGIOPLASTY: A combination regimen using aspirin and ticlopidine the month following stent implantation has allowed a very significant reduction in acute (within 24 hours) and subacute (within 30 days) coronary occlusions. Currently the aspirin-clopidogrel combination tends to be used instead of the aspirin-ticlopidine combination due to the lower hematological risk for a similar effect. GPIIBIIIA INHIBITORS: Injectable GPIIbIIIa inhibitors have changed management of the acute phase of coronary artery disease. Among these compounds, abciximab has the most extensively proven efficacy. It is mainly indicated for severe forms of coronary angioplasty with or without stent insertion. It provides a significant short-term and long-term reduction in severe events (myocardial infarction + death + revascularization). Oral formulations of GPIIbIIIa can be used to maintain and/or amplify the benefits obtained with injectable formulations. They are not currently available on the market. ASPIRIN: Due to its very low cost and low side-effect profile, aspirin plays an essential role in most indications where it remains the most widely used first-line platelet anti aggregate.     

Thoughts on how to think (and talk) about RNA structure

Recent events have pushed RNA research into the spotlight. Continued discoveries of RNA with unexpected diverse functions in healthy and diseased cells, such as the role of RNA as both the source and countermeasure to a severe acute respiratory syndrome coronavirus 2 infection, are igniting a new passion for understanding this functionally and structurally versatile molecule. Although RNA structure is key to function, many foundational characteristics of RNA structure are misunderstood, and the default state of RNA is often thought of and depicted as a single floppy strand. The purpose of this perspective is to help adjust mental models, equipping the community to better use the fundamental aspects of RNA structural information in new mechanistic models, enhance experimental design to test these models, and refine data interpretation. We discuss six core observations focused on the inherent nature of RNA structure and how to incorporate these characteristics to better understand RNA structure. We also offer some ideas for future efforts to make validated RNA structural information available and readily used by all researchers.