This study, which included 24 Rtx-treated ASS patients with severe ILD, reports improved PFTs after a median 52 months follow-up post-Rtx. The best outcome was observed in patients with a disease duration <12 months and/or acute onset/exacerbation of ILD. The study indicates that Rtx could be a treatment option for selected ASS patients, but infections should be given attention.
This large international radiation dose survey demonstrates considerable reduction of radiation exposure in coronary CTA during the last decade. However, the large inter-site variability in radiation exposure underlines the need for further site-specific training and adaptation of contemporary cardiac scan protocols.
In the course of attempts to purify the antibacterial agent we had extracted from Spanish moss (Tillandsia usneosides) (1), by adsorption on charcoal, we found that a powerful antibacterial substance for certain organisms could be recovered from charcoal itself. Blood charcoal and previously acidified animal charcoal contained it, but norit did not. This antibacterial substance recovered from charcoal proved to be elemental sulfur?Although sulfur is one of the oldest remedies known to man surprisingly little experimental work has been carried out with it. Colloidal sulfur was first prepared in 1888 (2), and since then many preparations have been used in the treatment of different conditions with varying degrees of success. It has been administe.red orally and by injection in the treatment of mental disease 0-5), by injection in the treatment of arthritis (6-8), and topically, as a fungicide in the treatment of cutaneous infections (9, 10). In both the precipitated and the colloidal forms, sulfur has been used extensively with notable success in the treatment of certain plant diseases (11,12).It is generally assumed that the size of the sulfur particles is basic in the activity of a preparation, the smaller the particles the more active the preparation obtained. In the skin it is thought that the particles of sulfur are converted through the medium of certain cells in the epidermis to sulfur-containing compounds (for example sulfides or pentathionic acid) and that these compounds are responsible for the antimicrobial action (9, 10).We are aware of only two reports of experiments showing the in vitro antimicrobial activity of sulfur upon human pathogenic organisms. The first was of experiments conducted in 1934 by Lawson (13), who investigated the effect of precipitated sulfur incorporated into Corper's mashed-potato medium on the growth of tubercle bacilli. He found that the addition of as little as 3 rag. of sulfur to 100 cc. of medium completely inhibited the growth of this organism. He stated that sulfur appears to have no inhibitory effect upon the growth of some of the ordinary pathogenic bacteria, not specified by him.The second report was of experiments conducted in 1935 by Kingery (14) who'stated that colloidal sulfur was fungicidal and fungistatic for Trichoi~hyton interdigitale and tinea corporis. The fungicidal experiments were carried out by adding a broth suspension of the organism to be tested, to a 1 per cent or 5 per cent dilution of colloidal sulfur. The mixture was shaken for 2 minutes and then several loopfuls were streaked on a suitable agar medium. No growth occurred in the streaks from the preparation a We are indebted to Dr. E. G. Miller, Jr., for these analyses. 531
Stress is a precipitating agent in neuropsychiatric disease and initiates relapse to drug-seeking behavior in addicted patients. Targeting the stress system in protracted abstinence from drugs of abuse with anxiolytics may be an effective treatment modality for substance use disorders. α-adrenergic receptors (α-ARs) in extended amygdala structures play key roles in dampening stress responses. Contrary to early thinking, α-ARs are expressed at non-noradrenergic sites in the brain. These non-noradrenergic α-ARs play important roles in stress responses, but their cellular mechanisms of action are unclear. In humans, the α-AR agonist guanfacine reduces overall craving and uncouples craving from stress, yet minimally affects relapse, potentially due to competing actions in the brain. Here, we show that heteroceptor α-ARs postsynaptically enhance dorsal bed nucleus of the stria terminalis (dBNST) neuronal activity in mice of both sexes. This effect is mediated by hyperpolarization-activated cyclic nucleotide-gated cation channels because inhibition of these channels is necessary and sufficient for excitatory actions. Finally, this excitatory action is mimicked by clozapine--oxide activation of the G-coupled DREADD hM4Di in dBNST neurons and its activation elicits anxiety-like behavior in the elevated plus maze. Together, these data provide a framework for elucidating cell-specific actions of GPCR signaling and provide a potential mechanism whereby competing anxiogenic and anxiolytic actions of guanfacine may affect its clinical utility in the treatment of addiction. Stress affects the development of neuropsychiatric disorders including anxiety and addiction. Guanfacine is an α2A-adrenergic receptor (α2A-AR) agonist with actions in the bed nucleus of the stria terminalis (BNST) that produces antidepressant actions and uncouples stress from reward-related behaviors. Here, we show that guanfacine increases dorsal BNST neuronal activity through actions at postsynaptic α2A-ARs via a mechanism that involves hyperpolarization-activated cyclic nucleotide gated cation channels. This action is mimicked by activation of the designer receptor hM4Di expressed in the BNST, which also induces anxiety-like behaviors. Together, these data suggest that postsynaptic α2A-ARs in BNST have excitatory actions on BNST neurons and that these actions can be phenocopied by the so-called "inhibitory" DREADDs, suggesting that care must be taken regarding interpretation of data obtained with these tools.
JIA patients with long-term active disease had altered arterial haemodynamics compared with controls in our study. PWV was mainly determined by increased DBP, a parameter that again was associated with JIA disease and treatment variables.
We evaluated an extensive profile of clinical variables and immune markers to assess the inflammatory milieu associated with cardiac allograft vasculopathy (CAV) assessed by intravascular ultrasound (IVUS) and virtual histology (VH). In total, 101 heart transplant (HTx) recipients were included and underwent IVUS/VH examination and measurement of plasma C-reactive protein (CRP), soluble tumor necrosis factor receptor-1, interleukin-6, osteoprotegerin, soluble gp130, von Willebrand factor, vascular cell adhesion molecule-1 (VCAM-1) and neopterin. Mean Maximal Intimal Thickness (MIT) was 0.61 ± 0.19 mm and mean fibrotic, fibrofatty, dense calcified and necrotic core components were 55 ± 15, 14 ± 10, 15 ± 13 and 17 ± 9%, respectively. In multivariate analysis, CRP > 1.
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