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81.
David C. Sheridan Amber Lin B. Zane Horowitz 《Clinical toxicology (Philadelphia, Pa.)》2018,56(5):360-364
Objective: Bupropion is often categorized as a newer generation antidepressant and assessed with serotonin reuptake inhibitors as a lower risk than older tricyclic antidepressants (TCAs). The objective of this study was to compare outcomes in adolescent suicide from ingestions between bupropion and TCA medications.Study design: An analysis of the National Poison Data System for exposures coded “suspected suicide” in adolescents (age: 13–19) was undertaken for the years 2013–2016 and included TCAs or bupropion. We compared clinical effects, therapies and medical outcomes.Results: Over the four-year period there were 2253 bupropion and 1496 TCA adolescent suspected suicide calls. There was a significant linear increase in bupropion ingestions over the four years. Across all years, there were on average 189.2 (95% CI: 58.1–320.4; p?=?.01) more ingestions of bupropion than TCA. When comparing bupropion to a TCA, ingestions of bupropion were significantly more likely to be accompanied by seizure (30.7% vs 3.9%; p?.01), to be admitted (74.8% vs 61.6%; p?.01) and medical outcomes to be coded as a major outcome (19.3% vs 10.0%; p?.01). The number of cases with death or major clinical outcome for both increased over the four-year period. Ingestions of bupropion were less likely to have hypotension (2.7% vs 8.0%; p?.01) and less likely to be intubated (5.6% vs 16.4%; p?.01) as compared to ingestions of TCA.Conclusions: Adolescents who overdose on a single medication in a suicide attempt with bupropion have a statistically significant higher incidence of major outcomes and seizures. The risks of bupropion as a potential means of suicidal gesture by overdose must be considered, and weighed against its benefits and side effect profile when choosing an appropriate agent for the treatment of depression in adolescents. 相似文献
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The production of collagenase by adherent mononuclear cells cultured from human peripheral blood 总被引:3,自引:0,他引:3
J S Louie J Weiss L Ryh?nen K M Nies S Rantala-Ryh?nen J Uitto 《Arthritis and rheumatism》1984,27(12):1397-1404
Mononuclear cells were isolated from human peripheral blood by Ficoll-Hypaque centrifugation, and the cells adherent to plastic substrata were cultured in serum-free media supplemented with lactalbumin hydrolysate. These cell cultures, which consisted predominantly of monocyte-macrophages as judged by nonspecific esterase staining, accumulated collagenase in the medium. This collagenase resembled other vertebrate collagenases in that it cleaved native triple-helical type I collagen at a locus 3/4-length away from the amino-terminal end of the molecule. The collagenase activity was inhibited by Na2EDTA, dithiothreitol, and fetal calf serum, while the addition of Ca++ or N-ethylmaleimide enhanced the enzyme activity. The accumulation of collagenase in the culture media was markedly enhanced by the incubation of cells with concanavalin A or phorbol myristic acetate. In the presence of cycloheximide, the levels of collagenase activity were markedly reduced, suggesting that active protein synthesis was required to express the enzyme activity. In additional experiments, monocytes were further purified by counterflow centrifugation-elutriation. The collagenase production was markedly increased in cultures enriched in monocyte-macrophages and devoid of polymorphonuclear leukocytes. The accumulation of collagenase in monocyte cultures incubated for 48 hours in the presence of concanavalin A or phorbol myristic acetate was of the same order of magnitude as in parallel cultures containing the same number of polymorphonuclear leukocytes purified by Ficoll-Hypaque centrifugation and Plasmagel sedimentation.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
85.
Alexander Egbe Sorin V. Pislaru Mahmoud A. Ali Arooj R. Khan Amber N. Boler Hartzell V. Schaff Emmanuel Akintoye Heidi M. Connolly Vuyisile T. Nkomo Patricia A. Pellikka 《JACC: Cardiovascular Imaging》2018,11(7):951-958
Objectives
The purpose of this study was to review the institutional practice of surveillance transthoracic echocardiography (TTE) for diagnosing early prosthetic valve dysfunction (PVD).Background
Bioprosthetic valve thrombosis (BPVT) is an important cause of PVD, and guidelines do not recommend routine TTE during the first 5 years after valve implantation.Methods
The authors performed a retrospective case-control study of all suspected (imaging diagnosis) or confirmed (histopathological diagnosis) cases of BPVT from January 1997 through December 2016. Patients were matched 1:2 (age, sex, prosthesis position) to patients whose prostheses were explanted because of structural failure (SF). PVD was defined as a 50% increase above baseline gradient at valve implantation and classified as early (≤5 years) or late (>5 years) after implantation.Results
There were 94 BPVT (51 suspected, 43 confirmed) and 188 SF cases; patient age 61 ± 9 years; men 61 (65%). The prosthesis positions were aortic 56%; mitral 26%; tricuspid 15%; and pulmonary 3%. Early PVD was more common in the BPVT versus SF group: 83 of 94 (88%) versus 20 of 188 (11%) (p < 0.001). Time from implantation to PVD was shorter for BPVT than SF: 26 months (interquartile range [IQR]: 12 to 43 months) versus 74 months (IQR: 48 to 102 months) (p < 0.001). At the initial PVD diagnosis, 81% of BPVT and 90% of SF patients were asymptomatic. However, BPVT patients had rapid symptomatic deterioration, requiring intervention sooner after PVD diagnosis: 6 months (IQR: 4 to 7 months) versus 51 months (IQR: 22 to 55 months) (p < 0.001).Conclusions
Most patients with PVD due to BPVT were asymptomatic at initial diagnosis, which was made based on routine surveillance TTE, often performed before 5 years. BPVT, an acute disease process, requires timely diagnosis because patient conditions rapidly deteriorate. Further studies are needed to determine whether routine surveillance TTE should be considered for patients with bioprosthetic valves to identify pre-symptomatic features of BPVT in order to provide effective, appropriate therapy. 相似文献86.
Trypsin suppression of pancreatic enzyme secretion. Differential effect on cholecystokinin release and the enteropancreatic reflex 总被引:1,自引:0,他引:1
We have recently demonstrated that intraduodenal perfusion of trypsin inhibits phenylalanine-stimulated pancreatic enzyme secretion by suppression of release of cholecystokinin (CCK). It is not known whether trypsin in the duodenum inhibits pancreatic secretion stimulated by a cholinergic mechanism. To investigate this question gastrointestinal intubation and perfusion were performed in 12 healthy subjects. Volume and osmoreceptors in the duodenum, which are known to elicit pancreatic secretion through cholinergic pathways, were stimulated by infusing increasing volumes (1.0, 2.5, and 5.0 ml/min) of normal saline or increasing osmolality (300, 400, 500 mosmol) of NaCl solution. Increasing the rates of intraduodenal perfusion of normal saline or increasing the osmolality of the duodenal perfusates caused a dose-related increase in pancreatic trypsin and chymotrypsin outputs without affecting basal plasma CCK levels (0.9 +/- 0.1 pM). The volume- or osmolality-stimulated pancreatic secretions were abolished by atropine, but not by intraduodenal perfusion of trypsin. In contrast, intraduodenal perfusion of phenylalanine (10 mM) produced a significant increase in plasma CCK levels (6.7 +/- 0.8 pM) and a three- to fourfold increase in pancreatic enzyme outputs. Perfusion of the duodenum with bovine trypsin (1 g/L) reduced the plasma CCK levels to basal values and significantly attenuated the phenylalanine-stimulated enzyme secretion to 63% +/- 4% of control. Simultaneous administration of atropine and intraduodenal perfusion of trypsin completely abolished the pancreatic enzyme response to phenylalanine stimulation. These studies indicate that the intestinal phase of human pancreatic enzyme secretion is under both hormonal and neural control. Intraduodenal trypsin inhibits only pancreatic secretion mediated by CCK release, and not that mediated by cholinergic mechanisms. These observations suggest that feedback regulation of pancreatic enzyme secretion is stimulus specific. 相似文献
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88.
Peikert T Finkielman JD Hummel AM McKenney ME Gregorini G Trimarchi M Specks U 《Arthritis and rheumatism》2008,58(5):1546-1551
OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) binding to neutrophil elastase (NE) and proteinase 3 (PR3) are detectable in most patients with cocaine-induced midline destructive lesions (CIMDL), but the pathogenic role and antigen specificity of these antibodies are unknown. This study was undertaken to assess the effects of NE ANCA on the enzymatic activity of NE, to determine whether these antibodies interfere with the physiologic effect of secretory leukoprotease inhibitor (SLPI), and to investigate the antigen specificity of both NE and PR3 ANCA in patients with CIMDL. We also compared the binding of PR3 ANCA in patients with CIMDL with that in patients with Wegener's granulomatosis (WG). METHODS: PR3 ANCA and NE ANCA were detected by capture enzyme-linked immunosorbent assays (ELISAs) and by indirect immunofluorescence. IgG was purified from the patients' sera, and the influence of NE ANCA on the enzymatic activity of NE and on the inhibitory activity of SLPI was investigated by determining the hydrolysis of N-methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide by NE. RESULTS: IgG from NE ANCA-positive sera of patients with CIMDL inhibited the enzymatic activity of NE and did not interfere with the activity of SLPI. In contrast to the findings in WG sera, measurement of PR3 ANCA in CIMDL sera showed only fair to moderate concordance between the 2 different capture ELISAs. Cross-inhibition experiments demonstrated that NE ANCA and PR3 ANCA represent distinct autoantibodies in patients with CIMDL. CONCLUSION: The functional effects of NE ANCA on the enzymatic activity of NE or on the activity of SLPI cannot be implicated in the pathogenesis of CIMDL. The autoimmune reaction that targets neutrophil serine proteases in patients with CIMDL is frequently directed against more than one antigen. The ANCA response, including the reactivity of PR3 ANCA, in patients with CIMDL differs from what has been described in patients with WG. 相似文献
89.
Hanchen Xu Kevin Van der Jeught Zhuolong Zhou Lu Zhang Tao Yu Yifan Sun Yujing Li Changlin Wan Ka Man So Degang Liu Michael Frieden Yuanzhang Fang Amber L. Mosley Xiaoming He Xinna Zhang George E. Sandusky Yunlong Liu Samy O. Meroueh Chi Zhang Aruna B. Wijeratne Cheng Huang Guang Ji Xiongbin Lu 《The Journal of clinical investigation》2021,131(10)
One of the primary mechanisms of tumor cell immune evasion is the loss of antigenicity, which arises due to lack of immunogenic tumor antigens as well as dysregulation of the antigen processing machinery. In a screen for small-molecule compounds from herbal medicine that potentiate T cell–mediated cytotoxicity, we identified atractylenolide I (ATT-I), which substantially promotes tumor antigen presentation of both human and mouse colorectal cancer (CRC) cells and thereby enhances the cytotoxic response of CD8+ T cells. Cellular thermal shift assay (CETSA) with multiplexed quantitative mass spectrometry identified the proteasome 26S subunit non–ATPase 4 (PSMD4), an essential component of the immunoproteasome complex, as a primary target protein of ATT-I. Binding of ATT-I with PSMD4 augments the antigen-processing activity of immunoproteasome, leading to enhanced MHC-I–mediated antigen presentation on cancer cells. In syngeneic mouse CRC models and human patient–derived CRC organoid models, ATT-I treatment promotes the cytotoxicity of CD8+ T cells and thus profoundly enhances the efficacy of immune checkpoint blockade therapy. Collectively, we show here that targeting the function of immunoproteasome with ATT-I promotes tumor antigen presentation and empowers T cell cytotoxicity, thus elevating the tumor response to immunotherapy. 相似文献
90.