Scedosporium apiospermum endopthalmitis treated early with intravitreous voriconazole results in recovery of vision

AIM: The purpose of this study is to report a case of endogenous endopthalmitis caused by Scedosporium apiospermum with a favorable outcome and review previously reported cases, their treatment regimens and outcomes. METHODS: An 83-year-old man with diabetes mellitus, no other immunocompromising risk factors, and a history of S. apiospermum endopthalmitis in the left eye developed endopthalmitis in the right eye. Within 72 h of presentation, he was treated with a pars plana vitrectomy and intravitreal voriconozole. RESULTS: Vitreous cultures confirmed S. apiospermum. The patient responded to treatment, with a favorable outcome and full recovery of vision. CONCLUSIONS: Recognition of S. apiospermum endopthalmitis and appropriate early intervention with pars plana vitrectomy and intravitreal voriconozole can lead to a favorable outcome with restoration of visual acuity

Expression of the Na(+)/l(- )symporter (NIS) is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus

BACKGROUND: The sodium/iodide symporter (NIS) is a plasma membrane glycoprotein that mediates iodide (I(-)) transport in the thyroid, lactating breast, salivary glands, and stomach. Whereas NIS expression and regulation have been extensively investigated in healthy and neoplastic thyroid and breast tissues, little is known about NIS expression and function along the healthy and diseased gastrointestinal tract. METHODS: Thus, we investigated NIS expression by immunohistochemical analysis in 155 gastrointestinal tissue samples and by immunoblot analysis in 17 gastric tumors from 83 patients. RESULTS: Regarding the healthy Gl tract, we observed NIS expression exclusively in the basolateral region of the gastric mucin-producing epithelial cells. In gastritis, positive NIS staining was observed in these cells both in the presence and absence of Helicobacter pylori. Significantly, NIS expression was absent in gastric cancer, independently of its histological type. Only focal faint NIS expression was detected in the direct vicinity of gastric tumors, i.e., in the histologically intact mucosa, the expression becoming gradually stronger and linear farther away from the tumor. Barrett mucosa with junctional and fundic-type columnar metaplasia displayed positive NIS staining, whereas Barrett mucosa with intestinal metaplasia was negative. NIS staining was also absent in intestinalized gastric polyps. CONCLUSION: That NIS expression is markedly decreased or absent in case of intestinalization or malignant transformation of the gastric mucosa suggests that NIS may prove to be a significant tumor marker in the diagnosis and prognosis of gastric malignancies and also precancerous lesions such as Barrett mucosa, thus extending the medical significance of NIS beyond thyroid disease

Interleukin 2 gene transcription is regulated by Ikaros-induced changes in histone acetylation in anergic T cells

In T cells anergy may be evoked by an unbalanced stimulation of the T-cell receptor in the absence of costimulation. Anergic T cells are unresponsive to new antigen receptor engagement and do not produce interleukin 2. We present evidence that anergizing stimuli induce changes in histone acetylation, which mediates transcriptional repression of interleukin 2 expression. In response to calcium signaling, anergic T cells up-regulate the expression of Ikaros, a zinc finger transcription factor essential for lymphoid lineage determination. Ikaros binds to the interleukin 2 promoter where it induces histone deacetylation. Confirming the role of Ikaros in the induction of T-cell anergy, cells with reduced Ikaros activity show defective inactivation in response to an anergizing stimulus. We propose a model in which tolerizing stimuli induce epigenetic changes on the interleukin 2 locus that are responsible for the stable inhibition of the expression of this cytokine in anergic T cells

The Na+/I− symporter mediates active iodide uptake in the intestine

Absorption of dietary iodide, presumably in the small intestine, is the first step in iodide (I−) utilization. From the bloodstream, I− is actively taken up via the Na+/I− symporter (NIS) in the thyroid for thyroid hormone biosynthesis and in such other tissues as lactating breast, which supplies I− to the newborn in the milk. The molecular basis for intestinal I− absorption is unknown. We sought to determine whether I− is actively accumulated by enterocytes and, if so, whether this process is mediated by NIS and regulated by I− itself. NIS expression was localized exclusively at the apical surface of rat and mouse enterocytes. In vivo intestine-to-blood transport of pertechnetate, a NIS substrate, was sensitive to the NIS inhibitor perchlorate. Brush border membrane vesicles accumulated I− in a sodium-dependent, perchlorate-sensitive manner with kinetic parameters similar to those of thyroid cells. NIS was expressed in intestinal epithelial cell line 6, and I− uptake in these cells was also kinetically similar to that in thyrocytes. I− downregulated NIS protein expression and its own NIS-mediated transport both in vitro and in vivo. We conclude that NIS is functionally expressed on the apical surface of enterocytes, where it mediates active I− accumulation. Therefore, NIS is a significant and possibly central component of the I− absorption system in the small intestine, a system of key importance for thyroid hormone biosynthesis and thus systemic intermediary metabolism

The use of therapeutic plasma exchange as adjunctive therapy in the treatment of coronavirus disease 2019: A critical appraisal of the current evidence

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a major pandemic. While vaccine development moves forward, optimal treatment continues to be explored. Efforts include an ever-expanding number of clinical trials along with newly proposed experimental and off-label investigational therapies; one of which is therapeutic plasma exchange (TPE). There have been a number of publications on TPE use as adjunctive therapy for coronavirus disease 2019 (COVID-19), but no prospective randomized controlled trials (RCTs) have been completed. This article critically appraises the current available evidence on TPE as a treatment modality for SARS-CoV-2 infection

The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake

The KCNQ1 α subunit and the KCNE2 βsubunit form a potassium channel in thyroid epithelial cells. Genetic disruption of KCNQ1-KCNE2 causes hypothyroidism in mice, resulting in cardiac hypertrophy, dwarfism, alopecia, and prenatal mortality. Here, we investigated the mechanistic requirement for KCNQ1-KCNE2 in thyroid hormone biosynthesis, utilizing whole-animal dynamic positron emission tomography. The KCNQ1-specific antagonist (-)-[3R,4S]- chromanol 293B (C293B) significantly impaired thyroid cell I- uptake, which is mediated by the Na+/I- symporter (NIS), in vivo (dSUV/dt: vehicle, 0.028±0.004 min-1; 10 mg/kg C293B, 0.009±0.006 min-1) and in vitro (EC50: 99±10 μM C293B). Na+-dependent nicotinate uptake by SMCT, however, was unaffected. Kcne2 deletion did not alter the balance of free vs. thyroglobulin-bound I- in the thyroid (distinguished using ClO 4-, a competitive inhibitor of NIS), indicating that KCNQ1-KCNE2 is not required for Duox/TPO-mediated I- organification. However, Kcne2 deletion doubled the rate of free I- efflux from the thyroid following ClO4- injection, a NIS-independent process. Thus, KCNQ1-KCNE2 is necessary for adequate thyroid cell I- uptake, the most likely explanation being that it is prerequisite for adequate NIS activity. © FASEB.Fil: Purtell, Kerry. Weill Cornell Medical College; Estados UnidosFil: Paroder-Belenitsky, Monika. Yeshiva University; Estados UnidosFil: Reyna-Neyra, Andrea. Yeshiva University; Estados UnidosFil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. University of Yale; Estados UnidosFil: Koba, Wade. Yeshiva University; Estados UnidosFil: Fine, Eugene. Yeshiva University; Estados UnidosFil: Carrasco, Nancy. Yeshiva University; Estados Unidos. University of Yale; Estados UnidosFil: Abbott, Geoffrey W.. Weill Cornell Medical College; Estados Unido

The KCNQ1-KCNE2 K⁺ channel is required for adequate thyroid I⁻ uptake.

The KCNQ1 α subunit and the KCNE2 β subunit form a potassium channel in thyroid epithelial cells. Genetic disruption of KCNQ1-KCNE2 causes hypothyroidism in mice, resulting in cardiac hypertrophy, dwarfism, alopecia, and prenatal mortality. Here, we investigated the mechanistic requirement for KCNQ1-KCNE2 in thyroid hormone biosynthesis, utilizing whole-animal dynamic positron emission tomography. The KCNQ1-specific antagonist (-)-[3R,4S]-chromanol 293B (C293B) significantly impaired thyroid cell I(-) uptake, which is mediated by the Na(+)/I(-) symporter (NIS), in vivo (dSUV/dt: vehicle, 0.028 ± 0.004 min(-1); 10 mg/kg C293B, 0.009 ± 0.006 min(-1)) and in vitro (EC(50): 99 ± 10 μM C293B). Na(+)-dependent nicotinate uptake by SMCT, however, was unaffected. Kcne2 deletion did not alter the balance of free vs. thyroglobulin-bound I(-) in the thyroid (distinguished using ClO(4)(-), a competitive inhibitor of NIS), indicating that KCNQ1-KCNE2 is not required for Duox/TPO-mediated I(-) organification. However, Kcne2 deletion doubled the rate of free I(-) efflux from the thyroid following ClO(4)(-) injection, a NIS-independent process. Thus, KCNQ1-KCNE2 is necessary for adequate thyroid cell I(-) uptake, the most likely explanation being that it is prerequisite for adequate NIS activity