Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder associated with thyroid disease which affects ocular and orbital tissues. GO follows a biphasic course in which an initial active phase of progression is followed by a subsequent partial regression and a static inactive phase. Although the majority of GO patients have a mild, self-limiting, and nonprogressive ocular involvement, about 3–7% of GO patients exhibit a severe sight-threatening form of the disease due to corneal exposure or compressive optic neuropathy. An appropriate assessment of both severity and activity of the disease warrants an adequate treatment. The VISA (vision, inflammation, strabismus, and appearance), and the European Group of Graves' Orbitopathy (EUGOGO) classifications are the two widely used grading systems conceived to assess the activity and severity of GO and guide the therapeutic decision making. A critical analysis of classification, assessment, and management systems is reported. A simplified “GO activity assessment checklist” for routine clinical practice is proposed. Current treatments are reviewed and management guidelines according to the severity and activity of the disease are provided. New treatment modalities such as specific monoclonal antibodies, TSH-R antagonists, and other immunomodulatory agents show a promising outcome for GO patients.
Collagenase A digestion successfully harvested aggregates with viable HCECs that were preservable for at least 3 weeks in a serum-free, high-calcium medium and, with brief trypsin/EDTA treatment, expanded in the SHEM into a monolayer with hexagonal cells that exhibited characteristic cell junctions.
Renal transplantation in children with severe bladder dysfunction can achieve similar results to those obtained in the general population. Meticulous selection of patients and surgical reparative techniques ensuring voiding and adequate control of urinary infections are mandatory. Augmentation cystoplasty and intermittent catheterization are appropriate techniques currently used for achieving this outcome.
Alport syndrome is a rare hereditary renal disorder with no etiologic therapy. We found that osteopontin (OPN) is highly expressed in the renal tubules of the Alport mouse and plays a causative pathological role. OPN genetic deletion ameliorated albuminuria, hypertension, tubulointerstitial proliferation, renal apoptosis, and hearing and visual deficits in the Alport mouse. In Alport renal tubules we found extensive cholesterol accumulation and increased protein expression of dynamin-3 (DNM3) and LDL receptor (LDLR) in addition to dysmorphic mitochondria with defective bioenergetics. Increased pathological cholesterol influx was confirmed by a remarkably increased uptake of injected DiI-LDL cholesterol by Alport renal tubules, and by the improved lifespan of the Alport mice when crossed with the Ldlr-/- mice with defective cholesterol influx. Moreover, OPN-deficient Alport mice demonstrated significant reduction of DNM3 and LDLR expression. In human renal epithelial cells, overexpressing DNM3 resulted in elevated LDLR protein expression and defective mitochondrial respiration. Our results suggest a potentially new pathway in Alport pathology where tubular OPN causes DNM3- and LDLR-mediated enhanced cholesterol influx and impaired mitochondrial respiration.
Icare ONE may be useful for patients monitoring their IOP values; most individuals can use the device after a short training session. Icare PRO had better results compared with Icare ONE in all IOP ranges.
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