RESUMO
The ever-changing landscape of dieting and its correlation with health outcomes have continued to evolve with time. New diets appear and disappear just as quickly as they gain notoriety. This is a rare case of a 67-year-old female with a history of type II diabetes who presented with generalized weakness, nausea, and vomiting, and was found to have severe anion gap metabolic acidosis. In an effort to lose weight, she was combining a ketogenic diet with prolonged fasting and exogenous ketone supplement use that she purchased online. The patient reported drinking an exogenous ketone ester supplement that contained 30 g of D-beta hydroxybutyrate (BHB) per serving, three times per day. This case is unique in that the patient was initially thought to be in diabetic ketoacidosis upon arrival, but after further investigation into her initial labs, medication, and social history, the underlying factor for hospitalization became evident; that is, a combination of a ketogenic diet with prolonged fasting and exogenous BHB-induced ketoacidosis in the setting of type II diabetes. Thus, this case highlights the importance of thorough history taking, the dangers of over-the-counter supplement consumption, and the risks consumers inherit with trend dieting.
RESUMO
Complement activation, an integral arm of innate immunity, may be the critical link to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Whereas we have previously reported elevated anaphylatoxins-complement component 3a (C3a) and complement component 5a (C5a)-in IPF, which interact with TGF-ß and augment epithelial injury in vitro, their role in IPF pathogenesis remains unclear. The objective of the current study is to determine the mechanistic role of the binding of C3a/C5a to their respective receptors (C3aR and C5aR) in the progression of lung fibrosis. In normal primary human fetal lung fibroblasts, C3a and C5a induces mesenchymal activation, matrix synthesis, and the expression of their respective receptors. We investigated the role of C3aR and C5aR in lung fibrosis by using bleomycin-injured mice with fibrotic lungs, elevated local C3a and C5a, and overexpression of their receptors via pharmacologic and RNA interference interventions. Histopathologic examination revealed an arrest in disease progression and attenuated lung collagen deposition (Masson's trichrome, hydroxyproline, collagen type I α 1 chain, and collagen type I α 2 chain). Pharmacologic or RNA interference-specific interventions suppressed complement activation (C3a and C5a) and soluble terminal complement complex formation (C5b-9) locally and active TGF-ß1 systemically. C3aR/C5aR antagonists suppressed local mRNA expressions of tgfb2, tgfbr1/2, ltbp1/2, serpine1, tsp1, bmp1/4, pdgfbb, igf1, but restored the proteoglycan, dcn Clinically, compared with pathologically normal human subjects, patients with IPF presented local induction of C5aR, local and systemic induction of soluble C5b-9, and amplified expression of C3aR/C5aR in lesions. The blockade of C3aR and C5aR arrested the progression of fibrosis by attenuating local complement activation and TGF-ß/bone morphologic protein signaling as well as restoring decorin, which suggests a promising therapeutic strategy for patients with IPF.-Gu, H., Fisher, A. J., Mickler, E. A., Duerson, F., III, Cummings, O. W., Peters-Golden, M., Twigg, H. L., III, Woodruff, T. M., Wilkes, D. S., Vittal, R. Contribution of the anaphylatoxin receptors, C3aR and C5aR, to the pathogenesis of pulmonary fibrosis.