Fluoride exposure is widespread, with drinking water commonly containing natural and artificially added sources of the ion. Ingested fluoride undergoes absorption across the gastric and intestinal epithelia. Previous studies have reported adverse gastrointestinal effects with high levels of fluoride exposure. Here, we examined the effects of fluoride on the transepithelial ion transport and resistance of three intestinal epithelia. We used the Caco-2 cell line as a model of human intestinal epithelium, and rat and mouse colonic epithelia for purposes of comparison. Fluoride caused a concentration-dependent decline in forskolin-induced Cl -secretion and transepithelial resistance of Caco-2 cell monolayers, with an IC 50 for fluoride of about 3 mM for both parameters. In the presence of 5 mM fluoride, transepithelial resistance fell exponentially with time, with a t 1/2 of about 7 hours. Subsequent imaging by immunofluorescence and scanning electron microscopy showed structural abnormalities in Caco-2 cell monolayers exposed to fluoride. The Young's modulus of the epithelium was not affected by fluoride, although proteomic analysis revealed changes in expression of a number of proteins, particularly those involved in cell-cell adhesion. In line with its effects on Caco-2 cell monolayers, fluoride, at 5 mM, also had profound effects on Cl -secretion and transepithelial resistance of both rat and mouse colonic epithelia. Our results show that treatment with fluoride has major effects on the structure, function, and proteome of intestinal epithelia, but only at concentrations considerably higher than those likely to be encountered in vivo, when much lower fluoride doses are normally ingested on a chronic basis.
An 11-year-old girl presented to the Paediatric department with a non-blanching rash, which was vasculitic in appearance and tender to touch, but not pruritic. The typical feature was hyperaesthesia, starting on her left forearm. The child was well and afebrile, with no history of: musculoskeletal problems; red eyes; mouth ulcers; trauma or insect bites. The girl lived with her parents and two siblings, and had neither a past medical history nor family history of vasculitis.At initial presentation, the paediatrician corroborated the GP’s working diagnosis of shingles with neuropathic pain; the patient was given an extended course of acyclovir, plus amitriptyline. During follow up, the patient reported improved pain, whilst the rash had completely subsided.However, two weeks later, the girl returned with a similar painful rash. Upon dermatological review, she received IV antibiotics for suspected chronic meningococcemia. Over the next eight months, the rash waxed and waned, and often healed completely.She received, at various stages, diagnoses of: shingles with neuropathic pain; chronic meningococcemia; segmented pigmented dermatosis; cutaneous vasculitis; atypical Henoch-Schönlein purpura; and potential urticarial vasculitis.Altogether, this patient had 13 paediatric outpatient appointments, one admission, two reviews in the acute paediatric unit and two tertiary dermatology referrals.She had 29 blood tests, and numerous urine dipsticks. Her full blood count, coagulation screen, inflammatory markers and autoimmune screen were normal.She received three courses of acyclovir, one course of antibiotics, regular analgesia, amitriptyline and six weeks of prednisolone.She also had two skin biopsies, which reported an element of purpura without any vasculitis.Given purpura without vasculitis, the revelation that our patient was a teenager going through a stressful period at school caused us to consider and discuss an exogenous cause (deliberate self-infliction). The rash’s subsequent complete resolution within a few months strengthens this hypothesis.Clinicians frequently care for children with complex or unconventional presentations. In an era of defensive medicine, we request a plethora of investigations and specialist opinions before diagnoses like self-inflicted injuries are considered. This case raises ethical questions about how far we should go in our pursuit of an intellectually satisfying definitive diagnosis.
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