SUMMARY BackgroundObesity surgery is acknowledged as a highly effective therapy for morbidly obese patients. Beneficial short-term effects on common comorbidities are practically undisputed, but a growing data pool from long-term follow-up reveals increasing evidence of potentially severe nutritional and pharmacological consequences. AimsTo assess the prevalence, causes and symptoms of complications after obesity surgery, to elucidate and compare therapy recommendations for macro-and micronutrient deficiencies, and to explore surgically-induced effects on drug absorption and bioavailability, discussing ramifications for long-term therapy and prophylaxis. MethodsPubMed, Embase and MEDLINE were searched using terms including, but not limited to, bariatric surgery, gastric bypass, obesity surgery and Roux-en-Y, coupled with secondary search terms, e.g. anaemia, micronutrients, vitamin deficiency, bacterial overgrowth, drug absorption, pharmacokinetics, undernutrition. All studies in English, French or German published January 1980 through March 2014 were included. ResultsMacro-and micronutrient deficiencies are common after obesity surgery. The most critical, depending on surgical technique, are hypoalbuminemia (3-18%) and deficiencies of vitamins B 1 (≤49%), B 12 (19-35%) and D (25-73%), iron (17-45%) and zinc (12-91%). Many drugs commonly administered to obese patients (e.g. anti-depressants, anti-microbials, metformin) are subject to post-operative and/or PPI-associated changes affecting bioavailability and absorption. ConclusionsComplications are associated with pre-operative and/or post-operative malnutrition or procedure-related changes in intake, absorption and drug bioavailability. The high prevalence of nutrient deficiencies after obesity surgery makes life-long nutritional monitoring and supplementation essential. Post-operative changes to drug absorption and bioavailability in bariatric patients cast doubt on the validity of standard drug dosage and administration recommendations.

Evidence is emerging that oestrogen, besides acting via classical nuclear receptors, can rapidly influence the physiology of nerve cells through other mechanisms. Oestrogens have been shown to modulate the differentiation and function of embryonic midbrain dopaminergic neurones by stimulating neurite outgrowth, expression of tyrosine hydroxylase mRNA, dopamine uptake and release in spite of the fact that dopaminergic cells in the prenatal midbrain do not express the classical oestrogen receptor. This study therefore intended to unravel possible signal transduction pathways activated by oestrogen which might be associated with the above oestrogen effects. As a physiological second-messenger mechanism, we studied the influence of oestrogen on fluctuations of intracellular Ca2+ levels [Ca2+]i by microspectrofluorimetry of the Ca2+-sensitive indicator Fura-2, in primary cultures from embryonic mouse midbrains. 17Beta-estradiol (10 nM-1 pM) but not 17alpha-estradiol increased [Ca2+]i within 1-3 s in a dose-dependent way. Removal of extracellular Ca2+ abrogated K+-stimulated Ca2+ rise but did not affect 17beta-estradiol stimulation. Pretreatment of cells with thapsigargin (1 microM, 10 min), an inhibitor of Ca2+-pumping ATPases in the endoplasmic reticulum, abolished the 17beta-estradiol effect but not the K+-stimulated [Ca2+]i rise. Oestrogen effects on [Ca2+]i were completely mimicked by using a membrane-impermeant oestrogen-BSA construct. In order to identify oestrogen-sensitive cells, some cultures were subsequently immunostained for microtubule-associated protein II, tyrosine hydroxylase, or GABA. All oestrogen-sensitive cells were immunocytochemically characterized as neurones, and about half of these responsive neurones was found to be dopaminergic or GABAergic. These results demonstrate that 17beta-estradiol is capable of rapidly modulating physiological parameters of developing midbrain neurones by directly interacting with specific membrane binding sites coupled to a signal transduction mechanism that causes a calcium release from intracellular Ca2+ stores. It is suggested that oestrogen effects on differentiation and function of midbrain dopaminergic neurones are mediated by intracellular Ca2+ signalling.

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