Medical hypotheses
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Isoflurane is one of the most commonly used inhalation anesthetic in neonatal anaesthesia. It has been suggested that isoflurane can induce caspase activation and apoptosis when applied in a clinically relevant concentration in the developing brain. Recent researches have indicated that a clinically relevant isoflurane treatment may induce neurodegeneration and apoptosis by activating the endoplasmic reticulum (ER) membrane inositol 1,4,5-trisphosphate (IP(3)) receptor, producing excessive calcium release from ER to the cytoplasm and triggering apoptosis. ⋯ Previous studies have found that during early postnatal life, activation of gamma-aminobutyric acid (GABA(A)) receptor reduces the voltage-dependent Mg(2+) block of N-methyl-d-aspartate (NMDA) channels in neurons and increases cytosolic calcium levels by potentiated the Ca(2+) influx through NMDA channels; while in the adult, it may enhance the voltage-dependent Mg(2+) block of NMDA channels and decrease the Ca(2+) influx through NMDA channels. Since isoflurane acts at the GABA(A) receptor in an agonistic manner, here we presume that isoflurane increases intracellular calcium in neonatal neurons not only by activating IP(3) receptors in the endoplasmic reticulum (ER) membrane, but also by activating the GABA(A) receptor and depolarizing the postsynaptic membrane enough to facilitate NMDA receptor-mediated Ca(2+) influx. Meanwhile, we hypothesized that ketamine, a widely used pediatric anesthetic, acts as a noncompetitive antagonist of the NMDA type of glutamate receptors, which may be the best partner for isoflurane in neonatal anesthesia for it may attenuate isoflurane-induced caspase activation and apoptosis in the neonatal neurons by inhibiting the isoflurane-induced elevation in cytosolic calcium not only by blocking the NMDA receptors, but also by suppressing inositol triphosphate formation in the cytoplasm.
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Possible link of food-derived advanced glycation end products (AGEs) to the development of diabetes.
China Da Qing diabetes prevention study has recently shown that group-based lifestyle interventions over six years can prevent or delay the development of diabetes in patients with impaired glucose tolerance (IGT) for up to 14 years after the active intervention. These findings suggest the sustained beneficial effects of lifestyle interventions to prevent diabetes in at-risk patients for diabetes. Therefore, the clinical study suggests that so-called 'metabolic memory' is involved in the development of diabetes. ⋯ That is, intake of food-derived AGEs may be suppressed in the lifestyle intervention group, which could reduce the risk for the development of diabetes in high-risk patients with IGT. Therefore, it is an interesting issue to clarify whether food-derived AGEs are actually restricted during the active intervention period and if circulating or tissue AGE levels at the closure of the China Da Qing diabetes prevention study could predict the risk for the development of diabetes 14 years after the trial. This additional, clinical investigation may provide us more information about whether restriction of food-derived AGEs is beneficial for the prevention of the development of diabetes in high-risk patients and may be a novel therapeutic target to prevent diabetes and its related complications.
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Recurrent aphthous ulcer (RAU) is the most common ulcer of oral non-keratinized mucosa, but the treatment is always limited at present. Considering the multifactorial etiology of RAU, a novel therapeutic agent with multi-bioactivties should be presented. ⋯ The major component of garlic is allicin, which could effectively decrease inflammatory factors secretion, reduce the migration of neutrophils, inhibit bacterium and virus, antagonize oxidation and regulate immunity. By these bioactivities of anti-inflammation, anti-microbial activity, anti-oxidation and immunomodulation, the allicin may be an effective therapeutic candidate to control the pain, promote ulcer healing and prevent the recurrence of RAU.