Obesity-associated insulin resistance (IR) is a major risk factor for developing type 2 diabetes and an array of other metabolic disorders. In particular, hepatic IR contributes to the increase in hepatic glucose production and consequently the development of fasting hyperglycemia. In this study, we explored whether kaempferol, a flavonoid isolated from Gink go biloba, is able to regulate hepatic gluconeogenesis and blood glucose homeostasis in high-fat diet-fed obese mice and further explored the underlying mechanism by which it elicits such effects. Oral administration of kaempferol (50 mg/kg/day), which is the human equivalent dose of 240 mg/day for an average 60 kg human, significantly improved blood glucose control in obese mice, which was associated with reduced hepatic glucose production and improved whole-body insulin sensitivity without altering body weight gain, food consumption or adiposity. In addition, kaempferol treatment increased Akt and hexokinase activity, but decreased pyruvate carboxylase (PC) and glucose-6 phosphatase activity in the liver without altering their protein expression. Consistently, kaempferol decreased PC activity and suppressed gluconeogenesis in HepG2 cells as well as primary hepatocytes isolated from the livers of obese mice. Furthermore, we found that kaempferol is a direct inhibitor of PC. These findings suggest that kaempferol may be a naturally occurring antidiabetic compound that acts by suppressing glucose production and improving insulin sensitivity. Kaempferol suppression of hepatic gluconeogenesis is due to its direct inhibitory action on the enzymatic activity of PC.

In diabetes mellitus, excessive rate of glucose production from the liver is considered a primary contributor for the development of hyperglycemia, in particular, fasting hyperglycemia. In this study, we investigated whether kaempferol, a flavonol present in several medicinal herbs and foods, can be used to ameliorate diabetes in an animal model of insulin deficiency and further explored the mechanism underlying the anti-diabetic effect of this flavonol. We demonstrate that oral administration of kaempferol (50 mg/kg/day) to streptozotocin-induced diabetic mice significantly improved hyperglycemia and reduced the incidence of overt diabetes from 100 % to 77.8%. This outcome was accompanied by a reduction in hepatic glucose production and an increase in glucose oxidation in the muscle of the diabetic mice, whereas body weight, calorie intake, body composition, and plasma insulin and glucagon levels were not altered. Consistently, treatment with kaempferol restored hexokinase activity in the liver and skeletal muscle of diabetic mice while suppressed hepatic pyruvate carboxylase activity and gluconeogenesis. These results suggest that kaempferol may exert antidiabetic action via promoting glucose metabolism in skeletal muscle and inhibiting gluconeogenesis in the liver.

An evidence-based review of the drugs available for the medical management of childhood glaucoma is presented; almost all of the drugs are not licensed for use in children. Despite this, most topical drugs are safe; however, there are some significant exceptions, such as brimonidine, which may cause apnea, among other life-threatening adverse events, in infants. Broad families of drugs are available including topical adrenoceptor antagonists, topical and systemic carbonic anhydrase inhibitors, prostaglandin analogs, adrenoceptor agonists, parasympathomimetics, and combination preparations. These drugs help to reduce intraocular pressure by reducing aqueous production or increasing the outflow facility. The variety of anti-ocular hypertensive medications for childhood glaucoma has increased in recent years. The vast majority of data on these medications are from adult studies but each year more experience of their use in pediatric glaucoma is gained. In general, topical treatment is well tolerated; however, the prescribing clinician and carers should be aware of potential adverse effects and how they may present.

ICU antioxidant supplementation did not decrease the incidence of atrial arrhythmias, nor alter the time from admission to development of arrhythmia. A longer expected survival time was observed in the antioxidant group compared with the control group but without a change in overall mortality between groups.

Proteus syndrome arises as a result of a post-zygotic mosaic activating mutation in the AKT1 oncogene, resulting in disproportionate overgrowth of affected tissues. A number of ocular complications have also been reported. We present a unique finding in a patient with Proteus syndrome, fulfilling the clinical criteria with molecular confirmation (3)(15), who was found to have misaligned foveal architecture and additional segmental retinal dysfunction in her right eye. Pattern electroretinography and multi-focal ERG findings demonstrate retinal dysfunction, which was correlated with structural alterations identified with ultrawide-field imaging and optical coherence tomography of the maculae. We propose this patient has an asymmetric development of her fovea as the result of AKT1 mutation, either through disruption in the AKT1 pathway or disproportionate inner retinal growth.