Molecular mechanisms predisposing people to insulin resistance are starting to emerge. Altered insulin signaling for hepatic gluconeogenesis and muscle glucose uptake is thought to play a central role. Development under suboptimal conditions is also known to increase the risk of insulin resistance in adulthood. However, the partial contributions of reduced oxygen vs. nutrient delivery to the fetus, two common adverse conditions in utero, to developmental programming of insulin resistance remain unknown. The aim of this study was to determine the effects of developmental hypoxia or undernutrition on the expression of insulin-signaling proteins in liver and skeletal muscle in adult rat offspring. We show that the expression of hepatic phospho-Akt and muscle Akt2 were significantly reduced in offspring of hypoxic, relative to offspring from normoxic or undernourished, pregnancies. Hepatic Akt-1, Akt-2, and PKCζ protein expression was reduced in offspring from both hypoxic and undernourished pregnancies. Muscle GLUT4 expression was decreased in undernourished, and further decreased in hypoxic, offspring. These findings link prenatal hypoxia to down-regulation of components of hepatic and muscle Akt expression in adult offspring. Akt may represent a pharmaceutical target for clinical intervention against the developmental programming of metabolic disease resulting from prenatal hypoxia.

The cell population kinetics of the villus epithelium of the mouse have been analysed with respect to the size, flux and time. Microdissection methods were employed to measure the villus cell population size and yielded reproducible, precise results. There was a proximodistal negative size gradient in villus cell population and, in those villi of normal morphology, there was a good correlation with the usual morphometric estimators such as height and row count, although correlation was improved by a product variable consisting of a height multiplied by a width parameter.

Palmoplantar pustulosis is a chronic pustular dermatitis of the palms and soles, which is frequently associated with significant pruritus and pain that often limit daily activities. We present the case of a 36-year-old man with severe palmoplantar pustulosis who failed multiple medical therapies and demonstrated marked improvement with high-dose rate brachytherapy. Brachytherapy has the advantage of providing a conformal dose distribution over complex curved surfaces, such as the foot and ankle. Our observation suggests that brachytherapy may be a well-tolerated treatment option for patients with severe, refractory palmoplantar pustulosis.

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SUMMARY A case report is presented giving details of a patient who showed the unusual combination of secondary hypothyroidism associated with primary testicular disease; the latter was probably prepubertal in origin, and there was evidence of eunuchoidism. Reference is made to previous reports of the co-existence of deficiency in both thyroid and testis, and to possible mechanisms involved in the relationships which may exist between these conditions.