Androgens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, we demonstrate that megalin, an endocytic receptor in reproductive tissues, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females. Both processes are critically dependent on sex-steroid signaling, and similar defects are seen in animals treated with androgen- or estrogen-receptor antagonists. Thus, our findings uncover the existence of endocytic pathways for protein bound androgens and estrogens and their crucial role in development of the reproductive organs.

There was no significant relationship between the survival rate in dogs with nonseptic SIRS or sepsis and the initial serum CRP concentrations. There was a correlation between decreasing CRP concentrations and recovery from disease. However, the changes in CRP concentrations over a 3-day period correctly predicted survival in 94% of dogs and death in 30% of the dogs (false positive rate 22%).

Background: In mammals the composition of milk changes during early lactation showing a rapid decline in fat-soluble vitamins and a continuous increase in total lipids. Changes in the concentrations of carotenoids, vitamin A, α-tocopherol and total lipids in human milk (colostrum, transitory and mature milk) were studied to understand this not well characterised phenomenon. Methods: Colostrum, transitory and mature milk was collected from 21 women and analysed for carotenoids, vitamin A and α-tocopherol by HPLC. Results: Total lipids increased from the lowest levels in colostrum (1.5 ± 1.6 mg/ml) to the highest in transitory milk (3.6 ± 2.5 mg/ml, p < 0.01). Contrary to this, levels of total carotenoids (236.7 ± 121.9 ng/ml), vitamin A (1.02 ± 0.56 µg/ml) and α-tocopherol (11.8 ± 6.3 µg/ml) were highest in colostrum and declined significantly during the first weeks of lactation (63.2 ± 23.3 ng/ml, 0.33 ± 0.14 µg/ml, 2.7 ± 1.1 µg/ml, respectively; p < 0.001). Conclusions: The magnitude of decrease was not the same for all carotenoids and was dependent on the polarity of the carotenoid with the smallest decrease in the polar carotenoids. This might be due to differences in the distribution of carotenoids among plasma lipoproteins and might point to possible selective mechanisms being involved in the transfer of these components in early human milk.

In mammals the composition of milk changes during early lactation, with a rapid decline of fat-soluble vitamins and a continuous increase in total lipids. The mechanisms underlying this phenomenon are not well understood, but might involve selective mechanisms related to mammary uptake or secretion into the milk. Since carotenoids are specifically distributed among the lipoprotein fractions in plasma, the simultaneous determination of carotenoids in plasma, lipoprotein fractions and milk might offer an opportunity to gain insight into this phenomenon. In 21 healthy mothers carotenoids in plasma and lipoprotein fractions were investigated at day 2 and 19 and milk on day 4 and 19 after delivery. Plasma levels of alpha-tocopherol and cholesterol as well as lutein, zeaxanthin and cryptoxanthin were significantly lower later in lactation (day 19) than shortly after birth (P < 0.01). The stage of lactation had no effect on the distribution of carotenoids and alpha-tocopherol among the plasma lipoprotein fractions. In milk, triacylglycerol increased (P < 0.01). In contrast, levels of carotenoids, alpha-tocopherol and vitamin A were highest in colostrum and declined (P < 0.01). Because the magnitude of decrease was not the same in all carotenoids, the carotenoid pattern changed substantially. In colostrum the carotenoid pattern resembled those of plasma and the low-density lipoprotein fraction. In mature milk it was similar to the pattern found in the high density lipoprotein fraction. Based on these observations a selective mechanism might be responsible for the transfer of these components in milk involving different lipoprotein fractions at specific times of lactation.

The noncovalent binding of selected phenolic compounds (chlorogenic-, ferulic-, gallic acid, quercetin, rutin, and isoquercetin) to proteins (HSA, BSA, soy glycinin, and lysozyme) was studied by an indirect method applying the quenching of intrinsic tryptophan fluorescence. From the data obtained, the binding constants were calculated by nonlinear regression (one site binding; y = Bx/k + x). It has been reported that tannins inhibit human salivary amylase and that these complexes may reduce the development of cariogenic plaques. Further, amylase contains two tryptophan residues in its active site. Therefore, in a second part of the study involving 31 human subjects, evidence was sought for noncovalent interactions between the phenols of green tea and saliva proteins as measured by the fluorescence intensity. Amylase activity was determined before and after the addition of green tea to saliva of 31 subjects. Forty percent of the subjects showed an increase in amylase activity contrary to studies reporting only a decrease in activity. The interactions of tannin with amylase result in a decrease of its activity. It still remains to be elucidated why amylase does not react uniformly under conditions of applying green tea to saliva. Further, in terms of using phenols as caries inhibitors this finding should be of importance.

Malnutrition, poor health, hunger, and even starvation are still the world's greatest challenges. Malnutrition is defined as deficiency of nutrition due to not ingesting the proper amounts of nutrients by simply not eating enough food and/or by consuming nutrient-poor food in respect to the daily nutritional requirements. Moreover, malnutrition and disease are closely associated and incidences of such diet-related diseases increase particularly in low-and middle-income states. While foods of animal origin are often unaffordable to low-income families, various neglected crops can offer an alternative source of micronutrients, vitamins, as well as health-promoting secondary plant metabolites. Therefore, agricultural and horticultural research should develop strategies not only to produce more food, but also to improve access to more nutritious food. In this context, one promising approach is to promote biodiversity in the dietary pattern of low-income people by getting access to nutritional as well as affordable food and providing recommendations for food selection and preparation. Worldwide, a multitude of various plant species are assigned to be consumed as grains, vegetables, and fruits, but only a limited number of these species are used as commercial cash crops. Consequently, numerous neglected and underutilized species offer the potential to diversify not only the human diet, but also increase food production levels, and, thus, enable more sustainable and resilient agro-and horti-food systems. To exploit the potential of neglected plant (NP) species, coordinated approaches on the local, regional, and international level have to be integrated that consequently demand the involvement of numerous multi-stakeholders. Thus, the objective of the present review is to evaluate whether NP species are important as "Future Food" for improving the nutritional status of humans as well as increasing resilience of agro-and horti-food systems.

Plasma retinol-binding protein 4 (RBP4) may be a new adipokine linked to obesity-induced insulin resistance and type 2 diabetes. The impact of diabetic nephropathy on plasma RBP4 levels, however, is not known. We tested the hypothesis that microalbuminuria is associated with elevated plasma concentrations of RBP4 in type 2 diabetic subjects. Retinol, its binding protein and transthyretin (TTR) were measured in the plasma and urine of 62 type 2 diabetic subjects, 26 of whom had microalbuminuria. The results were compared to 35 healthy control subjects. Despite no differences in plasma retinol, concentrations of the RBP4 were significantly elevated in plasma of diabetic patients and significantly higher in those with microalbuminuria. The higher plasma levels of the binding protein in subjects with microalbuminuria were accompanied by both significantly elevated plasma TTR and increased urinary levels of RBP4. There were no correlations of plasma-binding protein levels and parameters of insulin resistance. Our study suggests that plasma RBP4 levels in type 2 diabetic patients are affected by incipient nephropathy. Therefore, further studies evaluating RBP4 as a regulator of systemic insulin resistance and type 2 diabetes will need to take renal function into consideration.

OBJECTIVE-It has been suggested that retinol-binding protein 4 (RBP4) links adiposity, insulin resistance, and type 2 diabetes. However, circulating RBP4 levels are also affected by kidney function. Therefore, the aim of this study was to test whether RBP4 serum levels are primarily associated with kidney function or type 2 diabetes.RESEARCH DESIGN AND METHODS-RBP4 serum concentration was determined by enzyme-linked immunosorbent assay in 126 nondiabetic and 104 type 2 diabetic subjects. The study population was divided according to estimated glomerular filtration rate (eGFR) into the following groups: eGFR Ͼ90 ml/min per 1.73 m 2 (n ϭ 53), 60 -90 ml/min per 1.73 m 2 (n ϭ 90), 30 -60 ml/min per 1.73 m 2 (n ϭ 38), and Ͻ30 ml/min per 1.73 m 2 (n ϭ 49). Each group was subdivided into nondiabetic and type 2 diabetic subjects.RESULTS-RBP4 serum concentration was elevated (2.65 vs. 2.01 mol/l; P Ͻ 0.001) and eGFR was reduced (56 vs. 74 ml/min per 1.73 m 2 ; P Ͻ 0.001) in type 2 diabetic vs. nondiabetic subjects, respectively. By stratifying for eGFR, no more differences in RBP4 serum concentration were detectable between type 2 diabetic and nondiabetic subjects. A linear regression analysis revealed an influence of eGFR (r ϭ Ϫ0.477; P Ͻ 0.001) but not A1C (r ϭ 0.093; P ϭ 0.185) on RBP4 serum concentration.CONCLUSIONS-Existing human data showing elevated RBP4 levels in type 2 diabetic patients may be the result of moderate renal insufficiency rather than support for the suggestion that RBP4 links obesity to type 2 diabetes. Diabetes 57:3323-3326, 2008 R etinol-binding protein 4 (RBP4) is a small visceral protein (ϳ21 kDa), mainly synthesized in the liver and catabolized in the kidneys after glomerular filtration (1). To prevent the renal loss of RBP4 before delivering its ligand retinol to the target tissues, RBP4 is complexed by transthyretin, a homotetrameric protein with a molecular weight of ϳ55 kDa, formerly known as prealbumin (2). RBP4 was recently discussed as a new adipokine that is possibly linked to insulin resistance and type 2 diabetes (3-5). Although it is known that RBP4 serum levels are elevated in states of impaired kidney function (1,6 -8) (which is a common feature of diabetes, metabolic syndrome, and obesity [9,10]), parameters of kidney function have not been reported in most of the studies concerning RBP4 and insulin resistance and/or diabetes (3-5). Therefore, the aim of this study was to determine whether RBP4 serum concentration is associated with kidney function rather than type 2 diabetes. RESEARCH DESIGN AND METHODSSerum samples of 230 age-matched subjects (131 male, including 59 with type 2 diabetes, and 99 female, including 45 with type 2 diabetes) were collected by the Department of Endocrinology, Diabetes and Nutrition and the Department of Nephrology-both of Charité -Universitä tsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany-and by the Department of Clinical Nutrition of the German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany. The study protocol was approved by ...