Repair of human endometrium after menstruation and preparation of the endometrium for implantation involves profound angiogenic changes. Vascular endothelial cell growth factor (VEGF) is a recently identified growth factor with significant angiogenic properties. Four species of mRNA encoding VEGFs were identified in human endometrium and myometrium. All species were present throughout the menstrual cycle. Two species, VEGF165 and VEGF121, were present in peripheral leukocytes, indicating tissue-specific splicing of the two other VEGF transcripts. In situ hybridization of mRNA encoding VEGF was not restricted to vascular smooth muscle but was present in epithelial and stromal cells of endometrium throughout the cycle, and the distribution changed during the course of the cycle. All four species of VEGF were expressed by the endometrial carcinoma cell lines Ishikawa, HEC 1-A, and HEC 1-B. Estradiol increased steady-state levels of mRNA encoding VEGF in a dose- and time-dependent manner in HEC 1-A cells. Conditioned medium from these cells possessed angiogenic activity that was depleted by passage through a heparin affinity column. None of the cell lines demonstrated mRNA for acidic or basic fibroblast growth factor (FGF), despite previous reports of the identification of immunoreactive basic FGF in HEC 1-A and HEC 1-B cells. These findings show that VEGFs, not FGFs, are the principal angiogenic growth factors secreted by these cells and that human endometrium expresses a secreted angiogenic growth factor whose site of expression changes during the menstrual cycle.

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The concentrations of Cu and Zn were determined in the plasma, granulocytes and mononuclear cells of 26 patients with diabetes mellitus and 26 age and sex-matched controls. In addition, Cu was measured in both washed and unwashed red blood cells, and Cu,Zn-superoxide dismutase (SOD) activity measured in washed red blood cells. Cu and Zn were determined by Zeeman-effect graphite furnace atomic absorption spectrometry following separation of plasma and red blood cells, and the white blood cell fractions (granulocytes and mononuclear cells) by density gradient centrifugation. There were no significant differences in any of the matching factors, or lipid profiles, between the groups. Plasma Zn was reduced by 17% in diabetics, compared with the controls (P = 0.0001). Neither the plasma nor the red blood cell Cu concentrations were significantly different. Of the white blood cell fractions, only mononuclear cell Cu was significantly different (30% lower in diabetics P = 0.0035, The red blood SOD activity was reduced in diabetics by over 12%, but this difference was non-significant (P = 0.0872). There was a significant negative correlation between washed red blood cell Cu and the duration of diabetes (r = -0.613, P = 0.0069). In conclusion, the copper and zinc status of these diabetic patients was reduced, providing further evidence of a role for these antioxidant trace elements in this disease.

The presence of mRNA for epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) was demonstrated in small fragments of human endometrium and decidua by use of the technique of reverse transcriptase-polymerase chain reaction with nested oligonucleotide primers. The presence of mRNA encoding EGF and TGF alpha has not been shown in human endometrium previously. Other studies using conventional techniques, such as Northern blot or in-situ hybridization, showed the presence in low copy number of EGF but not TGF alpha in murine endometrium. Messenger RNA for EGF was not present in peripheral leukocytes or platelets, suggesting an endometrial source for the message. Messenger RNA for TGF alpha was found in these blood components, thus preventing confirmation of the source of TGF alpha mRNA.

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Twenty-four middle-aged healthy men were given a low-fat high-carbohydrate (5 . 5 g fat; L), or a moderately-fatty, (25 . 7 g fat; M) breakfast of similar energy contents for 28 d. Other meals were under less control. An oral glucose tolerance test (OGTT) was given at 09.00 hours on day 1 before treatment allocation and at 13.30 hours on day 29. There were no significant treatment differences in fasting serum values, either on day 1 or at the termination of treatments on day 29. The following was observed on day 29: (1) the M breakfast led to higher OGTT C-peptide responses and higher areas under the curves (AUC) of OGTT serum glucose and insulin responses compared with the OGTT responses to the L breakfast (P < 0 . 05); (2) treatment M failed to prevent OGTT glycosuria, eliminated with treatment L; (3) serum non-esterified fatty acid (NEFA) AUC was 59 % lower with treatment L than with treatment M, between 09.00 and 13.20 hours (P < 0 . 0001), and lower with treatment L than with treatment M during the OGTT (P = 0 . 005); (4) serum triacylglycerol (TAG) concentrations were similar for both treatments, especially during the morning, but their origins were different during the afternoon OGTT when the Svedberg flotation unit 20-400 lipid fraction was higher with treatment L than with treatment M (P = 0 . 016); plasma apolipoprotein B-48 level with treatment M was not significantly greater than that with treatment L (P = 0 . 086); (5) plasma tissue plasminogen-activator activity increased after breakfast with treatment L (P = 0 . 0008), but not with treatment M (P = 0 . 80). Waist:hip circumference was positively correlated with serum insulin and glucose AUC and with fasting LDL-cholesterol. Waist:hip circumference and serum TAG and insulin AUC were correlated with factors of thrombus formation; and the OGTT NEFA and glucose AUC were correlated. A small difference in fat intake at breakfast has a large influence on circulating diurnal NEFA concentration, which it is concluded influences adversely glucose tolerance up to 6 h later.

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