Progression of carotid atherosclerosis and the role of endothelin in diabetic patients.

An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. Since vascular endothelium is the site of formation of several substances, we have investigated the rate of progression of carotid atherosclerosis and the contribution of endothelin (ET-1), lipid peroxides [measured as thiobarbituric acid reacting species (TBARS)] and 6-keto-Prostaglandin-F1A (6-keto-PG-F1A) at baseline and after 30-months. Fifty patients with Type 2 diabetes without evidence of macroangiopathy, hypertension, proteinuria or proliferative retinopathy, and 27 healthy, non-diabetic persons were studied. Arterial wall thickness was measured as the mean of the maximum intimal-medial thickness (IMT) in 16 carotid segments by b-mode ultrasound. The IMT values was significantly increased in diabetic subjects (at baseline: 1110 +/- 310 microm, after 30 months: 1260 +/- 280 microm, p < 0.01), but not in control subjects (1100 +/- 280 microm, 1200 +/- 290 microm, respectively). At baseline time both groups had similar levels of ET-1, TBARS and 6-keto-PG-F1A. In 30-months follow-up, the ET-1 level 8.0 pmol/l (5.8-10.7) was significantly elevated in diabetic subjects, compared with the level at baseline time 7.43 pmol/l (4.8-11.1) p < 0.01. No significant differences were found in the other examined parameters in the studied groups. Although insulin levels remained unchanged in the two studied groups, in 30 months follow-up, the insulin level in the diabetic subjects, 92.4 +/- 35.1 pmol/l was significantly elevated compared with those of control subjects 76.0 +/- 31.0 pmol/l, p < 0.05. In conclusion, endothelis is the main associate of the change of IMT value over 30 months in diabetic patients, in whom the extent of atherosclerosis was significantly greater than in control subjects.

Plasma levels of endothelin and early carotid atherosclerosis in diabetic patients.

An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. Since plasma endothelin concentrations were released from vascular endothelial cells, we have investigated the possible relationship between endothelin 1 (ET-1) and arterial wall thickness. Ninety-eight patients with Type 2 diabetes without evidence of macroangiopathy, hypertension, proteinuria or proliferative retinopathy, and 50 non-diabetic subjects were studied. After an overnight fast, blood was taken for ET-1, glucose, HbA1c, lipids, insulin and C-peptide. Arterial wall thickness was measured as the mean of the maximum intimal-medial thickness (IMT) in 16 carotid segments by B-mode ultrasound. ET-1 levels were significantly elevated in diabetic patients with IMT>1100 microm, 8.3 pmol/l (5.2-12.9) compared with control subjects, 7.6 pmol/l (5.0-11.0), p<0.01 and with diabetic subjects with IMT<500 microm, 7.43 pmol/l (4.8-11.1), p<0.01. The diabetic (IMT>1100 microm) study group had also significantly higher levels of insulin, 102.8 +/- 46.4 pmol/l vs control subjects, 77.5 +/- 32.4 pmol/l, p<0.01. In diabetic subjects, no correlation was found between ET-1 and IMT with glucose, HbA1c, lipids, age or duration of diabetes, respectively. We conclude that ET-1 levels are elevated in Type 2 diabetic patients with increased IMT. Thus providing further support for the role of endothelin in atherosclerosis.

Detection of interferon inhibitors or antagonists in gastrointestinal malignancies.

BACKGROUND/AIMS: The aim of this study was to investigate the IFN-inhibiting activity in sera from patients with gastrointestinal malignancies, exerted in a variety of cellular types, as well as to elucidate the determinants of cellular sensitivity to such IFN-inhibitors. METHODOLOGY: Sera from 16 patients with gastric cancer and 18 with colon cancer were tested, while sera from 37 healthy blood donors were used as controls. All serum samples, collected before any kind of treatment, were tested for IFN-blocking and endogenous IFN-like activity. These activities were determined by assaying the inhibition of the vesicular stomatitis virus specific cytopathic effect in three cell lines: A549 cells, intestine 407 and Chang liver cells. RESULTS: There was no endogenous IFN in any of the serum samples of patients or controls. Concerning the IFN blocking activity of serum, there was no significant difference between gastric and colon cancer, while a marked variability was prominent depending on the cell line used. 76.4% of serum samples exerted IFN-blocking activity in the A549 cells, 47.05% in the Int-407 cell line and 32.3% in the Chang Liver cells. No control sample had IFN-blocking activity in any of the cell lines tested. CONCLUSIONS: The results support a cytokine and cytokine inhibitors network, mediating pathophysiological events at the cellular level as well as the whole organism. The limited responsiveness of many neoplasias, including digestive system cancer, to IFN treatment might be due to the presence of IFN inhibitors in the patient's serum.

Effect of fosinopril sodium on early carotid atherosclerosis in diabetic patients with hypertension.

An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. We have investigated the effects of fosinopril sodium in asymptomatic diabetic hypertensive subjects on the 12-month progression of arterial wall thickness. Forty non-insulin-dependent diabetics with hypertension and without hyperlipidemia were studied. After a 4-week run-in-diet phase, oral fosinopril sodium was administered (20 mg once daily) to 20 patients randomly selected, while 20 subjects were treated only with diet. The two groups were matched for age, sex, body mass index (BMI), duration of diabetes and glycemic control. Arterial wall thickness was measured as the mean of the maximum intimal-media thickness (IMT) in 16 carotid segments by B-mode ultrasound. The IMT increase over 12 months was 4.3% in the fosinopril sodium group vs 15.1% in subjects with diet. We conclude that fosinopril sodium treatment may be useful in decreasing the progression rate.