ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01801.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01802.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01803.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.To elucidate the biosynthetic processing of the precursor for vasoactive intestinal peptide (prepro‐VIP) in tumours producing VIP we have used newly developed radioimmunoassays directed against the five functional domains of the VIP precursor molecule: preproVIP 22–79, peptide histidine methionine (PHM), preproVIP 111–122, VIP and preproVIP 156–170 in combination with HPLC to identify and quantify the peptides in tumour specimen and plasma from patients with the watery diarrhoea syndrome. Elevated quantities of all the five peptides were found in the 13 tumours (nine neurogenic tumours, one pheochromocytoma, three pancreatic carcinomas) examined. The preproVIP derived peptides were expressed in non‐equimolar amounts and the relative proportion of the various peptides differed markedly from tumour to tumour. The pheochromocytoma was the only tumour type which contained large amounts of preproVIP 156–170 in comparison with the other peptides. A proportion of the VIP precursor which varied from 7% to 73% followed a pathway in which the dibasic conversion site after PHM was uncleaved as evidenced by the presence of PHV, a C‐terminally extended form of PHM. It was also found that unlike normal tissue a fraction of the C‐terminal VIP pre‐cursor peptide, preproVIP 156–170, was having its C‐terminal lysine residue removed during processing. The findings indicate that various post‐translational processing pathways of preproVIP exist. All the peptide sequences produced in the tumour tissue were secreted as evidenced by their presence in plasma in elevated concentrations. The plasma levels of preproVIP 22–79, prepro VIP 111–122 and PHV exceeded those of the remaining preproVIP‐derived peptides suggesting that determination of these peptides in patients with VIP‐secreting tumours

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01804.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.Abnormalities in cholesteryl ester transfer (CET) may play a role in the development of diabetic arterial vascular complications. To assess this important step systematically in reverse cholesterol transport, we have studied 20 treated, clinically stable, normolipidaemic patients. Contrary to the impairment in CET described previously in NIDDM, the mass of CE transferred from HDL to VLDL+LDL was significantly greater in IDDM patients than in controls at 1,2, and 4 h (P<0.001). When thed<1.063 plasma fractions from IDDM subjects were combined with controlsd1.063 fractions.Changes observed in lipoprotein core lipid composition were consistent with accelerated CET occurring in IDDMin vivo: the TG/CE core lipid ratio was decreased in VLDL from six subjects (diabetic 9.5±0.8 vs control 12.9±3.4;P<0.1) and increased in their HDL (diabetic 0.55±0.11 vs control 0.42±0.04;P<0.025). No correlation was demonstrable between estimates of diabetic control (glycoalbumin, fasting glucose) and CET. These data indicate that CET may be abnormally increased in normolipidaemic IDDM patients. A defect of this type may be atherogenic because it increases the number of lipoprotein particles in plasma which resemble cholesteryl ester‐enriched chylomicron and VLDL remnants but whose normal receptor‐mediated catabolism may be

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01805.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.We investigated the dose‐response characteristics of glucose‐induced insulin release and the influence of hyperglycaemia on arginine‐induced insulin secretion in eight non‐obese subjects with NIDDM and in eight non‐diabetic volunteers. Plasma C‐peptide levels, achieved during 60 min hyperglycaemic clamps with and without the infusion of a primed continuous infusion of arginine (infusion rate 15 mg kg‐1min‐1) during the last 30 min, were analysed with a modified Michaelis‐Menten equation. The insulin secretory capacity (Vmax) for glucose‐stimulated insulin release snowed a trend towards a negative correlation with the fasting blood glucose in the NIDDM subjects (r=0.68,P=0.6); it was lower than theVmaxof non‐diabetic controls (2.2±0.2 vs 4.2±0.4 nmol 1‐1respectively;P0.2).Combined glucose‐arginine stimulation significantly increased insulin release. TheVmaxfor both phases were significantly lower in NIDDM patients than in controls (2.3±0.2 vs 5.0±0.9 and 3.8±0.5 vs 8.5±0.9 nmol 1‐1respectively;P<0.01). In both NIDDM patients and controls, the ED50of the influence of glucose on first‐phase arginine‐induced insulin release was significantly lower than the ED50for the second phase (8.2±0.8 vs 10.5±1.1 mmol 1‐1(NIDDM) and 9.4±1.4 vs 11.6±0.9 mmol 1‐1(non‐diabetic subjects) respectively;P<0.02). No differences in ED50were seen between the two groups.In NIDDM patients, the fasting blood glucose level was negatively correlated with the Vmaxof the second phase of glucose‐arginine‐induced insulin release (r=‐0.70,P=0.05).We conclude that (1) insulin secretory capacity is reduced in NIDDM both for stimulation with glucose and with arginine; (2)

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01806.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.We measured the renal haemodynamic and proteinuric response to a meat meal (MM) in ten persistently proteinuric insulin‐dependent diabetic patients in a randomized cross‐over study of 3 weeks on low protein diet (LPD) or normal protein intake (NPD). On LPD, protein intake (0.64±0.05 vs 1.15±0.09 g kg‐1body weight (BW) per day,P<0.001), plasma urea (6.6±1.3 vs 11.0±2.0 mmol 1‐1,P<0.01) and urea appearance (0.06±0.01 vs 0.16±0.03 gN kg‐1body weight per day,P<0.001) were lower. Baseline glomerular filtration rate (GFR), renal plasma flow (RPF) and renal vascular resistance (RVR) were similar on the two diets and there were no significant average changes in these variables after the meat meal on either diet (NPD, before vs after MM: GFR: 67±11 vs 71±13 ml min‐11±73 m‐2; RPF: 479±70 vs 512±81 ml min‐11±73 m‐2; RVR: 181±45 vs 179±52 mmHg min‐11‐1); (LPD, before vs after MM: GFR: 64±10 vs 67±11 ml min‐11±73 m‐2; RPF: 506±60 vs 533±52 ml min‐11±73 m‐2; RVR: 151±28 vs 146±32 mmHg min‐11‐1). However, all patients with baseline GFR above 60 ml min‐11.73 m‐2showed a GFR rise in response to the meat meal on both diets, while patients with lower baseline values tended to reduce their GRF. Baseline fractional albumin clearance was lower on LPD (geometric mean [range]: 1.15 [0.10–50.53].10‐4) than on NPD (l.74[0.17–56.99]×10‐4). MM produced a significant increase in the fractional clearance of albumin of ±69% on NPD to 2±94(0±37–113±42)×10‐4(P<0.02), and of ±62% on LPD to 1.86(0.13–82.90)×10‐4(P<0.01). The magnitude of these changes was not statistically different. In proteinuric insulin‐dependent diabetic patients on NPD the renal vasodilatory response to a meat meal is blunted particularly when basal GFR is depressed. LPD does not restore physiological renal response and, whil

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01807.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.The effects of leukotriene D4(LTD4) and leukotriene E4(LTE4) on renal microcirculation were determined on normal and hydronephrotic female Wistar rats. In normal kidneys, the effects of LTD4on total renal blood flow and glomerular filtration rate were measured by a flow meter and by inulin clearance. In the split hydronephrotic kidney, the LTD4‐ and LTE4‐mediated vascular effects were localized by intravital microscopy. Intravenous infusion of low‐dose LTD4(1×10‐9mol min‐1kg‐1) over 15 min induced a strong decrease in renal blood flow (‐43% and ‐70%) in the normal and the hydronephrotic kidney. After the infusion the glomerular filtration rate of the normal kidney was significantly reduced by 65% and the filtration fraction by 32%. The fall in filtration fraction is in accordance with the significant decrease in luminal diameters of the arcuate artery (–28%) and the proximal interlobular artery (–12%) in the hydronephrotic kidney under LTD4. The decrease in renal blood flow, glomerular filtration rate, filtration fraction and luminal diameters persisted in the normal as well as in the hydronephrotic kidney for more than 60 min beyond cessation of infusion. Local application of LTD4(1×10‐10mol 1‐1upto 1×10‐7mol 1‐1)and LTE4(1×10‐10mol 1‐1up to 1×10‐8mol 1‐1) induced a dose‐dependent constriction of the arcuate artery and the proximal interlobular artery. The distal interlobular artery, the afferent and the efferent arteriole were not significantly affected by LTD4or LTE4. The glomerular blood flow was dose‐dependently reduced up to 48% under local LTD4and 43% under LTE4. The LTD4/LTE4antagonist FPL 55712 (1×10‐8mol min‐1kg‐1, iv) significantly attenuated the effects of LTD4infusion and local LTE4application in the hydronephrotic kidney. This is indicative of the presence of receptors for LTD4and LTE4in the larger preglomerular vessels of the rat kidney. The LTD4effects on the normal kidney were attenuated by simultaneous infusion of dopamine (5 μg min‐1kg‐1) or plasma expansion, two principal methods in the treatment of acute renal failure. The results in the normal and hydronephrotic kidney demonstrate a preferential preglomerular vasoconstriction under LTD4and LTE4causing a marked decrease in renal and glomerular blood

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01808.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.We studied the effect of two diets, one rich in polyunsaturated and the other in saturated fatty acids, on the postprandial processing of exogenous and endogenous triglyceride‐rich lipoproteins (chylomicrons, very‐low‐density lipoproteins, and their remnants).For this purpose, 12 normolipidaemic young volunteers were fed, in a cross‐over design of 9 days on each diet, either a diet rich in saturated fat (21% of their daily energy intake from saturated fat, 12% from monounsaturated fat, and 3% from polyunsaturated fat) or a diet rich in polyunsaturated fat (10% saturated fat, 9% monounsaturated fat, and 18% polyunsaturated fat) (P/S ratios 0.14 and 1.8, respectively). On the last day of each dietary period blood samples were drawn six times over a 24‐h period for determination, by densitometric scanning of SDS gels, of the diurnal pattern of apoprotein B‐48 and B‐100 in thed<1.019 g ml‐1fractions, as estimates for the processing of chylomicrons and very‐low‐density lipoproteins.In addition to the usual decrease in the fasting and diurnal concentrations of total serum cholesterol and of cholesterol in the low‐density lipoprotein fractions (between 15 and 21%), the diet rich in polyunsaturated fat resulted in 43% lower daily concentrations of chylomicrons and their remnants. This was due to differences in the clearance rate of chylomicrons and their remnants, rather than to differences in the absorption rate of exogenous fat. In addition, the concentrations of very low density lipoproteins and their remnants during the day were 20% lower on the diet rich in polyunsaturated fat.As remnants, especially those from intestinal origin, are considered to be atherogenic, our observations provide an additional explanation why atherosclerosis is reduced on diets with a relatively high ratio of polyunsatur

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01809.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract.HMG‐CoA reductase inhibitors decrease serum cholesterol by inhibiting hepatic cholesterol synthesis, but their influence on biliary lipids is not well characterized. In the present study Pravastatin (80 mg) was administered as a single oral dose to 10 patients with external bile fistula, after 1 week of interruption of the enterohepatic circulation, in order to assess the effect of inhibition of hepatic cholesterol synthesis on biliary lipids in conditions of stimulated bile acid synthesis. Bile was collected every hour for 12 h. On the day before, the same procedure was applied with a placebo, and collected bile used as control. Pravastatin decreased both bile acid and phospholipid concentration to about 60% of basal values; this change was still significant after 10 h. Cholesterol concentration was also decreased to about 70% of basal values, but this change was significant only from the 5th to the 7th h. The per cent of cholic and chenodeoxycholic acid was not affected by the drug, but the ratio of glyco‐ to tauroconjugated bile acids was decreased to about half the initial values. Bilirubin concentration exhibited a late increase, suggesting a reduction in the bile flow. These results suggest that, in patients with interrupted enterohepatic circulation, biliary excretion of bile acids can be largely dependent on hepatic cholesterol synthe

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1991.tb01810.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY