Biomedical subjects

R S Tilvis

Publications and source records attributed to R S Tilvis.

At least 55 records · Page 3Linked to original sources

PubMed1990

Low serum ionized to total calcium ratio: association with geriatric diabetes mellitus and with other cardiovascular risk factors?

Serum total calcium concentrations (CaT) were increased, ionized calcium concentrations (CaI) normal, and the CaI/CaT ratios decreased in 125 geriatric diabetics as compared with 379 non-diabetic controls. In the whole population of 558 consecutive geriatric inpatients, the CaI/CaT ratios were inversely correlated with body weight, diastolic blood pressure and plasma glucose. The findings and calculations help to explain some inconsistencies and discrepancies in previous studies concerning calcaemia in diabetes, hypertension and the 'metabolic syndrome' of clustered risk factors for cardiovascular diseases. They also demonstrate that CaT and the 'correction' of CaT for serum albumin concentration can be biased in diabetes and other conditions closely associated with cardiovascular risks. Increased serum free fatty acids could at least in part explain low ratios.

Aged↗

PubMed1990

Metabolic variables of cholesterol during squalene feeding in humans: comparison with cholestyramine treatment.

Squalene, a key intermediate of cholesterol synthesis, is present especially in olive oil. Regulation of cholesterol metabolism by dietary squalene in man is unknown, even though olive oil users in Mediterranean areas have low serum cholesterol levels. We have investigated absorption and serum levels of squalene and cholesterol and cholesterol synthesis with the sterol balance technique and serum levels of cholesterol precursors in humans during squalene feeding (900 mg/d for 7-30 days). The results were compared with those during cholestyramine treatment. Fecal analysis suggested that about 60% of dietary squalene was absorbed. Serum squalene levels were increased 17 times, but serum triglyceride and cholesterol contents were unchanged. The squalene feeding significantly (P less than 0.05) increased serum levels of free (1.7-2.3 times) and esterified (1.9-2.4 times) methyl sterol contents, while elevations of free and esterified delta 8-cholesterol and lathosterol levels were inconsistent. Cholestyramine treatment modestly augmented free methyl sterol levels (1.3-1.7 times), less consistently than those of esterified ones, while, in contrast to the squalene feeding, serum contents of free and esterified delta 8-cholesterol and lathosterol were dramatically increased (3.3-8 times). Neither of the treatments significantly affected serum plant sterol and cholestanol levels. The squalene feeding had no consistent effect on absorption efficiency of cholesterol, but significantly increased (paired t-test, P less than 0.05) the fecal excretions of cholesterol and its nonpolar derivatives coprostanol, epicoprostanol, and coprostanone (655 +/- 83 SE to 856 +/- 146 mg/d) and bile acids (212 +/- 24 to 255 +/- 24 mg/d), indicating an increase of cholesterol synthesis by about 50%. We suggest that a substantial amount of dietary squalene is absorbed and converted to cholesterol in humans, but this squalene-induced increase in synthesis is not associated with consistent increases of serum cholesterol levels. The clearly increased serum contents of esterified methyl sterols may reflect stimulated tissue acyl CoA: cholesterol acyltransferase (ACAT, EC 2.3.1.26) activity during squalene feeding as these sterols are not esterified in serum.

Cholestanol↗

PubMed1989

Variations of hepatic cholesterol precursors during altered flows of endogenous and exogenous squalene in the rat.

Hepatic and serum levels of cholesterol precursors were analyzed in rats under basal (control) conditions and when cholesterol synthesis was activated by feeding 1% squalene or 5% cholestyramine. Exogenous squalene stimulated the activity of acyl-coenzyme A:cholesterol acyltransferase (ACAT) but strongly inhibited the activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase; cholestyramine did not affect ACAT but increased HMG-CoA reductase several-fold, indicating enhanced production of endogenous squalene. Activation of cholesterol synthesis by the two methods markedly increased the hepatic and serum contents of cholesterol precursor sterols. However, the sterol profiles were clearly different. Thus, exogenous squalene raised most significantly (up to 109-fold) free and esterified methyl sterols, and less so (up to 2-fold) demethylated C27 sterols (desmosterol and cholestenols) and also esterified cholesterol. Activation of endogenous squalene production by cholestyramine was associated with a depletion of esterified cholesterol and by a marked, up to 8-fold, increase of the free demethylated sterol precursor levels, whereas the increase of methyl sterols, up to 5-fold, was less conspicuous than during the squalene feeding. The changes were mostly insignificant for esterified sterols. The altered serum sterol profiles were quite similar to those in liver. Serum cholestenols and especially their portion of total serum precursor sterols were closely correlated with the hepatic activity of HMG-CoA reductase.

Animals↗

PubMed1989

Effects of cholestyramine and squalene feeding on hepatic and serum plant sterols in the rat.

Hepatic and serum phytosterol concentrations were compared in the rat under basal conditions and during activated cholesterol and bile acid production due to squalene and cholestyramine feeding. Both treatments consistently decreased hepatic and serum levels of sitosterol and campesterol and, unlike esterified cholesterol, esterified plant sterols were not increased in liver during squalene feeding. Serum levels of phytosterols were decreased quite proportionately to those in the liver. The hepatic levels of sitosterol and campesterol closely correlated with each other, but not with cholesterol levels. The percentage esterification of both phytosterols was lower than that of cholesterol. The results indicate that activation of hepatic sterol production leads to depletion of hepatic plant sterols. It is suggested that poor esterification of plant sterols may contribute to this decrease.

Animals↗

PubMed1989

Serum cholestanol and plant sterol levels in relation to cholesterol metabolism in middle-aged men.

Serum cholestanol was studied in relation to fecal cholestanol excretion and cholesterol metabolism in a random middle-aged population of 61 men. The serum concentrations of cholestanol ranged from 1.6 to 10.8 mumol/L and were positively correlated with those of serum total LDL and HDL cholesterol. In terms of millimole per mole of cholesterol, these correlations disappeared; inverse associations were found with VLDL cholesterol and triglyceride levels, the P/S ratio of dietary fat, and the amount of fecal plant sterols, but not with fecal cholestanol. The serum contents of cholestanol (1) were also closely positively associated with those of serum plant sterols (campesterol and sitosterol) and fractional cholesterol absorption, (2) were inversely related to the fecal excretion of neutral sterols and cholesterol synthesis which were measured either by the sterol balance technique or serum cholesterol precursor sterols (desmosterol and lathosterol), and (3) were unrelated to bile acid synthesis. Fecal cholestanol (mean = 12.5 mg/d) was (1) clearly higher than the dietary cholestanol intake (less than 2 mg/d), (2) unrelated to serum cholestanol, and (3) positively correlated with the intestinal cholesterol (dietary plus endogenous) flux as well as fecal plant sterols, neutral sterols, and bacterial products of cholesterol. The study emphasizes that, in normal men, high serum cholestanol levels reflect high efficiency of intestinal sterol absorption and low cholesterol synthesis. Thus, the changes in the serum contents of cholestanol are parallel with those of plant sterols and opposite to those of cholesterol precursor sterols.

Cholesterol↗

PubMed1989

Association of calcaemic status with survival of elderly inpatients.

In 485 long-term geriatric inpatients (mean age 80 years), serum ionized calcium (CaI) concentrations were significantly associated with 2-year mortality. The cumulative 2-year survival was 37% in the hypocalcaemic group (CaI less than 1.17 mmol/l), 49% in the hypercalcaemic group (CaI greater than 1.29 mmol/l) and 57% in the normocalcaemic group. The association of calcaemia and survival remained significant even when patients with low serum albumin and high serum creatinine were excluded. However, serum total calcium concentrations, whether or not 'corrected' for albumin, were not significantly associated with survival. The use of diuretics may have had some influence on the calcaemic grouping of the patients, but the excess mortality in the hypercalcaemic group was not explained by heart failure or hypertension. The impaired survival in dyscalcaemic groups was not associated with sex, age, immobility, diabetes, hypertension, or renal failure.

Aged↗

PubMed1988

Effect of insulin treatment on fatty acids of plasma and erythrocyte membrane lipids in type 2 diabetes.

Serum lipoproteins and fatty acid compositions of serum and erythrocyte membrane lipids were analyzed from sixteen Type 2 diabetic subjects with secondary drug failure before and after four weeks' insulin therapy. The insulin treatment clearly improved diabetic control (p less than 0.01), decreased serum total cholesterol (-14%, p less than 0.01), triglycerides (-50%, p less than 0.001), plasma free fatty acids (-28%, p less than 0.01), and especially serum VLDL-triglyceride levels (-62%, p less than 0.001) and resulted in a significant weight gain of patients (1.4 kg, p less than 0.05). Of the individual plasma fatty acids saturated (-32%) and monoenoic (-36%) fatty acids fell more than the polyunsaturated fatty acids of exogenous origin, eg linoleic acid (-11%), other n-6 polyunsaturated fatty acids (PUFA) (-11%), and n-3 PUFA (-13%) suggesting that the decrease in serum VLDL-triglycerides is mainly associated with the suppression of endogenous fatty acids. Before the insulin treatment but less strongly during it, the contents of linoleic acid were positively and those of dihomogammalinolenic acid, arachidonic acid, and arachidonic acid/linoleic acid ratios of plasma and erythrocyte membrane lipids inversely correlated with glycosylated HbA1 levels, suggesting that the conversion of linoleic acid to prostanoid precursor fatty acids is affected by the poor glycemic control in Type 2 diabetic patients.

Adult↗

PubMed1988

Cholesterol absorption regulates cholesterol metabolism and plasma lipoprotein levels in patients with gut exclusions.

The occurrence of cholesterol malabsorption and its role in the regulation of cholesterol metabolism were studied in 30 patients with an earlier gut resection and 9 patients with a jejunoileal bypass for treatment of obesity. Fractional cholesterol absorption varied from 0.1% to 70%, and was lowest in jejunoileal bypass (8.3%) associated with severe fat and moderate bile acid malabsorptions and in 15 patients with a long small-intestinal resection (20.4%) associated with severe bile acid and moderate fat malabsorption. Seven resected patients with normal fecal fat and bile acids and 8 resected patients with malabsorption of only bile acid had normal cholesterol absorption. Low fractional cholesterol absorption was associated with a short length of the remaining proximal small intestine, high dietary intake of plant sterol, and high fecal fat and neutral sterol excretions, but not with bile acid malabsorption. In the whole study population, plasma levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol were positively correlated with fractional cholesterol absorption and the amount of total, dietary, and biliary absorbed cholesterol and were negatively correlated with fecal cholesterol elimination as neutral sterols (less so as bile acids) and cholesterol synthesis. The results emphasize that, in patients with ileal exclusion, plasma levels of low-density lipoprotein and high-density lipoprotein cholesterol are regulated more effectively by cholesterol than by bile acid malabsorption. Moreover, although the fecal loss of bile acids is the main determinant in cholesterol elimination and stimulation of cholesterol synthesis in patients with intestinal exclusions, intestinal cholesterol absorption also contributes noticeably to the regulation of cholesterol synthesis.

Adult↗

PubMed1988

Physiological and pharmacological regulation of small intestinal cholesterol synthesis.

1. The small intestine is an important site of cholesterol synthesis in the body and at least in experimental animals, it also contributes to the circulating plasma pool of cholesterol. 2. Studies on synthesis regulation have been partly contradictory but it is now concluded that the cellular cholesterol balance is the basic regulatory factor of intestinal cholesterol synthesis. However, the balance is affected differently in various specialized cells and parts of the small intestine. 3. Most data on synthesis regulation are derived from experimental animals but the few human studies suggest that similar regulatory factors function in man, too.

Animals↗

PubMed1988

Raised plasma cholesterol precursors in patients with gut resections.

Cholesterol synthesis, faecal bile acids and neutral sterols, and plasma squalene and free and esterified cholesterol precursor sterols concentrations were studied in patients with previous ileal resection (n = 30) or jejunoileal bypass (n = 9) to elucidate the responses of different cholesterol precursors to enhanced cholesterol synthesis induced by cholesterol and bile acid malabsorption. A subgroup of seven resection patients without fat and bile acid malabsorption served as controls. Of the resection patients, eight had a pure bile acid malabsorption and 15 a combination of fat, bile acid, and modest cholesterol malabsorption. In the patients with jejunoileal bypass, cholesterol and fat absorption was greatly decreased in addition to bile acid malabsorption. The overall cholesterol synthesis was associated with proportionately increased plasma contents of free (and, less consistently, esterified) methyl sterols, the most marked increase, up to 18 times, being recorded for free and esterified lathosterols. The concentrations of the precursor sterols were similarly increased in the subjects with bile acid and cholesterol malabsorption, the two lathosterols showing the highest correlations with the overall cholesterol synthesis (r = 0.820-0.941). In the subjects with jejunoileal bypass cholesterol malabsorption effectively regulated cholesterol synthesis and the precursor levels. Gut exclusions large enough to cause cholesterol and/or bile acid malabsorption activate cholesterol synthesis leading to a proportional elevation in the plasma concentrations of cholesterol precursors, especially in those of lathosterols and free methyl sterols. Determination of the plasma concentration of total lathosterol by a single gas-chromatographic run is a suitable method for rapid screening of clinically significant cholesterol and bile acid malabsorption.

Bile Acids and Salts↗

PubMed1988

Assessment of calcaemic status in geriatric hospital patients: serum ionized calcium versus albumin-adjusted total calcium.

To evaluate the accuracy of total serum calcium (CaT) and albumin-adjusted total calcium (CaA) determinations in the assessment of calcaemic status in the elderly, serum ionized calcium (CaI), CaT and serum albumin (Alb) concentrations were measured in 558 geriatric hospital patients. As expected, CaT was correlated with Alb (r = 0.316, p less than 0.001) and CaI with serum pH (r = -0.351, p less than 0.001) and they were closely interrelated (r = 0.746, p less than 0.001). Various albumin-adjustment formulas from the literature decreased the correlation of CaT and CaI. Using conventional reference limits for CaT only 12% and 72% of patients with CaI above or below the reference limits for CaI, respectively, were found. This study demonstrates the low sensitivity of total and albumin-adjusted calcium in the detection of slightly or moderately abnormal calcaemic states.

Adult↗

PubMed1988

Faecal lipids in familial adenomatosis coli.

Faecal sterols and bile acids from six patients with familial adenomatosis coli (FPC) and 61 healthy men were analysed preoperatively. Faecal concentrations and secretion of neutral sterols, plant sterols, and degradation products of cholesterol were identical in the two groups. No increase was found in the faecal bile acid excretion, and the distribution of individual bile acids was normal in FPC. The results suggest that the development of adenomas in FPC is not associated with abnormal cholesterol and bile acid excretion.

Adenoma↗

PubMed1988

Prognosis of elderly hospital patients with cerebral thrombosis.

Over 8000 patients with cerebral thrombosis (ICD-8 number 433) hospitalised between 1970 and 1980 were surveyed retrospectively for outcome and additional diseases. The case-fatality rates and long-term prognosis of the patients were strongly affected by age, and the number of patients requiring permanent hospital care rose sharply with increasing age. The case-fatality rates in the different age groups were as follows: under 50 years 6%, 50-64 years 16%, 65-74 years 32%, 75-84 years 48% and over 85 years 66%. The cumulative survival rates at 1 and 5 years were as follows: under 50 years 54 and 46%, 50-64 years and 38%, 65-74 years 60 and 20% and over 75 years 45 and 10%. Clinical manifest coronary heart disease clearly affected the prognosis of patients under 75 years, but the impact diminished with rising age. Although hypertension led to an earlier onset of ischemic stroke, it did not significantly influence the survival prognosis. In patients over 75 years additional diseases, e.g. diabetes, had no significant effect on case-fatality or long-term prognosis underlining the malignant nature of cerebral thrombosis itself.

Age Factors↗

PubMed1988

Regulation of plasma plant sterol levels in patients with gut resections.

The role of cholesterol and bile acid malabsorption in the regulation of plasma plant sterol levels was studied in 30 patients with an ileal resection (seven without any malabsorption, eight with bile acid malabsorption alone and 15 with bile acid, fat and cholesterol malabsorption) and nine with jejunoileal bypass (modest bile acid, and severe cholesterol and fat malabsorption). In contrast to cholesterol, plant sterols are not synthesized by the body, and so the plasma levels are regulated by their intestinal absorption and biliary secretion. In fact, the plant sterol, especially campesterol, levels were low in patients with cholesterol and fat malabsorption. Cholesterol absorption efficiency was a significant determinant of the plant sterol levels, suggesting that it reflects overall sterol absorption efficiency and that the plasma plant sterol levels, in turn, reflect cholesterol absorption. Bile acid malabsorption, though it appeared to promote biliary plant sterol secretion, had little direct effect on the plasma plant sterol contents. The results indicate that plasma campesterol levels can be used to evaluate cholesterol absorption efficiency in general and may reveal clinically significant steatorrhoea in patients with gut exclusion.

Adult↗

PubMed1987

Low platelet arachidonic acid in young patients with brain infarction.

Fatty acid patterns of plasma and platelet lipids, platelet aggregation and thromboxane A2 (TxA2) production were studied in young patients (n = 12) with brain infarction and in healthy controls (n = 13). Platelet arachidonic acid content was significantly reduced in the stroke patients, but in vitro platelet aggregation was similar in the two groups. A low dose of acetosalicylic acid (ASA) (100 mg) suppressed thromboxane production and normalized the platelet arachidonic acid values. The low arachidonic acid in platelets is probably due to its increased consumption, indicating platelet activation in vivo.

Adult↗

PubMed1987

Effects of purified fish oil on platelet lipids and function in diabetic women.

Purified fish oil (MaxEpa, 10 g/day) treatment for six weeks increased consistently the content of eicosapentaenoic (20:5, n-3), docosapentaenoic (22:5, n-3) and docosahexaenoic acid (22:6, n-3) and decreased that of arachidonic acid (20:4, n-6) and other n-6 polyunsaturated C-20 fatty acids (PUFA) of platelets both in insulin dependent diabetic (IDDM) (n = 13) and healthy women (n = 7), but it had no effect on the number and aggregation of platelets or on plasma beta-thromboglobulin. Serum TxB2, produced by diabetic platelets was reduced, but the urine 6-keto PGF1 alpha excretion, believed to reflect prostacyclin (PGI2) production was normal in the diabetics. During the MaxEpa treatment the response of thromboxane B2 (TxB2) release to ADP was decreased in platelet-rich plasma in the healthy subjects. However, in diabetics the fish oil treatment resulted in increased TxB2 formation from exogenous arachidonic acid. The results demonstrate the dependence of platelets fatty acid composition on dietary sources and suggest that at least in the diabetic platelets the diminished arachidonic acid content could be compensated by an activation of enzymes of thromboxane B2 pathway.

6-Ketoprostaglandin F1 alpha↗

PubMed1987

Effects of ketoconazole on cholesterol synthesis and precursor concentrations in the rat liver.

Ketoconazole, an antimycotic agent, given to rats for a week as 0.05% food addition had no effect on the hepatic concentrations of free and esterified cholesterol or on the activity of acyl coenzyme. A: cholesterol-acyltransferase (ACAT). However, the levels of free methylated cholesterol precursors, especially lanosterols, less markedly delta 8,24 and delta 8-dimethyl sterols and monomethyl sterols, were increased after only one day's treatment, while those of esterified methyl sterols were increased inconsistently, and those of free and esterified delta 8-lathosterol, lathosterol and desmosterol were not affected at all. Cholestyramine treatment had no significant effect on ACAT in spite of a decrease in the hepatic content of esterified cholesterol and caused a marked increase in the free cholesterol precursor levels, especially in those of lathosterols. Cholestyramine given to ketoconazole-treated rats increased the hepatic levels of delta 8 and delta 7-lathosterols but not desmosterol or methylated cholesterol precursors. Ketoconazole increased and cholestyramine markedly decreased plant sterols, sitosterol and campesterol in the liver. In serum, the contents of both lanosterols and lathosterol were increased but that of cholesterol tended to be decreased by ketoconazole (-19%). The results indicate that ketoconazole impairs demethylation processes at C-14 and to some extent at C-4 in the rat liver, resulting in lowered serum cholesterol level.

Animals↗

PubMed1987

Serum lipids and fatty acids in ischemic strokes.

Lipid analysis of different constituents in the blood of patients with stroke revealed that an increased level of total serum cholesterol was infrequently (that of triglycerides more frequently) associated with stroke in middle-aged men, whereas the high-density lipoprotein cholesterol content was low in all but young patients with stroke. High contents of cholestanol and low contents of n-6 polyunsaturated fatty acids predict the development of stroke in middle-aged men and are found in both middle-aged men with stroke and elderly patients with multi-infarct dementia. Young patients with unexpected stroke had normal serum sterol, triglyceride, and fatty acid contents but markedly reduced arachidonic acid levels in the platelets, a change that was normalized by treatment with aspirin. The results emphasize that the etiopathogenesis of ischemic brain damage may vary markedly from one age group to another.

Adult↗