Tumor-induced osteomalacia: pre- and postoperative biochemical findings

A patient with late-onset hypophosphatemic osteomalacia was treated with oral supplements of phosphate (1.5 g/day) and calcitriol (1.5-3.0 micrograms/day) for 17 months, before a slowly growing tumor in the first metatarsal space became evident. Before treatment concentrations of inorganic phosphate (Pi) and calcitriol in serum and tubular reabsorption of phosphate (TRP) were very low, calcium and parathyroid hormone (PTH) in serum were normal, urinary cyclic adenosine monophosphate (cAMP) was strongly elevated. During the first weeks of conservative treatment urinary cAMP returned to normal; concomitantly there was a transient slight fall in PTH. Serum calcium was in the low normal range and did not significantly change during conservative therapy. During the further course PTH rose to pretreatment values, but urinary cAMP remained normal. When the dose of calcitriol was elevated to 3 x 1.0 micrograms/day, leading to slightly elevated serum concentrations of this substance, Pi in serum rose to the low normal range, but TRP remained low and bone pain, although improved, did not subside. The tumor was locally excised. Postoperatively calcitriol concentration became elevated within 48 hours and remained so for several weeks. The rise in calcitriol concentration preceded the elevation of Pi in serum, not, however, the increase of TRP. The elevation of urinary cyclic AMP before therapy may have been due to a direct action of the substance secreted by the tumor.     

Correlation between manifestations of digoxin toxicity and serum digoxin,calcium, potassium,and magnesium concentrations and arterial pH.

In 18 patients with gastrointestinal manifestations of digoxin toxicity the mean serum digoxin concentration (+/- SEM) was 3.16 micrograms/l (+/- 0.25), the calcium to potassium ratio 0.31 (+/- 0.01), and the mean arterial pH 7.406 (+/- 0.017). In contrast 19 patients with digoxin induced automaticity had a mean serum digoxin concentration of 1.24 micrograms/l (+/- 0.15; p less than 0.001), a calcium to potassium ratio of 0.38 (+/- 0.01; p less than 0.01), and an arterial pH of 7.498 (+/- 0.008; p less than 0.001). Eight out of 13 patients with digoxin induced cardiotoxicity had serum concentrations of the drug within the therapeutic range (0.8-2.0 micrograms/l). The calcium to potassium ratio, however, was lower than in the patients with automaticity (0.31 +/- 0.02; p less than 0.01) and the arterial pH was 7.370 (+/- 0.033; p less than 0.05). Serum magnesium concentrations were similar in all groups. In this study patients with digoxin induced gastrointestinal symptoms had high serum concentrations of the drug, whereas those with drug induced automaticity had therapeutic concentrations. This second group, however, was identified by their higher calcium to potassium ratios and higher pH values.     

The case for low dose diuretics in hypertension: comparison of low and conventional doses of cyclopenthiazide.

In a double blind placebo controlled randomised parallel study the antihypertensive activity and adverse biochemical effects of three doses of cyclopenthiazide were evaluated in patients with mild essential hypertension that had been recently diagnosed or was being treated with a single drug. After a four week placebo washout period 53 patients with diastolic blood pressures between 90-110 mm Hg were randomly assigned to 50, 125, or 500 micrograms cyclopenthiazide or matching placebo for an eight week period of treatment. Blood pressure was measured in the patients'' homes by the same observer every two weeks. Serum urea, electrolytes, urate, and creatinine concentrations and 24 hour urinary sodium excretion were monitored every four weeks and serum magnesium concentration and plasma renin activity at the end of the washout and treatment periods. After eight weeks of treatment systolic and diastolic blood pressures were significantly reduced in patients taking 125 and 500 micrograms cyclopenthiazide when compared with those taking placebo. The decrement in serum potassium concentration (0.6 mmol/l) and increase in serum urate concentration 0.06 mmol/l) were greatest with the 500 micrograms dose, the increase in serum urate concentration alone being significant. No change in serum magnesium concentration or 24 hour urinary sodium excretion was noted with any dose of cyclopenthiazide. Only the 500 micrograms dose of cyclopenthiazide significantly increased the mean plasma renin activity (1.8 (95% confidence interval 0.2 to 3.4)-5.4 (3.9 to 6.8) nmol angiotensin I/l/h); the other doses like the placebo had no effect. Cyclopenthiazide 125 micrograms, a dose lower than is currently marketed, produced a similar hypotensive response to 500 micrograms of the drug without upsetting the biochemical profile.     

Effect of parathyroid function on serum bone Gla protein

The serum bone Gla protein (BGP) level was measured in patients with idiopathic hypoparathyroidism, and primary hyperparathyroidism, and normal volunteers. The mean serum BGP level was 4.5 +/- 0.20 micrograms/l in 40 normal volunteers. It was significantly lower in 12 patients with idiopathic hypoparathyroidism (1.6 +/- 0.21 micrograms/l, p less than 0.001) and significantly higher in 33 patients with primary hyperparathyroidism (13.0 +/- 1.3 micrograms/l, p less than 0.001). When a single intravenous injection of 30 micrograms of human PTH 1-34 was administered to the patients with idiopathic hypoparathyroidism, there was no significant change in serum BGP within the next 24 hours. Following a therapeutic oral dose of alfacalcidol, serum BGP was appreciably increased (p less than 0.001) from the preadministration value of 1.6 +/- 0.21 micrograms/l to 3.9 +/- 0.34 micrograms/l. In patients with primary hyperparathyroidism, the surgical excision of parathyroid adenoma led to a sharp decrease in serum PTH but a gradual decrease in serum BGP. The latter approximately paralleled the decline in serum alkaline phosphatase. Thus, serum BGP is a marker that reflects bone turnover status in parathyroid disease. It appears that the active form of vitamin D directly increases the secretion of BGP in existing osteoblasts and PTH mainly affects serum BGP to stimulate the bone remodeling cycles with its long term effect.     

Influence of short-term fasting on the pituitary-testicular axis in normal men

To investigate whether short-term fasting affects serum testosterone (T) in normal subjects, 10 healthy men of normal weight were studied on two occasions: after an overnight fast (8 h), and after an additional 48 h of fasting. Blood glucose declined by 22 +/- 3% between the tests (p less than 0.001). Basal serum T fell from 8.7 +/- 0.7 to 5.7 +/- 0.8 micrograms/l (p less than 0.01), and LH from 6.9 +/- 0.8 to 5.0 +/- 0.7 U/l (p less than 0.01). Serum estradiol (E2) and FSH remained unaffected. To explore possible mechanisms behind the decreased basal release of T and LH, 9 small doses of glucose were given orally at regular intervals during a 56-hour fast to 9 additional normal men to maintain blood glucose levels. These men did not experience a fall in serum T or LH. Six additional normal men were given 50 micrograms GnRH intravenously after an overnight fast, and after a fasting period of 56 h. No acute increase in T was seen after the overnight fast, but after the 56-hour fast GnRH raised serum T by 55 +/- 14% (p less than 0.02). Moreover, fasting augmented the GnRH-induced LH response by 64 +/- 15% (p less than 0.02. These results imply that: short-term fasting exerts inhibitory influence on Leydig cell function via a mechanism which might involve a reduced hypothalamic and/or pituitary stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum prolactin in patients with Laron-type dwarfism: effect of insulin-like growth factor I.

Prolactin (PRL) secretion was studied in Laron-type dwarfism (LTD) patients (8 children and 9 adults) in basal condition, after acute insulin-like growth factor (IGF-I) or TRH injections and during 2 months of daily IGF-I treatment. Basal PRL was repeatedly higher (12.6 +/- 1.6 micrograms/l) than that in control subjects (7.6 +/- 1.2 micrograms/l, p < 0.05). Acute IGF-I injection caused an immediate slight decrease in serum PRL and growth hormone (GH), followed by a progressive rise to mean peak levels of 33.3 +/- 4.5 micrograms/l again parallel to serum hGH which rose to 86 +/- 20 micrograms/l--a response to the IGF-I-induced hypoglycemia. Intravenous TRH in LTD children induced a marked response in serum PRL, similar to that registered in estrogenized adult females. Serum PRL did not show consistent changes during chronic IGF-I treatment. It is suggested that the higher-than-normal PRL levels and release in LTD patients are due to a drift phenomenon of the mammosomatotropes which produce large amounts of hGH.     

The effect of calcitriol on natural killer cell activity in hemodialyzed patients

We report the effect of calcitriol on natural killer (NK) cell activity in patients with chronic renal failure undergoing long-term hemodialysis. Natural killer cytotoxicity was significantly decreased in these patients when compared to healthy control subjects (13.1 +/- 1.3 vs 38.8 +/- 2.4%, P less than 0.001). These patients also have decreased levels of calcitriol (17 +/- 3 vs 36 +/- 3 pg/ml, P less than 0.001). After 14 days of oral treatment with calcitriol at a dose of 0.5 micrograms per day, a significant increase in NK activity was observed (20.2 +/- 1.6%, P less than 0.001). This increase was maintained after 28 days of treatment (21.1 +/- 2%, P less than 0.001). These results suggest that the decreased serum calcitriol might contribute to the diminished NK activity found in hemodialyzed patients, and suggests a new potential therapeutical utility of calcitriol as modulator of the immune function in these patients.     

Nephrotoxicity of cyclosporin A in hereditary hypertriglyceridemic rats

It has been suggested that cyclosporin A (CsA) nephrotoxicity can be reduced by the concomitant administration of omega-3 fatty acids or vitamin E. The present study was designed to establish whether the effect of the above substances can also be demonstrated in rats with hereditary hypertriglyceridemia (HTG) whose sensitivity to the nephrotoxic effect is greater than in control AVN rats. CsA administration at a dose of 10 mg/kg/day to HTG rats resulted in a significant rise (p<0.001) in serum levels of creatinine (from 66.0+/-7.6 to 108.4+/-11.6 micromol/l) and urea (from 8.3+/-0.7 to 22.3+/-18 mmol/l) which was not found in AVN rats. The baseline values of systolic blood pressure (SBP) were significantly higher in HTG rats. However, in both strains CsA administration was associated with a similar SBP increase which was not prevented by omega-3 fatty acids (EPAX) or vitamin E administration. Concomitant administration of CsA with EPAX at a dose of 600 mg/kg b.w./day in HTG rats prevented the rise in the serum levels of creatinine (65.4+/-14.7 micromol/l) and reduced the increase in the serum urea levels (11.9+/-7.6 mmol/l). Concomitant administration of CsA and vitamin E (at a dose of 25 mg/kg/day) also reduced the increase (p<0.05) in the serum levels of creatinine (70.7+/-14.3 micromol/l) and urea (9.8+/-3.4 mmol/l) compared to the effects elicited by the administration of CsA alone (p<0.05). Administration of CsA alone or in combination with EPAX or vitamin E did not have a marked effect on diuresis, proteinuria, urinary osmolality, urinary excretion of urea, creatinine and potassium. Under all experimental conditions, the rate of urinary excretion of sodium in HTG rats was significantly lower (p<0.01) than in AVN rats. The results obtained support the assumption that omega-3 fatty acids and vitamin E at the doses used reduce CsA nephrotoxicity in rats with hereditary hypertriglyceridemia whose sensitivity to the nephrotoxic effect of CsA is significantly higher than in AVN rats.     

Postoperative hypoparathyroidism: long term observation and therapy]

Hundred thirty patients with surgical hypoparathyroidism were followed up. Group I involved 45 patients with mild and group II--85 patients with severe surgical hypoparathyroidism. A delay in vitamin D3 therapy was X +/- SD = 4.2 +/- 8.1 years. A delay in introducing vitamin D3 therapy correlated with the duration of hypoparathyroidism (r = 0.93; 8.9 +/- 9.6 years). Follow up period lasted for 15 years and was 4.3 +/- 3.8 years out of which the attempts to establish ultimate and effective dose of vitamin D3 lasted 1.8 +/- 2.4 years. Dose of vitamin D3 was adjusted 5 times, on the average. Effective daily dose was 4,200-22,500 IU (9,311 +/- 7,252) in group I, and 30,000-195,000 IU (51,385 +/- 32,978) in group II whereas maximum daily dose was 75,000 and 250,000 IU respectively (p < 0.001). Some patients were given 25-OH-D3 in daily doses of 50-225 micrograms or 25(OH)2-D3 in daily dose of 0.10-0.75 micrograms. Calcium oral doses of 400-1600 mg daily were administered to 115 patients. In case of high hypercalciuria (over 350 mg/24 h) hydrochlorothiazide (43 +/- 17 mg a day) or chlorthalidone (60 +/- 22 mg a day) normalized calciuria. Low phosphate diet and aluminium oxide (4.4 +/- 1.7 g a day) were more frequently used in group II. Period of time necessary to establish an effective dose of vitamin D3 is long in patients with surgical hypoparathyroidism. Several dose adjustments are required. Maximum daily vitamin D3 dose required for normocalcemia is approximately higher by 1/3 in the early period of the treatment than the effective maintenance dose. A decrease in diet phosphate content, inhibition of phosphates absorption in the gut or blocking increased calcium loss with the urine are necessary in some patients, only.     

X-linked hypophosphatemia: the mutant gene is expressed in teeth as well as in kidney.

Mutation at a locus (HPDR) on the X chromosome (McKusick 30780 [HPDR1]; 30781 [HPDR2]) causes impaired renal phosphate transport, hypophosphatemia, and an associated impairment in the process of mineralization in bone and teeth (X-linked hypophosphatemia [XLH]). We measured the dental pulp profile area (PRATIO [= pulp area/tooth area]) and serum phosphorus (Pi) values in uniformly treated XLH patients (six males, 81 teeth, 1,457 Pi values; 11 females, 129 teeth, 1,439 Pi values). Serum Pi values, reflecting the metabolic environment of tooth development, were obtained by repeated measurement between 1 mo and 26 years of age during treatment. PRATIO values calculated from standardized Rinn radiographs were used as outcome measurements of tooth development in XLH patients and in age-matched controls (12 males, 100 teeth; 27 females, 275 teeth). Age-dependent serum Pi values were not different in the treated XLH males and females. In teeth forming primary dentin there was no gene dosage effect on PRATIO values apparent in subjects below 15 years of age. However, in teeth forming secondary dentin a gene dosage was found in the subjects aged 15 to 25 years: XLH male teeth (n = 65) mean +/- SD = 0.163 +/- 0.046; XLH female teeth (n = 75) mean +/- SD = 0.137 +/- 0.039; control teeth (n = 209) mean +/- SD = 0.116 +/- 0.023; (higher PRATIO values mean less development or mineralization of secondary dentin); differences in these PRATIO values (males vs. female and XLH vs. control) were significant by mixed-model analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of aluminium hydroxide on serum ionised calcium,immunoreactive parathyroid hormone,and aluminium in chronic renal failure.

According to the Bricker-Slatopolsky theory, secretion of parathyroid hormone (PTH) is switched on in chronic renal failure by hypocalcaemia due to phosphate retention. In an attempt to reverse this process 20 patients in preterminal renal failure (plasma creatinine 569 +/- 195 mumol/l) were given aluminium hydroxide, 3.8 g daily. They were studied for four weeks and all measurements were made at the start and weekly, except measurements of serum aluminium concentration, which were made at the start and at the end of the fourth week. Mean serum phosphate fell from 1.89 to 1.47 mmol/l (5.9 to 4.6 mg/100), mean serum calcium rose from 2.07 to 2.24 mmol/l (8.3 to 9.0 mg/100 ml), and serum ionised calcium rose from 1.07 to 1.20 mmol/l (4.3 to 4.8 mg/100 ml), but serum immunoreactive PTH did not fall. Thirteen patients had initial serum immunoreactive PTH concentrations at or near to normal and 11 were taking beta-blockers but even in those with neither explanation, PTH concentrations did not fall. Serum aluminium concentrations rose from 0.4 to 1.02 mumol/l (10.9 to 27.4 microgram/l). Aluminium hydroxide corrects serum phosphate, total calcium, and ionised calcium at the price of a rise in serum aluminium concentration; in this study it did not affect serum immunoreactive PTH. The Bricker-Slatopolsky theory still needs verification in studies of patients with chronic renal failure.     

Effects of octreotide on lipid metabolism in acromegaly.

Hypertriglyceridemia is the most frequent modification of lipid metabolism observed in acromegaly. The somatostatin analog, octreotide (Sandostatin), widely used in the treatment of acromegaly, is able to produce a decrease in levels of growth hormone (GH), insulin, and Insulin-like Growth Factor 1 (IGF1). We have attempted to evaluate the influence of this treatment on the lipid status of acromegalic patients. Seventeen patients with active acromegaly were treated with octreotide, 100 to 500 micrograms/injection subcutaneously three times daily. The levels of fasting serum triglycerides (TG), total cholesterol, High Density Lipoprotein (HDL) cholesterol and IGF1, as well as mean plasma GH and insulin levels during a diurnal profile, were evaluated before and after three months of octreotide therapy. GH, insulin and IGF1 decreased by 61%, 42% and 36% respectively (p less than 0.05). Mean levels (+/- SEM) of TG and total cholesterol fell from 2.2 +/- 0.4 mmol/l to 1.6 +/- 0.3 mmol/l (p less than 0.05) and 6.4 +/- 0.39 mmol/l to 5.6 +/- 0.27 mmol/l (p greater than 0.05), respectively. There was no correlation between triglyceride decrease and hormonal changes or clinical status (BMI, age, sex). In conclusion, the administration of octreotide over a three month period to acromegalic patients is associated with a decrease in TG levels.     

Urinary N tau-methylimidazole acetic acid excretion in respiratory disease

N tau-methylimidazole acetic acid (N tau-MIAA) is the principal urinary metabolite of histamine. The basal urinary excretion rate of N tau-MIAA was determined as 0.117 +/- 0.008 (SE) mg/h, with a renal clearance for N tau-MIAA of 273 +/- 27 ml/min implying active secretion. After subpharmacological infusion of histamine (50 ng.kg-1.min-1 over 2 h) in five volunteers that increased plasma histamine from 0.28 +/- 0.04 to 0.71 +/- 0.15 ng/ml, urinary excretion of N tau-MIAA over 8 h was increased by less than 17% compared with a control saline infusion. Urinary N tau-MIAA excretion in normal controls (273 +/- 14 micrograms/mmol creatinine) was similar to that observed in patients with severe acute asthma (253 +/- 22 micrograms/mmol), antigen-induced bronchoconstriction (269 +/- 21 micrograms/mmol), seasonal allergic rhinitis (304 +/- 31 micrograms/mmol), and clinically stable bronchiectasis (270 +/- 22 micrograms/mmol). In contrast, large increases in metabolite excretion (greater than 7,000 micrograms/mmol creatinine) were observed in a patient with systemic mastocytosis where very high plasma histamine levels were recorded (greater than 500 ng/ml) and marked systemic hemodynamic effects occurred. We conclude that urinary N tau-MIAA will only be increased in pathologies where sustained hyperhistaminemia occurs and that increased local histamine production in the lung or the upper airway does not cause a measurable change in the basal urinary excretion of this metabolite.     

Pharmacokinetics of 24,25-dihydroxyvitamin D3 in humans

Pharmacokinetic properties of pharmacological doses of 24,25-dihydroxyvitamin-D3 [24,25(OH)2D3] were determined in healthy volunteers. Four male subjects received 25 micrograms of 24,25(OH)2D3 as an intravenous bolus injection. Plasma concentrations of 24,25(OH)2D3, 25-hydroxyvitamin D and 1,25-dihydroxy-vitamin D were monitored during 14 days. In addition, serum ionized calcium, total calcium, inorganic phosphate, albumin, creatinine and intact hPTH(1-84) were measured during 14 days. The concentration-time curve of 24,25(OH)2D3 could be described by a two-exponential curve with half-lives of 3.0 +/- 0.9 hrs and 8.2 +/- 2.9 days (mean +/- SD). The volume of distribution was 0.19 +/- 0.02 liters/kg. None of the mentioned biochemical parameters, except serum 24,25(OH)2D3, changed markedly. In 18 subjects suffering from primary hyperparathyroidism, taking 25 micrograms of 24,25(OH)2D3 daily during three months, an average plateau level of 39 +/- 12 nmol/l of serum was observed. Bioavailability as estimated from this plateau level was approximately 70%.     

Serum osteocalcin levels do not change during rapidly induced hypercalcemia in healthy subjects.

Since osteocalcin has been suggested to play a role in calcium homeostasis, we investigated its serum levels in 6 healthy subjects during a rapid calcium infusion. Serum levels of intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25-(OH) D3] and 1,25-dihydroxyvitamin D [1,25-(OH)2 D3] were also determined. The calcium infusion increased plasma-ionized calcium levels from 1.25 +/- 0.04 to 1.54 +/- 0.07 mmol/l at 30 min (p less than 0.05). Concomitantly, serum levels of intact PTH declined from 2.1 +/- 0.9 to 0.2 +/- 0.3 mmol/l (p less than 0.05). In contrast, serum osteocalcin levels did not change. Further, during calcium infusion, serum levels of 1,25-(OH)2 D3 decreased from 81 +/- 17 to 75 +/- 15 pmol/l (p less than 0.05) whereas serum levels of 25-(OH) D3 did not change. The results therefore suggest that calcium per se does not influence osteocalcin secretion.     

The role of serum fructosamine as a screening test for gestational diabetes mellitus

The serum fructosamine concentration indicates the degree of glycation of serum proteins, particularly albumin, and reflects an average blood glucose level over the previous 1-3 weeks. Serum fructosamine, glycated haemoglobin (HbA1c), total serum protein, serum albumin, fasting plasma glucose and oral glucose tolerance test (OGTT) have been measured in 127 healthy control subjects, 102 type 1 and 152 type 2 diabetes mellitus patients and 106 nondiabetic pregnant women. Fructosamine concentration of 2.24 +/- 0.16 and 3.21 +/- 0.41 mmol/l (mean +/- S.D.) has been found in control subjects and diabetics respectively (P less than 0.001). During the second trimester a significantly lower fructosamine level (1.92 +/- 0.21 mmol/l) has been found in pregnant women, most likely due to the low serum albumin concentration (31.35 +/- 3.97 g/l). None of them had a fructosamine level above the normal limit of 2.55 mmol/l. On the other hand, 12 pregnant women showed a disturbed OGTT with normal fructosamine. If the serum fructosamine concentration was adjusted for 40 g/l albumin, then a mean fructosamine of 2.16 +/- 0.24 mmol/l was found in patients with gestational diabetes. Our results show that serum fructosamine has a similar diagnostic value as HbA1c for non-pregnant adults, but neither can replace OGTT for the diagnosis of gestational diabetes.     

Serum and urinary estrone sulfate during the menstrual cycle, measured by a direct radioimmunoassay, and fate of exogenously injected estrone sulfate

Serum and early-morning urinary levels of estrone sulfate during the menstrual cycle were measured by a direct radioimmunoassay without hydrolysis. These levels were high and showed prominent peaks [serum, 2.67 +/- 0.37 ng/ml (mean +/- SE); urine, 5.82 +/- 2.3 micrograms/l] around the day of the preovulatory estradiol-17 beta peak, and increased again during the luteal phase. Following intravenous injection of estrone sulfate, serum estrone sulfate, estrone and estradiol-17 beta were measured. The conversion of estrone sulfate to estrone and/or estradiol-17 beta was very small during their transit in the general circulation.     

A comparison of the effects of troglitazone and vitamin E on the fatty acid composition of serum phospholipids in an experimental model of insulin resistance

The aim of this study was to investigate the effects of troglitazone (TRO)--a new insulin-sensitizing agent--on some metabolic parameters in an experimental model of hypertriglyceridemia and insulin resistance, hereditary hypertriglyceridemic rats, and to compare its effects with those of vitamin E, an antioxidant agent. Three groups of the above rats were fed diets with a high content of sucrose (70% of energy as sucrose) for four weeks. The first group was supplemented with TRO (120 mg/kg diet), the second one with vitamin E (500 mg/kg diet), and the third group served as the control. Vitamin E supplementation did not lower serum triglycerides (2.42 +/- 0.41 vs. 3.39 +/- 0.37 mmol/l, N.S.) while TRO did (1.87 +/- 0.24 vs. 3.39 +/- 0.37 mmol/l, p < 0.01). Neither TRO nor vitamin E influenced the serum levels of free fatty acids (FFA). Both drugs influenced the spectrum of fatty acids in serum phospholipids--TRO increased the levels of polyunsaturated fatty acids (PUFA) n-6 (36.04 +/- 1.61 vs. 19.65 +/- 1.56 mol %, p < 0.001), vitamin E increased the levels of PUFA n-3 (13.3 +/- 0.87 vs. 6.79 +/- 0.87 mol %, p < 0.001) and decreased the levels of saturated fatty acids (32.97 +/- 0.58 vs. 51.45 +/- 4.01 mol %, p < 0.01). In conclusion, TRO lowered the level of serum triglycerides but vitamin E did not have this effect in hypertriglyceridemic rats. Compared with TRO, vitamin E had a different effect on the spectrum of fatty acids in serum phospholipids.     

Short-term very low calorie diet reduces oxidative stress in obese type 2 diabetic patients

Oxidative stress is higher in obese diabetic than in non-diabetic subjects. This pilot study evaluates oxidative stress during short-term administration of a very low calorie diet in obese persons. Nine obese Type 2 diabetic patients (age 55+/-5 years, BMI 35.9+/-1.9 kg/m2) and nine obese non-diabetic control subjects (age 52+/-6 years, BMI 37.3+/-2.1 kg/m2) were treated by a very low calorie diet (600 kcal daily) during 8 days stay in the hospital. Serum cholesterol, triglycerides, non-esterified fatty acids (NEFA), beta-hydroxybutyrate (B-HB), ascorbic acid (AA), alpha-tocopherol (AT), plasma malondialdehyde (MDA) and superoxide dismutase (SOD) activity in erythrocytes were measured before and on day 3 and 8 of very low calorie diet administration. A decrease of serum cholesterol and triglyceride concentrations on day 8 was associated with a significant increase of NEFA (0.30+/-0.13 vs. 0.47+/-0.11 micromol/l, p<0.001) and B-HB (0.36+/-.13 vs. 2.23+/-1.00 mmol/l, p<0.001) in controls but only of B-HB (1.11+/-0.72 vs. 3.02+/-1.95 mmol/l, p<0.001) in diabetic patients. A significant decrease of plasma MDA and serum AT together with an increase of SOD activity and AA concentration (p<0.01) was observed in control persons, whereas an increase of SOD activity (p<0.01) was only found in diabetic patients after one week of the very low calorie diet. There was a significant correlation between NEFA or B-HB and SOD activity (p<0.01). We conclude that one week of a very low calorie diet administration decreases oxidative stress in obese non-diabetic but only partly in diabetic persons. Diabetes mellitus causes a greater resistance to the effects of a low calorie diet on oxidative stress.     

Amiodarone-induced changes in lipid metabolism

Hypothyroidism is a major cause of secondary hypercholesterolemia. Amiodarone treatment alters both the levels of serum lipids and thyroid hormones. We investigated whether the amiodarone-induced changes in lipid metabolism are related to the changes in thyroid hormone levels. Eighteen patients received amiodarone (31 +/- 3 g cumulative dose) for six weeks. Serum triglyceride, total-cholesterol, high density lipoprotein-cholesterol and its subfractions, apolipoproteins B and AI, and plasma post-heparin lipoprotein lipase and hepatic triglyceride lipase activities were determined. Amiodarone treatment caused significant increases in serum total-cholesterol (baseline 4.4 +/- 0.21 (SE), 6 weeks 5.12 +/- 0.26 mmol/l, P less than 0.01), in low density lipoprotein cholesterol (baseline 2.61 +/- 0.26, 6 weeks 3.36 +/- 0.21 mmol/l, P less than 0.05) and in apolipoprotein B (baseline 1.95 +/- 0.15, 6 weeks 2.26 +/- 0.13 mmol/l, P less than 0.01) concentrations. Serum high density lipoprotein and its subfractions, or apolipoprotein AI levels did not change. Plasma post-heparin lipoprotein lipase activity increased (baseline 137 +/- 21, 6 weeks 168 +/- 21 U/ml, P less than 0.01) while hepatic triglyceride lipase did not change. Amiodarone also caused an increase in serum thyroxine (baseline 110 +/- 8, 6 weeks 136 +/- 6 mmol/l, P less than 0.05), although values remained in euthyroid range. In summary, amiodarone therapy increased the concentrations of atherogenic lipoproteins in the serum similar to that seen in hypothyroidism. On the other hand the effect of amiodarone on lipoprotein lipase was opposite to that seen in hypothyroidism. Therefore, amiodarone-induced changes in lipid metabolism cannot be explained solely on the basis of the changes in circulating thyroid hormone levels.