Cholesterol-lowering effects of a new isolated soy protein with high levels of nondenaturated protein in hypercholesterolemic patients.

This study was undertaken to compare the effects on plasma cholesterol concentration of a new isolated soy protein in which the protein structure is kept in its native, nondenaturated form (verum 1) versus a conventional isolated soy protein (verum 2) and milk protein (placebo). This prospective, randomized, double-blind, placebo-controlled study was conducted in an outpatient clinical study center in Berlin, Germany. Over 8 wk, 120 patients (total cholesterol, 5.2-7.8 mmol/L) were given verum 1, verum 2, or placebo at a dosage of 25 g protein daily. At the end of the treatment period, total cholesterol levels were significantly reduced by 10.7% in the verum 1 group compared with placebo (P<.001), and levels were reduced by 5.8% in the verum 2 group (P=.008). The difference between the 2 verum groups was statistically significant (P=.008). Low-density lipoprotein cholesterol levels were significantly reduced with nondenaturated isolated soy protein only: levels were reduced by 9.4% in the verum 1 group (P=.002) and by 4.9% in the verum 2 group (P=.107). Again, the difference between the verum groups was significant (P=.05). The results of this study confirm that supplementation with isolated soy protein can lead to significant reductions in plasma concentrations of total and low-density lipoprotein cholesterol. These reductions are significantly more pronounced with an isolated soy protein that maintains the native protein structure than with a commercially available reference isolated soy protein.

Carob pulp preparation rich in insoluble fibre lowers total and LDL cholesterol in hypercholesterolemic patients.

BACKGROUND: Recently, insoluble fibre from carob pulp has been found to affect blood lipids in animals in a similar manner as soluble dietary fibre. AIM OF THE STUDY: To investigate whether a carob pulp preparation containing high amounts of insoluble fibre has a beneficial effect on serum cholesterol in humans. METHODS: Volunteers (n = 58) with hypercholesterolemia were recruited to participate in a randomised, double- blind, placebo-controlled and parallel arm clinical study with a 6 week intervention phase. All participants consumed daily both, bread (two servings) and a fruitbar (one serving) either with (n = 29) or without (n = 29) a total amount of 15 g/d of a carob pulp preparation (carob fibre). Serum concentrations of total, LDL and HDL cholesterol and triglycerides were assessed at baseline and after week 4 and 6. RESULTS: The consumption of carob fibre reduced LDL cholesterol by 10.5 +/- 2.2% (p = 0.010). The LDL:HDL cholesterol ratio was marginally decreased by 7.9 +/- 2.2 % in the carob fibre group compared to the placebo group (p = 0.058). Carob fibre consumption also lowered triglycerides in females by 11.3 +/- 4.5% (p = 0.030). Lipid lowering effects were more pronounced in females than in males. CONCLUSION: Daily consumption of food products enriched with carob fibre shows beneficial effects on human blood lipid profile and may be effective in prevention and treatment of hypercholesterolemia.

Determination of hyperforin, hypericin, and pseudohypericin in human plasma using high-performance liquid chromatography analysis with fluorescence and ultraviolet detection.

Hyperforin, hypericin and pseudohypericin are the main ingredients of St. John's wort extract, which is available over the counter for treatment of mild to moderate depression. To facilitate clinical studies we developed two sensitive HPLC methods for determination of hypericin/pseudohypericin and hyperforin, respectively, in human plasma samples. The achieved limits of quantitation of 0.25 ng/ml for hypericin and pseudohypericin and 10 ng/ml for hyperforin were low enough to allow determination of pharmacokinetic parameters of the substances. Following liquid-liquid extraction of human plasma the samples were separated by isocratic reversed-phase HLPC and analyzed using fluorimetric detection for hypericin/pseudohypericin and UV detection for hyperforin.

Carob pulp preparation for treatment of hypercholesterolemia.

The lipid-lowering effect of a carob pulp preparation rich in insoluble dietary fiber and polyphenols was investigated in a noncomparative, open-label pilot study. Over 8 weeks, 47 volunteers with moderate hypercholesterolemia (total cholesterol 232-302 mg/dL) consumed 15 g of carob per day in three products (breakfast cereal, fruit muesli bar, powdered drink) as a supplement to their regular diet. After 4 weeks, reductions of 7.1% in mean total cholesterol and 10.6% in LDL cholesterol were noted; respective decreases after 6 weeks were 7.8% and 12.2% (all P<.001). HDL cholesterol and triglyceride levels remained unchanged. Overall compliance was good. Only 3 volunteers (6%) reported a sensation of fullness, which led to 2 of the 3 dropouts. The carob preparation may have value in the dietary treatment of hypercholesterolemia.

Early urinary markers of target nephron segments as studied in cadmium toxicity.

A number of chemicals may adversely affect one or more of the anatomical structures of the kidney, such as the glomerulus, the tubular apparatus, the medullary, or interstitial cells. To recognize subclinical renal dysfunction, a battery of new, non-invasive tests was applied in comparison to established ones. The study on cadmium exposed subjects, performed within the framework of a collaborative European research project, exemplifies the concept of target selectivity within a nephron. One hundred seventy-two subjects were classified according to urinary cadmium excretion as controls (< 1.5 micrograms/g creatinine), or subjects with moderate or high cadmium body burden (1.5 to 5 micrograms/g creatinine, > 5 micrograms/g creatinine). Twenty-six urinary analytes (such as serum derived proteins, tubular enzymes, eicosanoids) and four plasma markers, related to the function or integrity of specific nephron segments, were investigated in a cross-sectional study. The group with the moderate cadmium body burden showed alterations of proximal tubular integrity, that is, increased excretion of tubular brush-border antigens. The group with higher cadmium body burden revealed an involvement of the whole nephron. The most prominent quantitative changes were found for the glomerular markers high molecular weight proteins, and thromboxane B2 and for the proximal tubular markers retinol binding protein, alpha 1-microglobulin, N-acetyl-beta-D-glucosaminidase, and the intestinal alkaline phosphatase. A diagnostic approach to screen for nephrotoxicity due to environmental hazards like cadmium should include proximal tubular markers (alpha 1-microglobulin and tubular enzymes, that is, intestinal alkaline phosphatase) but the measurement of glomerular markers is also advisable.

Urinary proteins and enzymes as early indicators of renal dysfunction in chronic exposure to cadmium.

We tested the diagnostic sensitivity of various urinary analytes for detecting cadmium-induced nephropathy at an early stage. We investigated 73 healthy persons (control group 1) and individuals exposed to cadmium, either environmentally (n = 36, risk group 2) or occupationally (n = 62, exposed group 3). All data were related to limits of the central 95% reference intervals of the control group. The serum creatinine and ribonuclease values, indicators of the glomerular filtration rate, were not different in the three groups. In the exposed persons (group 3), proximal tubular indicators (low-M(r) proteins lysozyme, ribonuclease, retinol-binding protein, and alpha 1-microglobulin) were more often increased than the glomerular indices (higher-M(r) proteins transferrin, IgG, and albumin). Both the low-M(r) proteins and tubular enzymes were differently altered in their excretion rates. Alanine aminopeptidase, alkaline phosphatase, and N-acetyl-beta-D-glucosaminidase increased even in the risk group 2. alpha 1-Microglobulin was increased in the exposed persons whose cadmium excretion was < 5 mumol/mol creatinine. The combined determination of alpha 1-microglobulin and N-acetyl-beta-D-glucosaminidase exceeded the corresponding upper reference limits in 30% of group 2 and 39% of group 3. We recommend screening for these two analytes to detect cadmium-induced renal dysfunction at an early stage.

[Excretion of beta-N-acetylglucosaminidase in urine of patients with kidney transplants and workers exposed to cadmium]. / Die Ausscheidung von beta-N-Acetylglucosaminidase im Harn bei Nierentransplantierten und bei cadmiumexponierten Arbeitern.

A new colorimetric test for kinetic determination of beta-N-acetylglucosaminidase activity in urine is evaluated according to the diagnostic usefulness in patients after kidney transplantation and in workers exposed to cadmium. The new test is suited to monitor renal parenchymal alterations.

[Use of the stable nitrogen isotope 15N in assessing liver metabolism in hormonal contraception]. / Einsatz des stabilen Stickstoffisotops 15N zur Beurteilung des Leberstoffwechsels bei hormonaler Kontrazeption.

In 37 women with long-term use of oral contraceptives (average use 13.4 years) and 12 women who had not taken oral contraceptives for at least 5 years we determined the serum enzymes ALAT, ASAT, Gamma-GT and conducted the 15N-ammonium test as a marker of partial metabolic performance of the liver. In addition we studied total protein, protein fractions in the serum and haematologic parameter. 18 out of 37 women showed a morbid result in the 15N-ammonium test. In 4 of these 18 women morphological changes representing hepatic damage caused by contraceptives could be detected. On the average ALAT, Gamma-GT and 15N-ammonium test in both groups are clearly different. Because the enzymic levels are being in the normal range, only the 15N ammonium test enables to give a hepatotoxic evidence. It is possible to conclude that long-term use of oral contraceptives influences the liver metabolism.

PIP: 49 women of reproductive age were included in the study and were divided in 2 groups. The ovulation inhibitor group (OI) consisted of 37 women aged 33.5-39 exposed to ovulation inhibitors for an average of 13.4 years (Ovosiston, Sequenzovosiston, Non-Ovlon), and the control group consisted of 12 women aged 35.5-41.5 who had taken no OI for at least 5 years. Aspartate-aminotransferase (serum glutamic oxaloacetic transaminase=SGOT) and alanine aminotransferase (serum glutamic pyruvic transaminase) enzymes were determined as indicators of liver damage, and gamma-glutamyl-transferase (gamma-GT) for indication of cholestasis or as a sensitive parameter of hepatopathy. By using a nonradiating, stabile isotop-marked tracer substance, 15 N-ammonium chloride, the uric acid synthesis performance and the ammonium excretion of the liver could be evaluated. The Q-value indicated an excess of ammonium and uric acid as demonstrated by the 15 N test. Significant differences were found between the 2 groups with regard to ALAT, gamma-GT, Q-value, and leukocyte count. The measured values of enzymes and leukocytes studied, however, stayed within the normal range. In the OI group, the decreased gamma-GT activity was surprising. Also, the Q-value showed a slightly pathological median value in 18 women of the OI group. In 4 women who has Q-values of 1.6 to 1.9 (vs. 1.4 median value), liver punction was performed. In each case, liver damage could be shown to be attributed to use of contraceptives. Morphological changes indicating enhanced detoxification activity, and liver cell fat formation of various severity were also found as uncharacteristic alterations. The described increase of the serum activity of aminotransferase, leucine aminopeptidase, alkaline phosphatase, and gamma-GT were interpreted as the expression of cellular adaptation. Long-term use of hormonal contraceptives influences the metabolism of the liver, whose partial disorder can be detected by the 15 N-ammonium test. Normal ALAT and gamma-GT serum enzyme activity in single cases does not allow conclusions on the behavior of the metabolism of the liver.

[Biochemical studies of the assessment of transplant function following clinical heart transplantation--initial experiences]. / Biochemische Untersuchungen zur Einschätzung der Transplantatfunktion nach klinischen Herztransplantationen--erste Erfahrungen.

Average and specific individual courses of the following parameters are reported in this paper, with reference being made to eight of eleven clinical heart transplantations so far performed at the authors' department: lactate, pyruvate, myoglobin, ASAT, ALAT, GGT, CK, CK-MB, LDH, LDH-1, and glycogen phosphorylase. Glycogen phosphorylase was found to deviate most strongly from normal, with the enzyme exhibiting two initial maxima. The enzyme activity in the serum vanished not later than twelve days from transplantation. The curve of myoglobin was largely parallel to that of phosphorylase. Phosphorylase seemed to be of particular suitability for assessment of ischaemic damage in the wake of transplantation. The individual courses seemed to suggest that none of the investigated parameters exhibited sufficiently sensitive correlations with pathomorphological signs of rejection.

[Value of various amino acid mixtures for the treatment of chronic liver damage]. / Wertigkeit verschiedener Aminosäurengemische für die Behandlung des chronischen Leberschadens.

A reproducible liver lesion was caused in 28 pigs by intermittent, intraperitoneal administration of thioacetamide. The morphological degree of the liver lesion was checked by histological investigations (material drawn from the liver by biopsy). During a 3-day infusion period a so-called liver solution (Aminofusin hepar) was given to one group of animals, a normal solution (Infesol) to a second group, and only an electrolyte infusion solution under oral nutrition ad libitum to a third one. The solutions were labelled with (15N) glycine. The amounts of total N, total 15N, 15N with single non-protein fractions, a number of enzymes of 15N incorporated into the liver protein were measured in urine, and the following points were established: 1. The catabolic situation of metabolism is eliminated both by the so-called normal solution and the specific amino acid solution. The two mixtures of L-amino acids thus have a nutritive effect. 2. The toxic liver lesion is an indication for parenteral nutrition. Oral nutrition alone is not sufficient. 3. The so-called liver solution influences the liver metabolism of the protracted liver lesion more than the so-called normal solution does, and considerably more than an electrolyte infusion solution under oral nutrition ad libitum.

[Physical exertion and the course of hepatitis]. / Körperliche Belastung und Hepatitisverlauf.

Twenty-five patients with clinically and histologically verified acute hepatitis were subjected to a submaximal bicycle ergometer exercise during the first week after inpatient admission and afterwards subdivided into two groups. The first group maintained bedrest, and the other group trained for 30 minutes a day over six weeks at an exercise level amounting to 70% of the submaximal performance of the initial ergometry. Histological, clinical and laboratory results did not differ between the groups. It is concluded that immobilization for a short time only is indicated in acute hepatitis.

[Liver diagnostics]. / Aspekte der Leberdiagnostik.

Prerequisite of a scientific and rational liver diagnostics is the knowledge of the physician of function and structure of the liver. The laboratory demand should always be an accomplishment of the physician and should be performed only upon such a scale that it is also followed by therapeutic consequences and/or consequences concerning the expert's opinion. The biochemical blood analysis gives information about the size of the injury to the parenchyma and about the disturbance of the various partial functions of the liver. In this case is to be taken into consideration that biochemical and histological parameters are no concurrent, but supplementing diagnostic methods. A progress in liver diagnostics is the use of the isoenzymes of the aspartate aminotransferase and the lactate dehydrogenase as well as of the enzymes of the metabolism of the connective tissue. With the entering into selected parameters of the liver diagnostics possibilities to the establishment of the disturbed liver metabolism by means of markers are shown and at the same time recommendations for the praxis of the liver diagnostics are derived.

[Acute viral hepatitis and body loading--a self-excluding therapeutic principle?]. / Akute Virushepatitis und körperliche Belastung--ein sich ausschliessendes Therapieprinzip?

Of 27 patients with acute virus hepatitis 16 patients performed successfully a daily training programme during their stay in hospital. On the basis of both clinical and clinical chemical parameters in comparison to the control group of 10 patients who observed the conventional rest in bed the course of healing did not deteriorate. Also with regard to the late prognosis no higher rate of recidivation or chronification could be proved. Our examinations support the thesis that the demand of strong rest in bed is to be regarded as out of date in the treatment of acute virus hepatitis.