[Glycosaminoglycans dysbolism in pathogenesis of idiopathic varicocele].

Ultrasound dopplerography (UD) was used to examine 50 patients with idiopathic varicocele (IV) and 20 healthy subjects. Such parameters were assessed as age, severity of IV, its duration, scrotal vessels UD data, vein diameter of the pampiniform plexus on the left, reflux at the height of the Valsalva test, uronic acids (UA), glycosaminoglycanes (GAG) and their fractions (hialuronic acid--HA, chondroitin sulphates--CS, heparansulphates--HS). UA and GAG fraction composition was studied with ion exchange chromatography. Calculations were made of mean values, standard deviations, Student's t-criterion, Pirson's correlation coefficient. It was found that HA and UA concentrations were high. In young patients HA metabolism was disturbed more, in adult patients--disturbance of UA metabolism. Two equal negative moderately strong links were revealed between the patients' age, HS and total GAG: r1 = r2 = -0.56; CI of UA in the patients--21.97-59.09 mcg/ml, in the control group --23.70- 43.42 mcg/ml. With age, the organism adapts to the disease and spontaneous regress may occur. In UA concentration in the serum above 43.42 mcg/ml surgical treatment is indicated, if it is lower--conservative treatment and follow-up.

Effect of Tulasi (Ocimum sanctum) leaf powder supplementation on blood sugar levels, serum lipids and tissue lipids in diabetic rats.

Tulasi leaf powder was fed at the 1% level in normal and diabetic rats for a period of one month to explore the effect on fasting blood sugar, uronic acid, total amino acids, and the lipid profile in serum and tissue lipids. The results indicated a significant reduction in fasting blood sugar, uronic acid, total amino acids, total cholesterol, triglyceride, phospholipids and total lipids. In liver, total cholesterol, triglyceride and total lipids were significantly lowered. Total lipids were significantly reduced in kidney. In heart, a significant fall in total cholesterol and phospholipids was observed. All these observations indicate the hypoglycemic and hypolipidemic effect of Tulasi in diabetic rats.

[Characterization of plasma glycosaminoglycans in hemodialysis patients]. / Caratterizzazione dei glicosaminoglicani plasmatici nel paziente in emodialisi.

Glycosaminoglycans are heteropolysaccharides composed of disaccharide repeating subunits, each one containing a uronic acid component (glucuronic or iduronic acid) and a hexosamine (N-acetyl-glucosamine or N-acetyl-galactosamine, which may be differently sulphated). The presence of GAGs in human plasma has been demonstrated in several studies; they are bound to plasma proteins through non-covalent linkages. However, very little is known about either their origin or their physiological role. Due to their anionic charge, they may influence some metabolic processes, such as blood coagulation, and they could also have a role in urolithiasis and atherogenesis. Moreover, they may be important in modulating the metabolism of some lipoproteins by affecting the rate of their catabolism. Modifications of GAG pattern have been described in a few pathological conditions such as mucopolysaccharidosis, connective tissue diseases and kidney diseases. A high frequency of accelerated atherosclerosis has been observed in haemodialysis patients (HD), probably associated with the altered lipoprotein profile, which is often described in these subjects. Since GAGs may play a role in lipoprotein metabolism, we isolated and characterized plasma GAGs from a group of HD patients and a group of normal matched subjects. Quantitative analysis of plasma GAGs showed a significant increase of these polysaccharides in the HD group. Circulating levels of GAGs were 8.21 +/- 1.89 micrograms/ml in control subjects, and 15.08 +/- 3.13 micrograms/ml in the HD group (p < 0.0001). The isolation of plasma GAGs by ion-exchange chromatography produced two uronic acid containing families: a low-charge (peak I) and a high-charge (peak II) species. Both of these contained GAGs associated with plasma proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on the effect of dry Sundakai (Solanum torvum) powder supplementation on lipid profile, glycated proteins and amino acids in non-insulin dependent diabetic patients.

The effect of dry Sundakai powder supplementation (7 g providing 1.23 g of crude fibre) on glycemic control, lipidemic control, total amino acids and uronic acid was studied on 30 non-insulin dependent diabetes mellitus patients. All the patients were on hypoglycemic drugs. The above parameters were monitored at day 1, 15 and 30 days. After one month of fibre supplementation, no significant changes were observed with respect to glucose, lipid profile, glycated proteins, total amino acids and uronic acid levels in these subjects.

Human serum and urine glycosaminoglycans in health and in patients with chronic renal failure.

Quantitation of uronic acid precipitable by cetylpyridinium chloride (CPC) and electrophoretic separation of glycosaminoglycans were performed on sera from patients with chronic renal failure and compared to normal controls. Serum CPC-precipitable uronic acid (CpUA) levels in patients with renal failure were significantly higher (mean 13.7 mg/L, range 7.1-23.6 mg/L) than normal controls (mean 9.6 mg/L, range 5.1-13.9 mg/L) due to increased concentrations of low sulphated chondroitin sulphate. A positive correlation between serum CpUA and creatinine was found in renal failure patients. Urine CpUA excretion was raised in renal failure patients compared to normal controls with an increased excretion of chondroitin sulphate (Ch-S) of reduced electrophoretic mobility. Heparan sulphate (HS), a major glycosaminoglycan in normal urine, was absent from the urine of these patients. The possible origin of urine glycosaminoglycans and the role of the kidney in glycosaminoglycan metabolism are discussed.

Chondroprotective action of salmon calcitonin in experimental arthropathies.

To assess whether calcitonin exerts an influence on cartilage, three models of arthropathies in rabbits--representing three different modes of cartilage destruction--were used: (1) corticosteroid administration (endocrinological disturbances model); (2) meniscectomy (mechanical stress model); and (3) immobilization of the hind leg (nutritional disorder model). After 12 weeks of methylprednisolone (MP) administration, the rabbit femur heads displayed cartilage erosions, marked decrease of glycosaminoglycans (GAG) content, and narrowing of joint spaces. Elevation of serum uronic acid, activity of alkaline phosphatase, and calmodulin content was evident. All these changes were minimal--close to normal--in the group treated for 12 weeks with MP + salmon calcitonin (sCT). Partial meniscectomy and hind leg immobilization caused statistically significant loss of GAG from the cartilage and narrowing of the knee joint space during the same experimental period, 12 weeks. In both these models the groups of rabbits treated simultaneously with sCT showed only insignificantly smaller joint spaces and GAG content. These results support our hypothesis of a chondroprotective property of calcitonin. However, the mechanism through which calcitonin influences joint cartilage remains unknown. A direct effect of calcitonin on cultivated chondrocytes, as well as the role of calmodulin, beta-endorphins, calcium, and interleukin-1 in the process are discussed.

Studies on the effect of curry leaves supplementation (Murraya Koenigi) on lipid profile, glycated proteins and amino acids in non-insulin-dependent diabetic patients.

Curry leaves powder supplementation (12g providing 2.5 g fibre) was carried out for a period of 1 month in 30 non-insulin dependent diabetes mellitus patients. The parameters monitored at 1, 15 and 30 days were fasting and 2 h post-prandial blood sugar levels, serum total cholesterol and its lipoprotein fractions, triglycerides, total amino acids, uronic acid, glycosylated serum proteins and glycosylated low density lipoprotein cholesterol fraction. The results indicated a transient reduction in fasting and post-prandial blood sugar levels at 15-day period with no appreciable changes in serum glycosylated protein levels, glycosylated low density lipoprotein cholesterol fraction, serum lipids, lipoprotein cholesterol levels, uronic acid and total amino acids were observed during the supplementation period, i.e, either at 15 days or 30 days.

Effects of Centella asiatica extract on mucopolysaccharide metabolism in subjects with varicose veins.

The effects were studied of the total triterpenic fraction of Centella asiatica on serum levels of the uronic acids and lysosomal enzymes involved in mucopolysaccharide metabolism (beta-glycuronidase, beta-N-acetylglucosaminidase, arylsulfatase) in patients with varicose veins. The basal levels of uronic acids (467.7 +/- 69.3 micrograms/ml) and of lysosomal enzymes (beta-glycuronidase 1.8 +/- 0.4 microM/min/l, beta-N-acetylglucosaminidase 23.1 +/- 0.4 microM/min/l, arysulfatase 0.078 +/- 0.003 microM/min/l) were elevated, indicating an increased mucopolysaccharide turnover in subjects with varicose veins. During treatment with Centella asiatica extract (60 mg/day for three months), these levels fell progressively. At the end of treatment the serum uronic acid (231.8 +/- 51.5 micrograms/ml), beta-glycuronidase (1.2 +/- 0.05 microM/min/l), beta-N-acetylglucosaminidase (17.7 +/- 0.7 microM/min/l) and arysulfatase (0.042 +/- 0.003 microM/min/l) levels were highly significantly lower than the basal levels (p less than 0.01). The results of this trial provide an indirect confirmation of regulatory effects of the extract of Centella asiatica on metabolism in the connective tissue of the vascular wall.

Serum and urine glycosaminoglycans in myeloid leukemia and myelodysplasia.

Urinary glycosaminoglycan excretion is increased in a variety of human diseases, including malignancy. We have measured serum and urine glycosaminoglycan levels by the carbazole method of uronic acid determination in patients with myeloid leukemia or myelodysplasia. Eleven patients were studied during active disease as well as eight in complete remission. Serum levels in patients with active disease did not differ significantly from 11 healthy volunteers with no hematological disease. In contrast, the median urine level for the patients with active disease was 7.6 mg uronate/g Creatinine (Creat) compared to 2.6 for controls (p less than 0.002). Interestingly, the eight patients in complete remission also had a significant increase in uronate excretion with a median of 7.3 (p less than 0.002). These results suggest that elevated urinary glycosaminoglycan levels in leukemia are not due to impaired ability of the liver to clear circulating glycosaminoglycans or overproduction by leukemic cells. The observed increase in glycosaminoglycan excretion may be due to altered bone marrow matrix metabolism that is often not reversed by the achievement of hematologic remission.

[Glycosaminoglycans in leukocytes in myeloproliferative disorders]. / Glikozaminoglikany leikotsitov pri mieloproliferativnykh zabolevaniiakh.

Content and composition of glycosaminoglycans (GAG) was studied in leukocytes of 30 healthy persons and of patients with different types of myeloproliferative disorders: 32 patients with chronic myeloid leukemia (CML), 10 patients with polycythemia vera (PV), 5 patients with idiopathic myeloid fibrosis (IMF) and 10 patients with acute myelo blast leukemia (AML). The total content of GAG in healthy persons was 97.7 +/- 3.9 micrograms of uronic acid per 100 mg of dry cells, in CML and IMF it was 2-4-fold increased, in PV it was elevated by 20%, in AML it was diminished 3-5-fold. The elevated level of GAG in CML and IMF was due to presence of basophils and considerable quantity of immature cell forms: promyelocytes and myelocytes. In these cells changes in GAGs composition and their properties were shown: an increase of chondroitins deficient in sulfate groups and of heparan sulfate content, especially in basophils. The observed changes in GAG content and composition may be important for biological activity of the leukemic cells.

The short-term effect of cortisol, dexamethasone and ACTH administration on the serum levels of hexuronic acids and monosaccharides in man.

The levels of serum monosaccharides (SMO) and hexuronic acids (SHA) were measured in subjects without any metabolic or endocrine disease after a short-time administration of cortisol, dexamethasone and ACTH. The effects of the three hormones were evaluated in regard to the urinary excretion of free cortisol and cortisone at basal conditions. In thirteen subjects a significant increase of SMO during cortisol treatment was registered after 24 hours. A distinct difference in the response of SMO to cortisol treatment was observed in patients with normal or increased cortisol excretion, respectively. In the subjects with high urinary free corticoids a peak of SMO occurred soon after 4 hours after cortisol administration, in the next 48 hours no tendency of return towards basal levels was observed. In the subjects with normal urinary free cortisol excretion only a slight increment was seen after 24 hours. Soon after 4 hours in eight subjects dexamethasone administration resulted in an increase of SMO without regard to the excretion of urinary free corticoids. The highest values were obtained after 28 hours of dexamethasone treatment. Ten hours after cessation of dexamethasone the levels of SMO reached the basal values. In the study in which ACTH was administered, an increment of SMO was registered only in the first four hours. In the group of subjects treated with ACTH a slight difference between subjects with normal and increased corticoid excretion was seen. The levels of SHA successively increased after the administration of all three hormones, without regard to the basal excretion of urinary free corticoids. This increase persisted also 10 hours after cessation of cortisol and dexamethasone, and 40 hours after the last dosis of ACTH, respectively. The possibility of an altered metabolism of glucose through the glucuronate pathway under conditions of glucocorticoid excess is discussed.

The relationship of serum hexuronic acid and monosaccharide levels to urinary free cortisol and cortisone excretion in healthy subjects and in patients with diabetes mellitus and atherosclerotic peripheral vascular disease.

The relationship of hexuronic acid and monosaccharide concentrations in serum to the excretion of urinary free cortisol and cortisone was studied in 14 healthy subjects, in 16 patients with diabetes mellitus, and in 14 patients with atherosclerotic peripheral vascular disease. In both groups of patients increased values of hexuronic acids, reducing monosaccharides and keto-sugars were registered. In diabetics the relative proportion of monosaccharides was increased, the proportion of hexuronic acids was lowered. In atherosclerotic peripheral vascular disease a significant preponderance of hexuronic acid and keto-sugar amounts in the composition of total sugar components was observed in comparison with healthy subjects. In healthy subjects there is a close correlation of urinary free cortisol and cortisone with reducing monosaccharides in blood, measured on the same day. In diabetes not any correlation of the increased values of free corticoids with the sugar components was registered. In atherosclerotic peripheral vascular disease a highly significant correlation between urinary free cortisol and cortisone and the hexuronic acid content in serum was observed. In patients with atherosclerotic peripheral vascular disease the results suggest an altered metabolism of glucose, which is shunted into insulin-insensitive glucuronate pathway in conditions of endogenous hypercortisolism.

Glycosaminoglycan metabolism in pregnancy.

An unselected group of pregnant patients was followed during pregnancy. Serial assays were made of maternal serum levels of hyaluronidase activity, free amino sugar and uronic acid. It was found that there was a highly significant correlation between the serum levels of hyaluronidase activity and uronic acid, both of which rose during pregnancy. In normal pregnancy the maternal serum amino sugar level showed a moderately significant correlation with length of gestation, which was not shown in abnormal pregnancies. Conversely the rise in uronic acid level with length of gestation was most signigicant in patients with complicated pregnancies.

Changes in chondroitin sulfate concentration in rabbit blood plasma depending on the method of its administration.

Glycosaminoglycans were determined in the blood plasma of rabbits as a function of time after intravenous, intramuscular and intragastric administration of chondroitin sulfate preparation. After intravenous administration two phases of chondoitin sulfate elimination from the blood with T1/2 131-135 min and 8.5-9.5 min, respectively were observed. The level of the blood plasma glycosaminoglycans did not increase after intragastric introduction of the chondroitin sulfate preparation. Excretion of glycoaminoglycans in the urine was also determined.