Lipid-bound Sialic Acid Levels Research Articles

Serum sialic acid fractions in Kangal breed bitches with transmissible venereal tumours

The serum sialic acid concentration has been reported to be a potentially useful as tumour markers in many types of tumoural disease. The purpose of this study was to investigate of the levels of serum total sialic acid (TSA) and lipid-bound sialic acid (LSA) in transmissible venereal tumours (TVT) in Kangal Breed (Turkish Anatolian Shepherd Dog) bitches. Blood samples were collected from seven untreated bitches with TVT (test group) and eight healthy bitches (control group). Serum lipid bound sialic acid levels determination was done by the spectrophotometric procedure of Katopodis with resorcinol. Serum total sialic acid levels determination was done by the spectrophotometric procedure of Sydow. The mean TSA and LSA levels in the treated and control groups were 13.46±0.66 mg/dl (11.82-16.94) and 6.13±0.46 mg/dl (4.42-7.58); 9.15±0.59 mg/dl (6.28-11.48) and 2.26±0.24 (1.473.63) mg/dl, respectively. Both of serum levels of TSA and LSA in the untreated TVT dogs (n: 7) were significantly (p<0.001) higher than in the healthy dogs (n:8) The data revealed significant elevation in sialic acid levels in TVT and suggested potential utility of these parameters in diagnosis of the TVT. Results of this study suggest that TSA and LSA levels in sera may use in diagnosis serve as a valuable in these tumoural diseases

Serum Selenium, Vitamin E, and Sialic Acids Concentrations in Lambs with White Muscle Disease

The aim of this study was to determine the serum concentrations of selenium, vitamin E, and total- and lipid-bound sialic acid (LBSA) in lambs with white muscle disease (WMD) before and after treatment with a commercial preparation containing selenite and vitamin E. Fifteen lambs with WMD and ten control animals were used as research materials. Blood samples were collected from both groups before- and 1 month after treatment for Se analysis by fluorimetry, whereas vitamin E and sialic acid were measured by HPLC and spectrophotometry, respectively. Compared to controls, in the diseased animals, there was a significant increase of serum total sialic acid (TSA) and LBSA, together with significant decreases of serum Se and vitamin E concentrations (p < 0.001). One month after treatment, a reversal of trend was observed with decreases of TSA and LBSA and increases of Se and vitamin E concentrations. The TSA and LBSA levels, however, remained significantly higher than those of the controls, p < 0.05 and 0.001, respectively. The Se and vitamin E concentrations of the treated animals were the same as those of controls. This is the first study on total and LBSA concentrations in lambs with WMD, showing that these markers can be used in the prognosis of the disease.

This month in J Lab Clin Med: Issue highlights for August 2002

This month in J Lab Clin Med: Issue highlights for August 2002

Association between serum total and lipid-bound sialic acid concentration and the severity of coronary atherosclerosis

Serum total sialic acid has recently been shown to be a cardiovascular risk factor. Increased levels of this substance are associated with higher cardiovascular mortality and with cerebrovascular disease. It has also been shown that serum concentrations of total and lipid-associated sialic acid are significantly increased in hypertriglyceridemia. On the other hand, several circulating lipoproteins have been suggested to be related to the severity of coronary atherosclerosis, but contradictory results have been reported in the possible relationship between the concentrations of sialic acid and the severity of coronary lesions in patients with coronary heart disease. The purpose of this study was to investigate the possible relationship between serum total sialic acid concentration, recently shown to be a cardiovascular risk factor, and serum lipid-bound sialic acid concentration and the severity of coronary lesions. The study comprised 90 subjects, divided into three subgroups according to angiography results: 30 patients with no vessel disease, 30 patients with single-vessel disease, and 30 patients with double/triple-vessel disease. Serum total sialic acid determination was carried out with the thiobarbituric acid method of Warren; lipid-associated sialic acid was assayed with the method of Katopodis. Mean serum total sialic acid levels in patients with single-vessel disease (P <.05) and patients with double/triple-vessel disease (P <.001) were found to be significantly increased compared with that in patients with no vessel disease, whereas mean serum lipid-bound sialic acid levels were found to be significantly different between patients with double- or triple-vessel disease and patients with no vessel disease (P <.001). We also noted a significant difference between the levels of serum total sialic acid (P <.001) and lipid-bound sialic acid (P <.001) in patients with single-vessel disease and patients with double/triple-vessel disease. We found a significant correlation only between serum lipid-bound sialic acid and coronary angiographic score in patients with double/triple-vessel disease (r = 0.425, P <.05). Although the concentration of serum total sialic acid is increased proportionally with the number of diseased coronary arteries, only the concentration of serum lipid-bound sialic acid is related to the severity of coronary atherosclerosis, especially in patients with double/triple-vessel disease. (J Lab Clin Med 2002;140:110-8)

Serum total and lipid-bound sialic acid levels following acute myocardial infarction.

Although serum total sialic acid has been shown to be a cardiovascular risk factor, with elevated levels associated with increased cardiovascular mortality and also with cerebrovascular disease, the reason for the elevation in serum sialic acid content remains obscure. It has been shown that an increased output of serum proteins by the liver due to some type of acute phase reaction may be one of the possible sources of an increased serum sialic acid concentration in patients with myocardial infarction. An increase in the activity of sialidase, which cleaves the terminal sialic acid residues from oligosaccharides, glycoproteins and gangliosides, may also play an important role in the elevation of serum total sialic acid in myocardial infarction. Elevated serum total sialic acid in the blood might result either from the shedding or secreting of sialic acid from the cell membrane surface, or releasing of cellular sialic acid from the cell into the bloodstream due to cell damage after myocardial infarction. The purpose of the present study is to investigate serum total and lipid-bound sialic acid and the enzymes serum lactate dehydrogenase, creatine kinase and aspartate aminotransferase in patients with acute myocardial infarction, at 24 h post-infarction (day 1), 48 h post-infarction (day 2) and 72 h post-infarction (day 3). A possible role of cell damage in the elevation of serum total and lipid-bound sialic acid levels in these patients was also evaluated. In this study, 40 patients with myocardial infarction ranging in age from 42 to 68 years, and 26 healthy volunteers ranging in age from 45 to 71 years were included. Serum total sialic acid determination was carried out by the thiobarbituric acid method of Warren and lipid-bound sialic acfd by the method of Katopodis. Our data shows that a) there is a gradual increase in the levels of serum total sialic acid and lipid-bound sialic acid during the first three days after the acute myocardial infarction and b) the elevation in serum total sialic acid levels correlates with the elevation in lactate dehydrogenase activity only on day 1 following infarction. Therefore, either the shedding or secreting of sialic acid from the cell or cell membrane surface may be partly responsible for an increased serum sialic acid concentration especially on day 1 following myocardial infarction.

Variation of the ganglioside compositions of human milk, cow's milk and infant formulas.

The ganglioside compositions of human milk, cow's milk and infant formulas were compared. The results showed that there was a drastic change in the ganglioside composition from the colostrum to later human milk, and that both the patterns and contents of gangliosides in human milk, cow's milk and infant formulas differed markedly. In human milk, the total lipid-bound sialic acid level was two times higher than those in cow's milk and infant formulas. The major ganglioside in the later human milk, GM3 (27.7%), was only a minor component in the colostrum, cow's milk and infant formulas (3.3, 2.8 and 0.4-2.6%, respectively). GD3 represented 49.0, 61.0 and 72.4-86.6%, respectively, of the colostrum, cow's milk and infant formulas, compared to 31.8% of the later human milk gangliosides. Another four gangliosides, which were assumed to be c-series gangliosides, were detected in the colostrum and the later human milk. They represented 33-38% of total lipid-bound sialic acid, and were tentatively designated as GX1, GX2, GX3 and GX4, respectively. However, only GX1 and GX2 were observed in cow's milk and infant formulas. The variation of the gangliosides in human and cow's milk, and infant formulas might have some biological significance regarding neonatal brain development, allergies, infant growth and non-immunoglobulin prophylactic activities against some bacterial toxins.

Role of sialic acid and alkaline DNase in breast cancer.

Serum levels of sialic acid and alkaline DNase (ADA) were analysed in 495 blood samples collected from 170 breast cancer patients before and during/after anticancer treatment. Fifty-six healthy females were included in the study to define the cutoff values. The markers were analysed by highly sensitive spectrophotometric methods. Statistical evaluation of the data was done using Student's 't' test, paired 't' test and ROC curve analysis. The total sialic acid (TSA), lipid bound sialic acid (LSA) and ADA in sera of untreated breast cancer patients were significantly higher than in controls. ROC curve analysis revealed TSA and LSA to be useful markers for diagnosis of breast cancer. Serum levels of TSA and LSA were significantly decreased in complete responders as compared to their pretreatment values. The pretreatment ADA values showed much individual variation. However, responders showed higher levels of ADA than untreated patients. In nonresponders the values of the biomarkers were comparable with pretreatment levels. The study suggested that TSA and LSA can be helpful in the diagnosis of breast cancer. All three markers can be used for assessment of response to anticancer treatment in breast cancer patients.

Serum lipid-bound sialic acid in lung cancer patients

Serum lipid-bound sialic acid (LSA) assay was evaluated for differential diagnosis between benign and malignant pulmonary disease. Mean serum LSA for normal controls was 13.7±3.7 mg/dl and the upper limit of the normal value was set at 19.8 mg/dl (95% confidence limit, one side). The specificity was 97.1% (95% confidence interval was 93.8%, 100.0%). The mean for benign pulmonary disease was 17.1±5.1 mg/dl, the specificity was 89.1% (95% confidence interval was 80.9%, 97.3%), and the sensitivity was 10.9%. The mean for malignant pulmonary disease was 27.1±7.9 mg/dl, and the sensitivity was 93.3% (95% confidence interval was 88.5%, 98.1%). The serum LSA levels for different malignant pulmonary diseases were different between small cell carcinoma and adenocarcinoma. The results indicate that serum LSA assay might be used as tumor marker to differentiate lung cancer from normal subjects or benign lung disease.

Evaluation of lipid-bound sialic acid (LSA) as a tumor marker.

The objective of this study is the evaluation of serum levels of lipid-bound sialic acid (LSA) as a of marker cancer. This is a case-control study, and the levels of LSA were determined with blinded duplicates of cases and controls. Histologic verification of all cancer cases was used to confirm the diagnosis. The study included 135 patients with cancer (breast carcinoma, head and neck squamous cell carcinoma, lung cancer and gastrointestinal cancer) and 95 controls (57 normal subjects and 38 with chronic non-malignant diseases). Marker determination was done by the spectrophotometric procedure of Katopodis with resorcinol. The mean LSA level in the 57 healthy individuals was 15.09 mg/dl(95% C.I., 13.51-16.67), in the entire control group of 95 non-tumoral individuals it was 19.21 mg/dl (17.18-21.24), and in the 135 cancer patients it was 26.64 mg/dl (24.42-28.87). There was a statistically significant difference between patients with chronic non-tumoral diseases and healthy individuals (p < 0.001) and also between cancer patients and healthy individuals (p > 0.001), but not between cancer patients and patients with chronic non-tumoral diseases (p> 0.05). The mean LSA serum values related to tumor site were (mg/dl): breast cancer, 21.49; gastrointestinal tumors, 28.45; head and neck cancer, 28.61 and lung cancer, 32.54. The means according to clinical stage were: complete remission, 18.50 significantly higher than the healthy controls (p< 0.05); local disease, 23.50 (p < 0.01); locoregional disease, (p < 0.05); local disease, 23.50 (p < 0.01); locoregional disease, 27.21 (p < 0.001); metastatic disease, 34.49 (p < 0.001), and relapses, 20.87 (p< 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The significance of serum lipid-bound sialic acid in bladder tumours.

Tumour markers with high sensitivity and specificity for bladder cancer are still lacking and several markers have been investigated up to now. Serum lipid-bound sialic acid (LSA) was claimed to be a tumour marker by some investigators and this study tried to assess the value of LSA as a tumour marker in patients with bladder cancer. The results obtained from 27 patients and 30 controls showed that serum LSA levels remained within the suggested normal limits of the method used but they were significantly higher than in the controls. The value of serum LSA is questionable as an initial tumour marker for bladder cancer, but variations from the basal level may indeed be helpful in monitoring the efficacy of the therapy and in detecting relapses during follow-ups.

The evaluation of putative tumor markers for malignant melanoma.

Biomarkers have long held out the promise that malignancies might be diagnosed early and that patients could be monitored more confidently during their clinical course to more reliably predict recurrence and the effect of therapy. Reliable tumor markers have been described for colon carcinoma, hepatomas, and other tumors, but no reliable marker has been identified to monitor the course of malignant melanoma. Recently, the plasma level of lipid-bound sialic acid (LASA-P) has been described as reflecting an alteration in the surface membrane of cancer cells. An attempt was made to correlate the LASA-P level, along with the serum level of neuron-specific enolase, a glycolytic enzyme specific to cells of neuroectoderm origin including melanocytes, with clinical disease activity with a follow-up to at least 2 years. Two hundred seventy patients had blood samples drawn at various times during their clinical course for assay of LASA-P and neuron-specific enolase. Eighty of the patients (30%) sampled developed a recurrence sometime during their clinical course, whereas another 10 patients had active disease noted at diagnosis with evaluative tumor markers. The sensitivity and specificity of neuron-specific enolase was 27% and 77%, respectively, and cannot be recommended as a marker for melanoma. LASA-P showed a sensitivity of 65%, with 55 patients recurring and having active disease with abnormally high markers and 35 patients recurring or having active disease with normal markers. Specificity of the LASA-P test was 76%. When recurrence was associated with elevated LASA-P levels, the elevated level preceded recurrence by a median of 9.3 months. LASA-P may be a useful marker to follow patients with malignant melanoma.

Tumor Markers in Leukemia: Evaluation of Serum Levels of Different Forms of Sialic Acid, Regan Isoenzyme and Lactate Dehydrogenase

A sensitive and specific serum marker can greatly help in the early diagnosis of malignancy as well as in monitoring the treatment of cancer patients. The present work was initiated for determining serum levels of Total Sialic Acid (TSA), Lipid Bound Sialic Acid (LSA), Free Sialic Acid (FSA). Regan Isoenzyme (RI) and Lactate Dehydrogenase (LDH), so as to evaluate their value as potential tumor markers. Fifty patients with anemia and 78 patients with leukemia were studied. The leukemia group consisted of 32 cases of Acute Myeloid Leukemia (AML), 29 cases of Chronic Myeloid Leukemia (CML) and 17 cases of Acute Lymphatic Leukemia (ALL). The levels were compared with the values obtained from 88 healthy individuals. Compared to the healthy controls, all the biomarkers were significantly elevated in patients with anemia as well as in those with leukemia. However, in leukemia patients significantly higher levels of TSA, LSA, FSA and LDH were observed compared to anemia patients. TSA levels were significantly higher in AML patients compared to CML and ALL patients. LSA levels were also significantly higher in AML patients compared to ALL patients. LSA was the most sensitive (84.6%) while FSA and RI levels were the most specific (78.0%) markers for leukemia. The combined use of the markers showed increased sensitivity and specificity (100.0% and 98.0%, respectively). The study suggested that the biomarkers investigated might be used for differentiating anemic from leukemic conditions, however, more in-depth studies are indicated to assess their utility in classifying various leukemias.

Usefulness of serum glycoconjugates in precancerous and cancerous diseases of the oral cavity

Sera from 47 healthy controls, 18 normal individuals with the habit of tobacco chewing, 43 patients with oral precancerous (PC) conditions, and 40 patients with oral cancer (OC) were studied for the levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), mucoid proteins, and protein-bound hexoses (PBH) (galactose and mannose). The changes in the glycoconjugate levels were insignificant between the controls and the normal tobacco chewers. All four parameters were significantly elevated in oral PC patients compared with controls. The levels of PBH and LSA showed significant increase in the oral PC patients compared with the normal tobacco chewers. A significant increase was observed in the levels of TSA, LSA, mucoid proteins, and PBH in OC patients compared with controls, normal tobacco chewers, and patients with oral PC. Increasing levels of all the biomarkers were found with progression of the malignant disease. Elevations in the levels of TSA and LSA were statistically significant in Stage IV patients compared with Stage III patients. The patients with metastases had higher levels of the biomarkers than the patients with primary OC. However, elevations only in LSA levels were statistically significant. These results suggest that evaluations of the serum glycoconjugate levels may be useful in diagnosis of the patients with oral PC or OC. In addition to their value in early detection, they can also help in staging of the disease.

Total and ganglioside-bound sialic acid content of lymphocytes from non-insulin-dependent diabetic patients

The total and ganglioside-bound sialic acid content of unfractionated blood lymphocytes obtained from normal-weight healthy subjects (n = 17) and non-insulin-dependent diabetic patients on oral hypoglycemic drugs arbitrarily divided into normal-weight (n = 11), moderately overweight (n = 14) and severely overweight (n = 17) subgroups were examined. In normal-weight diabetics the level of lipid-bound sialic acid (gangliosides) of lymphocytes was found to be reduced (p less than 0.01). A more pronounced decrease (p less than 0.001) was observed for the lymphocyte total sialic acid of normal-weight and moderately overweight diabetics as compared to healthy subjects. In severely overweight non-insulin-dependent diabetics the decrease of total sialic acid was less pronounced compared to that found in healthy subjects. Whether this finding was due to obesity in these patients remains to be clarified.

Increased levels of protein- and lipid-bound sialic acids in the renal cortex of rats injected with low doses of gentamicin

Administration of the aminoglycoside antibiotic, gentamicin, even at therapeutic doses, causes renal lysosomal phospholipidosis. We now report that protein- and lipid-bound sialic acid levels are increased significantly in a time-dependent fashion in the renal cortex of rats injected with gentamicin (10 mg kg body wt. per day) for 4–10 days and a significant relationship could be observed between these two parameters. This elevation was not due to tissue regeneration, since it was not observed in cisplatin-treated animals.

Plasma lipid-bound sialic acid alterations in neoplastic diseases

Plasma lipid-bound sialic acid (LSA) was assayed in normal volunteers, patients with non-malignant diseases, and a variety of cancer patients. Mean plasma LSA in 50 normal volunteers, 16 patients with non-malignant diseases, 54 breast cancer, 17 lung cancer, 15 colon cancer, 7 ovarian cancer, 5 prostate cancer, 4 leukemia, 4 gastrointestinal, 3 thyroid cancer, 3 pancreas cancer and 2 adrenal cancer patients were 17.7, 23.2, 58, 85, 56.7, 46.2, 56.7, 53.3, 31.1, 33.2 and 119.5 mg/dl, respectively. None of the normal volunteers had elevated plasma LSA values. Plasma LSA level was not significantly different in male and female volunteers. Two out of 114 different cancer patients had plasma LSA levels within normal range exhibiting 98.2% sensitivity of the assay. Plasma LSA, which is relatively simple to assay, may be used as a tumor marker in wide variety of neoplastic diseases.

Evaluation and limitations of the lipid-associated sialic acid test for the detection of human cancer.

Previous studies and those of the authors have reported about raised levels of lipid-bound sialic acid (LSA) in sera of patients with various neoplasms. Most authors have used the method of Katopodis and Stock for isolating serum LSA. Because of the discrepancy of the amount of extracted LSA with the content of pure gangliosides in sera reported by other groups the authors analyzed the composition of the extracted LSA by immunochemical approaches. They were able to isolate considerable amounts of glycoproteins containing sialic acid as acid alpha-1-glycoprotein, antitrypsin, haptoglobin, antichymotrypsin, and immunoglobulins from the so-called "LSA" fraction. There is a very strong correlation between the raised LSA levels and the content of acid-alpha-1-glycoprotein in the sera of patients with malignancy. Therefore the term lipid-bound sialic acid applied to this test is misleading, since glycoproteins containing sialic acid are mostly responsible for the high "LSA" levels.

Serum glycoconjugates in patients with anemia and myeloid leukemia.

Because of carbohydrate alterations in malignant cells, serum glycoproteins have drawn considerable attention. In the current investigation we determined total sialic acid (TSA), lipid bound sialic acid (LSA), protein bound hexoses (galactose + mannose), fucose, hexosamines (galactosamine + glucosamine) and mucoid protein concentrations in the serum of patients with anemia and myeloid leukemia. The results were compared with those obtained in healthy individuals. In the leukemia patients we observed significant increases in glycoconjugates compared with the controls (P less than 0.001), and in TSA and fucose levels compared with the anemia patients (P less than 0.001). LSA and hexosamine levels were significantly lower in anemia patients with respect to the leukemia patients (P less than 0.01 and P less than 0.05 respectively), whereas levels of mucoid proteins and hexoses did not show significant differences. Except for hexosamines, all the markers tested were significantly elevated in the anemia patients compared with the controls. The present study suggests that the glycoconjugates investigated might be useful biochemical markers for differentiating anemic from leukemic conditions.

Lipid composition of the cerebral gray and white matter in a case with fukuyama type congenital muscular dystrophy

When compared with an age-matched normal control and a Duchenne muscular dystrophy (DMD) case, the patient with FCMD had an unusual ganglioside pattern in the cerebral gray matter. The total level of lipid-bound sialic acid in the cerebral gray matter was also slightly decreased. However, other lipid compositions of the cerebral gray and white matter were normal compared with those in the control case.

Characterization of some minor gangliosides in Tay—Sachs brains

The ganglioside distribution of Tay—Sachs brain was re-examined in detail. In both the gray and white matter, the levels of lipid-bound sialic acid were increased 6- and 10-fold, respectively, over normal infant brain, and approximately 90% of the total ganglioside was G M2. The level of G M2 was increased about 90 times in gray matter and 220 times in white matter in comparison with that in normal controls. The level of G D1a-GaINAc was increased 19 times and 10 times in gray and white matter, respectively. The concentration of G D2 was increased about 4-fold in Tay-S-Sachs white matter. In addition, the G M3 level was increased 2.7 and 3.5 times and the G D3 level 2 and 2.4 times over normal gray and white matter, respectively. However, the levels of other complex gangliosides such as G M1, G D1a, G D1b, G T1b and G Q1b decreased remarkably. Since G M2, G D2, G D1a-GalNAc and a recently characterized ganglioside G M1b-GalNAc possess a common N-acetylgalactosaminyl terminal structure, their accumulation in Tay—Sachs brains is therefore consistent with the known hexosaminidase A deficiency. However, the accumulation of hexosamine-free G M3 and G D3 is not. The in vitro incorporation of N-acetylgalactosamine into G M3 to form G M2 was examined in a rat brain microsomal fraction in the presence of large amounts of other glycolipids. Acidic glycolipids were slightly stimulating and then became increasingly inhibitory when the molar ratio of lipid to substrate G M3 exceeded 10 to 1. Neutral glycolipids and the phospholipid, phosphatidylcholine, were inhibitory at all levels tested. The data suggest that the accumulation of G M3 and G D3 in Tay—Sachs brains could be due to an inhibition of N-acetylgalactosaminyl-transferas by high levels of glycolipids, and the inhibition is not due to chelation of the obligate divalent cation necessary for the activity of this enzyme. The inhibition of this enzyme may also be responsible for the decreased levels of other complex gangliosides.