Pathophysiology of liver diseases: impact of tumor necrosis factor alpha receptor 1 and hexosaminidase

Liver disease is the main cause of morbidity and mortality worldwide. The spectrum of the disease ranged from fatty liver to hepatic inflammation; necrosis, progressive fibrosis and hepatocellular carcinoma. We evaluated the serum levels of soluble tumor necrosis factor-alpha receptor 1, total B-hexosaminidase and its isoenzymes Hex A and B activities and nitric oxide in patients with liver diseases and their association with aminotransferase level. Seventy patients and 12 healthy subjects were recruited. Patients were divided into 3 groups; chronic hepatitis group [20 patients], liver cirrhosis group [30 patients] and malignant liver group [20 patients]. Serum levels of soluble tumor necrosis factor-alpha receptor 1, total B-hexosaminidase and its isoenzymes Hex A and B activities and nitric oxide were measured. Serum levels of soluble tumor necrosis factor-alpha receptor 1, total B-hexosaminidase activity and nitric oxide were significantly higher in the liver disease patients. Serum levels of isoenzvmes Hex A and B were significantly higher in malignant liver patients. Total Bhexosaminidase and its isoenzyme Hex A activity levels were significantly higher in +ve HBsAg and +ve Anti-HCV patients. Serum levels of soluble tumor necrosis factor-alpha receptor 1 were positively correlated with aminotransferase level. Taken together, these findings suggested that these biochemical indices might reflect ongoing disease activity and played an important role in the pathophysiology of liver diseases

Arginase activity in breast cancer: is it a significant biomarker?

Due to the importance of arginase enzyme in different malignant disorders, the purpose of the present study was to determine and compare the arginase activity in cancerous cells and their normal and benign counterparts. The tissue arginase activity level was evaluated in 30 females with breast cancer, in 6 females with benign breast disease and in 9 healthy control subjects. The arginase activity levels were significantly increased in malignant breast tissues in comparison to healthy ones, while the difference did not reach the level of significance in comparison to benign breast diseased tissues. Patients with advanced stage showed insignificantly higher arginase activity compared to those with early stage. In addition, estrogen receptor negative tumors showed insignificant higher arginase activity levels compared to estrogen receptor positive tumors. Moreover, tissues of premenopausal patients showed lower activity levels of arginase compared with those of posrmenopausal ones. Meanwhile, patients with bad prognosis revealed insignificantly higher activity levels of arginase compared to those with good prognosis. It could be concluded that tissue arginase activity seems to be involved in the biological behasiour of breast cancer and its determination in cancerous tissues could predict its outcome

Evaluation of plasma interleukin -18 in patients with acute coronary syndromes

Interleukin -18 [IL-18] is a recently evaluated cytokine synthesized by Kupffer cells. It has been shown to activate macrophages and has direct proinflammatory activities of many cells including inflammatory and vascular cells. This study aimed to evaluate the clinical implication of serum levels of IL-18 among patients with ACS in comparison with other markers of chronic inflammation and to assess the relation of IL-18 serum levels with various conventional cardiovascular risk factors, its role in plaque instability and myocardial dysfunction. The present hospital based observational study was conducted on 55 patients with acute coronary syndromes [ACS], admitted to the Coronary Care Unit of El-Minia University Hospital in the period from May 2004 to January 2005. These patients were divided into two groups. GROUP I: It consisted of 30 patients with acute myocardial infarction [AMI]. GROUP II: It consisted of 25 patients with unstable angina [UA]. For comparison purposes two additional groups were added whose individuals were age and sex matched to patient's groups I and II. GROUP III: It consisted of 1.5 patients with stable angina [SA] to form coronary control group. GROUP IV: This group consisted of 15 apparently healthy subjects to form the non-coronary control group. Full clinical examination was performed with specific emphasis on body mass index [BMI] and blood pressure measurement. Abdominal ultrasound, electrocardiogram [ECG], and echocardiography were done. Laboratory investigations were performed, including blood sugar, complete lipogram, renal function tests, liver function tests, cardiac enzymes, complete blood picture, erythrocyte sedimentation rate, C-reactive protein [CRP], nitric oxide [NO], fibrinogen, and IL-18. The current study reported increase serum levels of IL-18 in ACS group than in healthy volunteers as whole and even when stratified as AMI and UA groups. Furthermore, the current study revealed increase serum levels of IL-18 in ACS group than in SA group, as a whole and even when stratified as AMI and UA groups. The percentage of CRP positive patients were significantly higher in ACS, UA, and AMI groups than coronary and non coronary control groups. There were significant positive correlation between serum levels of IL-18 and each of the following: fibrinogen, OX-LDL, and NO among ACS, AMI, and UA groups. Also, it revealed significant positive correlation between serum levels of IL-18 and each of the following: cholesterol, triglycrides, and LDL-C in ACS and UA groups; however, there was significant positive correlation between its serum levels and each of the following cholesterol and LDL-C in AMI group. Serum levels of IL-18 in patients with EF% < 45% were statistically significant higher than its serum levels in patients with EF% > 45% in ACS, and AMI groups, and near significance in UA group. Serum levels of IL-18 were higher in ACS, UA, and AMI groups versus healthy volunteers. The proinflammatory role of IL-18 in the initiation and progression of atherosclerosis was proved in the present study by the presence of positive significant correlation between serum levels of IL-18 and some markers of chronic inflammation as fibrinogen, CRP and NO

study of some biochemical indices of early complications in diabetic children in Assiut

A study of some biochemical indices of early complications in diabetic children, was done. Plasma and urinary N-acetyl-B-glucosaminidase [NAG], B2-microglobulin [B2-MG], sialic acid as well as plasma fibronectin and lipid peroxides were determined in 23 children with insulin dependent diabetic children as well as 16 healthy children of matchable age and sex. Thirteen of these children had recently diagnosised disease while 10 were previously known to be diabetic. Urinary NAG and B2-MG excretions were significantly increased in diabetic compared to healthy children. Both indices were significantly intercorrelated and correlated with both blood glucose and whole blood glycosylation, which are indices of short and long term glycaemic control. These changes suggest the presence of reversible proximal renal tubular dysfunction. Plasma NAG activity was also significantly increased in diabetic children and correlated with urinary NAG and blood glucose as well as whole blood glycosylation levels. Plasma fibronectin and lipid peroxides levels were significantly increased in diabetic compared with control children. Both indices correlated significantly with whole blood glycosylation, and lipid peroxides correlated also with blood glucose levels. Plasma and urine sialic acid were significantly increased in diabetic compared with healthy children, both biomarkers were significantly correlated with blood glucose levels as well as whole blood glycosylation. No significant differences in the levels of the previous markers could be observed in diabetic children with a disease duration more than 1 year versus those with less than 1 year. The present results suggest that diabetic complications could occur early in the course of disease especially in poorly controlled subjects. These complications are not clinically manifest and could be in the reversible pre-clinical stage. These children should receive more strict observation and be screened by determination of urinary or plasma NAG together with plasma sialic acid and lipid peroxides, based on sensitivity, cost and stability of various indices

Evaluation of Phosphofructokinase inhibition test as a new tumor marker in pharyngeal cancer: comparison with conventional markers

Phosphofructokinase [PFK] inhibition test has been reported by the Japanese investigators to be a fruitful new tumor marker. In the present study PFK inhibition test was evaluated in diagnosis, prognosis and monitoring therapeutic efficacy in pharyngeal cancer. The study included 45 patients with pharyngeal tumors [4 benign and 41 malignant] together with 25 healthy subjects who were age matched with patients. Blood samples were obtained from each participant and sera were separated and used for determination of degree of phosphofructokinase suppression, carcinoembryonic antigen [CEA], B[2]-microglobulin [B[2]-MG] and ferritin. PFK inhibition in patients with benign pharyngeal tumors was comparable to controls but its levels in sera of patients with malignant pharyngeal tumors were significantly increased. The sensitivity of this test was 85% and the specificity was 100%. The sensitivities of CEA, B[2]-MG and ferritin were 78%, 54% and 51% respectively. Patients with well differentiated tumors exhibited greater amount of suppression, compared with moderately and poorly differentiated tumors. Follow up of some patients after completion of radiotherapy alone or combined with chemotherapy revealed that PFK suppression was superior to CEA, B[2]-MG and ferritin in prediction of therapeutic efficacy. Significant negative correlations were observed between PFK suppression, CEA, B[2]-MG and ferritin. The significant increase in lactic acid in cancer patients and its significant correlation with PFK suppression indicates that the lowered buffering capacity of serum in cancer patients could be involved in PFK suppression. It could be concluded that PFK is a valuable, easy, and non-invasive test that may represent a promising tumor marker and can serve as an indicator of successful therapy

Evaluation of measurement of glucose and protein glycosylation in dried blood spots in diabetic patients

Blood glucose and whole blood glycosylation were determined in dry blood spotted on to filter paper, as well as in fresh blood samples obtained from 92 non insulin dependent diabetics and 17 healthy subjects. Blood glucose levels and whole blood glycosylation measured in dried and fresh blood were significantly increased in diabetics compared with controls. Blood glucose levels and whole blood glycosylation in dried blood spots correlated strongly well with the corresponding levels in fresh blood samdples. Since these papers could be wetted with capillary blood from a finger prick, they can be easily used by the patients especially in far rural areas and kept at room temperature until brought to the hospital. The dried blood spot procedure does not add any extra cost to the conventional methods

Lipid peroxides and some antioxidants as indices of oxidant stress in children with non Hodgkin's lymphoma

Oxygen free radicals have been recently suggested to be implicated in the pathogenesis of malignant disorders. Therefore, lipid peroxides as an indicator of oxygen free radical induced damage, together with the enzymatic antioxidants namely ceruloplasmin, superoxide dismutase and the nonenzymatic antioxidant total thiols were determined in sera of 30 children with non Hodgkin 's lymphoma, before any therapeutic intervention. The same bioindices were studied in 20 of these children after completion of their therapeutic regimen together with 10 healthy children representing control group. Lipid peroxides were significantly increased while ceruloplasmin, superoxide dismutase and plasma thiols were significantly decreased in patients compared with healthy children. A significant negative correlation was observed between lipid peroxide levels and ceruloplasmin, superoxide dismutase and total thiols levels. Chemotherapy has no significant effect on the serum levels of the previous bioindices. These results clearly indicates that children with non Hodgkin's lymphoma are under oxidant stress which is manifested by increased lipid peroxides and decreased ceruloplasmin, superoxide dismutase and thiols. This change may contribute to propagation of the malignant process by interfering in the pateint's antitumorous immune surveillance

Evaluation of some serum indices of vitamin A and lipid peroxides in children with malignant diseases

In a trial to study the state of vitamin A in children with malignant diseases, serum B- carotene, retinol, -retinoic acid, prealbumin and retinol binding protein [RBP] in addition to lipid peroxides [LPER] were determined in a total of 50 children with various types of malignant diseases. They included 26 patients with non-Hodgkin lymphoma [NHL], 8 with Hodgkins lymphoma [HL], 9 with acute lymphoblastic leukemia [ALL] and 7 children with miscellaneous soft tissue malignancy. The cases were in different stages of treatment. The study also included 12 apparently healthy control children. Significant deterioration of studied indices of -vitamin A was observed in children with malignant diseases than in controls and they were significantly lower in cases with ALL than cases with lymphomas. Such deterioration could result in depressed status of cellular immunity with resultant decreased antioxidant defense mechanisms as shown by the presence of significantly increased levels of lipid peroxides in these children compared to controls. These changes were most marked in the stage of induction of therapy. It is recommended that vitamin A supplementation is given to children with malignant diseases paticulariy when cytostatic drugs are used

Biochemical studies in normal and complicated pregnancy

In this cross sectional study, serum and urinary N-acetyl-B- glucosamine [NAG], calcium, magnesium and urinary excretion of albumin were determined in 25 normal pregnant females, 10 non-complicated diabetic pregnant females and 29 preeclamptic pregnant females. The results were compared with those in 25 nonpregnant females who were age matched with other groups in the study. Serum NAG activity levels were increased significantly to the same extent in normal and complicated pregnancies originating most probably from chorionic villi. Urinary excretions of both NAG and albumin were increased in normal and complicated pregnancies. However, the excretions were significantly higher in complicated than normal pregnancy. It is probable that these results may be caused by physiologically disturbed glomerular, as well as tubular function, as indicated by the significant positive correlation observed between urinary MAG and albumin excretions. These changes are more marked in complicated pregnancies. Significant decrease serum calcium and magnesium levels were observed in normal and complicated pregnancies

Biochemical modifications of low density lipoprotein particles in diabetic patients

Modified forms of low density lipoprotein [LDL] are associated with increased atherogenicity in diabetic patients. Therefore, biochemical characteristics of LDL particles from 17 type I and 26 type II diabetic patients in the form of glycosylation, sialic acid content, thiobarbituric acid reactive substances [TBARS] as well as lipid composition were studied. The study also included 10 healthy control subjects. The study revealed that LDL from diabetic patients contained decreased amount of sialic acid, increased amounts of fructosyl lysine and TBARS compared with controls. The degree of glycosylation and sialic acid content were correlated with status of diabetic control as determined by blood glucose level and total fructosamine. Furthermore, the lipid composition of LDL from diabetic patients was changed, where triglycerides were increased and cholesterol was decreased compared with healthy subjects. Altogether, diabetic patients' LDL were characterized by a lowered lipid/protein ratio. In conclusion, the cholesterol accumulating effect of diabetic patient's blood sera is mainly related to atherogenic low density lipoprotein fraction, which is modified in various ways, by increased non-enzymatic glycosylation, desialylation and alterations in lipid composition. This multiple-modified LDL may contribute to the premature atherosclerosis development in diabetes mellitus

role of sialic acid in the development of anemia in chronic renal failure

Shortened life span of erythrocytes has been suggested as one of the causes of anemia in chronic renal failure. Decreased sialic acid content of erythrocytes lead to their rapid removal from the circulation. Abnormalities in metabolism of this substance with increased neuraminidase activity in sera of these patients may be responsible for this phenomenon. To clarify this hypothesis, sera of 50 patients with end stage renal failure were examined before and after dialysis for neuraminidase activity by assessing their effect on desialylation of erythrocytes of healthy subjects, matched for blood group and of fetuin [substrate rich in sialic acid] together with determination of total and lipid bound sialic acid content of their RBCs. The results were compared with corresponding values of 20 controls. The study showed a significantly enhanced neuraminidase like activity in sera of patients with chronic renal failure in comparison with sera of healthy controls [P<0.001] associated with significant decrease of total and lipid bound sialic acid of RBCs. The present data are indicating that increased neuraminidase activity in sera of patients with chronic renal failure could be a contributing factor involved in the mechanism of producing the marked anemia in uremic subjects by acting on erythrocytes, rendering them more liable to be cleared faster by the liver and spleen, shortening their life span, moreover, it could act on erythropoietin depriving it from its sialic acid content, shortening its life span therefore reevaluation of the therapeutic modalities of anemia in these patients whether blood transfusion or erythropoietin is needed

Endothelin-1 and nitric oxide in children with renal hypertension

Plasma and urinary endothelin-1[ET-1] and nitrate [NOx] as an index of nitric oxide generation were measured in 27 hypertensive children with renoparenchymal diseases, 15 normotensive children with renoparenchymal diseases and 20 healthy control children of matched age and sex. The mean value of plasma ET-1 concentration was significantly higher in hypertensive children with renoparenchymal diseases than both normotensive renal diseased children and normotensive healthy controls. Significant positive correlation was found between ET-1 levels and mean blood pressure in hypertensive children with renal diseases. The mean value of 24 hours urinary excretion of ET-1 was significantly higher in normotensive children with renal diseases than normotensive healthy controls, but significantly lower than hypertensive children with renal diseases. Significant increase in the plasma levels of NOx was observed among hypertensive renal diseased children than normotensive renal diseased children and normotensive healthy controls. Significant positive correlation was found between the levels of plasma ET-1 and plasma NOx in hypertensive renal diseased children

SHBG, insulin sensitivity and IGF-I IN NIDD males

Recent studies have indicated the role of sex hormone binding globulin [SHBG] as a predictor of development of diabetes where low levels have been found in type II diabetic males. In the present study, we extended the previous studies, and we evaluated the levels of SHBG and another important growth factor related to insulin, IGF-I, besides insulin levels in 51 diabetic males. The study also included, 17 completely healthy controls who were age comparable to patients. The study revealed significantly decreased levels of both SHBG and IGF-I in type II diabetic males and significantly elevated insulin levels in comparison with controls. The levels of the 2 proteins exhibited significant positive correlation with each other but significant negative correlation with blood insulin levels, body mass index and indices of glycemic control. Furthermore, diabetes associated with complications either retinopathy or neuropathy was associated with significant deviations of the indices studied in comparison with uncomplicated cases. The present data further indicated the role of insulin in regulating SEBG levels where hyperinsulinemia as reflected by enhanced insulin levels and insulin resistance manifested by high insulin levels and hyperglycemia in type II diabetes would result in its depressed levels. The low IGF-I would indicate defective insulin response, since both IGF-I and insulin share mechanism of action

Modified low density lipoprotein and lipoprotein [A] as atherogenic risk factors in haemodialysis patients

Biochemical characteristics of low-density lipoprotein [LDL] particles as well as serum lipids and lipoprotein [a] concentrations were determined in 32 uremic patients on maintenance HD and 20 healthy control. The study revealed that LDL from uremic patients contained significantly increased amount of fructosyl lysine as an index for the degree of glycosylation and thiobarbituric acid reactive substances as an index for the degree of oxidation and significantly decreased amounts of sialic acid and vitamin E compared with the controls. Furthermore, lipid composition of LDL changed where triglycerides increased significantly, while cholesterol decreased significantly in patients compared with controls. All together, serum triglycerides [TG], total cholesterol [TC]/HDL cholesterol ratio and serum lipoprotein [a] [Lp [a]] were increased significantly, HDL-cholesterol was decreased significantly; while TC and LDL- cholesterol showed insignificant changes in patients compared with the controls. Lp [a] and TC/HDL ratio were significantly negatively correlated with serum albumin levels and Lp [a] was significantly negatively correlated with creatinine clearance

Role of fetal hemoglobin and placentral alkaline phosphatases in cancer patients

Fetal hemoglobin and the 3 placental alkaline phosphatases; kasahara, Nagao and Regan isoenyzymes were determined in 37 patients having primary carcinomas of various tissue origins and 7 cases having benign neoplasms together with 13 healthy individuals who served as controls. It was evident that patients with benign neoplasms had significantly increased levels of fetal hemoglobin [P < 0.05] and 2 of these patients expressed Regan isoenzyme. Concomitant elevation of both fetal proteins was not found in any of these patients. In patients with malignant diseases significantly increased levels [P < 0.001] of fetal hemoglobin were present. The highest levels and incidences were present in patients with GIT tumors. After radical resection of the tumor in 8 operable cases, fetal hemoglobin returned to normal levels in 5 cases and remained elevated in 3 cases. In cancer patients, positive expression of Kasahara isoenzyme was present in 16%, while positive expression of Regan isoenzyme was present in 20% and positive expressing of Nagao isoenzyme was present in 14%. Again patients with GIT tumors had the highest frequency [60%] of expression placental alkaline phosphatases. After complete resection of the tumor, complete disappearance of placental alkalikne phosphatases occurred. Patients with GIT tumors has the highest incidence of concomitant elevations of fetal hemoglobin and placental alkaline phosphatases. The reappearance of HbF in cancer patients could be attributed to triggering of erythropoiesis in the bone marrow or even the liver by the tumor derived nuclear proteins. The appearance of placental isoenzymes could be attributed t o the re-expression of the placental phosphatase gene. The overall concordance between the 2 proteins was found in 21 [57%] while the overall discordance was found in 16 [43%] of patients. These data indicate that the regulation of synthesis of these proteins is not under coordinate control

prognostic value of phosphohexose isomerase in childhood leukemia and lymphomas

Serum phosphohexose isomerase [P.H.I.] activity was measured in 12 children suffering from acute lymphoblastic leukemia [A.L.L.], 8 children having acute nonlymphoblastic leukemia [A.N.L.L.], 17 children suffering from non-Hodgkin's lymphoma [N.H.L.] and 20 aparently healthy children of comparable age and sex as controls. Significantly increased activity of P.H.I. was observed in children with leukemias and lymphomas compared to controls. Children with A.N.L.L. had significantly higher P.H.I. activity than those with A.L.L. Follow up of the children during various stages of therapy showed significant decrease of P.H.I. after induction of remission. The levels were evidently elevated again several months before clinical and/or hematological relapses. It could be concluded that P.H.I. can be helpful adjuvant marker in childhood leukemias and lymphomas. Also, it can of therapy and to detect the early relapse

Glucose-6-phosphate dehydrogenase activity in erythrocytes of cancer patients

The specific activity of glucose-6-phosphate dehydrogenase, the key enzyme of hexose monophosphate shunt was determined in erythrocytes of 35 patients suffering from primary malignant neoplasia at different sites. Similarly, the enzyme activity was also evaluated in 7 patients having nonmalignant neoplasia as well as 13 control subjects. The enzyme activity in patients with benign diseases was similar to controls while in patients with malignant neoplasia the enzyme activity levels were significantly lower [P < 0.01] than control levels. Such decreased activity was not correlated with tumur locality. In 7 patients treated by radical tumur resection, the enzyme activity was increased insignificantly than preoperative levels. Such decreased activity in patients with malignant neoplasia seems to be an acquired erythroenzymophathy with an acquired qualitative disorder

study of hematotoxicity and nephrotoxicity in gasoline filling station workers in Assiut

This study included forty-three male workers from eight gasoline filling stations and eleven unexposed controls of comparable age. The study revealed significantly increased plasma levels of TNF-alpha in exposed workers compared with the controls which correlated with duration index of exposure as well as urinary phenol excretion representing a biological monitor of benzene exposure. TNF-alpha could be derived from bone marrow cells reflecting hematotoxicity or kidney tissues and reflecting nephrotoxicity. The decreased RBCs sialic acid seems to reflect the associated hemolytic effect of benzene. Meanwhile, increased urinary sialic acid besides enhanced urinary excretion of tubular enzymes seemed to reflect nephrotoxicity affecting the glomerular filter and proximal renal tubules manifested also by increased albumin excretion. The marked correlations observed between these indices and duration index of exposure suggested a common source of origin. The results proved that those workers were greatly affected by benzene so, they should be examined periodically at least by routine blood picture and urine analysis as well as by simple determination of sialic acid. The period of exposure should also be decreased

CSF cytokines, nitric oxide and prostaglandins in diagnosis and pathophysiology of childhood CNS leukemia and lymphoma

To clarify the role of cytokines, nitric oxide [NO] and prostaglandin- E2 [PG-E2] in diagnosis and pathogenesis of infiltration of central nervous system [CNS] in cases with leukemia and lymphoma, the levels of these indices in the cerebrospinal fluid [CSF] of those children were determined. Their levels were correlated with other laboratory studies of CSF and clinical criteria. This study included twenty- seven children with acute leukemia [twenty with acute lymphoblastic leukemia [ALL] and seven with acute myeloid leukemia [AML]] and fifteen with non- Hodgkin's lymphoma [NHL]. Clinical evidence of CNS involvement was present in seventeen patients with acute leukemia and seven cases with NHL. The study revealed significantly elevated levels of two types of cytokines [TNF-alpha, IL-6] NO and PG-E2 in CSF of children with acute leukemias and lymphoma compared with control group [children with tension headache or meningism]

Lymphoma: clinical study and the clinical significance of serum phospholipase A2

Phospholipase-A2 is an important enzyme in prostaglandin synthetic pathway. Its activity levels were studied in 25 patients with non- Hodgkins lymphoma [NHL] as well as 30 patients with Hodgkins disease, besides 15 patients with non-neoplastic lymphadenopathy and 20 healthy subjects. The study revealed significantly increased levels of enzyme activity in patients with lymphoma compared with controls and cases with non-neoplastic lymphadenopathy. The activity levels were higher in NHL compared with HL but the differences did not reach the level of significance. Patients with advanced stages [III and IV] had significantly higher levels than those with early stages [I and II]. Hepatosplenic involvement is also associated with significant increase in enzyme activity levels. The activity levels of the enzyme did not correlate with total leucocytic counts in all patients groups. The altered enzyme activity could reflect increased oxidant stress known to be present in these patients. It seems to be a valuable new tumor marker which can aids the diagnosis, staging and can reflect the prognosis in cases with lymphoma