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

effects of passive cigarette smoking on the respiratory system among the healthy wives of active smokers

This study included 50 adult healthy volunteers; 20 currently smokers, 20 wives of active smokers spouse [passive smokers] and the remaining 10 subjects were nonsmokers controls. Ventilatory pulmonary function tests [FVC% predicted, FEV1/FVC ratio, FEV1% predicted and FEF25-7.5% predicted] were made to all subjects. Urinary cotinine, serum cotinine and lipid peroxides levels were assessed using spectrophotometric method. Data demonstrated that passive smokers are at risk to develop subsequent destructive lung disease, which was evident by an increase in the level of lipid peroxides [marker of oxidative stress] and a decline in the spirometric indices [especially a decline in FEV1% predictive which is the most strongly predictive index of chronic obstructive lung diseases in adults]. The decline in FEF25-75% predictive indicated the possibility of small airway diseases. The benefit of the use of urinary and serum cotinine as cheap biomarkers of exposure to cigarette smoke was clarified

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

Circulating angiogenic factors in patients with chronic liver diseases

Platelet-derived endothelial cell growth Factor [PD-ECGF], basic fibroblast growth factor [b-FGF], gangliosides [Gs] and nitric oxide [NO] are angiogenic factors expressed in various cancer tissues as well as non malignant tissues. Little is known about the role of these factors in patients with chronic liver diseases such as chronic hepatitis [CH], cirrhosis, and hepatocellular carcinoma [HCC] with cirrhosis. The levels of these factors were determined in 28 patients with chronic hepatitis, 43 with cirrhosis and 29 patients with HCC. The study also included 18 normal individuals who are comparable to patients in age as a control group. The study revealed that the levels of these angiogenic factors are significantly increased in patients with HCC in comparison with either patients with hepatitis or liver cirrhosis. Moreover, both Gs and NO are also increased in patients with cirrhosis in comparison with controls. In HCC the levels of angiogenic factors reflected tumor burden where they were significantly increased in higher burden. These angiogenic factors are derived from HCC cells as well as inflammatory cells. In cirrhosis the elevation of these factors might be related to the extent of inflammation and angiogenesis in the cirrhotic liver. These factors showed significant positive correlations with liver enzymes in HCC. Assessment of the angiogenic factors in patients with chronic liver diseases would help to follow progression of liver affection. The expression of PD-ECGF in HCC would predict its chemosensitivity

Late onset involuntary movements, clinical and laboratory study

This study aimed to find the relative frequency of movement disorders, its etiology and presentation in relation to other neuropsychiatric illnesses throughout a period of 12 months. This study revealed that over a period of one year about 3100 patients aged 40 years and more with neuropsychiatric illness attended out patients clinic of neuropsychiatry, Assiut University Hospital. Ceruloplasmin and total thiol were significantly diminished in all groups of patients with movements disorders compared with the control. Lipid peroxide was significantly increased in all studied groups compared with control. These biochemical indices indicated the important role of increased oxidant stress in the etiopathogenesis of movements disorders

Role of norharman, harman and ceruloplasmin in the aetiopathogenesis of Parkinson's disease

Determination of serum levels of Norharman, Harman and Ceruloplasmin of 39 patients with PD and 54 age and sex matched control subjects was done. The study aimed to identify the possible role of these biochemical indices in the etiopathogenesis of PD. The study clarified that most of the PD patients [59%] had moderate degree of illness. The most frequent presenting signs were in the following order: Resting tremors and bradykinesia in 97.4% of cases for each, loss of upper limb swinging during walking in 94.9%, mask facies in 92.3%, rigidity in 84.6%, postural abnormalities and speech disorders in 71.8% for each. Highly significant increase of serum levels of Harman and Norharman and highly significant decrease of Ceruloplasmin level were found among PD patients compared with the control group. The study added more support to the possible roles of the biochemical substances in the etiopathogenesis of Parkinson's disease through defects in the enzymes that regulate potential nigral neurotoxins [Norharman and Harman] or by the deficiency of one of the major plasma antioxidants [Ceruloplasmin]

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

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

Cancer breast: surgical study and the clinical impact of plasminogen activators

In the present work clinical and surgical study together with study of the activity levels of urokinase tissue plasminogen activator in cytosols of 28 breast cancer patients together with 15 patients with non malignant breast lesions and 10 healthy breast tissues was done. The study revealed significantly enhanced activity of urokinase tissue plasminogen activator in malignant cytosols compared with both non malignant and healthy cytosols. However, the levels in non malignant, breast cytosols were significantly higher than normal cytosols, but in these cases the activity levels did not reach the levels observed in malignant tissues. Patients with advanced stages had higher levels compared with early stages of breast cancer. The activity levels were insignificantly higher in premenopausal compared with postmenopausal breast cancer cytosols. Despite the higher levels in estrogen receptor positive cases compared with estrogen receptor negative cytosols, the levels did not reach the level of significance. Patients with metastatic disease had significantly higher levels than patients with non-metastatic breast cancer. Nevertheless, patients with good prognosis have lower levels than patients with bad prognosis. Significant positive correlation existed between urokinase tissue plasminogen activator and number of lymph nodes with metastatic deposits [r = 0.8, p <0.001]. The present findings clearly indicated the utility of cytosolar urokinase tissue plasminogen activator as a valuably tumor marker in aiding diagnosis, staging and predicting prognosis of patients with breast cancer

Beta-glucuronidase enzyme in bladder cancer associated with bilharziasis [Histochemical and biochemical study]

To understand the status of beta-glucuronidase enzyme in bilharzial bladder cancer, the enzyme was evaluated histochemically in tissue specimens taken from 70 bilharzial patients suffering from bladder cancer and treated by total cystectomy. Specimens were taken from three different sites; apparently non-tumor area, edge of the tumor and center of the tumor deep to the necrotic tissue. Twenty of these patients were selected for biochemical evaluation of the enzyme in the tissue and serum. In addition, ten patients had benign bilharzial lesions were included for histochemical evaluation of the enzyme in the benign ulcer and biochemical estimation of the enzyme in the serum and these benign lesions. Seven non-bilharzial healthy persons were selected for serum estimation of the enzyme as control group

approach to the role of nitric oxide in hyperdynamic circulation in liver cirrhosis

Circulatory abnormalities arising in cirrhosis increased cardiac output and, possibly, heart rate coupled with reduced systemic vascular resistance, and possibly arterial pressure could result from peripheral vasodilatation. The locally acting vasodilator nitric oxide has recently been implicated as a possible mediator in the vasodilatation observed in cirrhosis. To investigate this hypothesis, total of 51 patients with liver cirrhosis were recruited in the present investigation, 14 had hyperdynamic circulation [HDC] and 37 had no manifestations of HDC the study also included 20 completely healthy controls. In each participant, serum and urinary nitric oxide [NO], urinary cyclic guanosine monophosphate [cGMP] excretions, serum endotoxin and C-reactive protein were determined. The study revealed significantly increased levels of serum NO, endotoxin and C-reactive protein as well as urinary excretions of NO and cGMP in patients with cirrhosis compared with controls. Patients with HDC had significant increase of all bioindices expcept C-reactive protein. Significant positive correlation existed between urinary CGMP, urinary NO, serum NO, endotoxin C-reactive protein. These findings would indicate that bacterial endotoxin rather than cytokines induce NO synthase expression in vessel walls with sustained NO release. The released NO through activation of guanylate cyclase, leads to increased intracellular cGMP concentrations and induces vasodilatation and hypotension. Inhibition of NO synthesis in these patients could be achieved by reduction of endotoxaemia through sterilization of the intestine. This would result in restoration of sensitivity to vasoconstrictors and reverse the haemodynamic abnormalities in liver cirrhosis

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