Antioxidant status and dialysis: plasma and saliva antioxidant activity in patients with fluctuating urate levels

PURPOSE: The aim of this study was to clarify the clinical usefulness of combined CT during arterial portography (CTAP), and CT arteriography (CTA), for the diagnosis of hepatocellular carcinoma. MATERIALS AND METHODS: CTAP and CTA were performed in 58 patients with a combined 144 hepatocellular carcinoma (HCC) lesions. Arterial vascular access was obtained through bilateral punctures of the femoral artery with selective placement of catheters in the hepatic artery and superior mesenteric artery. CT scans were performed first during injection of contrast media into the superior mesenteric artery, followed by repeated imaging of the liver during injection of contrast media into the hepatic artery. Delayed CT (DCT) was also obtained 5 min after CTA. RESULTS: The detection rates for all 144 lesions were 73.6% with conventional contrast enhanced CT, 90.3% with CTAP, 95.8% with CTA, 87.5% with DCT, and 98.6% with combined CTAP and CTA. Of early HCC lesions (n = 18), 88.9%, 33.3%, 77.8%, 100%, and 88.9% were detected by conventional contrast enhanced CT, CTAP, CTA, DCT, and combined CTAP and CTA, respectively. Of classical HCC lesions (n = 126), 71.4%, 98.4%, 98.4%, 85.7%, and 100% were detected by conventional contrast enhanced CT, CTAP, CTA, DCT, and combined CTAP and CTA, respectively. CONCLUSION: Combining CTAP and CTA improved the radiologist's ability to detect lesions with confidence and to differentiate perfusion abnormalities of HCCs.     

Fatty acid composition of plasma phosphatidylcholine and levels of lipids and lipoproteins in hyperlipoproteinemia. II. Relation with B lipoproteins

BACKGROUND: Epidemiological trials provided evidence that the cholesterol concentration in lipoproteins B, i.e. VDL, IDL and LDL, correlate significantly with the incidence of ischaemic heart disease (IHD). The objective of the present study was to assess how the fatty acid composition in plasma phosphatidyl choline affects the total and LDL cholesterol, triglyceride and apolipoprotein B concentrations in subjects with primary hyperlipoproteinaemia and dyslipidaemia. METHODS AND RESULTS: In a group of 142 subjects with primary hyperlipoproteinaemia and dyslipidaemia the concentrations of plasma lipids, lipoproteins apolipoproteins and fatty acids in plasma phosphatidyl choline (PC) were assessed. The authors provided evidence by discriminant analysis where the dependent variables were the lower quintiles (Q1 + Q2) and the upper quintiles (Q4 + Q5) of concentrations of total cholesterol, triglycerides, LDL-cholesterol and apolipoprotein B and the independent variables were FA concentrations in plasma PC, that the total cholesterol concentration was inversely associated with the concentration of docosahexaenic acid (22:6n-3). The concentration of LDL-cholesterol correlated inversely with the concentration of palmitoleic acid (16:1n-7). Triglyceridaemia was inversely associated with the linoleic acid concentration (18:2n-6). The concentration of apolipoprotein B correlated positively with myristic acid (14:0) and negatively with concentrations of oleic acid (18:1n-9) and linoleic acid (18:2n-6). CONCLUSIONS: The submitted results indicate that the fatty acid concentrations of PC in plasma are significantly and markedly correlated with concentrations of total cholesterol, triglycerides, LDL-cholesterol and apolipoprotein B. It is possible that atherogenic lipoproteins may be favourably influenced not only by the amount of fat but also by a suitable fatty acid composition.     

Developmental changes of antioxidant enzymes in kidney and liver from rats

The five principal antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase in the kidney and liver, and the total hepatic glutathione were determined in rats of different ages (1, 2, 3, 6, and 12 months). Variance analysis proved the effect of age on the measured enzymes in the respective organ with the exception of glutathione S-transferase. The behavior of the enzymes was not uniform, and there were both increased and decreased changes in the two organs. A clear correlation between cellular antioxidative capacity and the age-specific processes of growing or aging could not be seen. A far more complicated network of interactions has to be assumed.     

Expression and developmental profile of antioxidant enzymes in human lung and liver

Effect of recombinant human basic fibroblast growth factor (bFGF) on fracture healing was investigated using a tibial fracture in beagle dogs. Transverse fractures in the middle of the diaphyses were created in the right tibiae and bFGF was injected into the fracture sites at a single dose of 200 micrograms. The time course of changes in callus volume and morphology of the fracture sites were evaluated at weeks 2, 4, 8, 16, and 32 after treatment, and the fracture strength was analyzed at weeks 16 and 32. At week 2, a radiogram of the fracture site showed obvious membranous ossification in the group injected with bFGF. Basic FGF extended the callus area at week 4 and increased the bone mineral content (BMC) in the callus at week 8. bFGF also increased the osteoclast number in the periosteal callus at weeks 2 and 4. In the bFGF group, a maximal increase in the osteoclast index was found at week 4, and an identical increase was recognized in the control group at weeks 8 and 16. These findings strongly suggested that bFGF stimulated not only callus formation but osteoclastic callus resorption. BMC in the bFGF group was followed by a rapid decrease from week 8, while that in the control group was identical from week 4. Fracture strength of the bFGF group showed significant recovery by week 16, and recovery was still evident by week 32. We conclude that bFGF promotes the fracture healing in dogs by the stimulation of bone remodeling.     

Effects of chloroquine treatment on antioxidant enzymes in rat liver and kidney

The effect of chloroquine (CHQ) administration on antioxidant enzymes in rat liver and kidney was studied. Male Sprague-Dawley rats were administered 20 mg/kg CHQ once a week for 4 weeks (chronic treatment) or a single dose at 10 or 20 mg/kg (acute treatment). Antioxidant enzyme activities were determined in cytosolic fractions of liver and kidney, whereas reduced glutathione (GSH) and malondialdehyde (MDA) were determined in tissue samples. Results indicate minimal effects of acute CHQ treatment, whereas chronic treatment with CHQ differentially affected antioxidant enzymes in the two organs. Superoxide dismutase activity was increased nearly twofold, while activities of selenium glutathione peroxidase (GPX), catalase, and NAD (P) H: quinone oxidoreductase were decreased in livers of CHQ-treated rats compared to controls. No significant effects of CHQ on glutathione reductase, GSH, and MDA levels were seen in the liver. Fewer effects of CHQ were observed in the kidney where a decrease in GPX activity and an increase in MDA levels was seen. Lowering of antioxidant enzymes activities in the liver by CHQ could render the organ more susceptible to subsequent oxidative stress; while increased MDA production after CHQ treatment in the kidney indicate that the organ is being subjected to oxidative stress. This could have implications for prolonged chloroquine intake.     

Effects of acipimox on haemorheology and plasma lipoproteins in patients with mixed hyperlipoproteinaemia

Dolasetron mesilate is a selective 5-HT3 receptor antagonist that prevents chemotherapy-induced and postoperative nausea and vomiting. For the majority of patients in intravenous dolasetron trials for chemotherapy-induced nausea and vomiting, dosing has been based on body weight (mg/kg). The approved weight-based dose is 1.8 mg/kg based on results of controlled clinical trials. However, trials of dolasetron evaluating oral doses for prevention of chemotherapy-induced emesis, and intravenous doses for prevention and treatment of postoperative emesis have used a fixed milligram dose. To identify an appropriate intravenous fixed milligram dose for the prevention of chemotherapy-induced nausea and vomiting, this analysis was performed to derive efficacy results for fixed milligram doses from pooled results obtained with dosing based on body weight. Intravenous dolasetron doses for 1,598 patients treated on a mg/kg basis (0.3, 0.6, 1.2, 1.8, 2.4, 3.0 and 5.0 mg/kg) in 14 clinical trials were converted to fixed milligram doses based on weight. Fixed-dose groups were established at doses of 50, 75, 100, 125, 150, and 200 mg. Doses less than or equal to the midpoint between two dose groups were included in the lower dose group. Pooled results showed that the 100 mg intravenous dolasetron dose group (who received actual doses of 88-112 mg) produced the highest rate (53%) of complete response (0 emetic episodes and no rescue medication in the 24-h period following initiation of chemotherapy).     

Atherogenic and anti-atherogenic plasma lipoproteins modulate secretion of prostanoids by endothelial cells in vitro]

The authors present the evidence of atherogenic properties of VLDL and LDL potentiation on the model of endothelial cells-human umbilical vein endothelial cells, by preferable stimulation of the endothelial cell to thromboxane A1 production at in vitro conditions by atherogenic lipoproteins. The vasoconstrictive, thrombogenic and atherogenic effects of TXA2 are exerted on the vessel in this way. The ratio prostacycline/thromboxane, decisive for the maintenance of vascular homeostasis, is less than 1, this means the beneficial effect of prostacycline can not be applied. Protective, antiatherogenic effect of HDL and its subfractions HDL2 and HDL3/predominantly through their function in the reverse cholesterol transport from the periphery to the liver, antioxidative influence on LDL, as far as antiaggregation and fibrinolytic effects of HDL/is multiplied by the fact that HDL preferably stimulates the secretion of prostacycline by the endothelial cell. The ratio prostacycline/thromboxane A2 is higher than 1, that means beneficial vasodilative, antiaggregation and antiatherogenic effect of prostacycline on the vessel wall predominate. Quantitative evaluation of antiatherogenic effects of HDL subfractions (HDL2 and HDL3) revealed more significant antiatherogenic effect in HDL2 subfraction-in the sense of prostacycline secretion stimulation and exertion of its beneficial effects on the vessel. (Fig. 5, Ref. 33.)     

Screening for Wilson's disease in patients with liver diseases by serum ceruloplasmin

BACKGROUND/AIMS: A low serum ceruloplasmin level is considered a diagnostic test for Wilson's disease. To examine whether it is useful to detect presymptomatic patients with Wilson's disease, serum ceruloplasmin was determined by radial immunodiffusion (normal: 20-60 mg/dl) in all patients (n = 2867) admitted for evaluation of a liver disease in 1993 and 1994. METHODS: Patients with levels lower than 20 mg/dl were further evaluated by determination of serum copper concentration, urine copper excretion and ophthalmological examination. If possible, a liver biopsy was performed and the hepatic copper content was determined by flame atomic absorption spectroscopy. RESULTS: Seventeen patients had serum ceruloplasmin levels < 20 mg/dl. One had asymptomatic Wilson's disease (no Kayser-Fleischer rings or neurological symptoms). In the other 16 patients Wilson's disease was excluded. Based on elevated hepatic copper concentration, there were considered as heterozygous carriers of the WD gene. The remaining patients had various liver diseases (acute viral hepatitis in three, chronic hepatitis in two, drug-induced liver disease in three, alcoholic induced liver disease in two) or malabsorption (n = 3). CONCLUSIONS: The positive predictive value of low serum ceruloplasmin was only 5.9%. Although helpful for identifying presymptomatic Wilson's disease, screening by determination of serum ceruloplasmin in unselected patients with clinical or laboratory evidence of liver disease is neither feasible nor cost effective.     

Comparative status of oxidative damage and antioxidant enzymes in chronic tonsillitis patients

Comparative study of two modalities i.e. antioxidant therapy (by vitamin E) and tonsillectomy was done in chronic tonsillitis patients, the study included 80 cases. It was found that both modalities were affective than tonsillectomy. Thus the use of antioxidant may be a promising alternative for the tonsillectomy.     

Thyroid gland and thyroid status in patients with chronic liver diseases

We have conducted a prospective study aimed to analyse contraceptive use among women seeking for legal abortion in the State University Hospital "Ma?chin dom"--Sofia. Our date demonstrate that the patients were well informed about the existing contraceptive methods. On the contrary the percentage of women-using contraception and especially those, using highly effective ones is relatively low. The patients claim the possible side effects of the high effective contraception as a reason against use.     

Fatty acid composition in maternal milk and plasma during supplementation with cod liver oil

OBJECTIVE: We investigated how cod liver oil influences the amount of essential fatty acids in mothers' breast milk. DESIGN AND INTERVENTION: Lactating mothers (n =22) were randomized into four groups 3-8 weeks after parturition. They were supplemented for 14 days with 0, 2.5, 5 and 10 ml cod liver oil (7.7 g eicosapentaenoic acid (EPA, 20:5n-3), 10.2 g docosahexaenoic acid (DHA, 22:6n-3) and 22.9 g n-3 fatty acids in total per 100 ml). RESULTS: In maternal plasma phospholipids there was an increase in the content of EPA and DHA in the group supplemented with 10 ml cod liver oil daily (P < or = 0.05). DHA concentrations in breast milk pre-supplementation ranged from 0.15 to 1.56 wt% and increased in all supplemented groups (P< or =0.05). The concentration of EPA in breast milk increased in the groups supplemented with 5 or 10 ml cod liver oil (P< or =0.05), whereas the concentration of arachidonic acid (AA, 20:4n-6) did not change in any of the supplemented groups. Total intake of DHA adjusted to body mass index (BMI), correlated to DHA concentrations in plasma (r = 0.49, P = 0.02) and breast milk (r = 0.45, P = 0.04). The concentration of tocopherol did not change during the supplementation period, neither in plasma nor in breast milk. CONCLUSION: Dietary intake of DHA is reflected in the concentration of DHA in breast milk, without affecting the concentration of AA or tocopherol.     

Lipoprotein metabolism disturbances in patients with kidney diseases]

Lipoprotein(a) was discovered over 30 years age and it is an independent risk factor for atherosclerosis, coronary artery disease and peripheral vascular diseases. Among patients with end stage renal failure lipoprotein(a) levels are higher than in general population and being independent of the type of treatment. Cardiovascular diseases are the most important cause of mortality in ESRD patients. Moreover we have interesting information about possibility of influence of Lp(a) serum levels.     

Genotype effects on the antioxidant enzymes activity and mRNA expression in liver and kidney tissues of autoimmune-prone MRL/MpJ-lpr/lpr mice

Congeneic pairs of MRL/lpr and MRL/++ (+/+) mice differ in incidence of autoantibodies, lymphoproliferative disease and survival, characteristics that are linked to immunological abnormalities. MRL/lpr mice have a significantly shorter life span compared to +/+ mice. Because a weak antioxidant defense and an increased generation of free radicals are generally implicated in the severity of many autoimmune disease, the present study was undertaken to compare the influence of genotype on lipid composition, lipid peroxidation and expression of mRNA, and activity of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in the livers and kidneys of these mice. The expression of SOD, GSH-Px and CAT mRNAs was significantly higher (P < 0.05) in the livers of +/+ mice, while in the kidneys only SOD expression was found significantly higher in +/+ mice when compared to MRL/lpr mice. Further, the activity of cytosolic SOD and GSH-Px was also found significantly higher (P < 0.001) in the livers of +/+ mice. Both livers and kidneys of MRL/lpr mice exhibited significantly higher levels of arachidonic acid (20:4(n-6)), significantly higher generation of thiobarbituric acid reactive substances (TBARS) and higher estimated peroxidation index than the +/+ mice. In addition, the MRL/lpr mice had higher levels of serum anti-cardiolipin antibodies. In summary, the results from the present study indicate that besides several immune-related abnormalities, the MRL/lpr mice may exhibit their inability to cope with oxidative stress due to a poor antioxidant defense system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication

Cilostazol is an antiplatelet agent and vasodilator marketed in Japan for treatment of ischemic symptoms of peripheral vascular disease. It is currently being evaluated in the United States for treatment of symptomatic intermittent claudication (IC). Cilostazol has been shown to improve walking distance in patients with IC. In addition to its reported vasodilator and antiplatelet effects, cilostazol has been proposed to have beneficial effects on plasma lipoproteins. We examined the effect of cilostazol versus placebo on plasma lipoproteins in 189 patients with IC. After 12 weeks of therapy with 100 mg cilostazol BID, plasma triglycerides decreased 15% (P<0.001). Cilostazol also increased plasma high density lipoprotein cholesterol (HDL-C) (10%) and apolipoprotein (apo) A1 (5.7%) significantly (P<0.001 and P<0.01, respectively). Both HDL3 and HDL2 subfractions were increased by cilostazol; however, the greatest percentage increase was observed in HDL2. Individuals with baseline hypertriglyceridemia (>140 mg/dL) experienced the greatest changes in both HDL-C and triglycerides with cilostazol treatment. In that subset of patients, HDL-C was increased 12.2% and triglycerides were decreased 23%. With cilostazol, there was a trend (3%) toward decreased apoB as well as increased apoA1, resulting in a significant (9.8%, P<0.002) increase in the apoA1 to apoB ratio. Low density lipoprotein cholesterol and lipoprotein(a) concentrations were unaffected. Cilostazol treatment resulted in a 35% increase in treadmill walking time (P=0.0015) and a 9.03% increase in ankle-brachial index (P<0.001). These results indicate that in addition to improving the symptoms of IC, cilostazol also favorably modifies plasma lipoproteins in patients with peripheral arterial disease. The mechanism of this effect is currently unknown.     

Changes in plasma proteins and drug distribution in kidney and liver diseases

Kidney and liver diseases induce alterations in drug binding to plasma proteins. These alterations are caused by qualitative and quantitative changes of plasma proteins and the presence of endogenous substances which act as competitive inhibitors of drug binding to plasma proteins. These changes are the most prominent in nephrotic syndrome and uremia among kidney diseases and in cirrhosis among liver diseases. The more important drugs in which the free fraction is changed in these entities are listed in the tables. The changes in drug distribution caused by plasma protein alterations may induce significant changes in entire drug pharmacokinetics. Discussed are theoretically expected and experimentally proven changes in plasma proteins in kidney and liver diseases and their influence to drug action and dosing regimen.     

Quantitative composition of blood plasma prostaglandins in patients with ischemic heart disease

A 6-month prospective study was conducted among 1739 women who underwent therapeutic abortion at Kandang Kerbau Hospital in Singapore to ascertain the aftereffects of abortion. Results of the study indicate that induced abortion has no observable bad effects on the mental health of the patients. In fact, somatic and psychiatric complaints were reduced and sexual adjustment increased 6 months postoperative. Those who were also sterilized at the time of the abortion showed a slightly lower rate of somatic symptom reduction than the rest of the group.