Plasma levels of coenzyme Q(10), vitamin E and lipids in uremic patients on conservative therapy and hemodialysis treatment: some possible biochemical and clinical implications.

Coenzyme Q(10) (CoQ(10)), vitamin E, total cholesterol, HDL-cholesterol (HDLC) and triglycerides were measured in the plasma of 62 patients with kidney failure, 46 under hemodialysis treatment and 16 under conservative therapy, and 95 controls. The sum of LDL-cholesterol (LDL-C) and VLDL-cholesterol (VLDL-C) was also calculated for each patient. The ratio CoQ(10)/LDL-C+VLDL-C in both conservative therapy and hemodialysis populations was significantly lower (P<0.001) compared with normal controls and remained unchanged after the dialysis treatment. On the contrary the ratio vitamin E/LDL-C+VLDL-C was normal but decreased significantly (P<0.02) after each dialysis. Since coenzyme Q is the main inhibitor of the prooxidant action of vitamin E, it was hypothesized that its decrease in both the populations examined could make the lipoproteins of these patients more vulnerable to a peroxidative attack.

Determination of copper, zinc, and selenium in human plasma and urine samples by potentiometric stripping analysis and constant current stripping analysis.

Potentiometric stripping analysis and constant current stripping analysis are proposed as routine methods for analysis of copper, zinc and selenium in plasma and urine samples. The analytical performance of these methods is comparable with that reported for atomic absorption spectrometry. However the low cost, greater simplicity of the apparatus, and the facility of execution make this methodology a valid candidate for routine application in Clinical Chemistry laboratories.

Coenzyme Q: potentially useful index of bioenergetic and oxidative status of spermatozoa.

The concentration of coenzyme Q10 (CoQ10), a key intermediate of the mitochondrial respiratory chain, was determined in spermatozoa of 13 fertile subjects, 8 potentially fertile patients, and 12 infertile patients. CoQ10 concentrations were significantly higher (P < 0.001) in infertile patients than in fertile and potentially fertile subjects. The difference between potentially fertile and fertile subjects was also significant (P < 0.001). We propose that a decrease in consumption of CoQ10 in both infertile and potentially fertile populations is due to an autoregulatory mechanism of ATP production.

Coenzyme Q10 levels, plasma lipids and peroxidation extent in renal failure and in hemodialytic patients.

Coenzyme Q10 (CoQ10), vitamin E, triglycerides and conjugated dienes were measured in a group of 48 patients on chronic hemodialysis, in 15 uremic patients and in a control group of 10 normal subjects. CoQ10 levels were significantly lower (P < 0.001) in both hemodialytic and uremic patients compared with the normal group whereas triglycerides were significantly higher (P < 0.001) with respect to both normal subjects and uremic patients. Conjugated dienes were significantly higher (P < 0.001) in both hemodialytic and uremic patients with respect to normal subjects. The predialytic values of vitamin E were higher in hemodialytic patients with respect to both normal subjects and uremic patients whereas the postdialytic values were in the normal range. A restoration mechanism of vitamin E after hemodialytic treatment was hypothesized.

Serum coenzyme Q10 in uremic patients on chronic hemodialysis.

In a group of 48 chronic hemodialysis patients, serum levels of coenzyme Q10 (CoQ) have been measured and appeared abnormally low in 62% of cases. Figures were positively correlated to those of serum vitamin E (vit E), although the latter were within a normal range. The chronic hemodialysis (CHD) patients with normal serum values of CoQ exhibited higher blood triglycerides. Pathologically low levels of serum vit E were found only in uremic subjects on conservative regimen with dietary restrictions and low compliance to protein-caloric intake. The reduced CoQ levels may contribute to the defective serum antioxidant activity and the increased peroxidative damage in uremic patients on CHD.

Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study.

Inhibitors of HMG-CoA reductase are new safe and effective cholesterol-lowering agents. Elevation of alanine-amino transferase (ALT) and aspartate-amino transferase (AST) has been described in a few cases and a myopathy with elevation of creatinine kinase (CK) has been reported rarely. The inhibition of HMG-CoA reductase affects also the biosynthesis of ubiquinone (CoQ10). We studied two groups of five healthy volunteers treated with 20 mg/day of pravastatin (Squibb, Italy) or simvastatin (MSD) for a month. Then we treated 30 hypercholesterolemic patients in a double-blind controlled study with pravastatin, simvastatin (20 mg/day), or placebo for 3 months. At the beginning, and 3 months thereafter we measured plasma total cholesterol, CoQ10, ALT, AST, CK, and other parameters (urea, creatinine, uric acid, total bilirubin, gamma GT, total protein). Significant changes in the healthy volunteer group were detected for total cholesterol and CoQ10 levels, which underwent about a 40% reduction after the treatment. The same extent of reduction, compared with placebo was measured in hypercholesterolemic patients treated with pravastatin or simvastatin. Our data show that the treatment with HMG-CoA reductase inhibitors lowers both total cholesterol and CoQ10 plasma levels in normal volunteers and in hypercholesterolemic patients. CoQ10 is essential for the production of energy and also has antioxidative properties. A diminution of CoQ10 availability may be the cause of membrane alteration with consequent cellular damage.

Coenzyme Q10: blood levels and metabolic demand.

Blood levels of CoQ10 were found to be lower in patients affected by hyperthyroidism and in athletes during a severe training period. In patients who had received a kidney transplant decreasing CoQ10 levels were found, during the first 30 min after transplant, in the blood leaving the newly transplanted organ. No decrease was detectable in patients who had received the kidney from a sibling. It may reasonably be hypothesized that the ischaemia/reperfusion damage is responsible for a certain degree of impoverishment of CoQ10, leading to a CoQ10 uptake from perfusing blood. A comparable trend was also evident in liver transplants. Low CoQ10 plasma levels may therefore reflect increased metabolic needs from various tissues, on the basis of increased overall metabolic rate and/or peroxidative damage.

Coenzyme Q10 in dilated cardiomyopathy.

The authors have tried to study the therapeutic efficacy of coenzyme Q10 (CoQ10) in patients with dilated cardiomyopathy (DCM). In fact, CoQ10 has been shown to be deficient in myocardial tissue biopsies taken from DCM hearts, compared to normal hearts. Thirty patients with histological diagnosis of DCM were orally treated with CoQ10 (100 mg/die) for 2 months. Before and after treatment a clinical examination with determination of NYHA class and an echocardiographic examination with determination of ejection fraction (EF) and of telediastolic (TDV) and telesystolic (TSV) volumes were performed, and blood was drawn for plasma CoQ10 determination. In seven patients the pretreatment endomyocardial level of CoQ10 was also assayed. Seven patients left the study because of poor therapeutic compliance. In 47% of patients the clinical symptomatology regressed, with improvement of NYHA class. The EF improved from 0.31 +/- 0.09 to 0.37 +/- 0.11 (p less than 0.001). The TDV passed from 262.2 +/- 85 ml to 203.3 +/- 83 ml (p less than 0.05), and the TSV from 166.13 +/- 75 ml to 126.9 +/- 56 ml (ns). The CoQ10 plasmatic levels improved in 95% of the patients: from 0.74 +/- 0.37 micrograms/ml to 2.27 +/- 0.99 micrograms/ml (p +/- 0.0001). The CoQ10 myocardial levels did not show univocal values, but the patients with lower myocardial levels seemed to have a better therapeutic response. These data suggest that the CoQ10 deficiency in DCM may be reversible and that the therapeutic effects depend on the basal plasmatic and myocardial levels. Therapy with coenzyme Q10 may be considered to be an efficacious aid in the traditional treatment of chronic cardiac failure.

Oxidative stress of red blood cells stored for transfusion use.

Some oxidative indexes and the level of reduced glutathione have been determined on red blood cells stored for transfusion use. Conjugated dienes show a concentration which increases until around the third week of storage and then comes back to lower values. On the contrary malonyldialdeyde shows a decreasing level until the third week and then rises rapidly to very high values. Reduced glutathione rises until about the end of the second week and then falls to very low values. Free haemoglobin continuously rises through the whole period of storage; from these data it is evident that a storage time not exceeding 21 days gives the best transfusion results.

Evaluation of metabolic status in amiodarone-induced thyroid disorders: plasma coenzyme Q10 determination.

In previous works we have demonstrated that Coenzyme Q10 (CoQ10) levels have a significant inverse correlation with thyroid hormone concentration in patients with spontaneous hyper- or hypothyroidism. In order to verify whether this correlation is maintained in patients on long-term amiodarone therapy, in whom thyroid metabolism is altered by the iodine contained in the drug, we have studied 30 patients with thyroid dysfunction induced by chronic amiodarone treatment. We have distinguished four groups of patients: group A (n = 8): patients with true hyperthyroidism induced by drug administration; group B (n = 11): patients with mild hyperthyroid symptoms, but isolated thyroxine increase or dissociation between different indexes of thyroid function; group C (n = 5): patients with normal thyroid hormone levels, but increased TSH levels; group D (n = 6): patients who appeared really clinically euthyroid, with normal thyroid hormone levels and normal TSH response to TRH. In group A patients, plasma CoQ10 levels averaged 0.49 +/- 0.03 micrograms/ml, significantly lower than those in normal subjects and similar to those observed in spontaneous hyperthyroid patients. In group B patients, CoQ10 levels were in the normal range (0.88 +/- 0.10 microgram/ml). In group C patients, CoQ10 levels were lower than those in normal subjects and similar to those of group A patients (0.49 +/- 0.04 microgram/ml); they differed, in regards to CoQ10 values, in comparison with spontaneous primary hypothyroid patients, who had very high levels of plasma CoQ10. Finally, in group D patients, CoQ10 levels were in the normal range (0.77 +/- 0.04 microgram/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

[Products of lipid peroxidation in the blood and respiratory secretions in 3 patients with acute respiratory diseases]. / Prodotti della perossidazione lipidica nel plasma e nelle secrezioni respiratorie di tre pazienti affetti da ARDS.

Oxygen free radicals have been suggested to be involved in ARDS pathogenesis. Their production may be caused by leukocyte activation and by administration of high oxygen concentrations. Radicals can oxidize lipids with production of dienes. In order to gather an indirect proof of radical production, dienes were repeatedly assessed in plasma and bronchoalveolar lavage (BAL) samples from three patients affected by ARDS. Plasma levels resulted higher than normal ones in all the patients initially; concentrations in BAL samples were lower than in plasma. Successively dienes decreased progressively in the patient who survived, whereas an increase was observed in BAL samples from the other patients, who died. The last trend was accompanied by a smaller increase in plasma levels.

Peroxidative events in stored platelet concentrates.

Changes in metabolic and functional activity of platelets stored as platelet concentrates in plastic bags highly permeable to gases were investigated. The following parameters were measured daily: pH, pO2, pCO2, HCO3, glucose, lactic acid, lactic dehydrogenase, cellular ATP and platelet aggregation induced by different agents (collagen and ADP). As indexes of lipid peroxidative damage, the cellular levels of conjugated dienes, malonyldialdehyde and some antioxidant molecules such as coenzyme Q10 and vitamin E were determined. A marked increase in pO2, conjugated dienes, malonyldialdehyde, lactic acid and lactic dehydrogenase activity was observed during the preservation. Platelet ATP content was unmodified and a remarkable decrease in platelet aggregability was found. pCO2, cyclooxygenase activity, vitamin E, coenzyme Q10, bicarbonate and glucose showed a rapid fall. Our data seem to indicate a preservation of platelet metabolic activity and a correlation between increased lipid peroxidation and functional impairement.

Influence of diet with different lipid composition on neutrophil chemiluminescence and disease activity in patients with rheumatoid arthritis.

Neutrophil chemiluminescence was determined in patients with active rheumatoid arthritis. Twelve patients were randomly assigned either to a diet high in polyunsaturated fatty acids supplemented with eicosapentaenoic and docosahexaenoic acids or to a diet high in saturated fatty acids. A correlation with clinical and laboratory parameters is also reported. No statistical difference was observed in neutrophil chemiluminescence and in clinical parameters in the group of patients treated with a diet high in saturated fatty acids. Fish oil ingestion resulted in subjective alleviation of active rheumatoid arthritis and reduction of neutrophil chemiluminescence. This study corroborates the hypothesis of an anti-inflammatory role for polyunsaturated fatty acids in patients with chronic inflammatory diseases.

Biochemistry of packed red blood cell concentrates stored in PAGGS-sorbitol solution for 42 days.

We investigated metabolic, blood gas and acid-base balance modifications of erythrocyte concentrates resuspended in PAGGS-sorbitol solution during 6 weeks of storage. Glucose utilization was impaired during the last 2 weeks, while the intraerythrocytic ATP level decreased only 50% from the 1st to the 6th week. The K+ and Hb concentration in the medium showed a progressive increase which was more pronounced during the last 2 weeks. The decrease in pH progressed to reach 6.27 at the 6th week of storage. Intraerythrocytic 2,3-DPG dropped rapidly in the course of the 1st week and the percentage of oxyhemoglobin showed a remarkable increase after the 1st week (90%). Our data suggest that erythrocyte concentrates in PAGGS-sorbitol should be transfused, for optimal efficacy, within 4 weeks.

Biochemical and functional changes of platelet stored for transfusional use.

A protocol for the biochemical study of platelet stored for transfusional use at 22 degrees C and under continuous shaking in a plastic bag highly permeable to gases and with a suitable area/volume ratio, is described. Plasmatic dextrose, lactic acid, lactic dehydrogenase activity, cellular ATP and malonyldialdehyde were monitored during the storage, as well as some acid-base indexes namely: pH, pCO2, HCO3-, pO2. The platelet functional status was checked as aggregating power induced by ADP and collagen and by beta-thromboglobulin release. The results obtained are indicative of a discrete maintenance of aerobic metabolism by platelets which are able to give up CO2 and take up O2 so that the plasmatic pH is constant during the storage. However, the malonyldialdehyde increase suggests that platelets become increasingly susceptible to peroxidative attacks. The aggregating response was dramatically reduced even on the third day of storage. The data obtained point out that, under the conditions reported, platelets can be transfused up to the third day of storage.

Enhancement of peritoneal macrophage activity by bovine gamma globulin in mice.

Mice treated with bovine gamma globulins showed an increased resistance to Salmonella typhimurium infection. This phenomenon seems to be bound to an increase of peritoneal macrophage phagocytic activity, as shown by the method of chemiluminescence, in experiments performed on peritoneal macrophages from mice treated with bovine gamma globulin.