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H Alho

Publications and source records attributed to H Alho.

At least 55 records · Page 3Linked to original sources
PubMed1998

Diazepam binding inhibitor and total cholesterol plasma levels in cirrhosis and hepatocellular carcinoma.

Cholesterol is used by cells for biosynthetic processes and for steroid synthesis. Although the role of cholesterol in tumorigenesis is not clear it is known that steroids are important factors in human carcinogenesis. A polypeptide, diazepam binding inhibitor (DBI), which is an endogenous ligand for peripheral benzodiazepine receptors enhances steroidigenesis by promoting cholesterol delivery to the inner mitochondrial membrane which represents the rate-limiting step of steroid biosynthesis. We have assayed the total cholesterol (TC) and the DBI plasma concentrations in patients with liver cirrhosis complicated by hepatocellular carcinoma (HCC) in comparison with those of uncomplicated liver cirrhosis. TC and DBI levels have been studied in 73 cirrhotic patients and in 23 patients with HCC. Both TC and DBI levels were higher in HCC patients when compared with age, sex and Child-Pugh class matched cirrhotic controls. The values (mean+/-S.D.) in patients in Child-Pugh class B and C with and without HCC were respectively 128+/-30 mg/dl vs. 106+/-27 mg/dl (P < 0.01) and 2.05+/-0.78 pmol/ml vs. 0.78+/-0.84 pmol/ml (P < 0.0001). The data may be the result of the metabolic influence of tumors that enhances steroid biosynthesis during tumor proliferation.

Adult↗
PubMed1998

Up-regulation of peripheral benzodiazepine receptor system in hepatocellular carcinoma.

Increased number of peripheral benzodiazepine receptors (PBRs) have been found in some tumors outside the liver. The present study was to verify whether the PBR system is altered in hepatocellular carcinoma (HCC). The levels of endogenous benzodiazepine-like compounds (BZDs), measured by radioreceptor binding technique after HPLC purification and the endogenous ligand for PBRs, termed diazepam binding inhibitor (DBI), measured by radioimmunoassay utilizing a specific antibody for human DBI, were studied in the blood of 15 normal subjects, 12 liver cirrhosis and 10 patients with HCC. The levels of BZDs in serum were increased hundred fold in liver cirrhosis patients and slightly elevated in HCC patients. DBI was found to be increased in HCC patients. The binding recognition sites for PBRs (Bmax) were increased 4 to 7 fold in HCC tissue in comparison with that found in non-tumoral liver tissue (NTLT). On the contrary the concentrations of DBI were found to be significantly decreased in HCC tissue in comparison with the respective NTLT. These results seem to suggest an implication of PBRs and of their putative endogenous ligands in the metabolism of these neoplastic cells and possibly in their proliferation. The up-regulation of PBRs found in HCC tissue seems to indicate an increased functional activity of these receptors and opens up the possibility of new pharmacological and diagnostic approaches while the changes in the circulating endogenous ligands for the above receptors might be envisaged as early markers of tumorigenesis in liver cirrhosis.

Adult↗
PubMed1998

Neonatal noradrenaline depletion prevents the transition of Bergmann glia in the developing cerebellum.

The influence of neonatal administration of 6-hydroxydopamine (6-OHDA) on the cell proliferation in cerebellum was studied using 10-30 days-old rats. Compared to their littermates, treated rats had poor ability in searching, skills performance and orienting in the new environment. Elimination of noradrenergic terminals by 6-OHDA led to a delay in granular cell migration. The secondary foliation in neo-cerebellum was absent. The Bergmann glial cells were abnormally located, structurally different and did not form the intimate association with Purkinje cells. Our findings indicate that without noradrenergic influence neurones and glial cells do not proliferate normally and noradrenaline may act as an important trophic factor also for Bergmann glial cells.

Animals↗
PubMed1998

Diazepam binding inhibitor (DBI) in the plasma of pediatric and adult epileptic patients.

The polypeptide diazepam binding inhibitor (DBI) displays epileptogenic activity by binding to benzodiazepine receptors. We analyzed DBI concentrations in the plasma of pediatric and adult epileptic patients, as a possible peripheral marker in epilepsy. DBI plasma concentrations are significantly higher (+ 62%, P < 0.001) in adult patients and slightly but significantly higher (+15%, P < 0.01) in pediatric patients, compared to age-related controls. Strikingly, plasma DBI is much higher (+81%, P < 0.001) in generalized epilepsy in adults and in drug-resistant pediatric and adult patients. Based on these findings, plasma DBI may be considered as a peripheral biological marker of epilepsy and, in association with lymphocyte benzodiazepine receptor density, of anticonvulsant drug responsiveness.

Adolescent↗
PubMed1998

Control of arterial tone after long-term coenzyme Q10 supplementation in senescent rats.

1. Age-associated deterioration of arterial function may result from long-lasting oxidative stress. Since coenzyme Q (Q10) has been suggested to protect the vascular endothelium from free radical-induced damage, we investigated the effects of long-term dietary Q10 supplementation on arterial function in senescent Wistar rats. 2. At 16 months of age, 18 rats were divided into two groups. The control group was kept on a standard diet while the other group was supplemented with Q10 (10 mg kg(-1) day(-1)). In addition, nine rats (age 2 months) also ingesting a standard diet were used as the young control group. After 8 study weeks the responses of the mesenteric arterial rings in vitro were examined. 3. Endothelium-independent arterial relaxations to isoprenaline and nitroprusside (SNP) were attenuated in aged rats. Increased dietary Q10 clearly enhanced the relaxation to isoprenaline, but did not affect the response to SNP. In addition, vasodilation of noradrenaline-precontracted rings to acetylcholine (ACh), which was also impaired in aged vessels, was improved after Q10 supplementation. Cyclooxygenase inhibition with diclofenac enhanced the relaxation to ACh only in young rats, while it abolished the difference between the old controls and Q10 supplemented rats, suggesting that the improved endothelium-dependent vasodilation observed in Q10 supplemented rats was largely mediated by prostacyclin (PGI2). 4. In conclusion, long-term Q10 supplementation improved endothelium-dependent vasodilation and enhanced beta-adrenoceptor-mediated arterial relaxation in senescent Wistar rats. The mechanisms underlying the improvement of endothelial function may have included augmented endothelial production of PGI2, increased sensitivity of smooth muscle to PGI2, or both.

Acetylcholine↗
PubMed1998

Unaltered antioxidant activity of plasma in subjects at increased risk for IDDM.

Evidence suggests that free oxygen radicals are involved in the destruction of islet beta-cells in insulin-dependent diabetes mellitus (IDDM). Therefore, we determined the plasma antioxidant activity in 51 healthy unaffected children and adolescents randomly chosen from a study of beta-cell autoimmunity in schoolchildren in northern Finland. Twenty-two subjects tested positive for one or more IDDM-associated autoantibodies and 9 subjects had at least two of the three antibodies tested (antibodies against islet cells, ICA; glutamic acid decarboxylase, GADA; insulin, IAA). There was no significant association of total plasma antioxidant potential, plasma concentrations of alpha-tocopherol, ascorbic acid, protein thiols, or uric acid with the presence of ICA, GADA, or IAA. A reduced first-phase insulin response to intravenous glucose was also not associated with reduced plasma antioxidant activity. These results indicate that the plasma antioxidant activity is not decreased in subjects at increased risk for IDDM. Furthermore, the results suggest that the clinical onset of IDDM is not preceded by signs of increased systemic oxidative stress in plasma.

Adolescent↗
PubMed1998

The association between the total antioxidant potential of plasma and the presence of coronary heart disease and renal dysfunction in patients with NIDDM.

Oxidative stress may be an important pathogenetic factor in the development of diabetic vascular complications. The total antioxidative potential of plasma reflects the ability of an individual to resist oxidative stress. We measured the plasma total peroxyl radical-trapping potential (TRAP) and the concentrations of four plasma chain-breaking antioxidants in 81 patients with non-insulin-dependent diabetes mellitus (NIDDM) nine years after diagnosis and in 102 well-matched non-diabetic control subjects. The association between the total antioxidative potential and the presence of coronary heart disease (CHD) and diabetic kidney disease were also studied. There were no significant differences in plasma TRAP between NIDDM patients and control subjects (1250+/-199 vs. 1224+/-198 microM). Nor were there any significant differences in the concentrations of plasma uric acid, ascorbic acid, alpha-tocopherol, and protein thiols between NIDDM patients and control subjects. Patients with a low glomerular filtration rate and/or high urinary albumin excretion had elevated plasma uric acid. Plasma TRAP was not, however, associated with renal dysfunction. The plasma of NIDDM patients with CHD had a significantly higher value of unidentified antioxidative potential than that of patients without CHD. This relation was strongly dependent upon smoking. In conclusion, these data demonstrate that there are no major defects in the antioxidative potential of plasma caused by NIDDM per se. CHD and diabetic renal dysfunction were not associated with changes in plasma TRAP.

Aged↗
PubMed1998

The effects of lifelong ubiquinone Q10 supplementation on the Q9 and Q10 tissue concentrations and life span of male rats and mice.

The effect of lifelong oral supplementation with ubiquinone Q10 (10 mg/kg/day) was examined in Sprague-Dawley rats and C57/B17 mice. There were no significant differences in survival or life-span found in either rats or mice. Histopathologic examination of different rat tissues showed no differences between the groups. In Q10 supplemented rats, plasma and liver Q10 levels were 2.6 to 8.4 times higher at all age points than in control rats. Interestingly, in supplemented rats the Q9 levels also were significantly higher (p<0.05) in plasma and liver at ages 18 and 24 months. Neither Q9 nor Q10 levels were affected by supplementation in kidney, heart, or brain tissues. In spite of the significant changes in plasma and liver ubiquinone concentrations, lifelong Q10 supplementation did not prolong or shorten the lifespan of either rats or mice.

Aging↗
PubMed1998

Assay of antioxidant capacity of human plasma and CSF in aging and disease.

Oxidative damage to DNA and other macromolecules accumulates with age and has been postulated to be one of the major forms of endogenous damage leading to aging and has been implicated also in initiation of cancer and over a hundred other diseases. The human body has developed an antioxidant (AOX) defense system which contains enzymatic, metal chelating, and free radical scavenging properties. Thus, it is essential to consider the concentration of all AOXs in plasma and CSF when investigating the relationship between diet, oxidative stress, and disease. In the present study a luminometric TRAP-method (total peroxyl radical-trapping potential) was used to determine the activity of all chain breaking AOXs in several clinical states. We have measured TRAP of plasma, cerebrospinal fluid (CSF) and of low density lipoprotein (LDL, TRAPLDL), and the concentrations of main AOX-components (uric acid, protein SH-groups, alpha-tocopherol, ascorbic acid, ubiquinone and the fraction of unknown antioxidants) to study the effect of: 1) aging, 2) acute infection, 3) diabetes, 4) immobilization and 5) cancer. TRAP of CSF is five times lower than of plasma, mainly due to the low urate concentration in CSF. We have observed that plasma antioxidant defenses respond to the basic metabolic rate and the challenges caused by physiological or pathological stress: i) in a healthy normal population TRAP and TRAPLDL change with age and a substantial proportion of TRAP cannot be attributed to any known AOXs thus indicating the existence of unmeasured an unidentified antioxidant(s); ii) during acute infection and immobilization the exogenous AOXs (vitamin C and E) remained unchanged, whereas the activity of unidentified AOXs of plasma declined sharply; iii) in those NIDDM patients with coronary heart disease plasma TRAP is reduced. In conclusion, TRAP has revealed important information for evaluating the AOX status of human plasma, CSF and LDL. According to our studies, important, possibly endogenous AOXs still remain to be identified.

Journal Article↗
PubMed1998

Effects of surgical removal of lung cancer on total plasma antioxidant capacity in lung cancer patients.

Previous evidence suggests that malignant tumors cause an oxidative burden to human antioxidative defense systems. We followed the plasma total radical-trapping antioxidant parameters (TRAP) and their main antioxidant components (alpha-tocopherol, uric acid, protein sulfhydryl groups, and unidentified antioxidant proportions) in 13 lung cancer patients and 7 control patients scheduled for thoracotomy. Plasma samples were collected 9 times during a 5 month follow-up period in the cancer patients. The objective of the study was to evaluate the effects of surgical removal of lung cancer on human plasma total antioxidant capacity. A significant reduction of plasma TRAP (period effect of ANOVA, p = 0.0006) and its components appeared in both groups during the first postoperative day. This decrease was due to reduction of ascorbate (p = 0.002) alpha-tocopherol (p = 0.0001) and urate (p = 0.05) concentrations. At 3 and 5 months after the surgical removal of the tumor there was an augmentation in plasma TRAP concentrations (p = 0.02, 3 months; p = 0.07, 5 months). This was mainly due to the increases in plasma yet as unidentified antioxidant components (UNID) and protein SH-groups. The data indicates that, first, thoracotomy itself causes a reduction in plasma TRAP during the early hours after operation, and secondly surgical removal of lung cancer increases plasma TRAP concentrations compared to the baseline values possibly reflecting the relief of oxidative stress caused by malignant tumors.

Aged↗
PubMed1998

The level of autoantibodies against oxidized LDL is not associated with the presence of coronary heart disease or diabetic kidney disease in patients with non-insulin-dependent diabetes mellitus.

Oxidation of low-density lipoprotein (LDL) may be an important factor in the development of diabetic macrovascular and renal complications. The level of autoantibodies against oxidized LDL (oxLDL-Ab) can be used as an index of LDL oxidation in vivo. The purpose of this study was to investigate the association between the level of oxLDL-Ab and the presence of coronary heart disease and renal dysfunction in patients with non-insulin-dependent diabetes mellitus (NIDDM). We determined the plasma levels of oxLDL-Ab in 46 NIDDM patients and 48 well matched nondiabetic control subjects. NIDDM patients had a moderately higher level of oxLDL-Ab than control subjects (0.083 +/- 0.051 vs. 0.062 +/- 0.045, p = 0.04). However, there was no difference in the level of oxLDL-Ab between subjects with and without coronary heart disease, and the level of oxLDL-Ab was not associated with indices of glomerular filtration rate or urinary albumin excretion.

Aged↗
PubMed1998

Human plasma antioxidant capacity during radiotherapy for lung cancer: a clinical study.

Even though it is well established that oxygen-free radicals are the main mechanism responsible for the cytotoxicity produced during radiotherapy, the role of the human antioxidant defense system in clinical radiation oncology is still to be clarified. Changes in the human plasma total peroxyl radical trapping capacity (TRAP) and its individual components were followed during clinical radiotherapy for lung cancer. Sixteen patients receiving radical-aimed radiotherapy provided blood samples nine times during the treatment. Our hypothesis was that oxygen-free radical production increased by irradiation should decrease the plasma TRAP as a consequence of oxidative stress. Only a moderate reduction of the plasma TRAP was found during the therapy in the study group taken as a whole, but the development pattern of TRAP and its unidentified components were clearly different in those patients showing complete or partial response to the treatment and those in which the disease progressed unabated. Plasma ascorbate levels showed no significant changes during radiotherapy. A decrease in vitamin E concentrations was seen after 6 Gy (p=0.05). Uric acid concentrations increased towards the end of the radiotherapy in both response groups (p=0.02 at 50 Gy). In this study, 26.6% of the plasma TRAP was due to unidentified antioxidants (UNID).

Adult↗
PubMed1997

New biomarker evidence of oxidative DNA damage in patients with non-insulin-dependent diabetes mellitus.

Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been reported to serve as a sensitive biomarker of oxidative DNA damage and also of oxidative stress. We have investigated oxidative DNA damage in patients with non-insulin-dependent diabetes mellitus (NIDDM) by urinary 8-OHdG assessments. We determined the total urinary excretion of 8-OHdG from 24 h urine samples of 81 NIDDM patients 9 years after the initial diagnosis and of 100 non-diabetic control subjects matched for age and gender. The total 24 h urinary excretion of 8-OHdG was markedly higher in NIDDM patients than in control subjects (68.2 +/- 39.4 microg vs. 49.6 +/- 37.7 microg, P = 0.001). High glycosylated hemoglobin was associated with a high level of urinary 8-OHdG. The increased excretion of urinary 8-OHdG is seen as indicating an increased systemic level of oxidative DNA damage in NIDDM patients.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1997

Biomarker evidence of DNA oxidation in lung cancer patients: association of urinary 8-hydroxy-2'-deoxyguanosine excretion with radiotherapy, chemotherapy, and response to treatment.

Ratios of urinary 8-hydroxy-2'-deoxyguanosine to urinary creatinine (8-OHdG/creatinine) have been considered as a good biological indicator of DNA oxidation. Urinary 8-OHdG/creatinine levels of lung cancer patients were evaluated by enzyme-linked immunosorbent assay using a monoclonal antibody N45.1 during radiotherapy and chemotherapy. An increase in urinary 8-OHdG/creatinine was found in non-small-cell carcinoma (non-SCC) patients during the course of radiotherapy. SCC patients showed higher levels of urinary 8-OHdG/creatinine than the controls. Furthermore, SCC patients with complete or partial response to the chemotherapy showed a significant decrease in urinary 8-OHdG/creatinine while patients with no change or progressive disease showed an increase.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1997

Ubiquinol-10 and total peroxyl radical trapping capacity of LDL lipoproteins during aging: the effects of Q-10 supplementation.

Evidence is rapidly accumulating that oxidative modification of low density lipoprotein (LDL) may play an important role in the pathogenesis of atherosclerosis. In this study we measured the total peroxyl radical trapping capacity of human plasma LDL phospholipids (TRAPLDL) with a luminescent method. The study was carried out with 70 healthy volunteers, aged 28-77. In males an age-related decrease in TRAPLDL was observed. In the age group under 50 years the mean TRAPLDL was 31.36 +/- 1.45 pmol peroxyl radicals/nmol Pi; among those over 50 years it was significantly lower at 26.67 0.94 pmol/nmol Pi. As regards the components of TRAPLDL, the concentration of LDL-ubiquinol did not change and a non-significant decrease in the LDL-tocopherol concentration was detected with age. In females, the mean TRAPLDL, LDL-ubiquinol-10 and tocopherol concentrations did not differ between the age groups. When 17 of the participants were given coenzyme Q10 (Q10) supplementation, 100 mg/day, a highly significant increase in LDL-ubiquinol concentration was detected. Our results indicate that LDL antioxidant defenses tend to decrease with age in the Finnish male population. The decline is most significant in males under 50 years; in older age groups the values remain stable at a low level. Q10 supplementation doubles the number of ubiquinol-10-containing LDL molecules and may therefore have an inhibitory effect on LDL oxidation.

Administration, Oral↗
PubMed1997

The transcriptional and translational control of diazepam binding inhibitor expression in rat male germ-line cells.

The diazepam binding inhibitor [DBI, also known as acyl-CoA-binding protein, (ACBP), or endozepine] is a 10-kD protein that has been suggested to be involved in the regulation of several biological processes such as acyl-CoA metabolism, steroidogenesis, insulin secretion, and gamma-aminobutyric acid type A (GABA(A))/benzodiazepine receptor modulation. DBI has been cloned from vertebrates, insects, plants, and yeasts. In mammals, DBI is expressed in almost all the tissues studied. Nevertheless, DBI expression is restricted to specific cell types. Here we have studied DBI gene expression in the germ-line cells of rat testis. The DBI gene was intensively transcribed in postmeiotic round spermatids from stages VI to VIII of the seminiferous epithelial cycle. A prominent, spermatid-specific upstream transcription initiation site was identified in addition to the multiple common transcriptional initiation sites found in the somatic tissues. However, no DBI protein was detected in round spermatids, suggesting that the DBI transcripts were translationally arrested. The DBI protein was detected in the late spermatogenic stages starting from elongating spermatids from step 18 (stage VI) onward. The DBI protein was also detected in mature spermatozoa and in ejaculated human sperms. The majority of DBI was located at the middle piece of the spermatozoons tail enriched with mitochondria. On the basis of this observation and the well-established role of DBI in acyl-CoA metabolism, we propose that DBI expression in spermatozoa reflects the usage of fatty acids as a primary energy source by spermatozoa. The biological function of DBI in spermatozoa could thus be related to the motility function of sperm.

Animals↗
PubMed1997

Plasma peroxyl radical trapping capacity in lung cancer patients: a case-control study.

Increasing evidence suggests that cancer patients express oxidative disturbances. The main objective of this cross-sectional case-control study (n = 57 + 76) was to explore whether lung cancer patients, when compared to healthy controls, have alterations in their plasma peroxyl radical trapping capacity (TRAP). Group matching was used with respect to age, sex and smoking history. A secondary objective was to observe the effects of life-long cigarette consumption on plasma TRAP and its components. Mean TRAP values were significantly lower in the cancer patients than in the control group (1143 vs 1273 mumol/l, p = 0.0002). Moreover, all the components of TRAP (except uric acid) were significantly lower in the cancer group: protein SH-groups 442 vs 571 mumol/l, ascorbic acid 34.0 vs 46.5 mumol/l and vitamin E 25.0 vs 33.8 mumol/l. The as yet unidentified antioxidant compounds in plasma contributed 26.5% of plasma TRAP in the cancer group and 30.2% in the control group. There was no correlation between cigarette consumption in pack-years and plasma TRAP; however, plasma concentrations of uric acid and ascorbic acid were negatively correlated with cigarette consumption.

Adult↗