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Biomedical subjects

H Alho

Publications and source records attributed to H Alho.

At least 37 records · Page 2Linked to original sources

Low plasma antioxidant activity is associated with high lesion volume and neurological impairment in stroke.

BACKGROUND AND PURPOSE: Oxidative stress is probably involved in neuronal damage induced by ischemia-reperfusion. The purpose of this study was to assess the role of antioxidant activity in cerebral ischemic stroke. METHODS: Antioxidant activity of blood plasma and cerebrospinal fluid was assessed in 22 patients with cerebral hemisphere infarction that was verified and quantified by MRI. RESULTS: Low total peroxyl radical trapping potential of plasma, but not of cerebrospinal fluid, was associated with high lesion volume and high neurological impairment assessed by scores on NIH Stroke Scale, Barthel Index, and Hand Motor Score tests. The plasma concentrations of ascorbic acid, alpha-tocopherol, and protein thiols were also associated with the degree of neurological impairment. CONCLUSIONS: These data suggest that the antioxidant activity of plasma may be an important factor providing protection from neurological damage caused by stroke-associated oxidative stress.

Adult↗

Apoptosis in acute pancreatitis.

BACKGROUND: Apoptosis may be involved in the mechanism of acinar cell injury in acute experimental pancreatitis. AIM: This study was to investigate whether apoptosis also is involved in human acute pancreatitis. METHOD: A needle biopsy pancreatic specimen was obtained from a patient with acute oedematous pancreatitis. The specimen was stained with In Situ Cell Death Detection Kit. Similar specimen from a patient undergoing pancreatoduodenectomy for bile duct cancer served as a control. RESULTS: Extended acinar cell apoptosis was found in the pancreatitis specimen. No single apoptotic cell was found in the control pancreas. CONCLUSION: Apoptosis probably is involved not only in acute experimental pancreatitis but also in human acute oedematous pancreatitis. The induction and role of apoptosis in pancreatis is discussed based on literature.

Acute Disease↗

Enhanced clinical utility of gamma-CDT in a general population.

BACKGROUND: The use of a combination of markers to detect excessive alcohol consumption has been reported to provide better sensitivity in the diagnosis of alcohol abuse than single markers. However, the optimal combination of markers for the diagnosis of alcohol abuse has not yet been found. The aim of this study was to compare the diagnostic value of carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) to discriminate among heavy drinkers (>280 g/week), moderate drinkers (105-280 g/week), and light drinkers (<105 g/week). Their mathematical combination, named gamma-CDT, which has been found to be a strong marker of alcohol abuse in a former study, was also evaluated. METHODS: The study was conducted in a group of 6962 subjects (3974 males and 2988 females), between the ages of 25 and 74 years, who participated in a large cross-sectional risk factor survey carried out in five geographic areas in Finland. In each study area, an age- and gender-stratified random sample was drawn from the general population. Sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic curves were used to evaluate the performance of CDT, GGT, and gamma-CDT. RESULTS: For both sexes, the combined marker had the highest specificity (95%) and sensitivity in detecting heavy drinkers. In all cases, gamma-CDT had the highest area under ROC plots. Our results also showed that GGT and CDT have similar, and rather low, sensitivity but high specificity in a general population. CONCLUSIONS: Compared with single markers, a significant improvement of sensitivity was obtained when the combination of both markers was used, especially in females.

Adult↗

Effect of hormone balance on carbohydrate-deficient transferrin and gamma-glutamyltransferase in female social drinkers.

BACKGROUND: Carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) are the most commonly used markers for alcohol abuse, but their sensitivity and specificity are lower and have different reference values among females compared with males. In the present study, we evaluated the effect of women's hormone balance on these two alcohol markers, as well as on their mathematical combination, named gamma-CDT. METHODS: An age-stratified random sample of 3962 women, between 25-74 years old, was drawn from the normal population. Pregnancy, the use of oral contraceptives, intrauterine device for contraception, hormone replacement therapy, and hormone treatment for infertility were considered. A comparison between fertile, peri- and postmenopausal women was also done. RESULTS: Existing pregnancy increased CDT levels but decreased GGT values. Lower CDT and higher GGT levels were observed among those women using oral contraceptives and in postmenopausal women compared with women at the fertile stage. gamma-CDT was not influenced by hormone balance. CONCLUSIONS: The different hormonal status had an opposite effect on CDT and GGT. Women who were close to late menopause had levels of both markers closer to the values of men. It must be pointed out that the findings presented here are based on measurements of absolute CDT values and that no measurements of total transferrin were done. gamma-CDT, not influenced by hormone balance, indicates promising clinical utility among women.

Adult↗

Ultrathin cutting needle biopsy histology in the tissue diagnosis of acute pancreatitis--experimental study and application in a human case.

BACKGROUND AND AIMS: This study was to assess whether the tissue obtained with an ultrathin cutting needle, that is as thin as used for aspiration cytology and bacteriology, can give enough material to diagnose acute pancreatitis in rat model and in a human case. METHODS: Wistar rats were randomly allocated into control group (n = 6), cerulein group (n = 6), ligation group (n = 6) and bile salt group (n = 6). In the cerulein, ligation and bile salt groups acute pancreatitis was induced by cerulein intraperitoneal injections, low ligation of common biliopancreatic duct and sodium taurodeoxycholate intraductal injection, respectively. Serum amylase activity was measured and a large cut specimen and two ultrathin needle biopsy specimens were obtained from the pancreas for light microscopic histology. Oedema, acinar cell necrosis, haemorrhage or fat necrosis, and leukocyte infiltration were evaluated semiquantitatively and compared with large cut specimens. RESULTS: The pancreatitis groups revealed different severity in oedema, acinar cell necrosis, haemorrhage or fat necrosis, and leukocyte infiltration. The needle biopsy showed 100% sensitivity and 100% specificity in the diagnosis of acute pancreatitis. The histopathologic scores showed a good and significant correlation between ultrathin biopsy and large cut specimens in all the four histologic parameters, especially in oedema and acinar cell necrosis. A human case is presented, whose percutaneous ultrathin needle biopsy histology was successfully applied for diagnosing acute pancreatitis. CONCLUSIONS: The ultrathin needle biopsy histology can give enough material for the diagnosis of acute pancreatitis. Further studies with ultrasonography guided percutanous or endosonography guided transduodenal technique will be needed to assess the role of tissue sampling in acute pancreatitis.

Acute Disease↗

Coenzyme Q10 supplementation and recovery from ischemia in senescent rat myocardium.

Many studies have suggested that parenteral administration of coenzyme Q10 (Q10) protects the myocardium of young experimental animals from post-ischemic reperfusion injury. Although parenteral administration, in contrast to per os supplementation, seems to elevate coenzyme Q concentrations in heart tissue, it is not suitable for prophylactic use. In addition, the incidence of ischemic events is greatest in older age. We studied the effect of Q10 supplementation on myocardial postischemic recovery in 18-month-old Wistar rats. The treated group (n=9) received 10 mg/kg/day of Q10 for 8 weeks in their chow while the normal chow of the control group (n=9) contained less than 0.5 mg/kg/day of Q10. The treatment clearly elevated plasma Q10 concentration (286 +/- 25 micromol/l and 48 +/- 30 micromol/l, treated and controls, respectively, p<0.0001) but neither Q9 nor Q10 concentrations in heart tissue were affected by the supplementation. The isolated perfused hearts were subjected to 20 minutes of ischemia and 30 minutes of reperfusion. The preischemic values of developed pressure (DP) but not contractility (+DP/delta t) and relaxation (-DP/delta t) were improved by Q10 supplementation (p=0.034, p=0.057 and p=0.13, respectively) while in postischemic recovery no differences were observed between the groups (p>0.05 at all time points). Also, in myocardial flow, myocardial oxygen consumption (MVO2) and myocardial aerobic efficiency (DP/MVO2) the groups did not differ at any time points. Although dietary Q10 supplementation clearly elevated plasma Q10 concentrations in senescent rats, the coenzyme Q contents in heart tissue and myocardial recovery from ischemia were not affected. However, it is possible that the site of action for the reported beneficial effects of Q10 is in the coronary endothelium rather than myocardium itself.

Aging↗

Increased expression of peripheral benzodiazepine receptors and diazepam binding inhibitor in human tumors sited in the liver.

The peripheral benzodiazepine receptor system triggers intracellular metabolic events and has been associated with cell proliferation. Its endogenous ligand, the diazepam binding inhibitor, contributes to steroidogenesis by promoting cholesterol delivery to the inner mitochondrial membrane. The present study was undertaken to verify whether this system is altered in tumors sited in the liver. Peripheral benzodiazepine receptors and diazepam binding inhibitor were studied using immunocytochemistry and in situ hybridization in 9 human tumors sited in the liver, in liver hyperplasia, cirrhotic nodular regeneration, intestinal adenocarcinoma and in surrounding non-tumoral tissue. Immunocytochemical staining and in situ hybridization demonstrated that peripheral benzodiazepine receptors and diazepam binding inhibitor were more prominently expressed in neoplastic cells than in non-tumoral tissue. They were present in the same cells, suggesting that diazepam binding inhibitor may act in an intracrine manner in these cells. Higher peripheral benzodiazepine receptors and diazepam binding inhibitor expression in tumor cells suggest an implication of this system in the metabolism of neoplastic cells. Furthermore the evaluation of peripheral benzodiazepine receptor and diazepam binding inhibitor expression might be useful in evaluating malignancy and in diagnostic approaches of tumors in liver tissue.

Aged↗

Furosemide action on cerebellar GABA(A) receptors in alcohol-sensitive ANT rats.

Furosemide increases the basal tert-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding and reverses the inhibition of the binding by gamma-aminobutyric acid (GABA) in the cerebellar GABA(A) receptors containing the alpha6 and beta2/beta3 subunits. These effects are less pronounced in the alcohol-sensitive (ANT) than in the alcohol-insensitive (AT) rat line. The difference between the rat lines in the increase of basal [35S]TBPS binding was removed after a longer preincubation with ethylendiaminetetraacetic acid (EDTA) containing buffer, but long preincubation did not reduce the GABA content of the incubation fluid or remove the difference in GABA antagonism by furosemide. The GABA sensitivity of the [35S]TBPS binding did not differ between the rat lines. There was no nucleotide sequence difference in the beta2 or beta3 subunits between the rat lines and similar beta2/3 subunit-dependent agonistic actions by methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) in the rat lines were detected. The data suggest that there are still unknown structural alterations in the cerebellar GABA(A) receptors between the AT and ANT rat lines, possibly associated with differential alcohol sensitivity.

Alcoholism↗

CDKN2/p16 predicts survival in oligodendrogliomas: comparison with astrocytomas.

Cyclin-dependent kinase 4 inhibitor (CDKN2/p16) is a cell cycle regulatory protein that has been demonstrated to be inactivated by mutations, deletions or transcriptional silencing during pathogenesis of a variety of human malignancies. We studied the correlation of CDKN2/p16 expression with cell proliferation activity and patient survival in 42 oligodendrogliomas and 36 astrocytomas. CDKN2/p16 expression was frequently decreased in grade II and anaplastic oligodendrogliomas (17/42) where lack of CDKN2/p16 protein predicted poor survival (p = 0.0045). In astrocytomas low CDKN2/p16 expression was associated with high histologic malignancy grade (p = 0.002): CDKN2/p16 protein level was decreased in 9 out of 10 glioblastomas, in 5 out of 9 anaplastic astrocytomas, in 3 out of 10 grade II astrocytomas and in none of pilocytic astocytomas (0/7). Low CDKN2/p16 expression was also associated with high cell proliferation activity (MIB-1 immunocytochemistry: p = 0.004; mitotic index: p = 0.007) and poor patient survival (p = 0.025) in astrocytomas. Low CDKN2/p16 mRNA expression had the same topographic distribution as nuclear CDKN2/p16 immunoreactivity proving for reliability of the immunocytochemical findings. Our results are in agreement with earlier studies demonstrating CDKN2/p16 inactivation during tumorigenesis of astrocytic tumors. Furthermore, our findings suggest that loss of CDKN2/p16 expression may also play an important role in the progression of oligodendrogliomas. According to our findings CDKN2/p16 immunocytochemistry could be used as a tool to identify those oligodendrogliomas and low grade astrocytomas that are likely to progress and have poor outcome, and thus would need more aggressive therapy.

Adolescent↗

Plasma chain-breaking antioxidants in preterm infants with good and poor short-term outcome.

Many complications of prematurity have been suggested to result from free radical generation and an inadequacy of antioxidative capacity. We measured the plasma total peroxyl radical-trapping capability (TRAP) and concentrations of the main chain-breaking antioxidants contributing to it, i.e. uric acid, ascorbic acid, alpha-tocopherol, protein sulfhydryl groups and bilirubin, in 21 preterm infants with a mean birth weight of 1440 g and gestational age of 30 wk. The infants were divided into two groups according to their short-term outcome; the good outcome group (GOG) (N = 11) with no signs of morbidity and the poor outcome group (POG) (N = 10) with intraventricular haemorrhage and/or bronchopulmonary dysplasia and/or retinopathy. Arterial blood samples were obtained 3 and 10 days postpartum. TRAP was measured with a chemiluminescent method. As a comparison, venous blood samples from 13 adults (aged from 18 to 34) were used. At day 3 the poor outcome group had significantly higher TRAP than the good outcome or control group, mainly because of elevated uric acid concentration. Also the concentration of unidentified antioxidants was significantly lower in GOG. By day 10 the TRAP decreased substantially in both groups. However, from the components of TRAP, both ascorbate and the unidentified fraction decreased more in POG (p = 0.017 and 0.021, respectively). Furthermore in POG on day 10 urate concentration did not significantly differ from day 3 values. In conclusion, in preterm infants high TRAP was associated with high plasma uric acid concentration and a poor short-term prognosis.

Adolescent↗

Serum and saliva levels of sialic acid are elevated in alcoholics.

BACKGROUND AND METHODS: Recently, sialic acid has been suggested as a potential marker for alcohol abuse. In this study, social drinkers and alcoholics were analyzed with a modified version of Warren's method for sialic acid and traditional markers of alcohol abuse in serum (n = 38; n = 87), saliva (n = 36; n = 29), and urine (n = 37; n = 83), respectively. The alcoholics were participating in an alcohol dependency treatment program and were followed in this study for 5 weeks. RESULTS: The sialic acid concentrations in female and male alcoholics were significantly higher in serum (p < 0.001;p < 0.001 respectively) and saliva (p < 0.05; p < 0.05) but not in urine, compared with social drinkers. The diagnostic efficiency of serum sialic acid was higher than that for traditional markers: 77% for female subjects and 64% for male subjects. The corresponding results for saliva were 72% and 53%. The sialic acid concentrations were significantly decreased during the alcohol dependency treatment program (after 5 weeks of treatment) in both females and males. CONCLUSIONS: This study confirms that serum sialic acid is a valuable marker for detecting and monitoring alcohol abuse. This work also indicates that sialic acid in saliva could be used possibly as a noninvasive marker for alcohol abuse.

Adolescent↗

Enhanced in vivo lipid peroxidation at elevated plasma total homocysteine levels.

An elevated plasma total homocysteine level (tHcy) is considered an independent risk factor for atherosclerosis. The mechanisms by which hyperhomocysteinemia induces atherosclerosis are only partially understood, but promotion of LDL oxidation and endothelial injury have been suggested. The purpose of this study was to test the hypothesis that a high plasma tHcy is associated in men with increased in vivo lipid peroxidation, as measured by plasma F2-isoprostane concentrations. We investigated this association in a subset of the participants in the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study. Of 256 male participants, a subsample of 100 consecutive men was selected for F2-isoprostane assays. The mean tHcy was 11.0 micromol/L, and the mean F2-isoprostanes was 29.6 ng/L. The simple correlation coefficient for association between tHcy and F2-isoprostane was 0.40 (P<0.001). In a linear regression model, the variables with the strongest associations with F2-isoprostane were tHcy (standardized coefficient 0.33, P<0.001), serum triglycerides (0.21, P=0.042), carbohydrate-deficient transferrin (0.15, P=0.132), and plasma lipid-standardized alpha-tocopherol (-0.11, P=0.252) (R2=0.24, P<0. 001 for model). Plasma F2-isoprostane levels increased linearly across quintiles of tHcy (P<0.001). The unadjusted mean (95% confidence interval) F2-isoprostanes was 47.5% greater in the highest tHcy quintile (37.4, 31.1 to 43.6 ng/L) than in the lowest quintile (25.3, 21.3 to 29.3 ng/L). Adjustment for the strongest other determinants of F2-isoprostane reduced this difference to 28. 2% (P=0.010). Our present data suggest that elevated fasting plasma tHcy is associated with enhanced in vivo lipid peroxidation in men.

Arteriosclerosis↗

Extrapancreatic organ impairment in caerulein induced pancreatitis.

BACKGROUND AND AIMS: Multiorgan function failures are the major fatal complications in acute pancreatitis. In this experiment, we studied 1) the manifestation and time course of extrapancreatic organ damage in an acute pancreatitis model and 2) whether the obstructive liver damage in this model is caused by the obstruction of common biliopancreatic duct compressed by oedematous pancreas. MATERIAL AND METHODS: 80 male Wistar rats were divided into two groups: control and caerulein groups (five subgroups in each group). In the caerulein group, the acute pancreatitis was induced by caerulein intraperitoneal injections. In the controls equal volume of saline was injected. Two subgroups, one in caerulein and one in control groups, had an intrapancreatic bile duct stent inserted transduodenally before the injections. The pancreas, liver, lung and kidney tissues and blood samples were obtained for the measurement or analysis of interstitial oedema, plasma amylase, alanine aminotransferase, bilirubin, urea, creatinine, alkaline phosphatase, lactate dehydrogenase, blood gas and electron microscopy at 1, 6, 12 and 24 hours after the last injection in unstented animals, and at 6 hours in stented animals. RESULTS: Lungs and kidney remained unchanged. Liver damage was found during the first 6-12 hours, manifest as increased plasma alanine aminotransferase and bilirubin and dilatation of bile canaliculi and hepatocyte damage in electron microscopy. The intrapancreatic bile duct stent did not resolve these changes. CONCLUSIONS: The liver may be the first evolved extrapancreatic organ in the early stage in this mild oedematous pancreatitis model and the hepatocyte damage is not caused by the obstruction of common biliopancreatic duct compressed by the oedematous pancreas.

Animals↗

Serum sialic acid in a random sample of the general population.

BACKGROUND: The serum sialic acid (SA) concentration has been reported to be a potentially useful but nonspecific disease marker. We wanted to study which factors influence SA concentration in a well-characterized healthy population. METHODS: SA was determined in 97 women and 96 men with a colorimetric Warren method. RESULTS: The mean +/- SD concentrations of SA were 634 +/- 109 (95% confidence interval, 612-656) and 630 +/- 106 (95% confidence interval, 608-651) mg/L for women and men, respectively. The serum SA showed a significant positive association with body mass index and with systolic and diastolic blood pressure among both women and men. SA also correlated significantly with the use of contraceptive pills and age among women and with smoking among men. CONCLUSIONS: Our study suggests that SA does not increase with age in men but appears to increase with female menopause. The strong positive association with blood pressure may explain why SA predicts cardiovascular mortality.

Adult↗

Extrapancreatic multiorgan injury in a severe sublethal acute pancreatitis model.

In order to develop a new severe but sublethal acute pancreatitis model for the study of clinically relevant extrapancreatic multiorgan injury, we have induced acute pancreatitis in a rat model by intraductal injection with low dose and moderate concentration of bile acid under low pressure. We examined the structural and functional features in the pancreas, lung, liver and kidney. The animals were divided into two groups: the bile acid injection group and the control group. In the bile acid injection group, acute necrotizing pancreatitis was induced by intraductal administration of 0.2 ml of 2.0% bile acid under 30 cm H2O pressure, while the controls underwent the sham operation. The two groups were divided into six subgroups (8 rats for each) and sacrificed at 12, 24, 36, 48, 72 and 144 h, respectively. The pancreatitis induced hyperamylasemia, ascites, pancreatic oedema, haemorrhage, acinar cell necrosis and extensive fat necrosis without early mortality. Accompanied with the pancreatic injury, the function and histologic changes have developed continuously in the kidney and liver for 72 and 144 h in the bile acid injection animals respectively. No pancreatitis associated pulmonary changes were found. Taking into account the results with the two previously developed models of pancreatitis, we conclude that the extrapancreatic injury in acute pancreatitis is found in the liver, kidney and lung, in that order, depending on the severity of pancreatitis. The present sublethal pancreatitis model, in comparison with the two previously studied acute pancreatitis models, is perfect for pathogenetic and therapeutic study of liver and renal changes in acute necrotizing pancreatitis.

Acute Disease↗

Extrapancreatic organ manifestations in a moderately severe acute pancreatitis model.

In order to study the extent of clinically relevant extrapancreatic organ injury in a moderately severe pancreatitis model, we examined the structural and functional features of the pancreas, lung, liver and kidney in a rat model simulating gallstone pancreatitis. The animals were divided into three groups: the low-ligation group, the high-ligation group and the control group, and sacrificed at 6, 24, 42, 60 and 96 h. In the low-ligation group, moderately severe acute pancreatitis was induced by the ligation of the common biliopancreatic duct plus intralipid intragastric injection, while controls underwent the ligation of the bile duct above the pancreas (the high-ligation group) or only sham operation (the control group) with fat injection. The pancreatitis induced hyperamylasemia, pancreatic oedema, haemorrhage, acinar cell necrosis and extensive fat necrosis. Accompanied with a peak value of serum amylase activity 24 h after the induction, the kidney changes developed, characterized by decrease in urine output, increase in serum urea and creatinine, and proximal convoluted tubular damage under electron microscope. There were no pancreatitis associated lung or liver changes. These results suggest that this model can be used to study the pathogenesis and therapy of renal injury during acute moderately severe pancreatitis.

Acute Disease↗

Susceptibility of LDL to oxidation is not associated with the presence of coronary heart disease or renal dysfunction in NIDDM patients.

Coronary heart disease (CHD) is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM) and the oxidation of low-density lipoprotein (LDL) may be an essential factor in the development of atherosclerotic lesions. Therefore, we studied the in vitro susceptibility of LDL to copper-induced oxidation in 72 NIDDM patients and 94 well-matched non-diabetic control subjects. There was no significant difference in the lagtime of LDL oxidation between NIDDM patients and control subjects (68.1+/-8.8 vs. 66.7+/-9.2 min, respectively, P=0.29). The plasma alpha-tocopherol/LDL-ratio was the most significant determinant of the lagtime in multiple regression analysis. High level of serum triglycerides was associated with decreased lagtime in control subjects, but not in NIDDM patients. Blood glucose balance was not associated with LDL susceptibility to oxidation in NIDDM patients. Subjects with CHD did not have LDL susceptibility to oxidation different from that of subjects without CHD in either of the study groups. Urinary albumin excretion or glomerular filtration rate was not associated with the lagtime of LDL oxidation in NIDDM patients. In conclusion, these data suggest that diabetes and hyperglycemia per se do not affect the susceptibility of LDL to oxidation. The presence of CHD or renal dysfunction were not associated with LDL susceptibility to oxidation.

Aged↗