CDTect-RIA and CDTect-EIA for determination of serum carbohydrate-deficient transferrin compared

Little is known of the factors that regulate CBF in sleep. We therefore studied 10 lambs to assess the vasodilatory processes that underlie cerebral autoregulation during sleep. Lambs, instrumented to measure CBF (flow probe on the superior sagittal sinus), sleep state, and cerebral perfusion pressure (CPP), were rapidly made hypotensive by inflating a cuff around the brachiocephalic artery to reduce CPP to 30 mm Hg in each state. During control periods, cerebral vascular resistance (CVR in mm Hg/mL/min) was lower in active sleep (2.8 +/- 0.3, mean +/- SD, P < or = 0.001) than in wakefulness (3.9 +/- 0.6) and quiet sleep (4.3 +/- 0.6). The CVR decreased promptly in each state as CPP was lowered. The time (seconds) required for maximal cerebral vasodilation to occur was longer in active sleep (35 +/- 11) than in quiet sleep (20 +/- 6, P < or = 0.001) and wakefulness (27 +/- 11, P < or = 0.05). The CVR decreased less in active sleep (0.6 +/- 0.3, P < or = 0.001) than in quiet sleep (1.5 +/- 0.3), although the changes in CPP induced with brachiocephalic occlusion were equal in each state. In conclusion, our studies provide the first evidence that the vasoactive mechanisms that underlie autoregulation of the cerebral circulation function during sleep. Moreover, our data reveal that the speed and the magnitude of the vasodilatory reserves available for autoregulation are significantly less in active sleep than in quiet sleep.     

Optimized determination of carbohydrate-deficient transferrin isoforms in serum by capillary zone electrophoresis

Carbohydrate deficient transferrin (CDT) is one of the most reliable markers of chronic alcohol abuse. It consists of a group of minor isoforms of human transferrin (the main iron transport serum protein) deficient in sialic acid groups (asialo, monosialo and disialo) with a pI > 5.7, while the main isotransferrin (tetrasialo) has a pI of 5.4. The aim of the present work was to develop a capillary electrophoretic method to determine CDT in serum, suitable for routine use as a confirmatory technique of the current screening methods based on immunoassays. Serum samples (0.5 mL) were saturated with iron by incubation with 10 mM FeCl3 (9 microL) and 500 mM NaHCO3 (12 microL) for 30 min, then diluted 1/10 in water and injected by positive pressure (0.5 psi for 10 s). Separation was performed with a capillary zone electrophoretic method using bare fused-silica capillaries (20 microm ID, 37 cm in length) and a buffer composed of 100 mM sodium tetraborate adjusted with boric acid to pH 8.3. Applied voltage was 10 kV and temperature 25 degrees C. Detection was by UV absorption at 200 nm wavelength. Under the described conditions, asialo-, monosialo-, disialo-, trisialo- and tetrasialo-transferrin were separated in human serum. The limit of detection (signal-to-noise ratio of 2) was about 0.3% for disialo-transferrin, and 0.4% of trisialo-transferrin, expressed as percentages of the terasialo-transferrin peak area. Relative standard deviations (RSD) of absolute migration times were < 1%, while RSD of relative migration times (on the basis of tetrasialo-transferrin) were < 0.1%. Intra-day and day-to-day peak quantitation precision studies showed RDS ranging from 4 to 9% and from 13 to 24% for disialo- and trisialo-transferrin, respectively. The results from 30 control subjects, including social drinkers, and 13 alcoholics showed disialo- and trisialo-transferrin significantly increased in patients by a factor of about 4.5 (P < 0.0001).     

The use of serum carbohydrate-deficient transferrin in the assessment of 'high risk offenders' in Great Britain

The potential role of serum carbohydrate-deficient transferrin (CDT) measurement in the assessment of 'High Risk Offenders (HROs)' applications for licence reinstatement in Great Britain was examined. Serum CDT determination would have provided useful confirmation of licence decisions in 70% of HROs assessed, would have resulted in a change in the licence decision in 8%, and most likely would have confounded the licence decisions made in the remaining 22%. Estimation of serum CDT could provide useful information to assist in decisions regarding licence reinstatement in selected HROs.     

Comparison of serum beta-hexosaminidase isoenzyme B activity with serum carbohydrate-deficient transferrin and other markers of alcohol abuse

We have compared beta-hexosaminidase (beta-Hex) activity, carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values in serum from male alcoholic patients with the corresponding values in moderate and non-drinking subjects. The total beta-Hex activity was 2.5 times higher in the alcoholics than in the moderate drinkers and this increase was mainly due to a 5-fold increase in the activity of the B-isoform of the enzyme. This was expressed as a percentage of the total beta-Hex activity and called 'beta-Hex B%'. Strong correlations were found between alcohol consumption (g/ day) and beta-Hex B% (r = 0.757, P < 0.001, n = 42), alcohol consumption and CDT (r = 0.671, P < 0.001, n = 42), and beta-Hex B% and CDT (r = 0.628, P < 0.001, n = 57). Serum beta-Hex B% had a sensitivity of 94% and a specificity of 91% in detecting alcoholic drinking of > 60 g/day. As a single marker of alcoholic drinking, it was markedly more sensitive than MCV and the liver enzymes GGT, AST and ALT, and slightly more sensitive than serum CDT (94 vs 83%). At the CDT cut-off level of 20 U/l, 17% of the moderate and non-drinkers would have been classified as alcoholic drinkers and 17% of the alcoholics would have been classified as moderate drinkers. Some of these misclassifications were eliminated if the beta-Hex B% results were taken into account. We suggest that serum beta-Hex B% can be a useful and inexpensive laboratory test for alcohol abuse.     

Evaluation of the efficacy of naltrexone in alcoholism by the determination of serum carbohydrate-deficient transferrin

Naltrexone (NTX) has been shown to be a useful drug for the treatment of alcohol dependence (AD). Carbohydrate-deficient transferrin (CDT) in serum is a new biologic marker of alcohol abuse. To evaluate the efficacy of NTX (50 mg/d) in AD, a group of 20 alcoholics with CDT > 20 U/l was studied using monthly laboratory tests (CDT, ESR, AST, ALT, GGT) and specific psychological testing (CAGE). After the second month statistically significant differences in CDT levels were found. By the end of the study, 13 patients (responders) had normalized their CDT levels. There was no correlation between CDT values and the other laboratory markers. The difference in routine laboratory markers between responders and non responders was not significant. NTX was well tolerated by all the patients and significant alcohol abstinence was achieved. CDT was demonstrated to be a effective marker for the evaluation of alcoholic abstinence during treatment with NTX. Superior results were obtained in comparison with the routine customary markers for AD.     

Absolute or relative measurement of carbohydrate-deficient transferrin in serum? Experiences with three immunological assays

The mechanism of anti-tumour activity by BCG is not known clearly. However, many studies suggest that immunological response is related to effectiveness of intravesical instillation of BCG in the therapy for superficial bladder carcinoma. Peripheral blood mononuclear cells (PBMC), urine and serum were obtained from patients with superficial carcinoma at various times during the course of BCG instillation. Urine of patients showed increased levels of IL-1beta, IL-2, IL-6, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and macrophage colony-stimulating factor (M-CSF) after BCG instillation. Levels of IL-2 and IFN-gamma in the serum also increased after BCG instillation, but IL-1beta, IL-6, TNF-alpha and M-CSF were not detectable. Maximal levels of IL-2 and IFN-gamma in the urine or serum were shown after the fourth instillation. BCG-induced killer cell activity in PBMC increased significantly after the third BCG instillation. These results suggest that BCG instillation involved not only local immunological efforts but also systemic immune responses. Tumour-free patients produced higher BCG-induced killer cell activity than tumour recurrence patients. BCG-induced killer cell activity may be useful for monitoring the effectiveness of intravesical BCG instillation.     

Utility of biological markers during outpatient treatment of alcohol-dependent subjects: carbohydrate-deficient transferrin responds to moderate changes in alcohol consumption

A group of 25 alcohol-dependent subjects in outpatient treatment were monitored for a period of 4 weeks. They were weekly interviewed for their alcohol consumption and their serum levels of carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GT) were analyzed. The majority of the patients reported an excessive and fairly constant alcohol intake during the observation period. When selecting those patients that reported periods of 1 or 2 weeks with moderate changes in alcohol consumption, corresponding changes in CDT were demonstrated. Thus, of 14 patients reporting an increased alcohol consumption for 2 weeks (mean values increased from 57 to 101 g/day), 11 showed an increase in CDT at the end of the period. The mean CDT value of all 14 increased from 5.5 to 6.7% (p < 0.05). Slight, but not significant, increases were noted in GT, indicating that CDT is more sensitive than GT in detecting increased alcohol consumption. Furthermore, of 17 patients that reported decreased alcohol consumption for one or several weeks, 14 showed decreased CDT and GT values. The mean values of all 17 were reduced from 5.1% to 4.5% (CDT) and from 126 units/liter to 97 units/liter (GT) (p < 0.05 for both parameters). The results indicate that CDT responds to moderate changes in alcohol consumption in alcohol-dependent patients and may thus be useful as a corrective tool to self-reports of alcohol consumption during outpatient treatments.     

The relationship between serum gamma-glutamyl transpeptidase levels and hypertension: common in drinkers and nondrinkers

Lesions in CNS white matter involving loss of glial cells with concurrent destruction of the glia limitans lead to widespread remyelination of CNS axons by Schwann cells. Previous studies have demonstrated that this situation can be changed by transplanting cultured CNS glial cells into lesions early on in the repair process. In this study we have transplanted cultured astrocytes into the sub-arachnoid space above such a lesion in order to (1) influence the normal repair process by transplant-assisted reconstruction of the glia limitans, and (2) explore the potential of a minimally invasive route for introducing cells to white matter lesions. In some cases, it proved possible to influence normal repair by transplanting cells via the sub-arachnoid route, although the results were inconsistent. However, the experiment permitted observations to be made on the migration of transplanted astrocytes across the surface of and within the spinal cord.     

The effect of furosemide on serum prolactin levels in the postpartum period

Furosemide, in combination with breast binding and milk fluid restriction, seems to inhibit postpartum lactation effectively, but has no effect in reducing serum prolactin levels. Inhibition of milk secretion must therefore be mediated by other mechanisms.     

Isoforms and levels of transferrin, antithrombin, alpha(1)-antitrypsin and thyroxine-binding globulin in 48 patients with carbohydrate-deficient glycoprotein syndrome type I

To improve our understanding of the role of extracellular matrix (ECM) proteins and integrins during the processes of granuloma formation in sarcoidosis, we examined the distribution of ECM proteins and the expression of integrins in sarcoid lymph nodes by immunohistochemical methods. We also examined the expression of transforming growth factor-beta1 (TGF-beta1), which is one of major regulators for synthesis of ECM proteins. Most ECM proteins were detected in the periphery of the granulomas in a concentric pattern, and fibronectin was diffusely detected from an early to a regressive stage. Compared with normal lymph nodes, most beta1-integrin subfamilies (alpha1, alpha4, alpha5 and alpha6) were more strongly expressed on lymphocytes around the granulomas. Epithelioid cells exhibited strong expression of the alpha5 molecule. Fibroblasts exhibited the expression of the alpha2 and alpha5 molecules surrounding ECM proteins. The alpha5beta1 molecule had a distribution similar to that of fibronectin. TGF-beta1 was detected in epithelioid cells throughout the various evolutional stages and its expression was especially marked in mature granulomas. Interaction of fibronectin and the alpha5beta1 molecule may have an important role in the process of formation of sarcoid granuloma. The expression of TGF-beta1 may be involved in the regression of sarcoid granuloma by initiating fibrosis and atrophy of epithelioid cells.     

The effect of modelling on drinking rate

Interaction between cholesterine and phosphatidilcholines (PC) of three types: 1,2-disaturated (SS), 1,2-diunsaturated (UU) and 1-saturated-2-unsaturated (SU) was studied in bilayer vesicular membranes (BVM) by means of NMR-1H spectroscopy. BVM were obtained by sonification of aqueous (D2O) dispersions of individual (PC) and their mixtures. It is found that molecular special specificity of the interaction between PC AND cholesterine is preserved not only during phase division but also in the case when all the phospholipid components of the bilayer are in a liquid crystal state. At low content of cholesterine it favourably interacts with UU-PC, further on with the increase of concentration cholesterine starts to interact with SU- and SS-types of PC. It has been shown that such behaviour of cholesterine can not be explained by means of static models, i.e. by the differences in stability of its stechiometric complexes with CP molecules of different types. An attempt has been undertaken to interpret the selective character of PS-cholesterine interaction proceeding from the suggestion about the anisotropic character of lateral diffusion in the membranes, consisting of various structural types of PC.     

The effect of mifepristone on progesterone and estrogen receptors in human decidua and serum hormone levels

OBJECTIVE: To examine the effects of mifepristone on progesterone and estrogen receptors in human decidua and steroid hormone levels in serum for investigating the mechanisms of antigestational action of mifepristone. METHODS: Decidual progesterone receptor (PR) and estrogen receptor (ER) concentrations or binding sites were measured by both dextran coated charcoal (DCC) and histochemical methods in normal subjects and after 100 mg-mifepristone treatment. Meanwhile, the concentrations of serum beta-human chorionic gonadotropin (beta-hCG), estradiol (E2), progesterone (P) and testosterone (T) were also determined by radioimmunoassay. The reactions of these two groups were compared. RESULTS: Mifepristone therapy significantly reduced decidual cytosol PR content (P < 0.05) and increased decidual cytosol ER content (P < 0.05). Histochemical analyses indicated mifepristone treatment increased ER staining in vessel and glandular cells of decidua. The serum beta-hCG, E2 and T levels elevated significantly after mifepristone administration, while the progesterone levels were unaffected. CONCLUSION: Our data suggested that the anti-gestational effect of mifepristone may act through decreasing the decidual PR and increasing the ER concentrations, which interfered the balance between these two components, and also through increasing serum T levels.     

The effect of live measles vaccines on serum vitamin A levels in healthy children

In chordate phylogeny, changes in the nervous system, jaws, and appendages transformed meek filter feeders into fearsome predators. Gene duplication is thought to promote such innovation. Vertebrate ancestors probably had single copies of genes now found in multiple copies in vertebrates and gene maps suggest that this occurred by polyploidization. It has been suggested that one genome duplication event occurred before, and one after the divergence of ray-finned and lobe-finned fishes. Holland et al., however, have argued that because various vertebrates have several HOX clusters, two rounds of duplication occurred before the origin of jawed fishes. Such gene-number data, however, do not distinguish between tandem duplications and polyploidization events, nor whether independent duplications occurred in different lineages. To investigate these matters, we mapped 144 zebrafish genes and compared the resulting map with mammalian maps. Comparison revealed large conserved chromosome segments. Because duplicated chromosome segments in zebrafish often correspond with specific chromosome segments in mammals, it is likely that two polyploidization events occurred prior to the divergence of fish and mammal lineages. This zebrafish gene map will facilitate molecular identification of mutated zebrafish genes, which can suggest functions for human genes known only by sequence.     

Family history and antisocial traits moderate naltrexone's effects on heavy drinking in alcoholics.

Naltrexone's (NAL) effects on alcohol consumption are generally modest, so identifying patients likely to benefit would improve treatment utility. Several studies indicate that potentially significant moderators of NAL's effects might include family history of alcohol problems (FH), age of onset of alcohol problems, degree of antisocial traits, and comorbid drug use. Data from 128 alcoholic patients enrolled in a 12-week NAL treatment study (50 mg/day) were reanalyzed to determine the role of FH, age of onset, antisocial traits, and comorbid drug use in NAL's treatment effects on heavy drinking days. Dichotomized FH, age of onset of alcohol problems, and comorbid cocaine or marijuana use had no interaction effect with medication. Percentage of relatives with problem drinking (family history percentage [FHP]) moderated the effects of NAL on drinking such that NAL resulted in lower drinking rates only for patients with higher FHP. Antisocial traits also moderated the effects of medication on drinking for patients compliant with =70% of medication. Patients with more antisocial traits had less heavy drinking on NAL than on placebo, whereas patients low on antisocial traits had no benefit from NAL. Covarying antisociality in regressions of drinking outcome on FHP showed that the effects of FHP were not attributable to antisociality. Thus, NAL may selectively benefit alcoholics with antisocial traits or 20% or more relatives with problem drinking. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of intellectual deterioration on retention deficits in amnesic alcoholics.

The performance of matched groups of alcoholic Korsakoff's syndrome patients, amnesic alcoholics with intellectual deterioration, and nonamnesic alcoholic control patients was assessed on three experimental memory tests. On a task measuring rate of short-term forgetting, the Korsakoff's syndrome and demented groups were found to have equivalent forgetting rates and both showed significantly more rapid decay than the control group. The Korsakoff's syndrome and demented groups also performed similarly on a task designed to assess semantic encoding deficits by examining sensitivity to, and release from, proactive interference. In a third experiment, the findings of Graf, Squire, and Mandler (1984) were replicated, with both the amnesic and demented groups having normal semantic priming performance on word completion test. Again, no difference was found between the two amnesic groups on verbal free- and cued-recall tasks. These results suggest that the contribution of concurrent intellectual deterioration to the poor performance of alcoholic Korsakoff's syndrome patients on verbal retention tasks may not be as great as has been assumed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of erythritol on the stability of gamma-glutamyl transpeptidase and N-acetyl glucosaminidase in human urine

In toxicology studies and clinical trials of erythritol, treated animals and human subjects had higher urine gamma-glutamyl transpeptidase [gamma-glutamyl transferase (gamma-GT)] than untreated controls. It has previously been reported that gamma-GT activity in frozen urine decreases with time; therefore, a study was undertaken to examine the effects of storage temperature, time, and the presence of erythritol on the stability of gamma-GT and N-acetyl glucosaminidase in human urine. In this study, it was found that the rate of decrease of the activity of gamma-GT is much greater at -20 degrees C than at -70 degrees C. Variation in the storage temperature of the frozen urine is particularly deleterious to gamma-GT. The addition of erythritol in a concentration of 5% reduces this decrease. Approximately 15% of N-acetyl glucosaminidase activity is lost in the initial process of freezing the urine. Thereafter, conditions of temperature, time, and the presence or absence of erythritol account for little additional loss of activity.