LONGITUDINAL COMPARISON OF CARBOHYDRATE-DEFICIENT TRANSFERRIN AND GAMMA-GLUTAMYL TRANSFERASE: COMPLEMENTARY MARKERS OF EXCESSIVE ALCOHOL CONSUMPTION

The utility of carbohydrate-deficient transferrin (CDT) andgamma-glutamyl transferase (GGT) as biochemical markers of excessivealcohol consumption was studied in alcohol-dependent subjects.Serum samples were collected once weekly from 10 male out-patientsundergoing a 6-month alcohol treatment programme. Frequencyof relapse into drinking (defined as any intake of alcoholicbeverage) was assessed by self-reports during patient interviewsthree times per week and by daily determination of the 5-hydroxytryptophollevel in urine. A marked decrease in mean CDT and GGT valueswas observed during the initial month. Only one patient remainedtotally abstinent throughout the observation period, while fourhad sporadic relapses (2–5 days with alcohol consumption).Both CDT and GGT remained below the respective reference limitsin those patients. The other five patients drank more frequently(range 22–57 days) and increased their mean levels ofCDT and GGT after the initial decrease. As determined from thevalues at admission and during the course of the study, CDTappeared to be the most sensitive marker in six out of the 10patients. In one patient, both markers were affected in a parallelway, whereas two of those with frequent relapses responded toalcohol consumption with a marked increase in GGT, but withno or only a slight increase in CDT. One patient did not showany abnormal CDT or GGT values. In 54 female and 60 male serumsamples collected at random from patients during admission atan alcohol detoxification unit, 35% and 58% of the CDT valuesexceeded the reference limits for females and males, respectively.For GGT, 59% of the female and 67% of the male values were abovecut-off. Carbohydrate-deficient transferrin and GGT were notsignificantly correlated. Taken together, the present resultsindicate that measurement of both CDT and GGT will increasethe possibility of identifying excessive alcohol consumption.By following changes in CDT and GGT values during a period ofalcohol withdrawal, the most sensitive individual marker canbe determined. This in turn allows for improved detection ofrelapse into heavy drinking dunng long-term monitoring of out-patients.     

Comparison of the photochemical behavior of four different photoactivatable probes

The most commonly used photoaffinity labeling probes are compared, which are aryl azides, aryl diazirines, α-diazocarbonyls and benzophenone-derivatives. The compounds were used under identical conditions and crosslinking efficiency, influence of water, irradiation requirements, and by-products were investigated. Using the pentapeptide thymopentin (TP5) as a model system, we synthesized four analogues by solid-phase peptide synthesis and partially N-terminal modification to obtain [p-(3-trifluoromethyl)diazirinophenylalanine⁵] TP5, [p-benzoylphenylalanine⁵] TP5, 4-azidobenzoyl-TP5 and 2-diazo-3, 3, 3-trifluoropropionyl-TP5. The peptides were characterized by HPLC and ion-spray mass spectroscopy. Irradiation of the peptides with two different ultraviolet sources was carried out in water, n-propanol and water/n-propanol to imitate both hydrophobic and hydrophilic peptide/protein-interactions as well as the influence of the aqueous environment. Analysis of the products with HPLC, ion-spray MS, HPLC-MS and HPLC-CID-MS revealed that (Tmd)Phe is a highly potent carbene-precursor, which can be transformed easily into uniform crosslinking products by smooth photolysis. However, the electrophilic nature of the intermediate causes a high tendency to react with water molecules. The 4-azidobenzoyl group showed comparable crosslinking efficiency, but the probability to create non-uniform irradiation products (e.g. through rearrangement) is higher, whereas the reaction with water is less dominant. In contrast, Bpa was found to have an extremely low affinity to react with water, whereas prolonged UV irradiation is needed to get complete rearrangement into a variety of products. As the absorption band of α-diazocarbonyls at around 350 nm possesses a low extinction coefficient, 2-diazo-3, 3, 3-trifluoropropionyl-TP5 could not be activated at all with the optimized irradiation conditions that we have chosen for our comparative studies. © Munksgaard 1997.     

Neuropeptide Y: identification of the binding site

Based on the hypothetical 3D structure of neuropeptide Y (NPY), NPY 1-4-Aca-25-36, a 17 amino acid analogue, has been synthesized replacing the sequence NPY 5-24 by ε-aminocaproic acid (Aca). This low-molecular weight deletion analogue showed nearly comparable receptor affinity to NPY. In order to elucidate the structural requirements for receptor recognition each amino acid of 1-4-Aca-25-36 was exchanged by its D-enantiomer, glycine and L-alanine. In addition distinct amino acids were replaced by closely related residues. Multiple peptide synthesis was applied using Fmoc-strategy and BOP activation. Binding assay was performed on rabbit kidney membrane preparations. The results of structure affinity studies suggest that the C-terminal tetrapeptide NPY 33-36 is essential for receptor recognition.     

QT Dispersion Does Not Predict Early Ventricular Fibrillation After Acute Myocardial Infarction

Ventricular arrhythmias may be associated with increased QT dispersion (difference between maximum and minimum QT on standard 12-lead ECG). We performed a case control study to determine if QT dispersion on the admission ECG could predict early VF after acute myocardial infarction. The cases were 24 patients with acute myocardial infarction (14 inferior, 8 anterior, and 2 lateral) with VF within 12 hours of admission. There were 24 control patients without VF matched for site of infarction and ST segment score (sum of ST segment elevation). VF occurred a median of 153 minutes (interquartile range 93–245) after onset of chest pain and 33 minutes (range 7–104) after initial ECG. QT (399 ± 37 and 394 ± 37), QT corrected (440 ± 38 and 429 ± 29), and QT dispersion (68± 20 and 66 ± 27) were similar in patients and controls. By design, ST score was similar (11 ± 9 vs 9 ± 5 mV), although a good match could not be obtained for three patients with extreme ST elevation. Patients with VF presented to the hospital earlier after the onset of chest pain (median 95 min [range 65–188] compared to 150 min [range 80–270], P= 0.05) and had a lower serum sodium (138 ± 2.4 vs 140 ± 2.5, P = 0.05) than controls. Thus, QT interval and QT dispersion, measured on the presenting ECG, did not predict early VF after myocardial infarction.     

Comparison Among Different Approaches for Sampling Cerebrospinal Fluid in Rats

Two approaches for time-resolved sampling of cerebrospinal fluid (CSF) in rats were compared regarding performance, reproducibility, and extent of the inevitable trauma caused by the implantation of a sampling tube. Several parameters were checked to evaluate the injury: blood cell contamination of CSF; concentrations in CSF of the cytosolic proteins neuron-specific enolase (NSE) and S-100 (chiefly present in astrocytes); blood-brain barrier leakage of a dye-protein complex; viability of nervous tissue cells as assessed by dye exclusion; light and electron microscopy. In one sampling method, a tube was forced epidurally into the cisterna magna via a hole in the calvarium, consistently damaging the meninges and the nervous tissue. When using the alternative sampling method, the tube was instead affixed to the posterior atlanto-occipital membrane and connected with the cisterna magna via a hole in the membrane. Such a procedure caused negligible damage. Both techniques induced an inflammatory response. We advocate the use of the second approach, i.e., to sample CSF via a hole in the atlanto-occipital membrane, as the method of choice due to its high reproducibility. It is fairly rapid, and associated with a negligible injury. Copyright © 1996 Elsevier Science Inc.     

TRYPTOPHAN METABOLISM IN ALCOHOLISM. TRYPTOPHAN BUT NOT EXCITATORY AMINO ACID AVAILABILITY TO THE BRAIN IS INCREASED BEFORE THE APPEARANCE OF THE ALCOHOL-WITHDRAWAL SYNDROME IN MEN

Tryptophan (Trp) metabolism and disposition and excitatory andother amino acid concentrations were determined in alcohol-dependentsubjects in relation to the alcohol-withdrawal syndrome (AWS).Parameters were examined in 12 alcohol-dependent male subjects,undergoing elective upper digestive tract tumour resection,and 12 age-, gender-, and medication-matched controls on threeoccasions: pre-operatively, post-operatively, and immediatelybefore (i.e. within 24 h of) the appearance of the AWS. No significantdifferences were observed between controls and alcoholic subjectson the first or second of these occasions. On the third occasion,within 24 h of the appearance of the AWS, alcoholics showeda dramatic elevation (117%) in free serum Tip concentrationand a consequent increase (111%) in the ratio of [free Trp]/[competingamino acids], which is an accurate predictor of Trp entry intothe brain. Increases were also observed on this third occasionin concentrations of total Trp (49%), cortisol (123%), and norharman(137%). Concentrations of glutamate, glycine, aspartate, serine,and taurine did not differ significantly within or between thecontrol and alcohol-dependent groups of subjects on any of thethree occasions. The possible significance of the Trp and relatedmetabolic changes in relation to the behavioural features ofthe AWS is discussed.     

Coping Responses of Men Whose Partners Experience Premenstrual Symptomatology

While premenstrual syndrome (PMS) has received much attention from researchers and the media, little has been done to document systematically the effect of premenstrual symptomatology on relationships and family functioning. An exploratory study was conducted of the coping responses of men whose partners reported either high or low levels of premenstrual symptomatology. Men in this study used a wide variety and combination of coping responses. Men actively respond to their partners' premenstrual symptomatologies with a variety of coping strategies, some of which may be amenable to nursing intervention.