bluuebunny/crossref_metadata_2025 huggingface dataset:
EVOLUTION OF THYROID HORMONE DISTRIBUTION
Authors: Schreiber Gerhard , Prapunpoj Porntip , Chang Linus , Richardson Samantha J. , Aldred Angela R. , Munro Sharon L.
Published: June 2007

1. Appropriate distribution of thyroxine between the lipid‐soluble compartments of cells and tissues and the extracellular aqueous space is established by binding to extracellular proteins. Among these proteins, transthyretin is of particular interest because it is the only one synthesized in the brain.

2. The evolutionary onset of transthyretin synthesis in cells of the blood‐brain barrier precedes that in the liver, with the exception of a very short period of transthyretin synthesis in the liver of tadpoles, just prior to the climax of metamorphosis. In adult liver, transthyretin is only synthesized in endothermic vertebrates.

3. The affinity of transthyretin for thyroxine increases and that for 3,5,3′‐triiodothyronine decreases during the evolution of eutherians from reptile/bird‐like common ancestors.

4. A systematic change of the N‐terminal region of transthyretin occurred during evolution, leading to shorter and more hydrophilic transthyretin N termini in eutherians compared with those in reptiles and birds.

5. The molecular mechanism of the evolution of the transthyretin N termini is a stepwise shift of the splice site at the intron 1/exon 2 border in the 3’ direction. The most probable cause for this shift is a series of single base mutations.

6. As the N termini are located on the surface of transthyretin near the entrance to its central channel leading to the thyroxine binding sites, it is possible that a change in the structure of this region could influence the access of thyroxine to the binding sites. The increase in affinity for thyroxine could then be a driving force in the natural selection during evolution of transthyretins with shorter and more hydrophilic N termini.
PARATHYROID HORMONE‐RELATED PROTEIN IN LOWER VERTEBRATES
Authors: Danks JA , Trivett MK , Power DM , Canario AVM , Martin TJ , Ingleton PM
Published: June 2007

1. Parathyroid hormone‐related protein (PTHrP) is an important mediator of humoral hypercalcaemia of malignancy in humans. Normal human subjects have very low levels of PTHrP in their circulation.

2. Parathyroid hormone‐related protein has recently been demonstrated in high levels in the circulation and tissues of the sea bream and the dogfish, leading to the hypothesis that PTHrP may be a ‘classical’ hormone in fish.

3. Immunohistochemistry and in situ hybridization were performed to investigate the evolutionary history of PTHrP. Tissues were examined from a number of lower vertebrates, including lungfish, lamprey and several species of bony and cartilaginous fish. Parathyroid hormone‐related protein was localized to the skin and to kidney tubules in all animals studied. In the developing lungfish, PTHrP was observed in the notochord, developing brain and skeletal muscle layers. These results suggest that PTHrP is of ancient origin and has a basic and fundamental function in vertebrates.
CHAOTIC CHARACTERISTICS OF RENAL NERVE PEAK INTERVAL SEQUENCE IN NORMOTENSIVE AND HYPERTENSIVE RATS
Authors: Zhang Tao , Johns Edward J
Published: June 2007

1. The use of non‐linear dynamic analysis for the measurement of control processes in low‐dimensional signals, for example, blood pressure and heart rate variability, are well established and accepted. However, the application of these analytical techniques to a high‐dimensional signal, such as renal sympathetic nerve activity (RSNA), has not been validated.

2. The present study set out to develop an approach whereby the high‐dimensional signal of RSNA was reduced to a low‐dimensional one by extracting the peak interval sequence (PIS), using Cluster analysis, in order to allow the use of non‐linear dynamics analysis. Brachial nerves were electrically stimulated (1.6 Hz, 0.2 ms, 15 V) to elicit a sympatho‐excitation in groups of anaesthetized normotensive Wistar and stroke‐sprone spontaneously hypertensive rats (SHRSP).

3. It was found that, under basal conditions, the correlation dimension, D2, was stable over a range of embedding dimensions from 12 to 25. Moreover, the largest Lyapunov exponent had a small positive value that was also stable over these embedding dimensions. These values showed that the signal was of low dimensionality and that chaos was present.

4. In Wistar rats, brachial nerve stimulation significantly (P<0.05‐0.001) increased blood pressure (by 25%), heart rate (by 5%) and RSNA (by 200%), which was associated with significant (P<0.05) reductions in the correlation dimension D2 and the largest Lyapunov exponent of the PIS generated from the renal nerve signal. In contrast, in SHRSP, there were similar increases in blood pressure, heart rate and RSNA in response to brachial nerve stimulation, but neither the correlation dimension nor largest Lyapunov exponent was altered.

5. These findings demonstrate that by extracting the PIS from the renal sympathetic nerve signal, the application of non‐linear chaos analysis makes it possible to distinguish differences in the pattern of refiexly induced excitation in sympathetic traffic to the kidney in the pathophysiological state of hypertension. Whether this applies to sympathetic outflow to other organs and tissues remains to be investigated.
OXYGEN RADICALS AND NITRIC OXIDE IN RAT MESENTERIC ISCHAEMIA‐REPERFUSION: MODULATION BY L‐ARGININE AND NG‐NITRO‐L‐ARGININE METHYL ESTER
Authors: Haklar G , Ulukaya‐Durakbaś Ç , Yüksel M , Dagh T , Yalçin AS
Published: June 2007

1. The aims of the present study were to detect changes in superoxide anion (O2−), nitric oxide (NO) and other reactive oxygen species (ROS) directly by measurement of chemilumin‐escence (CL) and to investigate the role of L‐arginine, a nitric oxide synthase (NOS) substrate, and NG‐nitro‐L ‐arginine methyl ester (L‐NAME), a NOS inhibitor, together with their molecular enantiomers D‐arginine and D‐NAME, in a rat mesenteric ischaemia‐reperfusion (I/R) model.

2. Seventy‐nine female Wistar albino rats were divided into eight groups. The first three groups underwent sham operation; group 1 was the control group, group 2 received L‐arginine and group 3 received L‐NAME. Ischaemia was produced in the remaining five groups by ligation of the superior mesenteric artery for 30 min followed by 60 min reperfusion. Group 4 rats were control I/R rats and groups 5‐8 received either L‐arginine, L‐NAME, D‐arginine or D‐NAME, respectively.

3. Both luminol and lucigenin CL was significantly increased in I/R groups compared with sham‐operated groups. L‐Arginine significantly reduced CL measurements. D‐Arginine was also protective, but not as much as L‐arginine. Both L ‐ and D‐arginine had in vitro O2−‐scavenging potential, as tested by the xanthine‐xanthine oxidase system. NG‐Nitro‐L‐arginine methyl ester decreased lipid peroxidation values in addition to reducing CL measurements. Nitric oxide concentrations were significantly increased in I/R groups in comparison with sham‐operated groups. Peroxynitrite formation was increased by I/R. Treatment with L‐NAME was beneficial by reducing NO concentrations in the reperfused ileum.

4. In our I/R model, O2−, NO and other ROS were increased. Although NOS inhibitors were effective in reducing oxidative damage, increasing NO concentrations with L‐arginine was also beneficial, presumably due to the ability of L‐arginine to inhibit phagocyte adherence and its radical scavenging potential. In fact, NO may have different effects in terms of tissue injury or protection depending on the concentration of oxygen and the haemodynamic state of the tissue.
TEMPERATURE‐DEPENDENT INOTROPIC EFFECTS OF LIGNOCAINE AND ETHANOL ON RAT HEART PAPILLARY MUSCLES
Authors: Schulz Carlos S , Salvatici Raul P , Standen Dolly J , Cabezas Mirtha E , Carpentier Robert G
Published: June 2007

1. The main objective of the present study was to investigate the temperature dependence of the cardiac inotropic effects of lignocaine and ethanol (EtOH).

2. We studied the in vitro inotropic actions and interactions of EtOH (2.4 g/L) and lignocaine (25 mg/L) on rat papillary muscles superfused with Tyrode's solution and stimulated at 1 Hz at either 37 or 30°C. Peak tension developed (PTD), maximum velocity of development of tension (VmaxT) and time to peak tension (TPT) were measured.

3. At 37°C, EtOH depressed PTD, while VmaxT and TPT remained unchanged. At 37°C, lignocaine alone or in combination with EtOH depressed all three parameters.

4. At 30°C, EtOH did not modify PTD or VmaxT, whereas TPT decreased. At 30°C, lignocaine decreased TPT, but VmaxT did not change and the effect of lignocaine on PTD was smaller at 30°C than at 37°C. Ethanol and lignocaine in combination decreased all three parameters at 30°C. However, the depression of VmaxT by the combination of lignocaine and EtOH was less at 30°C than at 37°C.

5. Hypothermia (30°C) protected the myocardium against the depressant actions of EtOH and lignocaine, alone or in combination. With EtOH alone, the protection resulted in no change in PTD. When lignocaine was involved, the protection resulted in a weaker action on PTD and VmaxT. The temperature dependence of the action of lignocaine may explain, at least in part, the development of ventricular failure in cardiac surgical patients exposed to lignocaine during hypothermia and rewarming.
EFFECT OF GRAPEFRUIT JUICE ON URINARY 6β‐HYDROXYCORTISOL/CORTISOL EXCRETION
Authors: Seidegård Janeric , Dahlström Kerstin , Kullberg Annika
Published: June 2007

1. The aim of the present study was to evaluate the effect of grapefruit juice on urinary 6β‐hydroxycortisol and Cortisol excretion in healthy subjects.

2. The ratio of 6β‐hydroxycortisol/cortisol was significantly decreased (P= 0.036) in the 0–4 h fraction of urine after ingestion of grapefruit juice, but not in the 4–24 h fraction (P= 0.218) or for the compiled data, fraction 0–24 h (P= 0.114).

3. These results indicate that endogenous Cortisol metabolism may not only be of hepatic origin, but may also be dependent on the metabolic capacity of cytochrome P450IIIA (CYP3A) in the gut mucosa.

4. This finding may cast further doubts of the usefulness of the 6β‐hydroxycortisol/cortisol ratio as an indicator of hepatic CYP3A activity.
Estimates of economic burden of providing inpatient care in childhood rotavirus gastroenteritis from Malaysia
Authors: Lee Way Seah , Poo Muhammad Izzuddin , Nagaraj Shyamala
Published: June 2007

Aim:  To estimate the cost of an episode of inpatient care and the economic burden of hospitalisation for childhood rotavirus gastroenteritis (GE) in Malaysia.

Methods:  A 12‐month prospective, hospital‐based study on children less than 14 years of age with rotavirus GE, admitted to University of Malaya Medical Centre, Kuala Lumpur, was conducted in 2002. Data on human resource expenditure, costs of investigations, treatment and consumables were collected. Published estimates on rotavirus disease incidence in Malaysia were searched. Economic burden of hospital care for rotavirus GE in Malaysia was estimated by multiplying the cost of each episode of hospital admission for rotavirus GE with national rotavirus incidence in Malaysia.

Results:  In 2002, the per capita health expenditure by Malaysian Government was US$71.47. Rotavirus was positive in 85 (22%) of the 393 patients with acute GE admitted during the study period. The median cost of providing inpatient care for an episode of rotavirus GE was US$211.91 (range US$68.50–880.60). The estimated average cases of children hospitalised for rotavirus GE in Malaysia (1999–2000) was 8571 annually. The financial burden of providing inpatient care for rotavirus GE in Malaysian children was estimated to be US$1.8 million (range US$0.6 million−7.5 million) annually.

Conclusion:  The cost of providing inpatient care for childhood rotavirus GE in Malaysia was estimated to be US$1.8 million annually. The financial burden of rotavirus disease would be higher if cost of outpatient visits, non‐medical and societal costs are included.
COMPARISON OF INFECTION RATE USING DIFFERENT METHODS OF ASSESSMENT FOR SURVEILLANCE OF TOTAL HIP REPLACEMENT SURGICAL SITE INFECTIONS
Authors: Chiew Yoke‐Fong , Theis Jean‐Claude
Published: June 2007

Background:  The surveillance of surgical site infections (SSI) has been undertaken in many centres worldwide to ascertain the extent of the problem and where possible, to improve the incidence rates, thereby decreasing the undesirable outcomes. The study investigates the processes and outcomes of total hip replacement SSI surveillance carried out in Dunedin Public Hospital in 2004.

Methods:  Two hundred and six patients were enlisted in the study and 189 primary replacements and 22 revision replacements were carried out. Four methods of diagnosis of SSI were applied: (i) clinician diagnosis; (ii) ASEPSIS score; (iii) presence of pus cells; and (iv) assessment by a clinical microbiologist. Infection rates were calculated according to the risk indexes.

Results:  The incidence of infections varies considerably among these four methods. The infection rates for risk index 0 were 4.35% (method 1), 2.61% (method 2), 0.87% (methods 3 and 4); and for risk indexes 1 and 2 were 4.17% (method 1), 2.08% (method 2), 1.04% (methods 3 and 4).

Conclusion:  There is a need for accurate infection data so that the appropriate follow‐up responses, including infection control measures for total hip replacement SSI can be carried out. The preponderance of elderly patients in the study who are frequently on ‘polypharmacy’ regimens adds pressure to the need to obtain true infection rates. This is because when antimicrobials are prescribed to them, drug interactions, adverse effects of the antimicrobials and the selective pressure of antimicrobials causing resistances may occur. More resources and a multidisciplinary approach are required for future studies of similar nature.
Modelling linguistic taxonomic dynamics
Authors: Wichmann Søren , Stauer Dietrich , Lima F. Wellington S. , Schulze Christian
Published: June 2007

This paper presents the results of the application of a bit‐string model of languages (Schulze & Stauffer 2005) to problems of taxonomic patterns. The questions addressed include the following: (1) Which parameters are minimally needed for the development of a taxonomic dynamics leading to the type of distribution of language family sizes currently attested (as measured in the number of languages per family), which appears to be a power‐law? (2) How may such a model be coupled with one of the dynamics of speaker populations leading to the type of language size seen today, which appears to follow a log‐normal distribution?
The present tense with future meaning in the accusative and infinitive construction in Plautus and Terence
Authors: De Melo Wolfgang David Cirilo
Published: June 2007

In the accusative and infinitive construction in Archaic Latin, both present and future tense infinitives can be found if there is future meaning; semantic differences cannot be detected. Various scholars have tried to show that the present infinitive is colloquial here or that the alternation between the two tenses has to do with semantic differences in the governing verbs. However, on closer examination of the data such theories cannot be upheld. In this paper, I shall demonstrate that the present infinitive is restricted to telic events. Moreover, it is particularly frequent if the subjects of the superordinate and subordinate verbs are identical. The present infinitive of the verb ‘to give’ occurs more often than present infinitives of other verbs. Finally, we can observe how such present infinitives become less frequent if we compare Plautus and Terence.1
Constituent question formation and focus: a new typological perspective
Authors: Mycock Louise
Published: June 2007

All languages have strategies which enable speakers to ask constituent (‘wh’‐) questions. Of the strategies available, three types based on the notion of movement are usually cited in the literature: in situ, multiple fronting, and simple fronting. However, data reveal that focusing is the defining characteristic of constituent question formation cross‐linguistically. This paper therefore adopts a different approach, presenting a unified analysis within the non‐derivational framework of Lexical‐Functional Grammar which captures the relevant generalisations about focusing and in turn provides a fresh perspective on the typology of constituent question formation strategies.1
“EDGE” OR “EDGELESS” CITIES? URBAN SPATIAL STRUCTURE IN U.S. METROPOLITAN AREAS, 1980 TO 2000*
Authors: Lee Bumsoo
Published: June 2007

ABSTRACT This paper presents a descriptive analysis of spatial trends in six U.S. metropolitan areas. The results show that generalized job dispersion was a more common spatial process than subcentering during the 1980s and 1990s when jobs continued to decentralize from the metropolitan core to the suburbs. Three distinctive patterns of spatial development were found. Job dispersion was predominant in Portland and Philadelphia, whereas the polycentricity of Los Angeles and San Francisco was further reinforced. New York and Boston with large and long‐established CBDs were less prone to decentralization. Each metro seems to have developed a unique pattern of decentralization in light of their histories and circumstances, which has limited the growth of commuting times.
FIRE IN THE BRAZILIAN AMAZON: A SPATIALLY EXPLICIT MODEL FOR POLICY IMPACT ANALYSIS*
Authors: Arima Eugenio Y. , Simmons Cynthia S. , Walker Robert T. , Cochrane Mark A.
Published: June 2007

ABSTRACT This article implements a spatially explicit model to estimate the probability of forest and agricultural fires in the Brazilian Amazon. We innovate by using variables that reflect farm‐gate prices of beef and soy, and also provide a conceptual model of field management and deforestation fires to simulate the impact of road‐paving, cattle exports, and conservation area designation on the occurrence of fire. Our analysis shows that fire is positively correlated with the price of beef and soy, and that the creation of new conservation units may offset the negative environmental impacts caused by the increasing number of fire events associated with early stages of frontier development.
Citizenship through education. A comment on Social exclusion in Europe: some conceptual issues
Authors: Wagner Antonin
Published: June 2007

This contribution deals with the integrative model underpinning contemporary European social policy. It was conceived as a comment on the article by O’Brian and Penna, addressing the same topic and published in this issue of IJSW. The author looks at processes of social inclusion/exclusion through the lens of political theory and the notion of citizenship, which is at its core. Based on this approach, the comment provides a perspective that in many respects is complementary to the conceptual analysis presented by O’Brian and Penna in their article.
The invasive red swamp crayfish as a predictor of Eurasian bittern density in the Camargue, France
Authors: Poulin B. , Lefebvre G. , Crivelli A. J.
Published: June 2007

Few data exist on the relationships between food levels and breeding density of the Eurasian bittern Botaurus stellaris, a vulnerable species of high‐priority concern in Europe. Concurrent data were obtained on male bittern density and relative food abundance over a 3‐year period in two wetlands totalling 2500 ha of Mediterranean reed marsh enclosing 25% of the French bittern population. Food abundance was estimated by sampling up to 25 hydrological units using a beach seine in early June of 2002, 2003 and 2004. The density of booming males in each hydrological unit was obtained by point counts and acoustic triangulation in May of the same years. The impact of food abundance on male bittern density was assessed by general regression models using a forward stepwise procedure with mosquitofish Gambusia affinis, carp Cyprinus carpio, other fish species, amphibians, red swamp crayfish Procambarus clarkii and other invertebrates as prey groups. Of these, only to crayfish abundance was bittern density related, contributing to 45% of the variance observed. When the impact of water level was taken into account, the relative abundance of crayfish explained 56% of the inter‐annual differences in bittern density. Because crayfish are rich in calcium and well adapted to fluctuating hydroperiods alternating with drought intervals, they provide a good food source for the bitterns throughout the breeding season at the study sites. The loss of diversity and degradation reported from macrophyte‐dominated marshes following crayfish invasion does not seem to apply to reed‐dominated wetlands. It is further suggested that the recent increase in bittern numbers in the Camargue, while other French populations were decreasing, could in part be related to red swamp crayfish abundance.
Strategy‐switching in the gaffing bat
Authors: Todd V. L. G. , Waters D. A.
Published: June 2007

Foraging in Daubenton's bats Myotis daubentonii, at two altitudinal locations along a river gradient in North Wales was investigated in relation to aerial insect density and to the density of prey on the water surface. Prey capture in Daubenton's bats consisted of aerial hawking, where prey was taken in the air, and trawling, where bats gaffed invertebrates from the water surface. Aerial hawking accounted for 86% of all prey capture attempts, despite aerial insect availability falling close to zero for much of the night. Conversely, prey density on the water surface was an order of magnitude higher than aerial prey density and increased through the night due to aquatic invertebrate drift. At the higher altitude site, M. daubentonii switched prey capture strategy to gaffing, possibly to reflect this change in prey availability on the water's surface, but at the lower altitude site, they maintained aerial hawking as the preferred strategy. The switch to gaffing may be inhibited by the significant downstream accumulation of large numbers of inedible exuviae of caddis flies, Trichoptera, at the low‐altitude site, which form both acoustic clutter and increase the probability of capturing inedible prey, making foraging less efficient. These small altitudinal differences in foraging strategy should be factored into the design of future altitudinal bat foraging studies and if found to be a widespread strategy, taken into consideration by conservation planners when reviewing the habitat requirements of Daubenton's bats in river valleys within the United Kingdom.
Commentary: Cabanna M et al. (1999). Why don’t physicians follow clinical practice guidelines? A framework for improvement
Authors: Scholes Julie
Published: June 2007

Despite wide promulgation, clinical practice guidelines have had limited effect on changing physician behaviour. Little is known about the process and factors involved in changing physician practices in response to guidelines. The aim is to review barriers to physician adherence to clinical practice guidelines. We searched the MEDLINE, Educational Resources Information Center and Health STAR databases (January 1966 to January 1998), bibliographies; textbooks on health behaviour or public health and references supplied by experts to find English language article titles that describe barriers to guideline adherence. Of 5658 articles initially identified, we selected 76 published studies describing at least one barrier to adherence to clinical practice guidelines, practice parameters, clinical policies or national consensus statements. One investigator screened titles to identify candidate articles, then two investigators independently reviewed the texts to exclude articles that did not match the criteria. Differences were resolved by consensus with a third investigator. Two investigators organized barriers to adherence into a framework according to their effect on physician knowledge, attitudes or behaviour. This organization was validated by three additional investigators. The 76 articles included 120 different surveys investigating 293 potential barriers to physician guideline adherence, including awareness (n = 46), familiarity (n = 31), agreement (n = 33), self‐efficacy (n = 19), outcome expectancy (n = 8), ability to overcome the inertia of previous practice (n = 14), and absence of external barriers to perform recommendations (n = 34). The majority of surveys [70 (58%) of 120] examined only one type of barrier. Studies on improving physician guideline adherence may not be generalizable because barriers in one setting may not be present in another. Our review offers a differential diagnosis for why physicians do not follow practice guidelines, as well as a rational approach towards improving guideline adherence and a framework for future research.

Abstract reprinted from the Journal of the American Medical Association volume 282, Cabanna M et al., ‘Why don’t physicians follow clinical practice guidelines? A framework for improvement.’, pages 1458–1465. © 1999, reproduced with permission from the American Medical Association.
Noise levels in a general intensive care unit: a descriptive study
Authors: Christensen Martin
Published: June 2007

The aim of this small‐scale study was to measure, analyse and compare levels of acoustic noise, in a nine‐bedded general intensive care unit (ICU). Measurements were undertaken using the Norsonic 116 sound level meter recording noise levels in the internationally agreed ‘A’ weighted scale. Noise level data were obtained and recorded at 5 min over 3 consecutive days. Results of noise level analysis indicated that mean noise levels within this clinical area was 56·42 dB(A), with acute spikes reaching 80 dB(A). The quietest noise level attained was that of 50 dB(A) during sporadic intervals throughout the 24‐h period. Parametric testing using analysis of variance found a positive relationship (p≤ 0·001) between the nursing shifts and the day of the week. However, Scheffe multiple range testing showed significant differences between the morning shift, and the afternoon and night shifts combined (p≤ 0·05). There was no statistical difference between the afternoon and night shifts (p≥ 0·05). While the results of this study may seem self‐evident in many respects, what it has highlighted is that the problem of excessive noise exposure within the ICU continues to go unabated. More concerning is that the prolonged effects of excessive noise exposure on patients and staff alike can have deleterious effect on the health and well‐being of these individuals.
Cocaine‐induced myocardial infarction
Authors: Coombs Maureen
Published: June 2007

To date, cocaine‐induced myocardial infarction (MI) remains an infrequent reason for admission into hospital. However, reports identify rising cocaine usage in the UK. With 7–10% of all patients presenting chest pain having traces of cocaine in their urine, there is an increasing incidence of cardiovascular disease in the under 30s age group. The potential impact on health care resources must cause concern. This report describes the case of a young man admitted to the emergency department after an 18‐h cocaine session. With evidence of an anterolateral MI, left heart studies and thrombectomy were undertaken in cardiac catheters. Admission to critical care was required for ongoing respiratory and cardiac support therapies. Although there are many aspects of patient management that can be explored, specific issues to be discussed in this paper include evidence‐based treatment options, nursing management of inotrope administration and caring for family and friends.
The Prevalence of Type A Personality in the Children of Alcoholics
Authors: Manning D. Thompson , Balson Paul M. , Xenakis Stephen
Published: June 2007

Three studies are reported which investigate the prevalency of an excess risk of type A personality in the children of alcoholics (COAs). Reports in the clinical literature suggest there is an excess risk of type A in COAs, but this has never been empirically demonstrated. The Matthews Youth Test for Health (MYTH) was administered to nonalcoholic mothers of 46 COAs and 65 matched controls to measure children's type A competitiveness and impatience‐aggression. Results were significant only for greater impatience‐aggression in COAs. In a second study, 104 COAs and controls matched for age, sex, race, and father's occupational status were rated by military fathers of intact families using MYTH. The results of the first study were not repUcated for COAs, and there was no correlation between a father's Jenkins Activity Scale (JAS) score and his chil's type A personality. A third study of 70 matched COAs and controls used the Hunter‐Wolf A‐B Rating scale, a self‐rating scale for children and found no significant differences in children's type A personalities based on membership in an alcoholic family, sex, or birth order. It was concluded that the discrepancy between dmical reports and the present data may have been due to misperceptions about successful, hardworking COAs who, particularly in contrast to their more notorious siblings, may be viewed as “workaholics” and improperly labeled as type A personalities.
Use of Nuclear Magnetic Resonance Spectroscopy to Study the Effects of Ethanol Consumption on Liver Metabolism and Pathology
Authors: Cunningham Carol C.
Published: June 2007

The application of NMR spectroscopy to studies of intact organs represents a powerful technology applicable for investigations of alcohol‐induced liver disease in animal models. NMR‐assisted studies of ethanol metabolism and its related pathology are now possible utilizing the 13C and 31P nuclei primarily. The major advantage of the technology includes the capacity to investigate biochemical processes at the level of the intact organ which is analyzed as a perfused preparation or in situ in an anesthetized animal model. Quantitative measurements of compounds containing either 31P or 13C nuclei are possible, and the kinetics of precursor incorporation into compounds associated with carbohydrate, lipid, and amino acid metabolism are readily followed. The concentrations of free Mg2+ and the pH of the intact liver can be monitored as a function of external perturbation and/or metabolic disturbances.
Effects of 6‐Hydroxydopamine on Brain Catecholamines and on Acute Actions of Ethanol in LS/Ibg and SS/Ibg Mice
Authors: Erwin V. Gene , Cornell K.
Published: June 2007

LS/Ibg (LS) and SS/Ibg (SS) mice differ in ethanoHnduced duration of loss of righting response or sleep time, hypothermia, hyperglycemia, and blood ethanol concentrations at regaining righting response. These differences in response to ethanol are a result of differences in central nervous system sensitivity and are mediated by polygenic systems. Studies have indicated that catecholaminergic systems may be involved in the differential effects of ethanol in LS and SS lines of mice (Masserano JM, Werner N: Investigations into the neurochemical mechanisms mediating differences in ethanol sensitivity in two lines of mice. J Pharmacol Exp Ther 221:404–408, 1982). In this study the neurotoxin, 6‐hydroxydopamine (6‐OHDA), intracerebroventricular, was used to test this hypothesis. Administration of 6‐OHDA markedly altered thermoregulation in LS mice but produced little effect in SS mice, and ethanoHnduced hyperglycemia was attenuated in both LS and SS mice by 6‐OHDA. EthanoHnduced sleep time was increased in SS mice pretreated with 100 μg of 6‐OHDA, intracerebroventricular, whereas this response in LS mice was unaffected by 6‐OHDA administration. Changes in sleep time were not related to changes in blood ethanol concentrations, indicating that 6‐OHDA alters ethanoHnduced sleep time by mechanisms other than brain sensitivity. Levels of norepinephrine and dopamine were determined in three brain regions, and the altered capacities for thermoregulation and glucoregulation were associated with changes in hypothalamic catecholamine levels.
Relationship between Serum Cortisol, Liver Function, and Depression in Detoxified Alcoholics
Authors: Zem Mark A. , Halbreich Uriel , Bacon Kathleen , Galanter Marc , Kang Byong‐Jo , Gasparini Frank
Published: June 2007

High levels of serum Cortisol or abnormal dexamethasone suppression tests may be helpful in diagnosing major depressive disorder. However, a controversy exists as to whether abnormal Hver function associated with alcohol abuse may negate the diagnostic value of the dexamethasone suppression test in alcoholics. We investigated the value of the dexamethasone suppression test in alcoholics by analyzing the Kver function, Cortisol levels, and psychiatric status of inpatients from an alcohol detoxification treatment center. The subjects met the DSM III criteria for alcohol dependence but took no chronic medication and had negative screening for substance abuse. They had routine blood screening to evaluate liver function, the afternoon Cortisol test and dexamethasone suppression test to study glucocorticoid activity, and a structured evaluation to determine psychiatric diagnoses. The blood chemistry findings demonstrated a lack of significant fiver synthetic dysfunction in this group, although 43% of the subjects had some elevation of their liver enzymes. We did not find differences in the liver function between patients with normal and abnormal Cortisol levels. However, subjects with endogenous depression did have significantly elevated afternoon Cortisol levels, and they tended to have more normal liver tests. These results indicate that modest liver dysfunction does not contaminate the validity of the plasma Cortisol tests or the dexamethasone suppression test as diagnostic tools for assessing depression in this group of detoxified alcoholics. In addition, they demonstrate an association between depression and plasma Cortisol levels and suggest a correlation between depression and better liver function in alcoholics who seek detoxification.
Identification and Selective Precipitation of Human Aldehyde Dehydrogenase Isozymes Using Antibodies Raised to Horse Liver Aldehyde Dehydrogenase Isozymes
Authors: McMichael Margaret , Hellström‐Lindahl Ewa , Weiner Henry
Published: June 2007

Aldehyde dehydrogenase (ALDH) enzymes from human liver homogenates were recognized in immunoblotting experiments and precipitated in Ouchterlony double diffusion gels by antibodies raised to the horse liver mitochondrial and cvtosolic ALDH isozymes. The antibody raised to the cytosoRc horse liver ALDH (αHC) has been shown to be specific for cytosolic ALDH isozymes, while the antibody raised to the horse liver mitochondrial ALDH (αHM) precipitated both mitochondrial and cytosolic ALDH isozymes. It was possible to selectively remove the cytosolic ALDH from a homogenate of a liver sample from α Caucasian by preincubation with αHC; the remaining mitochondrial enzyme was then precipitated by aHM in double diffusion gels. The experiments were repeated with a liver sample from an Oriental, presumed to have been alcohol sensitive since no active mitochondrial ALDH was found. The precipitation of a relatively inactive mitochondrial enzyme by αHM from a cytosolic ALDH‐free sample confirmed previous reports of the existence of a mitochondrial ALDH in tissue from an alcohol‐sensitive Oriental. The results of immunoblotting experiments confirm the co‐migration, in electrophoresis, of the cytosolic and mitochondrial ALDHs from the liver of an alcohol‐sensitive Oriental. The results reported here, together with previous observations, indicate that the antibodies raised to horse liver ALDH isozymes can be used to determine the subcellular location of ALDH isozymes in various human tissues, including frozen tissue samples which are not amenable to subcellular fractionation.
Use of Regression Residuals to Quantify Individual Differences in Acute Sensitivity and Tolerance to Alcohol
Authors: Naqoshi Craw T. , Wilson James R. , Ptomin Robert
Published: June 2007

Due to the problem of correlation of errors inherent in the difference or ratio scores typically used to quantify individual differences in acute sensitivity and tolerance to alcohol, it is recommended that residual scores from regression analyses be used instead for such quantification. Conceptualizations of acute sensitivity and tolerance and problems with the reliability of change scores are also discussed.
Identification of Alcohol Abuse and Alcoholism with Biological Parameters
Authors: Watson Ronald R. , Mohs Mary E. , Eskelson Cteamond , Samptiner Richard E. , Hartmann Barbara
Published: June 2007

The prevalence and incidence of heavy alcohol consumption are major problems which have been increasing in many countries in recent years. It is crucial for physicians to consistently identify early drinking problems as well as the various end disease states in order to minimize suffering and maximize recovery. This paper reviews the evolutionary development of clinical tools for detection of alcohol abuse. The focus is primarily on dmical/biochemical indicators of alcohol abuse, emphasizing but not limited to changes in hematological characteristics, Hver enzyme activity, lipids, immune function factors, hormones, neurological factors, and some physicaty based tests. Use of test combinations and sophisticated statistical analysis of pattern changes in test batteries evidence increased diagnostic efficiency.
Regression of Severe Alcoholic Cardiomyopathy after Abstinence of 10 Weeks
Authors: Agatston Arthur S. , Snow Matthew E. , Samet Philip
Published: June 2007

Alcohofc cardiomyopathy usuaRy has a poor prognosis, but the case i presented here documents a dramatic regression of left ventricular i dysfunction in a patient with alcoholic cardiomyopathy. Ejection fraction determined by echocardiography increased from 12% at the time of presentation to 45% 10 weeks later. This was associated I with clinical resolution of conjestive heart failure and a decrease in i cardiac and left ventricular size documented by chest x‐ray and
Binding, Uptake, and Metabolism of Chylomicron Remnants by Hepatocytes from Control and Chronic Ethanol‐Fed Rats
Authors: Lakshmanan M. R. , Ezekiel Mildred , Campbell Barbara S. , Muesing Richard A.
Published: June 2007

Chylomicron remnants, but not lymph chylomicrons, showed a receptor‐dependent high affinity saturable binding to normal rat hepatocytes. The Scatchard analysis of the specific binding data showed a high affinity binding site for the remnants with a dissociation constant of 0.61 nut, assuming a molecular weight of 50 times 10s for chylomicron remnants. Based on the heparin‐releasable bound radioactivity, approximately 80% of the bound remnants seemed to be internalized. The binding process was markedly inhibited by pronase as wen as by protein synthesis inhibitors. Competitive binding studies revealed that the order of competition for the binding of labeled remnants by homologous unlabeled lipoproteins was remnants > chylomicrons > very low density lipoproteins > high density lipoproteins. Human low density lipoproteins showed virtually no competition.

Studies on the catabolism of triacylglycerol moiety of the remnants showed that 15.2% of the 14C label in the triacylglycerol moiety of the remnants was catabolized by the hepatocytes to 14CO2 due to specific interaction. This amounted to 93% of the total 14CO2 evolution. This was in sharp contrast to the catabolism of the triacylglycerol moiety of very low density lipoproteins from human and rat, where most of the 14CO2 evolution was due to pathways associated with nonspecific binding.

Chronic ethanol feeding caused a 29% (p < 0.02) decrease in the dissociation constant of the high affinity binding site of the liver cell for the remnants, whereas the extent of internalization was decreased by 19% (p < 0.01) as compared to the pair‐fed control animals. In contrast to these small decreases in binding affinity and internalization, the catabolism of both triacylglycerol and cholesterol ester moieties of remnants were markedly inhibited by 58% (p < 0.001) and 44% (p < 0.01), respectively, in hepatocytes from chronic ethanol‐fed animals. These results are compatible with the pathogenesis of fatty liver and defective regulation of hepatic cholesterol synthesis after chronic ethanol abuse.
The Effect of Chronic Ethanol Consumption on Salivary Gland Morphology and Function in the Rat
Authors: Maier H. , Bom I. A. , Veith S. , Adler D. , Seitz H. K.
Published: June 2007

Chronic ethanol consumption in rats resulted in a striking fat accumulation in the acinar cells of the parotid gland demonstrated by light microscopy. In addition, a significant decrease in parotid wet weight (p > 0.02) and in protein content of the gland (p > 0.02) was observed following alcohol feeding. Wet weight, protein content, and morphology of the submaxillar gland were not affected by ethanol feeding. Alcohol metabolism, similar to that found in the pancreas, via a cytosolic alcohol dehydrogenase could be demonstrated in both the parotid and the submaxillar gland. However, the activity of this enzyme was not affected by chronic ethanol ingestion. Subsequently, chronic ethanol consumption significantly decreased salivary flow rate stimulated by pilocarpine hydrochloride (p > 0.02), salivary a‐amylase activity (p > 0.02), and salivary sodium concentration (p > 0.01), whereas potassium concentration of the saliva was increased (p > 0.05). In contrast salivary total protein concentration was not affected by alcohol ingestion. The changes of salivary electrolyte composition observed after chronic ethanol feeding could be due to an altered aldosterone metabolism or to a change in aldosterone receptors of the parotid gland caused by ethanol administration. The reduced salivary flow could play a role in the pathogenesis of oropharyngeal cancer in the alcoholic.
Characterization of an Automated Apparatus for Precise Control of Inhalation Chamber Ethanol Vapor and Blood Ethanol Concentrations
Authors: Karanian John , Yergey James , Lister Richard , 'Souza Nympha , Linnoila Markku , Salem Norman
Published: June 2007

Inhalation chambers with a monitoring and control apparatus for ethanol vapor exposure of small animals were constructed. A thermal conductivity detector was employed for continuous measurement of inhalation chamber ethanol vapor concentration. The concentration was maintained within a very narrow range (± 1 mg/IHer) by incorporating into the design a feedback loop which controls the ethanol pump. As expected, the blood ethanol concentrations (BEC) of male Sprague‐Dawley rats were positively and linearly correlated to the chamber ethanol concentration. When rats were exposed for 24 hr to a chamber ethanol concentration of 17, 25, or 32 mg/lrter, correspondingly low, moderate, or high mean blood ethanol levels were obtained. When a large population of this strain of rats (n= 121) was exposed to a constant ethanol vapor concentration for 14 days (25 mg/lrter) considerable interindividual variation in blood levels occurred. There was also individual variation over time in the BEC of animals monitored. The mean ± so BEC was 189 ± 90 mg/100 ml for this population and a gaussian‐like distribution was obtained with regard to BEC. Behavior characteristic of alcohol withdrawal was observed In rats with BEC > 120 mg/100 ml after 3.5, 7, or 14 days of exposure. This apparatus and inhalation paradigm make possible (1) the precise control of chamber ethanol concentration which markedly enhances control over both intra‐ and intersubject fluctuation in blood ethanol levels during alcohol exposure and (2) the comprehensive examination of relationships between a wide range of blood ethanol concentrations and their physiological and biochemical effects.
Voluntary Ethanol Consumption in Rats: An Examination of Blood/Brain Ethanol Levels and Behavior
Authors: Gill K. , France C. , Amit Z.
Published: June 2007

The temporal pattern of food, water, and ethanol consumption was examined in rats maintained on a 24‐hr ethanol access schedule. These data demonstrated that rats consume ethanol in discrete, short bouts mainly during the lights‐out cycle. Simulation of a single ethanol drinking bout was carried out by limiting ethanol access to a short time period each day. Detectable levels of blood and brain ethanol were observed following these individual drinking bouts. Behavioral evidence is provided indicating that rats drink ethanol in quantities sufficient to produce pharmacological effects.
Effects of Chronic Ethanol Treatment on Neocortex
Authors: Ruttedge Lester T. , Sutter Mark A. , Chi Shu‐lng , Gray Todd A.
Published: June 2007

Neocortical inhibition and neuronal morphology were studied in rats following chronic ethanol treatment (CET). In terminal acute experiments, spontaneous neuronal discharges in pair‐fed and naive rats were inhibited by epieortical stimulation, a procedure known to produce postsynaptic inhibition. Few units in CET rats were inhibited by such stimulation. Cortical recurrent inhibition, indicated by a surface‐negative potential in response to antidromic stimulation of the cerebral peduncle, was little affected by a challenge dose of ethanol, compared with the response in pair‐fed animals. Recurrent inhibition involves inhibitory intemeurons. CET apparently made inhibitory intemeurons and inhibitory postsynaptic receptors less responsive to ethanol. Apical dendritic spines on some portions of pyramidal neurons increased in number with CET. This could reflect a compensatory growth in neurons not damaged by CET. The overall observations are consistent with ethanol affecting one or more specific systems of cortical motor control as opposed to its presumed general disinhibitory effect.
Degradation of Acetaldehyde Produced by the Nonalcohol Dehydrogenase Pathway
Authors: Yasuhara Minoru , Matsuda Yoshiro , Takada Akira
Published: June 2007

Acetaldehyde (Ac‐CHO) is produced via the oxidation of ethanol by two different pathways; alcohol dehydrogenase (AOH) and non‐ADH systems. However, degradation of Ac‐CHO in the liver, especially with respect to the relative amounts produced by the two pathways, remains unclear. In order to clarify the metabolic fates of Ac‐CHO produced by the two pathways, the ethanol metabHc rate (EMR) and hepatic Ac‐CHO levels in the rats fed an alcohol‐containing or control diet for 4 weeks were determined after a single administration or constant infusion of ethanol, with or without 4‐methytpyrazole pre‐treatment The EMR was increased in chronic alcoholic rats and decreased by treatment with 4‐methylpyrazole. Consequently, blood and hepatic Ac‐CHO levels were low in the pyrazole‐treated rats in both the single dose and infusion experiments. Hepatic Ac‐CHO levels and EMR were well correlated in both experiments. However, the correlations were curve linear and the slopes of the regression lines in the pyrazole‐treated rats were steeper than those in the nontreated rats. When the ratios of hepatic Ac‐CHO (subtracted by a constant which was obtained from the correlation equations for the curvilinear fit of hepatic Ac‐CHO levels and EMR) to EMR were calculated, they were significantly higher in the pyrazole‐treated rats than in the nontreated rats of the perfusion experiment, without relation to chronic alcohol ingestion. These results suggest that Ac‐CHO produced by the non‐ADH pathway degrades more slowly than that produced by the ADH pathway in the liver.
Similarities and Differences in Acute Cardiovascular Responses to Alcohol among Normal Men of European, Japanese, and Chinese Ancestry: A Univariate and Multivariate Analysis
Authors: Reed T. Edward , Hanna Joel M.
Published: June 2007

Normal young adutt males residing in Hawaii (46 of European ancestry, 30 Japanese, 27 Chinese) were tested for changes in heart rate and Wood pressure following a dose of 0.59 g of ethanoi/kg. The two Oriental groups did not differ in mean changes but, when pooled, differed from Europeans, having increased heart rate and decreased blood pressure. Within‐race analyses showed that, contrary to the literature, all three groups have great interindtvidual differences in cardiovascular responses. In addition, the three races show a basically similar multivariate response: blood pressure more variable than heart rate and Mood pressure changes uncorrected with heart rate changes.