bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of glycaemic control in indigent patients presenting with diabetic ketoacidosis
Authors: Maldonado M. , D'Amico S. , Otiniano M. , Balasubramanyam A. , Rodriguez L. , Cuevas E.
Published: April 2005

Aim:  To derive predictors of good glycaemic control in patients presenting with diabetic ketoacidosis (DKA) followed prospectively in a specialized clinic.

Methods:  One hundred and sixty‐one adult patients were admitted during a 31‐month period and followed for at least 12 months. After 1 year, the patients were classified into three groups: good control (GC) (HbA1c ≤ 7%), intermediate control (IC) (HbA1c 7–9%) and poor control (PC) (HbA1c > 9%). Characteristics of patients in the three groups were compared both at baseline and during follow‐up.

Results:  At 12 months, 36% of the patients were classified as GC, 27% as IC and 37% as PC. GC patients had higher fasting serum C‐peptide levels 0.7 ± 0.54 compared to 0.38 ± 0.29 and 0.16 ± 0.21 nmol/l, respectively, for the IC and PC patients (p < 0.0001). A higher proportion GC patient had a C‐peptide level greater than 0.33 nmol/l than that for IC and PC patients (86, 61 and 19%, respectively; p < 0.0001). Exogenous insulin was safely discontinued in 50, 30 and 3% of patients, respectively, in the GC, IC and PC groups (p < 0.0001). Compliance with life‐style interventions was higher in the GC than that in IC and PC patients (87, 41 and 5%, respectively; p < 0.0001). In the logistic regression analysis, predictors of good glycaemic control were having baseline fasting serum C‐peptide value ≥0.33 mmol/l, OR: 3.01 (95% CI 1.07–8.55, p = 0.03) and compliance with life‐style interventions OR 12.66 (95% CI 3.73–51.57, p = 0.0001).

Conclusion:  Among adult patients with DKA, significant predictors of good glycaemic control are preserved β‐cell function and compliance with life‐style modifications.
Comparison of air displacement plethysmograph and bioelectrical impedance for assessing body composition changes during weight loss in Japanese women
Authors: Miyatake N. , Takenami S. , Kawasaki Y. , Fujii M.
Published: April 2005

Objective:  To investigate the difference between air displacement plethysmograph (ADP) and bioelectrical impedance (BI) for assessing body composition changes during weight loss in Japanese women.

Design:  Cross‐sectional and longitudinal investigation study.

Subjects:  In a first cross‐sectional study, we used data of 7380 Japanese women aged 14–83 years [body mass index (BMI): 22.6 ± 3.7 kg/m2] at baseline. Among the participants, we used data of 54 women (BMI: 25.9 ± 3.9 kg/m2) for a 5‐month follow‐up study.

Measurements:  Body fat percentage was evaluated by ADP and BI, and body fat (kg) and lean body mass (kg) were calculated. Anthropometric parameters, such as height, weight, BMI, waist circumference, hip circumference and waist hip ratio, were also measured. In a second longitudinal study, they were also investigated before and after the study.

Results:  In a first cross‐sectional study, body fat percentage was 31.2 ± 7.0% in ADP and 25.7 ± 6.8% in BI. A significant relationship was observed between ADP and BI (r = 0.761, p < 0.01). In a second longitudinal study, body weight was significantly reduced. There were significant method (ADP vs. BI) and time (pre and post) effects but no interactions in assessing body fat percentage. There was a significant relationship between ADP and BI in body fat percentage, body fat and lean body mass. Delta body fat percentage (r = 0.386, p < 0.01) and delta body fat (r = 0.556, p < 0.01) measured by ADP were weakly correlated with those measured by BI. However, delta lean body mass measured by ADP was not correlated with that measured by BI.

Conclusion:  There was a discrepancy between ADP and BI for assessing body composition changes in Japanese women. ADP is preferentially recommended for evaluating body composition.
Letrozole normalizes serum testosterone in severely obese men with hypogonadotropic hypogonadism
Authors: De Boer H. , Verschoor L. , Ruinemans‐Koerts J. , Jansen M.
Published: April 2005

Background: Morbid obesity is associated with increased estradiol production as a result of aromatase‐dependent conversion of testosterone to estradiol. The elevated serum estradiol levels may inhibit pituitary LH secretion to such extent that hypogonadotropic hypogonadism can result. Normalization of the disturbed estradiol‐testosterone balance may be beneficial to reverse the adverse effects of hypogonadism.

Aim: To examine whether aromatase inhibition with Letrozole can normalize serum testosterone levels in severely obese men with hypogonadotropic hypogonadism.

Patients and Methods: Ten severely obese men, mean age 48.2 ± 2.3 (s.e.) years and body mass index 42.1 ± 2.6 kg/m2, were treated with Letrozole for 6 weeks in doses ranging from 7.5 to 17.5 mg per week.

Results: Six weeks of treatment decreased serum estradiol from 120 ± 20 to 70 ± 9 pmol/l (p = 0.006). None of the subjects developed an estradiol level of less than 40 pmol/l. LH increased from 4.5 ± 0.8 to 14.8 ± 2.3 U/l (p < 0.001). Total testosterone rose from 7.5 ± 1.0 to 23.8 ± 3.0 nmol/l (p < 0.001) without a concomitant change in sex hormone‐binding globulin level. Those treated with Letrozole 17.5 mg per week had an excessive LH response.

Conclusion: Short‐term Letrozole treatment normalized serum testosterone levels in all obese men. The clinical significance of this intervention remains to be established in controlled, long‐term studies.
Abdominal obesity predicts declining insulin sensitivity in non‐obese normoglycaemics: the Insulin Resistance Atherosclerosis Study (IRAS)
Authors: Karter A. J. , D'Agostino R. B. , Mayer‐Davis E. J. , Wagenknecht L. E. , Hanley A. J. G. , Hamman R. F. , Bergman R. , Saad M. F. , Haffner S. M. ,   for the IRAS investigators
Published: April 2005

Aim:  Cross‐sectional studies have demonstrated a relationship between obesity and insulin sensitivity (SI); however, there is a lack of evidence from longitudinal studies.

Methods:  The Insulin Resistance Atherosclerosis Study (IRAS) estimated SI (×10−4/min·µU/ml) directly using a frequently sampled intravenous glucose tolerance test with minimal model analysis in 504 normoglycaemic subjects. Partial correlation coefficients (r) were calculated to compare the relationship of change in SI from baseline to 5 years later (ΔSI) with baseline waist circumference (waist) as a measure of abdominal obesity and body mass index (BMI) as a measure of overall obesity. Mean ΔSI was −1.06 (SD = 1.85).

Results:  Higher baseline waist (r = −0.16; p = 0.0005), but not BMI (r = −0.005; p = 0.91), was associated with (–) ΔSI in models including sex, ethnicity, clinical centre and baseline SI, BMI, waist, age and physical activity. The waist–ΔSI relationship differed across the levels of baseline BMI, being significant only in normal weight (r = −0.21) and overweight subjects (r = −0.16), but not in obese subjects. ΔSI was correlated with a 5‐year change in either obesity measure (Δwaist: r = −0.22 and ΔBMI: r = −0.20; p = 0.0001).

Conclusions:  Among non‐diabetics, waist circumference was a strong predictor of declining SI among lean subjects, a modest predictor among overweight subjects, but was not predictive among obese individuals. Waist circumference should be considered, in addition to BMI, when identifying individuals at high risk of diabetes or the insulin resistance syndrome.
Low‐fat, high‐carbohydrate (low‐glycaemic index) diet induces weight loss and preserves lean body mass in obese healthy subjects: results of a 24‐week study
Authors: Bahadori B. , Yazdani‐Biuki B. , Krippl P. , Brath H. , Uitz E. , Wascher T. C.
Published: April 2005

Background:  The traditional treatment for obesity which is based on a reduced caloric diet has only been partially successful. Contributing factors are not only a poor long‐term dietary adherence but also a significant loss of lean body mass and subsequent reduction in energy expenditure. Both low‐fat, high‐carbohydrate diets and diets using low‐glycaemic index (GI) foods are capable of inducing modest weight loss without specific caloric restriction. The purpose of this study was to investigate the feasibility and medium‐term effect of a low‐fat diet with high (low GI) carbohydrates on weight loss, body composition changes and dietary compliance.

Methods:  Obese patients were recruited from two obesity outpatient clinics. Subjects were given advise by a dietician, then they attended biweekly for 1‐hour group meetings. Bodyweight and body composition were measured at baseline and after 24 weeks.

Results:  One hundred and nine (91%) patients completed the study; after 24 weeks the average weight loss was 8.9 kg (98.6 vs. 89.7 kg; p ≤ 0.0001). There was a significant 15% decrease in fat mass (42.5 vs. 36.4 kg; p ≤ 0.0001) and a decrease in lean body mass of 5% (56.1 vs. 53.3 kg; p ≤ 0.0001).

Discussion:  In this 6‐month study, a low‐fat, low‐GI diet led to a significant reduction of fat mass; adherence to the diet was very good. Our results suggest that such a diet is feasible and should be evaluated in randomized controlled trials.
Effect of orlistat on cardiovascular disease risk in obese adults
Authors: Swinburn B. A. , Carey D. , Hills A. P. , Hooper M. , Marks S. , Proietto J. , Strauss B. J. , Sullivan D. , Welborn T. A. , Caterson I. D.
Published: April 2005

Aim:  The aim of this study is to compare the effect of orlistat vs. placebo on the predicted 10‐year cardiovascular disease (CVD) risk in obese people with one or more cardiovascular risk factors treated for 12 months, in conjunction with a fat‐reduced, but otherwise ad libitum, diet.

Methods:  A double‐blind, randomized, placebo‐controlled, parallel study was performed in conjunction with a fat‐reduced diet and physical activity advice for 1 year. Participants (n = 339) from eight centres in Australia and New Zealand were randomized to either orlistat (120 mg) three times daily (n = 104 women, 66 men; mean ± s.d. age = 52.0 ± 7.5 years, body mass index (BMI) = 37.6 ± 5.1 kg/m2) or placebo three times daily (n = 89 women, 80 men; age = 52.5 ± 7.4 years, BMI = 38.0 ± 4.9 kg/m2). The primary efficacy criterion was the 10‐year risk of developing CVD calculated from the Framingham equation. Secondary efficacy criteria were body weight, waist circumference, blood pressure and serum concentrations of triglycerides, cholesterol (total, LDL and HDL), glucose, insulin and glycated haemoglobin and quality of life.

Results:  There was no difference in the change in 10‐year CVD risk between orlistat and placebo groups over 1 year. The orlistat group, however, had significant favourable changes in many of the individual CVD risk factors (total cholesterol, LDL‐cholesterol, glucose, glycated haemoglobin, insulin, body weight and waist circumference) and one of the domains of quality of life measured by means of the SF‐36 questionnaire (vitality), compared to the placebo group. Significant reductions in medication use for hypertension and diabetes were observed in the orlistat group, compared to those in placebo, but there were no significant differences in medication use for blood lipids.

Conclusions:  Orlistat may have reduced CVD risk, as judged by the favourable changes in individual risk factors and reductions in medication use, but the method used in order to measure absolute CVD risk in this study (Framingham CVD equation) was not sensitive enough to detect the changes in this relatively low‐risk group (approximately 10% of risk of a CVD event over 10 years).
Effects of cerivastatin on forearm vascular responses, blood pressure responsiveness and ambulatory blood pressure in type 2 diabetic men
Authors: Tran D. , Lowy A. , Howes J. B. , Howes L. G.
Published: April 2005

Objective:  The objective of the study was to investigate the effects of cerivastatin therapy on forearm endothelial dependent acetylcholine (ACH) and independent (nitroprusside) vasodilator responses, blood pressure (BP) responses to intravenous infusions of angiotensin II (AII) and noradrenaline (NA) and on 24‐h ambulatory BP recordings in type 2 diabetic men.

Design:  Eleven type 2 diabetic men aged 59 ± 9 years with total cholesterol levels of 5.0 ± 1.26 mmol/l, triglycerides of 2.23 mmol/l and high‐density lipoprotein cholesterol levels of 1.24 mmol/l completed a double‐blind, randomized, crossover trial comparing 8 weeks of cerivastatin therapy (800 µg of nocte) with placebo. Forearm vascular resistance (FVR) responses to intrabrachial‐arterial infusions of ACH (3–24 µg/min), nitroprusside (2–16 µg/min), the nitric oxide(NO) synthase inhibitor l‐nitro‐mono‐methyl arginine (l‐nmma) (8 µmol/min), ACH during l‐NMMA infusion and BP responses to intravenous infusions of AII (12.5–50 ng/min) and NA (20–400 ng/min) were measured at the end of each treatment period. Twenty‐four‐hour ambulatory BP recordings were also performed.

Results:   FVR responses to ACH during l‐NMMA infusion were significantly (p = 0.026) greater during cerivastatin than during placebo therapy. In contrast, FVR responses to ACH in the absence of NO synthase inhibition did not differ significantly between cerivastatin and placebo therapies (p = 0.81). FVR increased by 31.4 ± 57.3% in response to l‐NMMA infusion during cerivastatin therapy compared with 6.1 ± 41.2% during placebo therapy (p = 0.20). FVR responses to nitroprusside did not differ between cerivastatin and placebo therapies (p = 0.28), nor did BP responses to AII (systolic BP, p = 0.99; diastolic BP, p = 0.98) or NA (systolic BP, p = 0.21; diastolic BP, p = 0.48). Mean 24‐h BP was similar during cerivastatin (123 ± 10 or 70 ± 7 mmHg) and placebo therapies (129 ± 11 or 74 ± 7 mmHg) (systolic BP, p = 0.26; diastolic BP, p = 0.41).

Conclusion:  Cerivastatin increases FVR responses to ACH in type 2 diabetic men with mild dyslipidaemia but only following NO synthase inhibition. This may indicate an improvement in endothelium‐derived hyperpolarizing factor‐mediated responses.
Audiences’ judgements of speakers who use multimedia as a presentation aid: a contribution to training and assessment
Authors: Christie Bruce , Collyer Jenny
Published: April 2005

Multimedia technology in principle may help speakers to deliver more effective presentations. The present study examined what effectiveness might mean in terms of audience reaction. Understanding that may help educators to use multimedia more effectively themselves and to help their students to do so. Descriptors were elicited from audiences in response to a total of 56 live presentations in which speakers used multimedia as a presentation aid. Forty‐two rating scales were defined. A total of 20 presentations were rated using the scales, with the scales presented in one of two different random orders. The order did not appear to affect the ratings. A factor analysis suggests that three factors may be most important in describing the audiences’ responses. The first describes audience assessment of how well researched and informative the presentation seemed. The second concerns the design of the multimedia, including how creative and imaginative it was. The third reflects how entertaining  and  how  much  fun  the  audience  felt  the  experience  as  a  whole to be. The results suggest a three‐factor model that might be useful when designing multimedia‐supported presentations, for providing proactive guidance and feedback when training speakers, and for assessment purposes.
Users’ views about the usability of digital libraries
Authors: Koohang Alex , Ondracek James
Published: April 2005

This study examined users’ views about the usability of digital libraries—current and perceived importance. Age, gender, prior experience with the Internet, college status, and digital library proficiency are the independent variables. Users’ current views about the usability of digital libraries and users’ perceived importance of digital library usability are treated as dependent variables. The Digital Library Usability Survey, a Likert‐type instrument developed by Koohang, was used. The study's participants were 107 undergraduate students enrolled in an interdisciplinary and cross‐functional degree programme at a large state university in the Midwest, USA. The collected data were analysed through statistical procedures. The overall results yielded significant differences for the variables of users’ prior experience with the Internet and users’ proficiency level with the digital library. The univariate results  indicated  a  significant  difference  on  the  users’ perceived  importance of digital library usability. However, digital library proficiency produced a significant difference on users’ current views about the digital library's usability. These results are discussed. Recommendations are made for practice and future research.
Veni, vidi, vici: the neurohypophysis in the twentieth century
Authors: Russell John A. , Leng Gareth
Published: April 2005

We outline the key discoveries in the first 70 years of research on the neurohypophysis that provided the foundations for more recent studies in the last 30 years. We consider the extent to which these recent studies, which have exploited molecular technologies, cellular electrophysiological techniques and mechanistic behavioural investigations, have advanced or changed our understanding of the functions of oxytocin and vasopressin. The different evolutionary pressures on the oxytocin and vasopressin systems are discussed. Lastly, we focus on the mechanisms underlying the burst‐firing activity of oxytocin neurones in lactation as a problem not yet solved, and probably requiring a presently improbable conceptual leap to understand.
Regulation of vasopressin V1b receptors in the anterior pituitary gland of the rat
Authors: Aguilera Greti , Rabadan‐Diehl Cristina
Published: April 2005

Vasopressin secreted by parvocellular neurones of the hypothalamic paraventricular nucleus modulates pituitary adrenocorticotrophic hormone (ACTH) secretion by acting upon vasopressin V1b type receptors in the pituitary corticotroph coupled to phospholipase C. Regulation of V1b receptors contributes to the adaptation of the hypothalamic‐pituitary‐adrenal (HPA) axis to stress, as evidenced by the correlation between vasopressin receptor number and pituitary ACTH responsiveness. V1b receptor upregulation during chronic stress is associated with elevated circulating glucocorticoids and vasopressin expression in parvocellular neurones, suggesting that these factors control V1b receptor expression. Removal of circulating glucocorticoids by adrenalectomy causes sustained vasopressin receptor downregulation, but reduces V1b receptor mRNA only transiently. The latter effect is not mediated by increased corticotrophin‐releasing hormone (CRH) and vasopressin release, since it is not prevented by lesions of the hypothalamic paraventricular nucleus. Adrenalectomy causes sustained V1b receptor loss in Brattleboro rats, which lack hypothalamic vasopressin, suggesting that vasopressin mediates V1b receptor mRNA recovery. Exogenous glucocorticoid administration downregulates pituitary vasopressin binding but increases V1b receptor mRNA and facilitates coupling of the receptor to phospholipase C, effects which may contribute to the refractoriness of vasopressin actions to glucocorticoid feedback. The lack of parallelism between changes in pituitary vasopressin binding and V1b receptor mRNA levels during manipulation of the HPA axis indicates that V1b receptor content depends on post‐transcriptional mechanisms rather than steady‐state V1b receptor mRNA levels. These studies suggest that interaction between glucocorticoids and vasopressin plays an important role in regulating V1b receptor mRNA expression during alterations of the HPA axis. In addition, the recent characterization of a major part of the V1b receptor gene provides a basis for studying the molecular mechanisms regulating the V1b receptor.
Gene regulation of vasopressin and vasopressin receptors in cancer
Authors: North William G.
Published: April 2005

It is proposed that neuropeptide production by tumours is an important part of a special process of oncogenic transformation rather than a pre‐existing condition of progenitor cells; this concept is called Selective Tumour gene Expression of Peptides essential for Survival (STEPS). All small‐cell lung cancers and breast cancers evidently express the vasopressin gene, and this gene seems to be structurally normal in all but exceptional cases. Vasopressin gene expression in cancer cells leads to the production of both normal and abnormal forms of tumour vasopressin mRNA and proteins. Although the necessary post‐translational processing enzymes are expressed in these cells, most processing seems to be extragranular, and most of the protein products become components of the plasma membrane. Small‐cell lung cancer and breast cancer cells also express normal genes for all vasopressin receptors and produce normal vasopressin receptor mRNAs and V1a and V1b receptor proteins, and the vasopressin‐activated calcium mobilising (VACM) protein; plus both normal and abnormal forms of the V2 receptor. Through these receptors, vasopressin exercises multifaceted effects on tumour growth and metabolism. A normal protein vasopressin gene promoter seems to be present in small‐cell lung cancer cells, and this promoter contains all of the transcriptional elements known to be involved in gene regulation within hypothalamic neurones. Since these elements largely account for regulation of tumour gene expression observed in vitro, it is likely that as yet unknown factors are selectively produced by tumours in vivo to account for the observed seemingly autonomous or unregulated production of hormone in tumour patients. Promoter elements thought to be responsible for selective vasopressin gene expression in small‐cell lung cancer probably include an E‐box and a neurone restrictive silencer element close to the transcription start site. It is possible that transcription factors acting at these same elements can explain selective vasopressin expression, not only in small‐cell tumours, but also in all other tumours such as breast cancer. By extrapolation, similar mechanisms might also be responsible for the expression of additional features that characterize the ‘neuroendocrine’ profile of these cancers.
Molecular basis of ligand binding and receptor activation in the oxytocin and vasopressin receptor family
Authors: Chini Bice , Fanelli Francesca
Published: April 2005

Although it is now widely accepted that G‐protein‐coupled receptors exist in at least two allosteric states, inactive and active, and that the spontaneous equilibrium between the two is regulated by various events including the binding of specific agonists and antagonists, the molecular counterparts of these functionally different states are still poorly understood. In this paper, we review our current knowledge concerning the structure—function relationships of the oxytocin and vasopressin receptors, focusing in particular on the process of receptor activation. Using a combined approach of site‐directed mutagenesis and molecular modelling, we investigated the molecular events leading to agonist‐dependent and ‐independent receptor activation in the human oxytocin receptor. Our analysis allows us to propose that the active conformations of this receptor are characterised by similar rearrangements of its cytosolic regions that ultimately lead to the opening of a putative docking site for the G‐protein. Furthermore, the dynamics of these motions are similar to that observed in the α1B‐adrenergic receptor, thus suggesting that, although activated by different ligands, the process of receptor isomerization in these two receptors is regulated by the same cluster of highly conserved residues and that common molecular events are responsible for receptor activation in different G‐protein‐coupled receptors.
Behavioural impact of intraseptally released vasopressin and oxytocin in rats
Authors: Englemann M. , Wotjak C. T. , Ebner K. , Landgraf R.
Published: April 2005

The two nonapeptides arginine vasopressin and oxytocin are not only secreted from the neurohypophysis into the general circulation but are also released intracerebrally. Our recent research has focused on the release patterns and effects of oxytocin and vasopressin in brain areas, such as the septum and hypothalamus, that are thought to be involved in the regulation of (1) behavioural responses and (2) responses of the hypothalamo‐neurohypophysial system (HNS) to stressor exposure in rats. The results demonstrate that combined physical and emotional stress (induced by exposure to forced swimming) selectively triggers the release of vasopressin within all brain areas under study but not into the general circulation. Under emotional stress conditions (induced by exposure to the ‘social defeat’ procedure), however, oxytocin rather than vasopressin release increased within the hypothalamus and septum. Experiments aimed at revealing the neuroendocrine and behavioural relevance of the local nonapeptide release provided evidence for an involvement of vasopressin in the regulation of HNS activity (within the hypothalamus) and, moreover, in acute stress‐coping strategies, anxiety‐related behaviour and learning and memory processes (within the septum). The observed dissociation between central and peripheral nonapeptide release not only supports the hypothesis that plasma vasopressin and oxytocin concentrations do not necessarily reflect central release patterns but also suggests vasopressin and oxytocin neurones are able to independently release their nonapeptide from different parts of their neuronal surface (e.g. from somata/dendrites vs. axon terminals). This remarkable regulatory capacity provides the basis for an differential involvement of vasopressin, and probably also oxytocin, in the co‐ordination of neuroendocrine activity, emotionality and cognition at different brain levels to ensure an appropriate behavioural response of the organism to stressful stimuli
Dendritic secretion of peptides from hypothalamic magnocellular neurosecretory neurones: a local dynamic control system and its functions
Authors: Morris John F. , Christian Helen , Ma Dan , Wang Hui
Published: April 2005

The role of the dendrites of magnocellular neurones in the release of neurosecretory peptides and the synthesis of many proteins locally is reviewed. Oxytocin and vasopressin contained in dense‐cored neurosecretory vesicles are released from magnocellular dendrites not only by excitatory transmitters such as glutamate acting through well‐established receptors, but also by a rapid action of oestradiol acting by a mechanism which appears to involve NMDA receptors. Magnocellular dendrites also contain substantial amounts of the synthetic machinery which could synthesise proteins for local use. The presence in dendrites of polysomes and of mRNAs encoding microtubule‐associated protein 2, calcium calmodulin kinase II, α‐synapsin‐associated protein, and components of the GABAA and NMDA receptors strongly suggests that these proteins can be translated in the dendrites, close to the sites at which they function. Mechanism(s) which control the translation of these dendritic mRNAs and the insertion into the dendritic membranes of proteins translated by dendritic ribosomes remain to be determined. However, an overall picture emerges of magnocellular dendrites as active secretory and synthetic components of the neurosecretory neurones.
The role of steroid hormones in the regulation of vasopressin and oxytocin release and mRNA expression in hypothalamo neurohypophysial explants from the rat
Authors: Sladek Celia D. , Swenson Kerry L. , Kapoor Roger , Sidorowicz Hanna E.
Published: April 2005

Vasopressin and oxytocin release from the neural lobe, and the vasopressin and oxytocin mRNA contents of the supraoptic and paraventricular nuclei are increased by hypertonicity of the extracellular fluid. The factors regulating these parameters can be conveniently studied in perifused explants of the hypothalamo‐neurohypophysial system that include the supraoptic nucleus (but not the paraventricular nucleus) with its axonal projections to the neural lobe. Vasopressin and oxytocin release and the mRNA content of these explants respond appropriately to increases in the osmolality of the perifusate. This requires synaptic input from the region of the organum vasculosum of the lamina terminalis. Glutamate is a likely candidate for transmitting osmotic information from the organum vasculosum of the lamina terminalis to the magnocellular neurones, because agonists for excitatory amino acid receptors stimulate vasopressin and oxytocin release, and because increased vasopressin release and mRNA content induced in hypothalamo‐neurohypophysial explants by a ramp increase in osmolality are blocked by antagonists of both NMDA (N‐methyl‐D‐aspartate) and non‐NMDA glutamate receptors. Osmotically stimulated vasopressin release is also blocked by testosterone, dihydrotestosterone, oestradiol and corticosterone. Both oestrogen and dihydrotestosterone block NMDA stimulation of vasopressin release, and in preliminary studies oestradiol blocked AMPA stimulation of vasopressin release. Thus, steroid inhibition of osmotically stimulated vasopressin secretion may reflect inhibition of mechanisms mediated by excitatory amino acids. Recent studies have demonstrated numerous mechanisms by which steroid hormones may impact upon neuronal function. Therefore, additional work is warranted to understand these effects of the steroid hormones on vasopressin and oxytocin secretion and to elucidate the potential contribution of these mechanisms to regulation of hormone release in vivo.
Genetic models of vasopressin deficiency
Authors: Grant Frederick D.
Published: April 2005

Animal models of genetic hormone deficiency are useful as models for physiological studies of hormone deficiency and hormone action. Structure—function studies of the specific underlying gene defect may help in understanding mechanisms regulating gene expression and secretion of the peptide product. Spontaneous genetic models of vasopressin deficiency, such as the Brattleboro rat and human familial diabetes insipidus, have facilitated many studies of vasopressin. However, the Brattleboro rat may not be an ideal model of genetic vasopressin deficiency and therefore could be less useful for studies of the central nervous system or as a background strain for the introduction of new vasopressin gene constructs. The human model is appropriately limited by the constraints of human studies, so that engineered animal models of specific diseases, such as familial neurohypophysial diabetes insipidus, are required. The recent development of a vasopressin‐null mouse may provide insights into the various roles of vasopressin in the stress response, cardiovascular regulation and behaviour. Additionally, animals with a complete genetic deficiency of vasopressin can serve as a background strain for introduction of novel vasopressin gene constructs to enable sophisticated studies of the regulation of vasopressin expression and the intracellular processes required for appropriate secretion of vasopressin peptide. As advanced techniques of genetic manipulation become more reliable, conditional expression of vasopressin, regulated by time or body site will permit even more detailed studies in this field.
Role of water channels in fluid transport studied by phenotype analysis of aquaporin knockout mice
Authors: Verkman A. S. , Yang Baoxue , Song Yuanlin , Manley Geoffrey T. , Ma Tonghui
Published: April 2005

Aquaporin‐type water channels are expressed widely in mammalian tissues, particularly in the kidney, lung, eye and gastrointestinal tract. To define the role of aquaporins in organ physiology, we have generated and analysed transgenic mice lacking aquaporins (AQP) 1, 3, 4 and 5. Multiple phenotype abnormalities were found in the null mice. For example, in kidney, deletion of AQP1 or AQP3 produced marked polyuria whereas AQP4 deletion produced only a mild concentrating defect. Deletion of AQP5, the apical membrane water channel in the salivary gland, caused defective saliva production. Deletion of AQP1 or AQP5, water channels in lung endothelia and epithelia, resulted in a 90% decrease in airspace‐capillary water permeability. In the brain, deletion of AQP4 conferred marked protection from brain swelling induced by acute water intoxication and ischaemic stroke. The general paradigm that has emerged from these phenotype studies is that aquaporins facilitate rapid near‐isosmolar transepithelial fluid absorption/secretion, as well as rapid vectorial water movement driven by osmotic gradients. However, we have found many examples in which the tissue‐specific expression of an aquaporin is not associated with any apparent phenotypic abnormality. The physiological data on aquaporin null mice suggest the utility of aquaporin blockers and aquaporin gene replacement in selected human diseases.
Renal urea transporters. Direct and indirect regulation by vasopressin
Authors: Bankir Lise , Trinh‐Trang‐Tan Marie‐Marcelle
Published: April 2005

Urea is the most abundant urinary solute and is excreted in urine at a much higher concentration than in other body fluids. Urea concentration is achieved in the kidney through complex urea movements between blood vessels and renal tubules, which involve facilitated urea transport. Three major urea transporters expressed in the kidney have been cloned, UT‐A1, UT‐A2 and UT‐B1, the first two derived from the same gene by differential transcription. These membrane proteins enable facilitated diffusion of urea through specific parts of the nephron (UT‐A) and through renal vasculature (UT‐B) in the medulla. UT‐A1 is localised in the terminal part of the inner medullary collecting ducts and accounts for the vasopressin‐dependent increase in urea permeability of this segment. UT‐A2 is found in the descending thin limbs of Henle's loops. UT‐B1 is expressed in the endothelium of the descending vasa recta supplying blood to the renal medulla, and in red cells. All three urea transporters are primarily involved in the process of intrarenal urea recycling, which enables the establishment, and prevents the dissipation, of a high concentration of urea in the inner medulla. This is an essential feature for producing a concentrated urine and thus for water economy in mammals. Vasopressin, upon binding to V2 receptors in the inner medullary collecting ducts, increases urea permeability through activation of UT‐A1 molecules, thus enabling urea to diffuse into the inner medullary interstitium. Urea then taken up in ascending vasa recta is returned to the inner medulla via UT‐A2 and UT‐B1 by countercurrent exchange. These latter two urea transporters are not influenced acutely by vasopressin, but UT‐A2 expression is markedly increased in the descending thin limbs of the loops of Henle after sustained exposure to vasopressin or its V2 agonist dDAVP. This effect is indirect because vasopressin receptors are lacking in the descending limbs. The acute direct and delayed indirect actions of vasopressin on renal urea transporters will increase medullary urea accumulation and thus the ability of the kidney to conserve water. Atrial natriuretic peptide inhibits the vasopressin‐dependent increase in urea permeability in the inner medullary collecting ducts. The interruption of urea recycling probably contributes to the natriuresis. Impairing in this way the capacity of the kidney to concentrate urea enhances its capacity to concentrate sodium in the urine.
Vasopressin receptor antagonism — a therapeutic option in heart failure and hypertension
Authors: Burrell Louise M. , Risvanis John , Johnston Colin I. , Naitoh Mareo , Balding Leanne C.
Published: April 2005

The precise role of vasopressin in the pathophysiology of cardiovascular disease is controversial, but this peptide hormone is important for several reasons. Firstly, circulating concentrations of vasopressin are elevated in heart failure and some forms of hypertension. Secondly, there is evidence that vasopressin is synthesized not only in the hypophysial‐pituitary axis but also in peripheral tissues including the heart where it acts as a paracrine hormone. Thirdly, vasopressin has vasoconstrictor, mitogenic, hyperplastic and renal fluid retaining properties which, by analogy with angiotensin II, may have deleterious effects when present in chronic excess. Finally, the availability of orally active non‐peptide vasopressin receptor antagonists allows vasopressin receptor antagonism to be considered as a therapeutic option in cardiovascular disease.
Quo vadis neurohypophysial hormone research?
Authors: Douglas Alison J. , Ludwig Mike
Published: April 2005

Here we highlight just a few of the outstanding questions in the field of neurohypophysial hormones that we envisage will be addressed successfully in the new millennium. To begin, we focus on the regulation of receptors. Despite intensive investigation with new drugs, molecular modelling and transgenic models, the determinants of receptor selectivity remain elusive; there may even be more vasopressin or oxytocin receptor subtypes to be discovered. We discuss the controversy over the interesting studies that indicate modulation of oxytocin receptor‐binding by steroids. Oxytocin and vasopressin release and action in the brain are discussed from several aspects. Dendritically released oxytocin acting locally is important for the milk ejection reflex, and similarly released vasopressin is important in regulating patterning of vasopressin neurone activity. Such dendritically released oxytocin and vasopressin is likely to be important in paracrine modulation of neural circuitry involved in neuroendocrine control, and for a range of behaviours. Is it possible that the whole range of behaviours that comprise ‘social’ (or ‘anti‐social’) or ‘maternal’ behaviour can be engineered by modifying the expression of just these one or two peptides and their receptors? However, whether gene expression and knockout approaches will answer all the open questions about the real functions of oxytocin and vasopressin remains to be shown.
Differential sensitivity to calciseptine of L‐type Ca2+ currents in a ‘lower’vertebrate (Scyliorhinus canicula), a protochordate (Branchiostoma lanceolatum) and an invertebrate (Alloteuthis subulata)
Authors: Rogers Candida M. , Brown Euan R.
Published: April 2005

Voltage‐dependent calcium currents in vertebrate (Scyliorhinus canicula), protochordate (Branchiostoma lanceolatum), and invertebrate (Alloteuthis subulata) skeletal and striated muscle were examined under whole‐cell voltage clamp. Nifedipine (10 μM) suppressed and cobalt (5 mM) blocked striated/skeletal muscle calcium currents in all of the animals examined, confirming that they are of the L‐type class. Calciseptine, a specific blocker of vertebrate cardiac muscle and neuronal L‐type calcium currents, was applied (0.2 μM) under whole‐cell voltage clamp. Protochordate and invertebrate striated muscle L‐type calcium currents were suppressed while up to 4 μM calciseptine had no effect on dogfish skeletal muscle L‐type calcium currents. Our results demonstrate the presence of at least two sub‐types of L‐type calcium current in these different animals, which may be distinguished by their calciseptine sensitivity. We conclude that the invertebrate and protochordate L‐type current sub‐type that we have examined has properties in common with vertebrate ‘cardiac’ and ‘neuronal’ current sub‐types, but not the skeletal muscle sub‐type of the L‐type channel.
Control of breathing and muscle perfusion in humans
Authors: Haouzi Philippe , Chenuel Bruno , Chalon Bernard
Published: April 2005

Very brief and intense exercise triggers a biphasic metabolic and respiratory response with a second phase that occurs after the cessation of the muscular activity. The effects on minute ventilation (VE) produced by manipulation of the peripheral circulation in metabolically active muscles could thus be studied without the confounding effects of painful contractions. The second phase of breath‐by‐breath VE and pulmonary gas exchange responses to a brief change in work rate (400 W for 12 s) were studied in six healthy male subjects on four occasions (24 tests). An upper thigh cuff inflation was randomly applied either above or below the systolic blood pressure (200 or 90 Torr, respectively) for 90 s just after the cessation of the contractions prior to the delayed rise in pulmonary gas exchange (eight tests in each subject). Total occlusion produced a significant reduction in the delayed rise in VE (‐29 ± 3%) which normally occurred 20–25 s after the cessation of the contractions. In contrast, cuff inflation at a level predominantly impeding venous return while partially maintaining the arterial supply reduced the rise in pulmonary gas exchange in similar proportion to that during total obstruction but with a slight but not significant reduction in ventilation (‐9 ± 5%). VE during partial occlusion was if anything higher than in control tests with similar oxygen uptake (280 W), despite a higher blood pressure (BP) during occlusion (+7 Torr). It is concluded that the factors resulting from a reduction in venous return or from the involvement of the arterial baroreflex are not responsible for the changes in VE produced by the obstruction of the circulation to and from metabolically active muscles. It is proposed that factors related to the level of the perfusion pressure in hyperaemic muscles, possibly located at the venular end of the microcirculation, could account for the changes in VE observed.
Structural adjustment programmes and human well‐being
Authors: McGregor Sue
Published: April 2005

This paper provides a primer on structural adjustment programmes (SAPs) anticipating that a deeper understanding of these policies enables home economists to influence the global trend for SAPs that is profoundly impacting human well‐being. It addresses the issue of what SAPs are (their intended and actual impact on family well‐being), provides five reasons why home economists should care about SAPs and tenders seven ideas for what we can do, as professionals, to mitigate the negative impact of SAPs on familial well‐being and human security.
Fissures in the marketing strategies of South Asian restaurants in Edinburgh
Authors: Seaman Claire E.A. , Bent Richard , Ingram Arthur , Welsh Rita , Mederos Alicia
Published: April 2005

This exploratory study sought to investigate South Asian restaurants in Edinburgh, Scotland, UK in order to obtain a preliminary identification of marketing gaps compromising their future profitability. The aims of the study were to expose and understand the relative importance attached by owners and managers of South Asian restaurants in Edinburgh to the different elements of the marketing mix. South Asian restaurants form a small but important sector of the restaurant in market in towns throughout the UK and are characteristically of disproportionate financial and social importance to the communities who run them. South Asian restaurants in Edinburgh, as in most towns in the UK, are run primarily by the Bangladeshi community and are under increasing pressure as the variety of restaurants operating in the sector increases. The results of the study make evident that any initiatives taken to support South Asian restaurants should include awareness‐raising actions. Building awareness, which is perceived to be currently partially understood, of the importance of studying markets, customers and competitors is essential before any advice is given on how to accomplish these monitoring tasks. Equally, a fundamental priority is to encourage self‐critical and proactive approaches to business, thus increasing the capacity to identify possible problems and implement correcting measures.
Conjoint analysis of consumer preferences for roasted peanut products in Haiti
Authors: Nelson Robert G. , Jolly Curtis M. , Hinds Margaret J. , Donis Yanick , Prophete Emmanuel
Published: April 2005

This study evaluated Haitian consumers’ preferences for three attributes of roasted peanuts: form (dry‐roasted vs. honey‐roasted), country of origin (Haiti vs. USA) and price (lowest vs. most common vs. highest). A sample of 199 respondents from three locations near Port‐au‐Prince revealed that price was overwhelmingly the most important attribute, although three well‐differentiated consumer segments were identified: the largest (44% of the sample) based strictly on price; a second (29%) distinguished by preference for honey‐roasted peanuts of Haitian origin; and a third (27%) preferring dry‐roasted peanuts imported from the USA. Segment membership was predicted by gender, education, household size, survey location and whether or not respondents were themselves the purchasers of the peanuts and peanut butter they consumed. Market simulation of a proposed, new domestic product (honey‐roasted peanuts from Haiti) revealed that a price near that of the currently imported product would maximize domestic revenues at about 15% above the current base.
Estimation of meat demand system in Jordan: an almost ideal demand system
Authors: Jabarin Amer S.
Published: April 2005

This paper reports the results of the estimation of a linear approximate almost ideal demand system for Jordan meat demand using cross‐sectional data collected by the Department of Statistics in Jordan as part of the household expenditure survey. A censored regression method for the system of equation is used to analyse the meat consumption patterns. This method allows for inclusion of a large number of zero consumption for some foods. Two‐step demand system was estimated. In the first stage, Inverse Mill Ratio is estimated by using probit regression model. In the second stage, the estimated variable is included in the AIDS model to estimate food demand elasticities. The objective of this work is to provide econometric estimates of the different types of demand elasticities for meats in Jordan. To be consistent with the demand theory, the homogeneity, symmetry and adding up restrictions were satisfied in the estimated models. The estimated model was used to obtain estimates of Hicksian, Marshallian and expenditure demand elasticities for meats in Jordan. The results revealed that the demand for mutton and poultry is elastic while the demand for beef and fish is inelastic. The cross‐price elasticities indicate that poultry and beef are substitutes to mutton. The expenditure elasticities confirm that beef and mutton are luxury goods while poultry and fish are necessity goods.
Residential energy behaviour: does generation matter?
Authors: Carlsson‐Kanyama Annika , Lindén Anna‐Lisa , Eriksson Björn
Published: April 2005

In this study we tested the relevance of the generational hypothesis, that is, whether the era in which household members grew up matters when understanding and predicting their behaviour, on a sample of 600 Swedish households. These households participated in a survey where they answered questions about their own energy‐related residential energy behaviour. The answers were analysed for differences between age groups, between different attitudes to environmental issues, between income levels and between dwelling types. The results showed that age was as good an indicator as the other parameters. In several areas, older households had a more energy‐efficient residential behaviour than younger ones. Examples are laundry practices and indoor heat regulation. According to the generational hypothesis, this finding implies higher energy use in the future. The study also shows that there is a broad scope for improving residential energy behaviour in Swedish society by implementing changes in laundry avoiding practices, dishwashing behaviour and indoor temperature regulation.