bluuebunny/crossref_metadata_2025 huggingface dataset:
Poverty amidst plenty: food insecurity in the United States
Authors: LeBlanc Michael , Kuhn Betsey , Blaylock James
Published: October 2005

The United States faces domestic food security issues that differ from those encountered by many countries. Yet, in 2001, 10.7% of U.S. households were estimated to be food insecure at some point during the year. Food security, poverty, and food insecurity are strongly linked by economic conditions. Job transitions, layoffs, and family disruptions result in periods of low income and vulnerability to food insecurity. Economic and food assistance programs have helped protect many U.S. households when the market economy has failed to do so. These programs have reduced vulnerability to falling income and food insecurity during economic downturns in the business cycle. However effective food assistance programs have been for reducing short‐term vulnerability, they do not enhance a household's ability to achieve sustainable food security. Prospects for improving long‐term food security are tied to the same economic forces shaping a household's income and budget, particularly those related to labor productivity and wages.
Agricultural biotechnology: implications for food security
Authors: Santaniello Vittorio
Published: October 2005

In 2015 under nourishment and famine will still be at higher levels than the targets set by the World Food Conference. Agricultural biotechnology is the major technological innovation to be made available to farmers after the end of the green revolution. The research activities of the biotech community, to provide solutions to the agricultural production problems, is intense and the results might be far reaching. The development of those technologies has been at times controversial but economic analysis of their impact have shown that producers and consumers, especially in developing countries, can benefit substantially. Although agricultural biotechnology is not a silver bullet to solve food insecurity problems, it can provide a significant help. Those technologies however need to be linked to the real needs of farmers and consumers.
The poverty of sustainability: rescuing economics from platitudes
Authors: Bromley Daniel W.
Published: October 2005

The idea of sustainability has become confused and incoherent. If sustainability is to regain a plausible pertinence to economic policy it must be understood to encompass two realms: (1) human interaction with nature; and (2) human interaction with others with respect to their interaction with nature. The on‐going redefinition of the purposes of nature requires that institutions—norms, rules‐property regimes—undergo constant evolution so that human action conduces to nondestructive action. Caution in the social realm is the greatest risk to environmental sustainability.
Under‐investing in public goods: evidence, causes, and consequences for agricultural development, equity, and the environment
Authors: López Ramón
Published: October 2005

A common factor that explains why agriculture causes too much environmental degradation, grows too slowly, and has been ineffective in reducing rural poverty is the generalized tendency by governments to under invest in public goods despite the high rates of return to such investments. A large share of rural public expenditures is deviated to private goods (mostly subsidies to the wealthy), which generally have low or even negative rates of return. Behind such an obviously aberrant choice are political economy forces; a highly unequal political lobby market leads to government policies that are biased in favor of economic elites and detrimental for both the environment and rural development. Globalization may affect this important distortion on the allocation of government expenditures in various ways. One such way is by restricting the ability of governments to repress the political mobilization of the poor to counter the almost unchallenged power of the elites in the lobby market. This may contribute toward creating conditions that are more consistent with sustainable and socially equitable development.
Economic development and environmental management in the uplands of Southeast Asia: challenges for policy and institutional development
Authors: Rola Agnes C. , Coxhead Ian
Published: October 2005

Using a Philippine case study site, the forces driving the recent evolution of economic behavior and institutional arrangements in upland and forest margin areas of Southeast Asia are considered. In early modern development, subsistence agriculture using long‐phase forest–fallow rotations and regulated by customary law was replaced by more intensive, commercially oriented farming systems, a process heavily influenced by internal migration to the agricultural frontier. Traditional land and resource use institutions were quickly displaced during this shift—both de facto, through the actions of colonists, and de jure, through the state's assertion of ownership over forests and uplands and the introduction of private title to agricultural lands. Yet the effective implementation of natural resource use constraints lagged substantially behind the pace of agricultural development and forest exploitation, resulting in a period in which high demand for such resources coincided with virtually open access. These processes were noticeably subject to the influence of policies and reforms affecting markets, prices, and institutions.
Risk factors for non‐cardiac chest pain in the community
Authors: WISE J. L. , LOCKE G. R. , ZINSMEISTER A. R. , TALLEY N. J.
Published: October 2005

Background:  Non‐cardiac chest pain is a common and expensive condition. Risk factors for non‐cardiac chest pain are poorly understood and lack description in the USA community.

Aim:  To explore risk factors and health‐seeking behaviour in non‐cardiac chest pain in a USA community.

Methods:  Olmsted County, MN subjects who reported at least monthly or severe chest pain in response to a validated questionnaire were compared with controls. All the Mayo Clinic medical records were reviewed; those with cardiac disease or relevant organic conditions were excluded.

Results:  Of 2118 eligible subjects, 1524 (72%) returned a questionnaire, 389 subjects (26%) reported any chest pain and 186 (12.2%) at least monthly or severe chest pain. Of these, 62 were excluded for a cardiac diagnosis or another organic cause. Thus, 124 subjects (9.1%, 95% CI: 7.6–10.8%) reported at least monthly or severe non‐cardiac chest pain, of which 65 (52.4%) had frequent reflux symptoms. Independent risk factors for non‐cardiac chest pain were obesity (OR 3.0, 95% CI: 1.64–5.50), family history of reflux (OR 2.8, 95% CI: 1.73–4.32), previous cigarette use (OR 2.0, 95% CI: 1.27–3.18), aspirin use (OR 1.5, 95% CI: 1.00–2.31) and use of antiarthritis medicines (OR 2.0, 95% CI: 1.27–3.16). Compared with subjects with non‐cardiac chest pain and associated gastro‐oesophageal reflux symptoms, subjects with non‐cardiac chest pain without associated gastro‐oesophageal reflux symptoms were less likely to have a family history of reflux, more likely to be younger, and less likely to be obese. Compared with controls, subjects with non‐cardiac chest pain without gastro‐oesophageal reflux symptoms were younger (OR 0.97, 95% CI: 0.95–0.99), reported higher somatic symptom scores (OR 1.1, 95% CI: 1.08–1.73) and were more likely to be obese (OR 2.6, 95% CI: 1.15–5.93).

Conclusions:  Recurrent or severe non‐cardiac chest pain is common in the community. Half of the people with significant non‐cardiac chest pain have frequent reflux symptoms, thus, risk factors for non‐cardiac chest pain are similar to risk factors for gastro‐oesophageal reflux disease. People with non‐cardiac chest pain without reflux symptoms have a slightly different risk factor profile.
Effects of grapefruit juice on the pharmacokinetics of pitavastatin and atorvastatin
Authors: Ando Hitoshi , Tsuruoka Shuichi , Yanagihara Hayato , Sugimoto Koh‐ichi , Miyata Masaaki , Yamazoe Yasushi , Takamura Toshinari , Kaneko Shuichi , Fujimura Akio
Published: October 2005

Aims

To compare the effects of grapefruit juice (GFJ) on the pharmacokinetics of pitavastatin and atorvastatin.

Methods

In a randomized, four‐phase crossover study, eight healthy subjects consumed either GFJ or water t.i.d. for 4 days in each trial. On each final day, a single dose of 4 mg pitavastatin or 20 mg atorvastatin was administered.

Results

GFJ increased the mean AUC0−24of atorvastatin acid by 83% (95% CI 23–144%) and that of pitavastatin acid by 13% (−3 to 29%).

Conclusions

Pitavastatin, unlike atorvastatin, appears to be scarcely affected by the CYP3A4‐mediated metabolism.
Effect of azole antifungals ketoconazole and fluconazole on the pharmacokinetics of dexloxiglumide
Authors: Jakate Abhijeet S. , Roy Partha , Patel Alpita , Abramowitz Wattanaporn , Persiani Stefano , Wangsa Julie , Kapil Ram
Published: October 2005

Aims

Dexloxiglumide is a new CCK1 receptor antagonist under investigation for treatment of functional gastrointestinal disorders and is metabolized by CYP3A4 and CYP2C9. The objectives of these two separate randomized, two‐period, two‐treatment crossover studies were to investigate the effects of steady‐state ketoconazole, a model CYP3A4 inhibitor (Study 1), and steady‐state fluconazole, a model CYP2C9 inhibitor (Study 2), on the pharmacokinetics of dexloxiglumide in healthy subjects.

Methods

Plasma samples were analysed for dexloxiglumide and its primary metabolites: O‐demethyl dexloxiglumide (ODM; Study 1 and 2) and dexloxiglumide carboxylic acid (DCA; Study 2).

Results

Following ketoconazole coadministration, dexloxiglumide Cmax increased by 32% (90% confidence intervals (CI) 112–154), with unchanged ODM Cmax; AUC of dexloxiglumide and ODM increased by 36% (90% CI 124–140 and 128–142, respectively). No changes were observed in dexloxiglumide or ODM t½. Fluconazole coadministration caused a 77% increase (90% CI 154–204) in dexloxiglumide Cmax, no change in ODM Cmax and a 32% decrease (90% CI 62–75) in DCA Cmax. Fluconazole coadministration resulted in a 2.5‐fold increase (90% CI 235–267) in dexloxiglumide AUC, 40% increase (90% CI 136–156) in ODM AUC and an 18% decrease (90% CI 82–94) in DCA AUC. The t½ of all three analytes increased by approximately 2‐fold with fluconazole coadministration (P‐value < 0.05).

Conclusions

Ketoconazole caused a minimal increase while fluconazole caused a moderate increase in dexloxiglumide systemic exposure with no change in the adverse event profile of dexloxiglumide.
Fluvoxamine impairs single‐dose caffeine clearance without altering caffeine pharmacodynamics
Authors: Culm‐Merdek Kerry E. , Von Moltke Lisa L. , Harmatz Jerold S. , Greenblatt David J.
Published: October 2005

Background

Coadministration of fluvoxamine impairs the clearance of caffeine and prolongs its elimination half‐life, which is attributable to inhibition of CYP1A2 by fluvoxamine. The clinical importance of this interaction is not established.

Aim

To evaluate the effects of fluvoxamine on the kinetics and dynamics of single doses of caffeine.

Methods

Seven healthy subjects received single 250 mg doses of caffeine (or matching placebo) together with fluvoxamine (four doses of 100 mg over 2 days) or with matching placebo in a double‐blind, four‐way crossover study. For 24 h after caffeine or placebo administration, plasma caffeine and fluvoxamine concentrations were determined. Psychomotor performance, sedation, and electroencephalographic (EEG) ‘beta’ frequency activity were also assessed.

Results

Fluvoxamine significantly reduced apparent oral clearance of caffeine (105vs.9.1 mL min−1,P < 0.01; mean difference: 95.7 mL min−1, 95% CI: 54.9–135.6), and prolonged its elimination half‐life (4.9vs.56 h,P < 0.01; mean difference: 51 h, 95% CI: 26–76). Caffeine produced CNS‐stimulating effects compared with placebo. However, psychomotor performance, alertness, or EEG effects attributable to caffeine were not augmented by coadministration of fluvoxamine.

Conclusions

Fluvoxamine greatly impaired caffeine clearance, but without detectable changes in caffeine pharmacodynamics. However, this study does not rule out possible adverse effects due to extensive accumulation of caffeine with daily ingestion in fluvoxamine‐treated individuals.
Relationships between sirolimus dosing, concentration and outcomes in renal transplant recipients
Authors: Dansirikul C. , Duffull S. B. , Morris R. G. , Tett S. E.
Published: October 2005

Aim

To explore relationships between sirolimus dosing, concentration and clinical outcomes.

Methods

Data were collected from 25 kidney transplant recipients (14 M/11 F), median 278 days after transplantation. Outcomes of interest were white blood cell (WBC) count, platelet (PLT) count, and haematocrit (HCT). A naive pooled data analysis was performed with outcomes dichotomized (Mann–Whitney U‐tests).

Results

Several patients experienced at least one episode when WBC (n = 9), PLT (n = 12), or HCT (n = 21) fell below the lower limits of the normal range. WBC and HCT were significantly lower (P < 0.05) when sirolimus dose was greater than 10 mg day−1, and sirolimus concentration greater than 12 µg l−1. No relationship was shown for PLT and dichotomized sirolimus dose or concentration.

Conclusions

Given this relationship between sirolimus concentration and effect, linked population pharmacokinetic–pharmacodynamic modelling using data from more renal transplant recipients should now be used to quantify the time course of these relationships to optimize dosing and minimize risk of these adverse outcomes.
Trimethoprim–sulphamethoxazole does not affect the pharmacokinetics of sirolimus in renal transplant recipients
Authors: Böttiger Ylva , Brattström Christina , Bäckman Lars , Claesson Kerstin , Burke James T.
Published: October 2005

Aims

The influence of the trimethoprim–sulphamethoxazole combination on the steady‐state pharmacokinetics of sirolimus, a potent macrocyclic immunosuppressant, was studied in renal transplant recipients.

Methods

Fifteen kidney transplant recipients were treated with sirolimus 8–23 mg m−2 in combination with azathioprine and prednisolone from the day of transplantation. Whole blood sirolimus AUC and Cmax were determined on days 6 and 7 after transplantation. On day 7, sirolimus was coadministered with the first dose of trimethoprim (80 mg) and sulphamethoxazole (400 mg).

Results

On day 6, the mean (95% confidence interval) whole blood sirolimus AUC(0−24 h) was 1040 (846, 1234) ng ml−1 and mean Cmax was 109 (88, 129) ng ml−1. Corresponding values on day 7 were AUC(0−24 h) 1060 (826, 1293) ng ml−1 and Cmax mean 107 (87, 127)  ng ml−1.  The  mean  difference  in  the  dose‐corrected  AUC(0−24 h)  was  0.40% (−9.4, +10).

Conclusions

A single dose of trimethoprim–sulphamethoxazole does not affect the pharmacokinetics of sirolimus in renal transplant patients.
Suicide and self‐harm following prescription of SSRIs and other antidepressants: confounding by indication
Authors: Didham Rebecca C. , McConnell Doug W. , Blair Hayden J. , Reith David M.
Published: October 2005

Aim

To identify the incidence and risk of suicide and self harm, among patients prescribed antidepressant drugs.

Methods

A retrospective cohort study, with nested case control, of patients identified from a nonrandom sample of general practices in New Zealand from 1996 to 2001. A total of 57 361 patients who received a prescription for a single antidepressant were identified from the RNZCGP Research Unit Database. Suicides within 120 days of a prescription were identified from the New Zealand National Mortality Database and self‐harm events within 120 days of a prescription were identified from the New Zealand Hospital discharge database.

Results

26 suicides and 330 episodes of self‐harm were identified within 120 days of an antidepressant prescription. On univariate analysis the association, expressed as OR (95% CI), between selective serotonin reuptake inhibitors (SSRIs) and self harm and suicide were 2.26 (1.27–4.76) and 1.92 (0.77–4.83), respectively. When corrected for the confounding effects of age, gender and depression/suicidal ideation there was an association between SSRIs and self harm, OR 1.66 (95% CI 1.23–2.23), but not for suicide, 1.28 (0.38–4.35). Paroxetine was a significant risk factor for suicide on univariate analysis, 4.23 (1.19–14.95), but not when corrected for age, gender and depression/suicidal ideation, 2.76 (0.30–24.87).

Conclusions

Age, gender and pre‐existing depression/suicidal ideation are important confounders in observational studies of the association between antidepressants and suicide or self harm.
Prediction ofin vivodrug–drug interactions fromin vitrodata: impact of incorporating parallel pathways of drug elimination and inhibitor absorption rate constant
Authors: Brown Hayley S. , Ito Kiyomi , Galetin Aleksandra , Houston J. Brian
Published: October 2005

Aims

Success of the quantitative prediction of drug–drug interactions via inhibition of CYP‐mediated metabolism from the inhibitor concentration at the enzyme active site ([I]) and thein vitroinhibition constant (Ki) is variable. The aim of this study was to examine the impact of the fraction of victim drug metabolized by a particular CYP (fmCYP) and the inhibitor absorption rate constant (ka) on prediction accuracy.

Methods

Drug–drug interaction studies involving inhibition of CYP2C9, CYP2D6 and CYP3A4 (n = 115) were investigated. Data onfmCYPfor the probe substrates of each enzyme andkavalues for the inhibitors were incorporated intoin vivopredictions, alone or in combination, using either the maximum hepatic input or the average systemic plasma concentration as a surrogate for [I]. The success of prediction (AUC ratio predicted within twofold ofin vivovalue) was compared using nominal values offmCYP = 1 andka = 0.1 min−1.

Results

The incorporation offmCYPvalues intoin vivopredictions using the hepatic input plasma concentration resulted in 84% of studies within twofold ofin vivovalue. The effect ofkavalues alone significantly reduced the number of over‐predictions for CYP2D6 and CYP3A4; however, less precision was observed compared with thefmCYP. The incorporation of bothfmCYPandkavalues resulted in 81% of studies within twofold ofin vivovalue.

Conclusions

The incorporation of substrate and inhibitor‐related information, namelyfmCYPandka, markedly improved prediction of 115 interaction studies with CYP2C9, CYP2D6 and CYP3A4 in comparison with [I]/Kiratio alone.
Favourable dermal penetration of diclofenac after administration to the skin using a novel spray gel formulation
Authors: Brunner Martin , Dehghanyar Pejman , Seigfried Bernd , Martin Wolfgang , Menke Georg , Müller Markus
Published: October 2005

Aims

The study was designed to evaluate the relative bioavailability of diclofenac in plasma, subcutaneous adipose and skeletal muscle tissue after repeated topical administration using MIKA Diclofenac Spray Gel (4%), a novel formulation, and after oral dosing using VOLTAREN“ 50 mg enteric coated tablets.

Methods

Diclofenac (48 mg) was administered topically three times daily for 3 days onto a defined area of the thigh of 12 healthy males. After a 14‐day wash out period, subjects were orally treated with 50 mg diclofenac three times daily for 3 days. In vivo microdialysis in subcutaneous and muscle tissues was performed immediately after the final doses from both treatments on day 4, and 48 h later. Plasma samples were taken simultaneously.

Results

The relative bioavailability of diclofenac in subcutaneous adipose and skeletal muscle tissue was substantially higher after topical compared with oral dosing (324% and 209%, respectively) whereas relative plasma bioavailability was 50‐fold lower. Plasma Cmax values were approximately 250‐fold lower after topical compared with oral drug administration (i.e. median values = 4.89 ng mL−1; 95% CI: 3.37–7.68 and 1240 ng mL−1; 95% CI: 787–1389 ng mL−1). Both treatments were well tolerated.

Conclusions

Owing to its favourable penetration characteristics and low systemic availability, MIKA Diclofenac Spray Gel 4% is a rational alternative to oral diclofenac formulations for the treatment of inflammatory soft tissue conditions.
Haploinsufficiency of Runx1/AML1 promotes myeloid features and leukaemogenesis in BXH2 mice
Authors: Yamashita Namiko , Osato Motomi , Huang Liqun , Yanagida Masatoshi , Kogan Scott C. , Iwasaki Masayuki , Nakamura Takuro , Shigesada Katsuya , Asou Norio , Ito Yoshiaki
Published: October 2005

Haploinsufficiency of RUNX1/AML1 is associated with familial platelet disorder with a predisposition to acute myeloid leukaemia (FPD/AML), but the causal relationship remains to be addressed experimentally. Mice heterozygous for the Runx1 null mutation, Runx1+/−, are considered to be genetically comparable with human FPD/AML patients but do not develop spontaneous leukaemia. To induce additional genetic alterations, retroviral insertional mutagenesis was employed with the use of BXH2 mice, which develop myeloid leukaemia because of the random integration of retrovirus present in the mouse. Heterozygous disruption of Runx1 in BXH2 mice resulted in a shortening of the latency period of leukaemia. In addition, BXH2‐Runx1+/− mice exhibited more marked myeloid features than control mice. Moreover, the c‐Kit gene, mutated in human RUNX leukaemias, was recurrently activated in BXH2‐Runx1+/− mice, and a colony‐forming assay revealed synergism between the Runx1+/− status and c‐KIT overexpression. In conclusion, the BXH2‐Runx1+/− system is a promising mouse model to investigate the mechanism of leukaemogenesis in FPD/AML.
Managing the risk of transmission of variant Creutzfeldt Jakob disease by blood products
Authors: Ludlam Christopher A. , Turner Marc L.
Published: October 2005

Whereas plasma‐derived clotting factor concentrates now have a very good safety record for not being infectious for lipid enveloped viruses, concern has arisen about the possibility that prion diseases might be transmitted by blood products. There is epidemiological evidence that classical sporadic Creutzfeld Jakob disease (CJD) is not transmitted by blood transfusion. There is now good evidence that the abnormal prion associated with variant CJD can be transmitted by transfusion of fresh blood components and infect recipients. To reduce the risk of the pathological prion in the UK infecting recipients of clotting factor concentrates, these are now only manufactured from imported plasma collected from countries where there has not been bovine spongiform encephalopathy (BSE) in cattle and the risk of variant CJD in the population is, therefore, considered negligible. The safety of these concentrates is also enhanced because prion protein is, to an appreciable extent, excluded by the manufacturing process from the final product. To help reduce the chance of prion transmission by fresh blood products, donations are leucodepleted, there is increasing use of imported fresh frozen plasma (especially for treating children) and potential donors, who have been recipients of blood since 1980 (the beginning of the BSE epidemic in cattle) are deferred.
Erythropoietin levels in the different clinical forms of hereditary spherocytosis
Authors: Rocha S. , Costa E. , Catarino C. , Belo L. , Castro E. M. B. , Barbot J. , Quintanilha A , Santos‐Silva A.
Published: October 2005

Erythropoietin (EPO), the main growth factor responsible for the regulation of red blood cell production, may be overproduced when blood loss or haemolysis occurs. Patients with mild hereditary spherocytosis (HS) are able to maintain normal haemoglobin concentration, whereas typical and severe HS patients develop an anaemic state. Splenectomy usually reverses anaemia. We aimed to clarify the role of EPO in the response to enhanced spherocyte destruction, and to look for a linkage with the broad clinical spectra of HS. EPO levels, reticulocyte count and production index (RPI), other parameters used to classify HS and the protein deficiencies underlying HS were evaluated in previously diagnosed unsplenectomised (n = 24) and splenectomised (n = 10) patients presenting mild, typical or severe HS. A significant increase in EPO was observed in all unsplenectomised HS patients. In the mild form, a significant correlation of EPO with reticulocyte count and RPI was observed; however, this correlation disappeared in typical HS patients. Splenectomised HS patients presented a correction in EPO levels in all forms of HS, although the reticulocyte count and RPI sustained slightly higher values. Our data show HS as a disease linked to an overproduction of EPO, according to the severity of the disease; however, a disturbance in erythropoiesis seems to occur in typical HS. Moreover, splenectomy leads to a correction in the EPO levels.
Monitoring gastric lymphoma in peripheral blood by quantitative IgH allele‐specific oligonucleotide real‐time PCR and API2‐MALT1 PCR
Authors: Schreuder M. I. , Hoeve M. A. , Groothuis L. , Boot H. , Boerrigter L. H. , de Jong D. , Veenendaal R. A. , Jansen J. H. , van Krieken J. H. J. M.
Published: October 2005

Gastric extranodal marginal zone lymphoma (EMZL) often shows prolonged localised disease, but the present study demonstrated the presence of tumour cells in peripheral blood (PB) of low stage patients. We studied the presence of tumour cells in PB in gastric lymphoma patients harbouring or lacking t(11;18)(q21;q21), by real‐time immunoglobulin (Ig)H allele‐specific oligonucleotide‐polymerase chain reaction (ASO‐PCR) and API2‐MALT1 PCR. Tumour cells were exclusively detected in PB of t(11;18)(q21;q21)+‐EMZL patients. The presence of tumour cells in PB and gastric biopsy follow‐up samples showed a good correlation in these patients, suggesting clinical relevance for monitoring of tumour cells in PB of gastric t(11;18)(q21;q21)+‐EMZL patients.
Ectopic expression of vasopressin V1b and V2 receptors in the adrenal glands of familial ACTH‐independent macronodular adrenal hyperplasia
Authors: Lee Sihoon , Hwang Ranjoo , Lee Junho , Rhee Yumie , Kim Dae Jung , Chung Ung‐il , Lim Sung‐Kil
Published: October 2005

Objective  ACTH‐independent macronodular adrenal hyperplasia (AIMAH) is a rare and unusual cause of Cushing's syndrome, characterized by bilateral nodular adrenocortical hyperplasia and hypersecretion of cortisol. Familial AIMAH has rarely been reported. Recently, the aberrant expression of adrenal receptors for various ligands in AIMAH patients has become important in explaining the pathogenesis of AIMAH. In this study, we present the cases of two sisters who were affected with AIMAH.

Patients and Measurements  Two sisters, aged 46 and 58, respectively, at the time of diagnosis, were found to have Cushing's syndrome due to AIMAH. We performed provocation tests with various materials and reverse transcription polymerase chain reaction (RT‐PCR) with their resected adrenal tissues to examine the hyper‐responsiveness to steroidogenesis and the overexpression of related receptors, respectively.

Results  Provocation tests in vivo indicated that arginine vasopressin (AVP) promoted cortisol secretion through vasopressin V1a as well as V1b and V2 receptors. RT‐PCR analysis revealed an abnormal cDNA expression of vasopressin V1b and V2 receptors, none of which is known to be normally expressed in the adrenal glands.

Conclusion  The expression of ectopic vasopressin V1b and V2 receptors may be involved in the aetiology of AIMAH, at least in the case of the sibling patients presented here.
Discoloration of polyvinyl chloride (PVC) tape as a proxy for water‐table depth in peatlands: validation and assessment of seasonal variability
Authors: BOOTH R. K. , HOTCHKISS S. C. , WILCOX D. A.
Published: October 2005

Discoloration of polyvinyl chloride (PVC) tape has been used in peatland ecological and hydrological studies as an inexpensive way to monitor changes in water‐table depth and reducing conditions.

We investigated the relationship between depth of PVC tape discoloration and measured water‐table depth at monthly time steps during the growing season within nine kettle peatlands of northern Wisconsin. Our specific objectives were to: (1) determine if PVC discoloration is an accurate method of inferring water‐table depth in Sphagnum‐dominated kettle peatlands of the region; (2) assess seasonal variability in the accuracy of the method; and (3) determine if systematic differences in accuracy occurred among microhabitats, PVC tape colour and peatlands.

Our results indicated that PVC tape discoloration can be used to describe gradients of water‐table depth in kettle peatlands. However, accuracy differed among the peatlands studied, and was systematically biased in early spring and late summer/autumn. Regardless of the month when the tape was installed, the highest elevations of PVC tape discoloration showed the strongest correlation with midsummer (around July) water‐table depth and average water‐table depth during the growing season.

The PVC tape discoloration method should be used cautiously when precise estimates are needed of seasonal changes in the water‐table.
p63 correlates with both BRCA1 and cytokeratin 5 in invasive breast carcinomas: further evidence for the pathogenesis of the basal phenotype of breast cancer
Authors: Ribeiro‐Silva A , Ramalho L N Z , Garcia S B , Brandão D F , Chahud F , Zucoloto S
Published: October 2005

Aims:  To study the expression of p63, cytokeratin (CK) 5 and CK8/18 in invasive ductal carcinomas and their relationship with BRCA1 and other pathological and immunohistochemical features of clinical significance.

Methods and results:  Immunohistochemistry with the antibodies p63, CK5, CK8/18, BRCA1, oestrogen receptor, progesterone receptor, p53, c‐erbB‐2 and Ki67 was performed in 102 formalin‐fixed paraffin‐embedded samples of invasive ductal carcinomas. The CK5+ cases were submitted to a double‐immunolabelling study with p63. There was a strong relationship between CK5 and p63 expression and both markers were associated with hormonal receptor‐negative high‐grade carcinomas with high proliferative rate. Furthermore, there was coexpression of CK5 and p63 in neoplastic cells, indicating that p63, like CK5, is a marker of the basal phenotype of breast cancer. There was a strong relationship between reduced expression of BRCA1 with both p63 and CK5 expression as well as an inverse correlation between p63 and CK8/18 expression, suggesting that loss of p63 expression is required for the transition between a basal to a luminal phenotype of breast carcinoma.

Conclusions:  Since p63 is thought to be a marker of stem cells and may act as an oncogene, our data support the idea that BRCA1 acts as stem cell regulator.
The optimization of the formulation for a chocolate cake containing inulin and yacon meal
Authors: Moscatto Janaina Andrea , Borsato Dionisio , Bona Evandro , de Oliveira Antonio Sérgio , de Oliveira Hauly Maria Celia
Published: October 2005

The research aimed at determining, using surface response methodology, an optimal chocolate cake formulation when wheat flour was partially replaced with inulin and/or yacon meal. The yacon meal used in the formulation was prepared by using tuberous roots of yacon (Polymnia sonchifolia Poepp. & Endl.). The optimization indicated that a formulation with 20% of the wheat flour replaced with yacon meal, 153 mL of water and no inulin showed the best values for hardness (3.638 N), cohesiveness (0.691) and specific volume (1.86 cm3 g−1). A formulation with 40% of the wheat flour replaced with yacon meal, 6% replaced with inulin and containing 126 mL of water showed similar values to the optimized formulation for the three responses mentioned earlier but, in addition, it had a greater content of fructooligosaccharides and inulin. Consequently, both formulations may give useful functional foods with physical parameters comparable with the control formulation.
The occurrence of mass transport processes during the leaching of amygdalin from bitter apricot kernels: detoxification and flavour improvement
Authors: Silem Abdelmadjid , Günter Hans‐Otto , Einfeldt Jörn , Boualia Abdelkader
Published: October 2005

Because of their appreciable protein content apricot kernels could be used as a good source of food. However, their wide use for human or animal nutrition is dependent on their adequate detoxification. This is because apricot kernels have a strong bitter flavour that is caused by the presence of amygdalin, a toxic cyanogenic glycoside. The aim of the present work was to investigate an unusual method of detoxifying apricot kernels by soaking them in water. The method was energetically relatively inexpensive as uncrushed kernels and cold water were used. Furthermore, the use of intact kernels minimized the loss of nutritious soluble matter during the detoxification. On the basis of a simple but adequate mechanistic model, a mathematical description of the extractive detoxification of apricot kernels is proposed. The two‐resistance mass transfer system is based on external film mass transfer and an effective solid diffusion. A linear equilibrium curve arises from the assumption that the concentration profile inside the solid phase can be well approximated with a second order polynomial calculation, this then leads to an analytical formulation of the mathematical model. The liquid‐phase mass transfer coefficient and the internal diffusion coefficient in the kernels can be then determined. Finally, the model is used to describe extractor behaviour and predict process performance under real operation conditions.
Trends in the production and storage of fresh meat – the holistic approach to bacteriological meat quality
Authors: Nowak Bernhard , Sammet Katharina , Klein Guenter , Mueffling Theda v.
Published: October 2005

The aim of this review paper is to introduce readers to the modern approach to meat production as recommended by public authorities. No part of the food chain can be regarded alone but has to be seen as part of the whole. A holistic approach to fresh meat storage and retailing must therefore start with the living animal and cannot end with the sale of the meat. It must also include the consumers. One of the highest priority issues for consumers, producers and governments is food safety, and with it, consumer safety. Here we briefly describe the possibilities of keeping initial amounts of bacteria in meat low and modern storage of fresh meat. In future, the consumer must be incorporated in the meat food chain.
Melatonin Does Not Inhibit Hypothalamic‐Pituitary‐Adrenal Activity in Waking Young Men
Authors: Perras B. , Özcan S. , Fehm H. L. , Born J.
Published: October 2005

The pineal hormone melatonin is mainly secreted during night‐time which, in humans, is the normal time of sleep. It has been proposed that, during this period, melatonin exerts an inhibitory influence on secretory activity of the hypothalamic‐pituitary‐adrenal (HPA) system, although there is little evidence for this view in humans. In blind humans, a single oral dose of melatonin at bed time suppressed nocturnal cortisol secretion. However, suppression could have been secondary to an improved sleep after melatonin in these experiments. In the present study, we examined whether melatonin exerts a similar inhibitory effect on HPA activity in waking subjects. Fourteen healthy young men were tested at bed time, but kept awake throughout the experimental epoch. Thirty minutes after oral ingestion of 5 mg melatonin, activity of the HPA‐system was stimulated through a standard insulin‐induced hypoglycaemia. Adrenocorticotrophin hormone and cortisol concentrations under basal conditions before insulin injection, as well as in response to insulin‐induced hypoglycaemia, were almost identical for the melatonin and placebo control conditions (P > 0.5). However, melatonin increased plasma prolactin concentrations (P < 0.01) and reduced systolic blood pressure in the time interval following hypoglycaemia (P < 0.05). Based on a review of the literature and our results, we conclude that melatonin per se has no substantially suppressing effect on HPA secretory activity, although such an effect can be gated by sleep‐related processes.
Dopamine D2‐Like Receptor Function is Converted from Excitatory to Inhibitory by Thyroxine in the Developmental Hippocampus
Authors: Oh‐Nishi A. , Saji M. , Furudate S.‐I. , Suzuki N.
Published: October 2005

The mechanism by which a lack of thyroid hormone in the early development of the brain causes permanent mental retardation in cretins is currently unknown. On the other hand, an abnormality in dopamine‐related brain function is believed to underlie some forms of mental illness. In this study, we demonstrate that although the activation of a dopaminergic D2‐like receptor inhibited glutamatergic transmission in the hippocampal slices of normal adult rats, indicating the inhibitory action of the D2‐like receptor on glutamatergic transmission, it markedly enhanced glutamatergic transmission both in a mutant hypothyroid rat with a missense mutation in thyroglobulin and in hypothyroid rats treated with methylmercaptoimidazole (MMI), indicating the excitatory action of the D2‐like receptor on glutamatergic transmission. Paired pulse facilitation of field excitatory postsynaptic potentials was reduced by the activation of the D2‐like receptors from MMI‐induced hypothyroid rats, suggesting a presynaptic locus of the excitatory action of the D2‐like receptors. In normal rats, the excitatory D2‐like dopamine receptors were observed in the developing stages and were completely replaced by normal inhibitory responses up to adulthood. Furthermore, the continuous supplement of thyroxine from birth exerted a normalising effect on the abnormal excitatory property of D2‐like dopamine receptors in the hippocampal slices of MMI‐treated hypothyroid rats. From these results, it is suggested that thyroxine may play a crucial role in reversing the excitatory property of D2‐like dopaminergic receptors in the immature brain to an inhibitory one in the mature brain. Moreover, we suggest that the abnormal excitatory property of D2‐like dopaminergic receptors may develop in response to a lack of thyroxine and may contribute to some central nervous system deficits, including cognitive dysfunctions accompanied by hypothyroidism.
Rush allergen specific immunotherapy protocol in feline atopic dermatitis: a pilot study of four cats
Authors: TRIMMER ANN M. , GRIFFIN CRAIG E. , BOORD MONA J. , ROSENKRANTZ WAYNE S.
Published: October 2005

Abstract  Rush immunotherapy has been shown to be as safe as conventional immunotherapy in canine atopic patients. Rush immunotherapy has not been reported in the feline atopic patient. The purpose of this pilot study was to determine a safe protocol for rush immunotherapy in feline atopic patients. Four atopic cats diagnosed by history, physical examination and exclusion of appropriate differential diagnoses were included in the study. Allergens were identified via liquid phase immunoenzymatic testing (VARL: Veterinary Allergy Reference Labs, Pasadena, CA). Cats were premedicated with 1.5 mg triamcinolone orally 24 and 2 h prior to first injection and 10 mg hydroxyzine PO 24, 12 and 2 h prior to first injection. An intravenous catheter was placed prior to first injection. Allergen extracts (Greer Laboratories, Lenoir, North Carolina) were all administered subcutaneously at increasing protein nitrogen units (pnu) every 30 minutes for 5 h to maintenance dose of 15,000 pnus ml‐1. Vital signs were assessed every 15 minutes. Two cats developed mild pruritus and the subsequent injection was delayed 30 minutes. No changes in either cat's vital signs were noted, nor was there any further pruritus. All four cats successfully completed rush immunotherapy. Two cats developed a dermal swelling on the dorsal neck one week later. In these four cats, this protocol appeared to be a safe regimen to reach maintenance therapy. A larger sample of feline patients is needed to determine the incidence of adverse reactions and to follow the success of ASIT based upon this method of induction.
Efficacy of topical administration of eprinomectin for treatment of ear mite infestation in six rabbits
Authors: ULUTAS BULENT , VOYVODA HUSEYIN , BAYRAMLI GOKSEL , KARAGENC TULIN
Published: October 2005

Abstract Six rabbits naturally infested withPsoroptes cuniculiwere treated topically on the skin at the base of the neck with 0.5 mg kg−1of 0.5% pour‐on eprinomectin for cattle, twice at 14‐day intervals. Efficacy of the drug was based on the disappearance of clinical signs and the absence of live mites for a period of 6 weeks. Clinical improvement was seen within 3 days of the first application; however, complete recovery of clinical signs and elimination of mites in 5/6 rabbits did not occur until the end of the study. No adverse reactions attributable to eprinomectin treatment were observed during the observation period. Results of this trial indicated that eprinomectin was partially effective in the treatment of psoroptic mange in rabbits.
Multiple papillomavirus‐associated epidermal hamartomas and squamous cell carcinomasin situin a dog following chronic treatment with prednisone and cyclosporine
Authors: CALLAN MARY BETH , PREZIOSI DIANE , MAULDIN ELIZABETH
Published: October 2005

Abstract A 4‐year‐old, spayed female toy fox terrier developed multiple epidermal hamartomas and squamous cell carcinomasin situfollowing chronic immunosuppressive therapy with prednisone and cyclosporine for management of an immune‐mediated nonregenerative anaemia. Immunohistochemical staining was positive for papillomavirus antigen within both benign (n = 19) and malignant (n = 8) cutaneous lesions that developed during a 3‐year period of observation, with positive staining most often seen in keratinocytes in the granular cell layer. Treatment of the papillomavirus infection with interferon‐α was discontinued after 2 weeks because of diarrhoea and a further increase in liver enzymes. The cutaneous lesions of this dog persisted and new lesions developed during the year following discontinuation of both cyclosporine and prednisone. This is the first reported case of papillomavirus‐associated squamous cell carcinomain situdeveloping in a dog following chronic administration of cyclosporine and prednisone.
Detection of novel papillomaviruses in canine mucosal, cutaneous and in situ squamous cell carcinomas
Authors: ZAUGG N. , NESPECA G. , HAUSER B. , ACKERMANN M. , FAVROT C.
Published: October 2005

Abstract  Papillomavirus (PV) DNA is frequently uncovered in samples of human skin squamous cell carcinomas (SCC). However, the role of these viruses in the development of such cancers in canine species remains controversial. While approximately 100 human PVs are known, only one single canine oral PV (COPV) has been identified and studied extensively. Therefore, we applied a narrow‐range polymerase chain reaction (PCR) suitable for the detection of classical canine and feline PVs, as well as a broad‐range PCR, which has been used for the detection of various novel PVs in humans, in order to analyse 42 paraffin‐embedded samples, representing three different forms of canine SCCs. Ten samples of skin tissues with various non‐neoplastic conditions served as controls. While none of the negative controls reacted positively, PV DNA was discovered in 21% of the tested SCC samples. Interestingly, the classical COPV was amplified from only one sample, while the other positive cases were associated with a variety of thus far unknown PVs. This study suggests that a fraction of canine SCC is infected with PVs and that a genetic variety of canine PVs exists. Therefore, these results will facilitate the future study of the role of PVs in the development of canine skin cancers.
Isotretinoin in the treatment of multiple benign pilomatrixomas in a mixed‐breed dog
Authors: TOMA STEFANO , NOLI CHIARA
Published: October 2005

Abstract An 18‐month‐old cross‐breed dog developed multiple skin nodules, which over 8 months had increased in size and number. Biopsy samples were submitted for histopathological examination and revealed multiple benign pilomatrixomas. The dog was treated with 1 mg kg−1isotretinoin daily, which led to a stabilization of the size and number of the lesions. Attempts to lower the dosage to an every other day regimen led to an increase in the nodules’ size and number. Monthly complete blood count and chemistry tests and Schirmer tear tests were performed to monitor any adverse effects of the retinoid treatment. No adverse effects were noted. To the authors’ knowledge, this is the first report of multiple pilomatrixomas arising in a young dog and successfully controlled with oral retinoids.
Atopy patch test reactions in high‐IgE beagles to different sources and concentrations of house dust mites
Authors: MARSELLA ROSANNA , NICKLIN CONNIE , LOPEZ JENNIFER
Published: October 2005

Abstract  Protocols for atopy patch testing (APT) were evaluated on six high‐IgE dogs sensitized to house dust mites (HDM) using various concentrations and sources of HDM. Two sources of HDM were compared: Heska slurry and four concentrations of Greer HDM. Saline was used as a negative control. Patches were removed after 48 h and the sites evaluated at 0, 6, 24, 48, 72 and 96 h for erythema, macules, papules and pustules. Each sign was scored from 0 to 3 (0 = absent and 3 = severe). Total score was used for analysis. Mean total scores significantly increased for both Greer and Heska HDMs from 6 h, peaking at 48 h for G100 (100 mg mL−1), G300 and G668, and at 72 h for Heska and G31.25. Across all times, Heska HDM scores were significantly higher than those of G31.25 with the largest difference at 96 h. Heska scores, however, were significantly lower than those of other Greer concentrations (G100, G300 and G668) particularly at 96 h. No reactions were noted at saline sites. It is concluded that Greer–HDM at 100 mg mL−1 is the most suitable concentration for APT in dogs because it induces reactions comparable if not higher than more concentrated HDM preparations.
Inhibition of the growth in vitro of Trichophyton mentagrophytes, Trichophyton erinacei and Microsporum persicolor by miconazole and chlorhexidine
Authors: PERRINS NATALIE , HOWELL SUSAN A. , MOORE MARY , BOND ROSS
Published: October 2005

Abstract  An agar dilution technique was used to assess the minimum inhibitory concentrations (MICs) of miconazole, chlorhexidine and a 1:1 combination of both agents for 9 isolates of Trichophyton mentagrophytes, 9 isolates of Trichophyton erinacei and 5 isolates of Microsporum persicolor. MICs of chlorhexidine did not vary significantly between the three dermatophyte species tested, but the MICs of miconazole alone and in combination with chlorhexidine for T. erinacei were significantly greater that those for T. mentagrophytes and M. persicolor. A synergistic drug interaction was noted with one isolate of T. erinacei and one isolate of M. persicolor. An additive effect was demonstrated for 13 isolates (5 T. mentagrophytes, 6 T. erinacei, 2 M. persicolor), and indifference was noted in 8 isolates (4 T. mentagrophytes, 2 T. erinacei, 2 M. persicolor). Although synergy was less often seen when compared with a previous study of Microsporum canis, the synergistic or additive effects seen with the majority (15 out of 23) of isolates studied in vitro provides a rationale for the combined use of miconazole and chlorhexidine in the adjunctive topical therapy of dermatophytosis caused by T. mentagrophytes, T. erinacei and M. persicolor.