bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactation and gestation in dairy cows: flexibility avoids nutritional extremes
Authors: Knight Christopher H.
Published: September 2008

The modern dairy cow has been selectively bred to produce large amounts of milk. Partly as a result, food consumption is considerably less than milk energy output in early lactation. It is only at 2 months or more postpartum that intake increases to the point where positive energy balance is regained, the initial production being achieved by a substantial mobilisation of body reserves. These reserves are laid down before parturition, but it is certainly not the case that the pregnant cow will accumulate adipose tissue recklessly; in the last third of pregnancy well-fed cows in good body condition exhibit reduced, not increased, appetite. There is a fine balancing act to perform. Excessive body condition at parturition quickly leads to metabolic problems such as ketosis, but cows who subsequently become too thin have increased risk of metabolic diseases such as mastitis and lameness. The biological mechanisms regulating output of milk are reasonably well understood, those controlling appetite less well so, and there has been little attempt at systematic integration of the two. The transition from pregnancy to lactation represents a major challenge to homeostasis, made more complicated in multiparous cows by the fact that much of gestation is concurrent with lactation. Herein lies the potential for nutritionally-entrained flexibility. In the wild, concurrent pregnancy and lactation only occur when nutritional conditions are favourable. If conditions are poor, rebreeding will be delayed and lactation will continue, at an energetically-sustainable level, for much longer than its ‘normal’ duration. In this way the twin energetic burdens of pregnancy and lactation are separated, and extremes are avoided. Given the increasing public concern about stresses suffered by intensively-managed dairy cows, this case may be one where commercial dairying could learn useful lessons from nature.
Immunity induced after a feed of antigen during early life: oral tolerancev. sensitisation
Authors: Strobel S.
Published: September 2008

There is good clinical and experimental evidence that oral tolerance exists in man and that the timing of antigen (food) administration is an important factor in the development of food allergic sensitisation and disease. Induction of tolerance is often seen as a T-helper 2-skewed response, which on one side may prevent harmful mucosal immune reactions, but on the other side may contribute to adverse responses in the susceptible individual. The primary mechanisms by which tolerance may be mediated include T-cell deletion, anergy, suppression ‘ignorance’ and apoptosis. Cell-mediated delayed hypersensitivity reactions (T-helper 1), which are implicated as a pathogenetic principle in the development of autoimmune and gastrointestinal inflammation are particularly well suppressed. Regulatory events during the induction of tolerance (or sensitisation) are not well characterised and remain at times controversial. The balance between tolerance (suppression) and sensitisation (priming) is dependent on several factors, such as: (a) genetic background; (b) nature of antigen and dose of antigen; (c) frequency of administration; (d) age (maturityv. immaturity) at first antigen exposure; (e) immunological status of the host (e.g. virus infection); dietary exposure of the mother; (g) antigen transmission via breast milk, and others. Overall, there is evidence in rodents that multiple low-dose feeds are more likely to induce regulatory cytokines (e.g. transforming growth factor-β, interleukins 10 and 4) in part secreted by CD4+CD25+ T-regulatory cells. Despite the powerful suppressive effect of oral antigen exposure observed in experimental models, its application in clinical trials of autoimmune diseases has not yet yielded the expected beneficial results.
Modification of enteral diets in inflammatory bowel disease
Authors: Aldhous Marian C. , Meister Doris , Meister Subrata
Published: September 2008

The provision of food is thought to promote the maintenance of gut integrity. Nutrients are able to elicit and affect both systemic and mucosal immune responses. Enteral diet therapy has long been known to be efficacious in inflammatory bowel disease (IBD), particularly in childhood Crohn's disease. However, the mechanisms of action of these diets are not clear. Nutritional repletion, direct effects on the gut mucosa or decreased intestinal permeability have all been postulated as being important in nutritional therapy. There is some evidence that the enteral diet has a direct effect on the gut mucosa by reducing cytokine production and the accompanying inflammation, thus leading to decreased intestinal permeability. Modifications of enteral diet composition have been evaluated in many studies. Such modifications include fat and/or protein content and the addition of bioactive peptides. The fatty acid composition of the enteral diet seems to have a much greater impact on its efficacy than modification of the N source. As specific fatty acids are precursors of inflammatory mediators derived from arachidonic acid, the reduction in these components may be beneficial in nutritional therapy for IBD. Addition of bioactive peptides to enteral diet formulas may also have a role; such peptides may have specific growth factor or anti-inflammatory actions. There is still much work to be done to define disease-specific enteral diet formulas that are effective as therapies for both Crohn's disease and ulcerative colitis.
Overweight, obesity and physical activity levels in Irish adults: evidence from the North/South Ireland Food Consumption Survey
Authors: McCarthy S. N. , Gibney M. J. , Flynn A. , Livingstone M. B. E.
Published: September 2008

In the present paper the prevalence of obesity (BMI 30 kg/m2) and current physical activity levels in Irish adults have been evaluated. The prevalence of obesity in Irish adults is currently 18 %, with men at 20 % and women at 16 %. A further 47 % of men and 33 % of women are overweight (BMI 25·0–29·9 kg/m2). Since 1990, obesity has more than doubled in men from 8 % to 20 %, and increased from 13 % to 16 % in women. The highest prevalence of obesity (30 %) was found in women aged 51–64 years. Defined waist circumference action levels identified 48 % of the population who are in need of weight management and who also are at a 1·5–4·5 times increased risk of having at least one cardiovascular disease risk factor. Physical activity levels were low overall. Men were more active in work and recreational pursuits than women, but women were more active in household activities. Walking was the most popular recreational pursuit. However, TV viewing occupied most of the leisure time of men and women. Higher levels of activity were associated with a lower BMI and waist circumference. The results indicate the need for sensitive and individualised strategies to promote physical activity and to achieve a healthy weight status.
The use of food consumption data in assessments of exposure to food chemicals including the application of probabilistic modelling
Authors: Lambe Joyce
Published: September 2008

Emphasis on public health and consumer protection, in combination with globalisation of the food market, has created a strong demand for exposure assessments of food chemicals. The food chemicals for which exposure assessments are required include food additives, pesticide residues, environmental contaminants, mycotoxins, novel food ingredients, packaging-material migrants, flavouring substances and nutrients. A wide range of methodologies exists for estimating exposure to food chemicals, and the method chosen for a particular exposure assessment is influenced by the nature of the chemical, the purpose of the assessment and the resources available. Sources of food consumption data currently used in exposure assessments range from food balance sheets to detailed food consumption surveys of individuals and duplicate-diet studies. The fitness-for-purpose of the data must be evaluated in the context of data quality and relevance to the assessment objective. Methods to combine the food consumption data with chemical concentration data may be deterministic or probabilistic. Deterministic methods estimate intakes of food chemicals that may occur in a population, but probabilistic methods provide the advantage of estimating the probability with which different levels of intake will occur. Probabilistic analysis permits the exposure assessor to model the variability (true heterogeneity) and uncertainty (lack of knowledge) that may exist in the exposure variables, including food consumption data, and thus to examine the full distribution of possible resulting exposures. Challenges for probabilistic modelling include the selection of appropriate modes of inputting food consumption data into the models.
Maternal carbohydrate intake and pregnancy outcome
Authors: Clapp III James F.
Published: September 2008

Experimental evidence indicates that the primary maternal environmental factor that regulates feto–placental growth is substrate delivery to the placental site, which is the product of maternal substrate levels and the rate of placental-bed blood flow. Thus, maternal factors which change either substrate level or flow alter feto–placental growth rate. The best-studied substrate in human pregnancy is glucose, and there is a direct relationship between maternal blood glucose levels and size at birth. Altering the type of carbohydrate eaten (high-v.low-glycaemic sources) changes postprandial glucose and insulin responses in both pregnant and non-pregnant women, and a consistent change in the type of carbohydrate eaten during pregnancy influences both the rate of feto–placental growth and maternal weight gain. Eating primarily high-glycaemic carbohydrate results in feto–placental overgrowth and excessive maternal weight gain, while intake of low-glycaemic carbohydrate produces infants with birth weights between the 25th and the 50th percentile and normal maternal weight gain. The calculated difference in energy retention with similar total energy intakes is of the order of 80 000 kJ. Preliminary information from subsequent metabolic studies indicates that the mechanisms involved include changes in: daily digestible energy requirements (i.e. metabolic efficiency), substrate utilization (glucose oxidationv.lipid oxidation), and insulin resistance and sensitivity. Thus, altering the source of maternal dietary carbohydrate may prove to be a valuable tool in the management of pregnancies at risk for anomalous feto–placental growth and for the prevention and/or treatment of obesity and insulin resistance in the non-pregnant state.
Dietary essential fatty acids and brain function: a developmental perspective on mechanisms
Authors: Wainwright Patricia E.
Published: September 2008

Brain development is a complex interactive process in which early disruptive events can have long-lasting effects on later functional adaptation. It is a process that is dependent on the timely orchestration of external and internal inputs through sophisticated intra- and intercellular signalling pathways. Long-chain polyunsaturated fatty acids (LCPUFA), specifically arachidonic acid and docosahexaenoic acid (DHA), accrue rapidly in the grey matter of the brain during development, and brain fatty acid (FA) composition reflects dietary availability. Membrane lipid components can influence signal transduction cascades in various ways, which in the case of LCPUFA include the important regulatory functions mediated by the eicosanoids, and extend to long-term regulation through effects on gene transcription. Our work indicates that FA imbalance as well as specific FA deficiencies can affect development adversely, including the ability to respond to environmental stimulation. For example, although the impaired water-maze performance of mice fed a saturated-fat diet improved in response to early environmental enrichment, the brains of these animals showed less complex patterns of dendritic branching. Dietaryn-3 FA deficiency influences specific neurotransmitter systems, particularly the dopamine systems of the frontal cortex. We showed that dietary deficiency ofn-3 FA impaired the performance of rats on delayed matching-to-place in the water maze, a task of the type associated with prefrontal dopamine function. We did not, however, find an association over a wider range of brain DHA levels and performance on this task. Some, but not all, studies of human infants suggest that dietary DHA may play a role in cognitive development as well as in some neurodevelopmental disorders; this possibility has important implications for population health.
An obesity clinic model
Authors: Munnelly Patricia , Feehan S.
Published: September 2008

The high incidence of obesity in Ireland is of growing concern. The Irish Universities Nutrition Alliance North/South Food Consumption Survey found that 18 % of the population are obese and 39 % overweight. Obesity and overweight increase the risk of developing CHD, type 2 diabetes, hypertension and some forms of cancer. It is well accepted that the best treatment for obesity is a combination of energy intake reduction and regular exercise. Previously, dietary compliance has been shown to improve when monitored on a regular basis. The lengthy delay between clinic visits to the dietitian has been reported by those who failed to lose weight to be the main reason for poor compliance. A weight monitoring clinic was designed to offer those requiring regular support and encouragement the opportunity to monitor their weights on a more regular basis, while waiting for their return visit to the dietitian in the Outpatient Departments. As resources were limited, an efficient use of time was essential. The clinic design was: 1 h/week; eight to fourteen appointments per clinic; weekly or fortnightly visit; return patients only. The clinic was started on a trial basis in June 1999, and was evaluated in December 2000. Referrals were only taken from other dietitians, and each participant was informed in advance of the necessity of having a return Outpatient Department appointment for full dietary review. Forty-eight participants attended more than three times up to and including December 2000 (seven males, forty-one females). The number of clinic visits ranged from three to twenty-eight. Mean weight at start of clinic was 92·94 kg. Of the group attending, 67 % (thirty-two) successfully lost weight and maintained this weight loss. This ranged from 0·1 kg to 23·5 kg. While in total 31 % (fifteen) of attendees had gained weight at December 2000, all attendees, including this fifteen, had lost weight at some point during the clinic. Self-reported reasons given for weight regain included: (1) non-attendance at weight clinic (40 %); (2) Christmas or holidays (13 %); (3) stress related to family, work (13 %); (4) ill-health or medication (13 %). The remaining 20 % reported no reason. Other findings included better compliance with diet and improved overall balance. There was an overall improvement in other dietary-related problems, e.g. reduced cholesterol, improved glycaemic control, reduced blood pressure. The participants attending the clinic reported decreased clothes size and improved self-image and confidence. They were more enthusiastic about dietary compliance, and all attendees expressed their satisfaction with the clinic and the service.
Evidence for consistent patterns between flavonoid structures and cellular activities
Authors: Depeint* F. , Gee J. M. , Williamson G. , Johnson I. T.
Published: September 2008

A wide variety of plant-derived compounds, including the polyphenolic flavonoids, is present in the human diet or is consumed for medicinal reasons. Epidemiological and animal studies tend to suggest a protective effect of flavonoids against cardiovascular diseases and some types of cancer. Although flavonoids have been studied for about 50 years, the cellular mechanisms involved in their biological activity are still largely unknown. Antioxidant properties of the flavonoids have been postulated as a mechanism for putative protective effect against cardiovascular disease. Nevertheless, these properties alone are not sufficient to explain the anti-carcinogenic potential of these polyphenols. The mechanisms by which the molecules interact with cells or are absorbed by them are very important for determining the intracellular concentration and distribution of the metabolites to internal organs. With the exception of the cells lining the gastrointestinal tract, all other cells in the body are only exposed to flavonoid metabolites and degradation products. No previous studies have addressed this aspect of cellular exposure, except for some methylated metabolites. Within the last decade, reports on flavonoid activities have been largely associated with enzyme inhibition and anti-proliferative activity. From our recent work on the human colon cancer cell line HT29 and comparison with published studies, structure–function relationships demonstrate that antioxidant, enzyme inhibitor or anti-proliferative activities are dependent on particular structure motifs. The present review also presents a summary of mechanistic data on a few selected compounds.
Genetically modified foods, science, consumers and the media
Authors: Rowland I. R.
Published: September 2008

In contrast to the situation in the USA, where a wide range of genetically modified (GM) foods is available, in Europe very few GM products have been approved for marketing as foods, and there is widespread public concern about their safety and environmental impact. The marketing of a GM crop for food use in Europe falls under the EC novel foods regulations, and applications require the submission of an extensive dossier of information. The safety evaluation of GM foods presents considerable problems both in the conduct and interpretation of experimental studies, because conventional toxicity tests used in the evaluation of simple chemicals may not be appropriate for whole foods. To rationalise the safety evaluation process and to circumvent the difficulties in toxicological assessment of food materials, the concept of substantial equivalence has been developed. The concept is that if it can be demonstrated that the novel food is essentially similar to its conventional counterpart in terms of critical nutritional or anutritional components, then it is likely to be no more or less toxic than the latter. The possible introduction of unintended effects by the genetic modification process is particularly problematic for the safety evaluation process. The new genomic and post-genomic techniques are potentially valuable in the safety evaluation of GM foods, although they are as yet in their infancy.
Nutrient insult in early pregnancy
Authors: Coad Jane , Al-Rasasi Buthaina , Morgan Jane
Published: September 2008

Nutrient insults in early pregnancy, such as nutrient deprivation during famines, are often associated with an unfavourable outcome. Suboptimal nutrition in the early stage of gestation has been linked to a number of adverse effects on fetal growth and development. Historically, nausea and vomiting in pregnancy (NVP) was an important contributor to pregnancy-related mortality; indeed, Charlotte Bronte died from starvation and dehydration after suffering very severe NVP 4 months into her first pregnancy (Gaskell, 1858). Although NVP seldom now progresses to be life-threatening, it affects the majority of pregnant women, and potentially presents a challenge to nutrient intake in the most vulnerable period of development. Symptoms range from mild (nausea only) to severe (a level of vomiting that restricts nutrient intake and ultimately threatens metabolic and electrolyte balance). Although NVP has been documented for thousands of years, its cause has not yet been satisfactorily elucidated, but seems to be related to endocrinological changes. Pregnant women also frequently report dietary cravings and aversions during pregnancy which can be linked to both the incidence and severity of NVP. Paradoxically, NVP appears to be positively associated with a favourable outcome of pregnancy, including increased birth weight and gestational age. The mechanisms by which NVP favours the outcome of pregnancy are not known. They may be related to women increasing their nutrient intake to alleviate symptoms, improving the quality of their diet or reducing energy expenditure. Alternatively, adaptation to a reduced nutrient intake might stimulate the expression of growth factors and affect placentation or metabolism, thus favouring fetal growth when NVP resolves.
Early diet and growth: impact on ageing
Authors: Aihie Sayer* A. , Cooper C.
Published: September 2008

The modification of ageing by nutritional intervention is well recognised. Post-weaning diet restriction is the only widely reproducible method to slow ageing, but the effects of prenatal and preweaning diet restriction have been less well characterised. There is some evidence that diet restriction instituted in utero or shortly after birth may have an opposite effect and be associated with increased ageing, and recent work suggests that it may shorten lifespan. Interest in this area has been rekindled by the growing body of epidemiological evidence showing that a number of age-related diseases are associated with poor growth and inadequate nutrition in early life. The relevance of this association to structural and functional ageing changes in different systems is now being considered. Work on musculo-skeletal ageing has demonstrated that loss of muscle strength and bone mass is greater in individuals who did not grow well in early life, and a range of studies suggests that maternal, developmental and nutritional factors are important. The underlying mechanisms remain speculative, and it remains to be determined whether they are system-specific or universal throughout the body. A new cohort of subjects aged between 60 and 70 years is being established to investigate how genetic factors interact with growth and nutritional influences to programme musculo-skeletal ageing in later life.
Steroid hormone receptors and dietary ligands: a selected review
Authors: Jacobs* Miriam N. , Lewis David F. V.
Published: September 2008

Members of the nuclear steroid hormone superfamily mediate essential physiological functions. Steroid hormone receptors (SHR) act directly on DNA, regulate the synthesis of their target genes and are usually activated by ligand binding. Both endogenous and exogenous compounds and their metabolites may act as activators of SHR and disruptors of endocrine, cellular and lipid homeostasis. The endogenous ligands are generally steroids such as 17β-oestradiol, androgens, progesterone and pregnenolone. The exogenous compounds are usually delivered through the diet and include non-steroidal ligands. Examples of such ligands include isoflavanoids or phyto-oestrogens, and food contaminants such as exogenous oestrogens from hormone-treated cattle, pesticides, polychlorinated biphenyls and plasticisers. Certain drugs are also ligands; so nuclear receptors are also important drug targets for intervention in disease processes. The present review summarises recent reports on ligand-activated SHR that describe the selective regulation of a tightly-controlled cross-talking network involving exchange of ligands, and the control of major classes of cytochrome P450 (CYP) isoforms which metabolise many bioactive exogenous compounds. Many CYP have broad substrate activity and appear to be integrated into a coordinated metabolic pathway, such that whilst some receptors are ligand specific, other sensors may have a broader specificity and low ligand affinity to monitor aggregate levels of inducers. They can then trigger production of metabolising enzymes to defend against possible toxic nutrients and xenobiotic compounds. The influence of dietary intakes of nutrients and non-nutrients on the human oestrogen receptors (α and β), the aryl hydrocarbon receptor, the pregnane X receptor, the constitutive androstane receptor, and the peroxisome proliferator-activated receptors (α and γ), can be examined by utilising computer-generated molecular models of the ligand–receptor interaction, based on information generated from crystallographic data and sequence homology. In relation to experimental and observed data, molecular modelling can provide a scientifically sound perspective on the potential risk and benefits to human health from dietary exposure to hormone-mimicking chemicals, providing a useful tool in drug development and in a situation of considerable public concern.
Long-term changes in adipose tissue in human disease
Authors: Pond Caroline M.
Published: September 2008

Redistribution of white adipose tissue is a long-term symptom of several chronic diseases. Although the roles of adipocytes in acute illness have been thoroughly studied, how or why short-term responses of adipose tissue to disease sometimes produce long-term redistribution, and the causal relationship between the anatomical changes and the associated metabolic syndromes are poorly understood. The present paper reviews explanations for the redistribution of adipose tissue after infection with HIV, and in Crohn's disease; both conditions that share the peculiarity of selective expansion of certain adipose depots while others are depleted. HIV adipose tissue redistribution syndrome (HARS) develops gradually after several months of infection with the HIV both in untreated patients and in those taking protease inhibitors and nucleoside reverse transcriptase inhibitors. Some current theories about the causes of HARS are critically assessed, and reasons presented for implicating local interactions between the immune system and perinodal adipocytes. Some evolutionary aspects of conspicuous long-term changes in the distribution of human adipose tissue are discussed. Adipose tissue acts as a social signal, indicating dietary history and previous exposure to pathogens. A distinctive symptom of Crohn's disease is selective enlargement of the mesenteric adipose tissue near the diseased lymph nodes and intestine. Perinodal adipocytes have site-specific properties not found in adipocytes from nodeless depots, such as perirenal and epididymal, that may equip them to interact locally with lymph-node lymphoid cells, making polyunsaturated fatty acids selectively and rapidly available to activated immune cells. Studies of the time course of activation of perinodal adipocytes via the lymph nodes they enclose indicate that prolonged or frequent stimulation recruits more adipocytes to control by immune cells, which may lead to selective enlargement of node-containing depots. These concepts suggest hypotheses about HARS and the anomalous development of mesenteric adipose tissue in Crohn's disease that could form the basis for further investigations.
Excitation–Contraction Coupling of the Mouse Embryonic Cardiomyocyte
Authors: Rapila Risto , Korhonen Topi , Tavi Pasi
Published: September 2008

In the mammalian embryo, the primitive tubular heart starts beating during the first trimester of gestation. These early heartbeats originate from calcium-induced contractions of the developing heart muscle cells. To explain the initiation of this activity, two ideas have been presented. One hypothesis supports the role of spontaneously activated voltage-gated calcium channels, whereas the other emphasizes the role of Ca2+ release from intracellular stores initiating spontaneous intracellular calcium oscillations. We show with experiments that both of these mechanisms coexist and operate in mouse cardiomyocytes during embryonic days 9–11. Further, we characterize how inositol-3-phosphate receptors regulate the frequency of the sarcoplasmic reticulum calcium oscillations and thus the heartbeats. This study provides a novel view of the regulation of embryonic cardiomyocyte activity, explaining the functional versatility of developing cardiomyocytes and the origin and regulation of the embryonic heartbeat.
Luminal Mg2+, A Key Factor Controlling RYR2-mediated Ca2+ Release: Cytoplasmic and Luminal Regulation Modeled in a Tetrameric Channel
Authors: Laver Derek R. , Honen Bonny N.
Published: September 2008

In cardiac muscle, intracellular Ca2+ and Mg2+ are potent regulators of calcium release from the sarcoplasmic reticulum (SR). It is well known that the free [Ca2+] in the SR ([Ca2+]L) stimulates the Ca2+ release channels (ryanodine receptor [RYR]2). However, little is known about the action of luminal Mg2+, which has not been regarded as an important regulator of Ca2+ release.

The effects of luminal Ca2+ and Mg2+ on sheep RYR2 were measured in lipid bilayers. Cytoplasmic and luminal Ca2+ produced a synergistic increase in the opening rate of RYRs. A novel, high affinity inhibition of RYR2 by luminal Mg2+ was observed, pointing to an important physiological role for luminal Mg2+ in cardiac muscle. At diastolic [Ca2+]C, luminal Mg2+ inhibition was voltage independent, with Ki = 45 μM at luminal [Ca2+] ([Ca2+]L) = 100 μM. Luminal and cytoplasmic Mg2+ inhibition was alleviated by increasing [Ca2+]L or [Ca2+]C. Ca2+ and Mg2+ on opposite sides of the bilayer exhibited competitive effects on RYRs, indicating that they can compete via the pore for common sites.

The data were accurately fitted by a model based on a tetrameric RYR structure with four Ca2+-sensing mechanisms on each subunit: activating luminal L-site (40-μM affinity for Mg2+ and Ca2+), cytoplasmic A-site (1.2 μM for Ca2+ and 60 μM for Mg2+), inactivating cytoplasmic I1-site (∼10 mM for Ca2+ and Mg2+), and I2-site (1.2 μM for Ca2+). Activation of three or more subunits will cause channel opening. Mg2+ inhibition occurs primarily by Mg2+ displacing Ca2+ from the L- and A-sites, and Mg2+ fails to open the channel.

The model predicts that under physiological conditions, SR load–dependent Ca2+ release (1) is mainly determined by Ca2+ displacement of Mg2+ from the L-site as SR loading increases, and (2) depends on the properties of both luminal and cytoplasmic activation mechanisms.
Steady-state Function of the Ubiquitous Mammalian Na/H Exchanger (NHE1) in Relation to Dimer Coupling Models with 2Na/2H Stoichiometry
Authors: Fuster Daniel , Moe Orson W. , Hilgemann Donald W.
Published: September 2008

We describe the steady-state function of the ubiquitous mammalian Na/H exchanger (NHE)1 isoform in voltage-clamped Chinese hamster ovary cells, as well as other cells, using oscillating pH-sensitive microelectrodes to quantify proton fluxes via extracellular pH gradients. Giant excised patches could not be used as gigaseal formation disrupts NHE activity within the patch. We first analyzed forward transport at an extracellular pH of 8.2 with no cytoplasmic Na (i.e., nearly zero-trans). The extracellular Na concentration dependence is sigmoidal at a cytoplasmic pH of 6.8 with a Hill coefficient of 1.8. In contrast, at a cytoplasmic pH of 6.0, the Hill coefficient is <1, and Na dependence often appears biphasic. Results are similar for mouse skin fibroblasts and for an opossum kidney cell line that expresses the NHE3 isoform, whereas NHE1−/− skin fibroblasts generate no proton fluxes in equivalent experiments. As proton flux is decreased by increasing cytoplasmic pH, the half-maximal concentration (K1/2) of extracellular Na decreases less than expected for simple consecutive ion exchange models. The K1/2 for cytoplasmic protons decreases with increasing extracellular Na, opposite to predictions of consecutive exchange models. For reverse transport, which is robust at a cytoplasmic pH of 7.6, the K1/2 for extracellular protons decreases only a factor of 0.4 when maximal activity is decreased fivefold by reducing cytoplasmic Na. With 140 mM of extracellular Na and no cytoplasmic Na, the K1/2 for cytoplasmic protons is 50 nM (pH 7.3; Hill coefficient, 1.5), and activity decreases only 25% with extracellular acidification from 8.5 to 7.2. Most data can be reconstructed with two very different coupled dimer models. In one model, monomers operate independently at low cytoplasmic pH but couple to translocate two ions in “parallel” at alkaline pH. In the second “serial” model, each monomer transports two ions, and translocation by one monomer allosterically promotes translocation by the paired monomer in opposite direction. We conclude that a large fraction of mammalian Na/H activity may occur with a 2Na/2H stoichiometry.
ATP Inhibition of CLC-1 Is Controlled by Oxidation and Reduction
Authors: Zhang Xiao-Dong , Tseng Pang-Yen , Chen Tsung-Yu
Published: September 2008

The effect of intracellular adenosine triphosphate (ATP) on the “common gating” of the CLC-1 chloride channel has been studied by several laboratories with controversial results. Our previous study on the channel expressed in Xenopus oocytes using excised inside-out patch-clamp methods showed a robust effect of ATP in shifting the open probability curve of the common gate toward more depolarizing voltages (Tseng, P.Y., B. Bennetts, and T.Y. Chen. 2007. J. Gen. Physiol. 130:217–221). The results were consistent with those from studying the channel expressed in mammalian cells using whole cell recording methods (Bennetts, B., M.W. Parker, and B.A. Cromer. 2007. J. Biol. Chem. 282:32780–32791). However, a recent study using excised-patch recording methods for channels expressed in Xenopus oocytes reported that ATP had no direct effect on CLC-1 (Zifarelli, G., and M. Pusch. 2008. J. Gen. Physiol. 131:109–116). Here, we report that oxidation of CLC-1 may be the culprit underlying the controversy. When patches were excised from mammalian cells, the sensitivity to ATP was lost quickly—within 2–3 min. This loss of ATP sensitivity could be prevented or reversed by reducing agents. On the other hand, CLC-1 expressed in Xenopus oocytes lost the ATP sensitivity when patches were treated with oxidizing reagents. These results suggest a novel view in muscle physiology that the mechanisms controlling muscle fatigability may include the oxidation of CLC-1.
Epidemiology of Vancomycin-Resistant Enterococci Among Patients on an Adult Stem Cell Transplant Unit: Observations From an Active Surveillance Program
Authors: Calderwood Michael S. , Mauer Andreas , Tolentino Jocelyn , Flores Ernesto , van Besien Koen , Pursell Ken , Weber Stephen G.
Published: September 2008

Objective.

To use the findings of an active surveillance program to delineate the unique epidemiology of vancomycin-resistant enterococci (VRE) in a mixed population of transplant and nontransplant patients hospitalized on a single patient care unit.

Design.

Surveillance survey and case-control analysis.

Setting.

A 19-bed adult bone marrow and stem cell transplant unit at a referral and primary-care center.

Patients.

The study included patients undergoing transplantation, patients who had previously received bone marrow or stem cell transplants, and patients with other malignancies and hematological disorders who were admitted to the study unit.

Methods.

Patients not previously identified as colonized with VRE had perirectal swab specimens collected at admission and once weekly while hospitalized on the unit. The prevalence of VRE colonization at admission and the incidence throughout the hospital stay, genotypes of VRE specimens as determined by pulsed field gel electrophoresis, and risk factors related to colonization were analyzed.

Results.

There was no significant difference in the prevalence or incidence of new colonization between nontransplant patients and prior or current transplant recipients, although overall prevalence at admission was significantly higher in the prior transplant group. Preliminary genotypic analysis of VRE isolates from transplant patients suggests that a proportion of cases of newly detected VRE carriage may represent prior colonization not detected at admission, with different risk factors suggestive of a potential epidemiological distinction.

Conclusion.

Examination of epidemiological and microbiological data collected by an active surveillance program provides useful information about the epidemiology of VRE that can be applied to inform rational infection control strategies.
Contamination of Hospital Curtains With Healthcare-Associated Pathogens
Authors: Trillis Floyd , Eckstein Elizabeth C. , Budavich Rachel , Pultz Michael J. , Donskey Curtis J.
Published: September 2008

In a culture survey, we found that 42% of hospital privacy curtains were contaminated with vancomycin-resistant enterococci, 22% with methicillin-resistant Staphylococcus aureus, and 4% with Clostridium difficile. Hand imprint cultures demonstrated that these pathogens were easily acquired on hands. Hospital curtains are a potential source for dissemination of healthcare-associated pathogens.
Viola changii sp. nov. (Violaceae) from Guangdong, southern China
Authors: Zhou Jin‐Song , Xing Fu‐Wu
Published: September 2008

Viola changii J. S. Zhou & F. W. Xing sp. nov. (Violaceae), a new species from the Guangdong Province, China is described and illustrated. It is compared with the morphologically similar V. lucens.
Reduced levels of GH during GnRH analogue treatment in pubertal short girls born small for gestational age (SGA)
Authors: Van Der Kaay Daniëlle C. M. , Rose Susan R. , Van Dijk Marije , Noordam Cees , Van Rheenen Eva , Hokken‐Koelega Anita C. S.
Published: September 2008

Context  Several studies showed a decrease in height velocity during GnRH analogue (GnRHa) treatment. No information is available on GH levels during GnRHa treatment in short SGA girls.

Objective  To study overnight GH profiles and IGF‐I and IGFBP‐3 levels in girls with Tanner stage 2 and stage 3, before and after 3 months of GnRHa treatment, and to compare levels with those found in prepubertal short SGA girls.

Patients  Twenty‐four pubertal and 16 prepubertal short SGA girls.

Intervention  After baseline overnight GH profiles, pubertal girls received leuprorelide acetate depots of 3·75 mg subcutaneously every 4 weeks.

Outcome measures  GH, IGF‐I and IGFBP‐3 levels.

Results  At baseline, GH levels were comparable to levels found in prepubertal short SGA girls and IGF‐I and IGFBP‐3 SDS were significantly below the population mean. After 3 months of GnRHa treatment, AUC0 (P = 0·02), mean (P = 0·02) and maximum GH levels (P = 0·008) had significantly decreased. Mean GH levels were significantly lower than in prepubertal short SGA girls (P = 0·03). Eight girls with more than 40% decrease in mean GH levels also had a significantly greater decrease in IGF‐I and IGFBP‐3 levels. Mean and maximum GH levels at baseline correlated significantly with those after 3 months of GnRHa treatment.

Conclusion  Short SGA girls lack the normal increase in GH levels seen in puberty and have reduced IGF‐I and IGFBP‐3 levels, which might explain their reduced pubertal growth spurt. GnRHa treatment led to a significant reduction in GH levels. Therefore, combining GnRHa treatment with GH treatment might improve adult height of short SGA girls.
Novel mutation in the adiponectin (ADIPOQ) gene is associated with hypoadiponectinaemia in Japanese–Brazilians
Authors: Vendramini Marcio F. , Kasamatsu Teresa S. , Crispim Felipe , Ferreira Sandra R. , Matioli Sergio R. ,   Japanese‐Brazilian Diabetes Study Group, Moisés Regina S.
Published: September 2008

Objective  Adiponectin is an important mediator of insulin sensitivity, encoded by the ADIPOQ gene. Here we describe two Japanese–Brazilian families with hypoadiponectinaemia due to a novel mutation in ADIPOQ.

Design and patients  In this study, we examined the entire translated regions of adiponectin in Japanese–Brazilians, a population with one of the highest prevalence rates of diabetes worldwide. We screened 200 patients with type 2 diabetes (DM) and 240 age‐matched subjects with normal glucose tolerance.

Results  A novel heterozygous T deletion at position 186 in exon 2 of ADIPOQ, causing a frameshift at codon 62 and leading to a premature termination at codon 168 (p.Gly63ValfsX106), was found in two individuals with diabetes. This mutation was not found in 240 nondiabetic control subjects. In addition, we screened the mutation in an expanded set of 100 nondiabetic subjects from the general Brazilian population, but we found no mutations. In addition, six family members of the probands were identified as mutation‐carriers. Individuals who were mutation‐carriers had markedly low plasma adiponectin concentrations compared with those without the mutation [DM: 0·65 (0·59–1·34) µg/ml vs. 5·30 (3·10–8·55) µg/ml, P < 0·0001; normal glucose tolerance: 0·95 (0·76–1·48) µg/ml vs. 8·50 (5·52–14·55) µg/ml, P = 0·003]. All individuals carrying the p.Gly63ValfsX106 mutation and older than 30 years were found to be diabetic.

Conclusions  We describe for the first time a frameshift mutation in exon 2 of the ADIPOQ gene, which modulates adiponectin levels and may contribute to the genetic risk of late‐onset diabetes in Japanese–Brazilians.
Seasonal polydomy in a polygynous supercolony of the odorous house ant, Tapinoma sessile
Authors: BUCZKOWSKI GRZEGORZ , BENNETT GARY
Published: September 2008

Abstract 1. The odorous house ant, Tapinoma sessile, is a native ant species common throughout North America. In its natural habitat, T. sessile is a low‐key species that consists of small colonies. In invaded urban areas, T. sessile exhibits extreme polygyny and polydomy and becomes a dominant invasive pest.

2. The current study examined: (i) the density, persistence, and the spatial distribution of nests in a large supercolony of T. sessile, (ii) trail abundance and overall colony connectivity as facilitated by the network of trails, (iii) the abundance and the spatial distribution of competing ant species, and (iv) the effect of environmental factors on the number and distribution of T. sessile nests.

3. A distinct pattern of seasonal polydomy was observed, whereby the colony undergoes an annual fission‐fusion cycle. The colony occupies one or a few nests during the winter, experiences rapid exponential growth in the spring to colonize available nesting sites, reaches maximum nest density in the summer, and again coalesces in the winter, returning to the same winter location year after year. The trails show spatio‐temporal variation as well, depending on the location of nesting and foraging sites. Furthermore, nest movements may be driven by soil microclimate and proximity to man‐made structures.

4. In total, 119 ant nests were discovered in a 3.15 ha plot, 90 (76%) of which belonged to T. sessile. Tapinoma sessile exhibited strong colony connectivity as 78/90 (87%) of nests were connected to at least one other nest by a trail. Mean persistence time for T. sessile nests was 133 ± 5 days.

5. Results indicate that T. sessile is a highly adaptable native ant species that exhibits a high degree of flexibility in its colony social structure. A high degree of polygyny and polydomy may contribute to its ecological dominance and pest status in urban environments.
Genetic analysis of feeding preference in two related species of Altica (Coleoptera: Chrysomelidae: Alticinae)
Authors: XUE HUAI‐JUN , LI WEN‐ZHU , YANG XING‐KE
Published: September 2008

Abstract 1. Genetic analysis of feeding preference can make an important contribution to our understanding of the evolution of host‐plant selection in phytophagous insects. Two closely related flea beetles, Altica viridicyanea (Baly) and Altica fragariae Nakane, with separate host plants [Geranium wilfordii Maxim. and Duchesnea indica (Andrews) Focke respectively] were hybridised to analyse the inheritance mode of feeding preference.

2. Adult hybrid F1 (A. viridicyanea female × A. fragariae male) preferred G. wilfordii to D. indica in two‐choice tests, regardless of which plant they had fed on as larvae. Adults of one backcross to A. fragariae preferred D. indica to G. wilfordii, and the two backcrosses to A. viridicyanea consumed only a very small percentage of D. indica. Adult females of F2 showed no significant preference, whereas males of F2 showed slight preference for G. wilfordii over D. indica.

3. Both the mean feeding preference and the segregation pattern of beetles indicate that the feeding preference of A. viridicyanea and A. fragariae for G. wilfordii and D. indica, respectively, is mainly controlled by a major dominant autosomal gene (or several genes).

4. The variance between feeding preference and oviposition preference of female F2 indicate that the two behaviour traits of Altica species are controlled by different gene(s).
Haemophilic arthropathy: the importance of the earliest haemarthroses and consequences for treatment
Authors: ROOSENDAAL G. , JANSEN N. W. D. , SCHUTGENS R. , LAFEBER F. P. J. G.
Published: September 2008

Summary.  In a case of massive bleeding, the possibility of puncturing the joint can be considered to reduce the total load of intra‐articular blood, and thus the total load of iron which, in time, can be found in the synovium with devastating long‐term effects. Subsequent initiation of prophylaxis, still very early in life, might be more beneficial for the preservation of joints. Thus, it might be argued that the initiation of primary prophylaxis should be based on joint haemorrhage history rather than age and, according to some authors, preferably after the bleed in a single joint. The high cost of recombinant factor VIII may make widespread acceptance of prophylaxis impractical. Thus, beneficial results should be balanced with cost considerations. In this balance of treatment cost and efficacy, it must be taken into account that improperly treated haemophilia patients make great demands on healthcare systems (in terms of costs) because of their need for additional treatments such as expensive joint replacement surgery. However, where resources are limited, it can be argued that prophylaxis may be stopped in adulthood, in a certain proportion of all adult patients, with acceptable consequences for orthopaedic outcome in the long term. By doing so, limited amounts of clotting factor can be used for young patients with optimal cost effectiveness.
Prevention of arthropathy in haemophilia: prophylaxis
Authors: SANTAGOSTINO E. , MANCUSO M. E.
Published: September 2008

Summary.  At present, when resources allow, the main issue in preventing arthropathy in patients with haemophilia is determining the ‘optimal’ prophylaxis regimen rather than the choice between primary prophylaxis and on‐demand treatment. Barriers to prophylaxis implementation are still relevant and include difficulties with venous access, adherence to treatment regimens and costs. Prospective studies with different prophylactic regimens and objective outcome measures are still needed to determine the best cost–benefit ratio. The results from large retrospective cohorts followed up for decades in several European countries have shown that regular prophylaxis started at an early age is able to reduce physical impairment from haemophilic arthropathy. The efficacy of primary prophylaxis was finally demonstrated also in the setting of a randomized clinical trial.
Articular status of haemophilia patients with inhibitors
Authors: MORFINI M.
Published: September 2008

Summary.  The incidence of haemarthrosis is similar in young haemophilia patients with or without inhibitors, but whether this is due to the effect of modern therapy is unknown. In comparison with younger patients with haemophilia, older haemophilia patients have a lower incidence of haemarthrosis because of very severe arthropathy (crippled joints). It is not known whether this could be due to the lack of therapy in previous years. In addition, the burden of orthopaedic complications and the impact on quality of life are more severe in patients with haemophilia who have developed an inhibitor compared with those without inhibitors. This article describes the results of the European Study on Orthopaedic Status of Haemophilia Patients with inhibitors (ESOS) which set out to determine how the inhibitor status of haemophilia patients may influence their quality of life and degree of arthropathy.