bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for the sucrose‐binding protein role in carbohydrate metabolism and transport at early developmental stage
Authors: Waclawovsky Alessandro Jaquiel , Loureiro Marcelo Ehlers , Freitas Rejane do Livramento , Rocha Carolina da Silva , Cano Marco Antonio Oliva , Fontes Elizabeth Pacheco Batista
Published: October 2006

Despite the large amount of data regarding sucrose‐binding proteins (SBP), their functions remain largely unknown and controversial. In this investigation we performed a detailed temporal and spatial characterization of the phenotypes related to photosynthesis, sucrose exudation and carbohydrate metabolism in SBP antisense plants to gain insights into the physiological role of SBP. Significant reductions in net photosynthesis and in stomatal conductance were observed in the SBP antisense lines but were restricted to the vegetative phase, and persisted during a daily time course at this phase. Photosynthesis was saturated at a substantially lower irradiance in source leaves of the antisense lines, suggesting that light utilization is decreased in these plants. A slight reduction in soluble sugars was observed throughout the development of source leaves, partially overlapping a decrease in sucrose synthase activity (EC 2.4.1.13); whereas a transient increase in starch and adinosine diphosphate (ADP)‐glucose pyrophosphorylase activity (EC 2.7.7.27) as well as decreased leaf sucrose exudation were detected in the beginning of the vegetative phase. These changes in source leaves were accompanied by reductions in sucrose and starch in sink leaves, hexoses and sucrose in roots and hexoses in shoot apex, which were observed before the occurrence of a significant reduction in height and in leaf number in the transgenic lines. These alterations in growth parameters did not persist throughout the development, but were associated with a delay in flowering time and leaf senescence in the SBP antisense lines. A likely involvement of SBP in sink strength is discussed.
Effect of short‐term salt stress on the metabolic profiles of pyrimidine, purine and pyridine nucleotides in cultured cells of the mangrove tree, Bruguiera sexangula
Authors: Suzuki‐Yamamoto Mihoko , Mimura Tetsuro , Ashihara Hiroshi
Published: October 2006

To investigate the short‐term (3 h) effect of salt on the metabolism of purine, pyrimidine and pyridine nucleotides in mangrove (Bruguiera sexangula) cells, we examined the uptake and overall metabolism of radiolabelled intermediates involved in the de novo pathways and substrates of salvage pathways for nucleotide biosynthesis in the presence and absence of 100 mM NaCl. Uptake by the cells of substrates for the salvage pathways was much faster than uptake of intermediates of the de novo pathways. The activity of the de novo pyrimidine biosynthesis estimated by [2‐14C]orotate metabolism was not significantly affected by the salt. About 20–30% of [2‐14C]uridine, [2‐14C]uracil and more than 50% of [2‐14C]cytidine were salvaged for pyrimidine nucleotide biosynthesis. However, substantial quantities of these compounds were degraded to 14CO2 via β‐ureidopropionate (β‐UP), and degradation of β‐UP was increased by the salt. The activities of the de novo pathway, estimated by [2‐14C] 5‐aminoimidazole‐4‐carboxamide ribonucleoside, and the salvage pathways from [8‐14C]adenosine and [8‐14C]guanosine for the purine nucleotide biosynthesis were not influenced by the salt. Most [8‐14C]hypoxanthine was catabolised to 14CO2, and other purine compounds are also catabolised via xanthine. Purine catabolism was stimulated by the salt. [3H]Quinolinate, [carbonyl‐14C]nicotinamide and [carboxyl‐14C]nicotinic acid were utilised for the biosynthesis of pyridine nucleotides. The salvage pathways for pyridine nucleotides were significantly stimulated by the salt. Trigonelline was synthesised from all pyridine precursors that were examined; its synthesis was also stimulated by the salt. We discuss the physiological role of the salt‐stimulated reactions of nucleotide metabolism.
Allopurinol as an adjunct to lithium and haloperidol for treatment of patients with acute mania: a double‐blind, randomized, placebo‐controlled trial
Authors: Akhondzadeh Shahin , Milajerdi Mehdi Rafiee , Amini Homayoun , Tehrani‐Doost Mehdi
Published: October 2006

Objective:  Allopurinol, a hypouricemic agent, has been shown to present therapeutic effects in mania associated with hyperuricemia. This study assessed the efficacy and safety of risperidone as an adjunctive agent to lithium and haloperidol for the treatment of acute mania in hospitalized bipolar patients.

Methods:  Eighty‐two patients aged between 18 and 49 were eligible to participate, as they met the DSM‐IV criteria for a current manic episode, on the basis of a clinical interview by two academician psychiatrists. In addition, a score of at least 20 points on the Young Mania Rating Scale was required representing at least a moderate‐to‐severe mania. Forty‐one patients were randomly allocated to lithium (1–1.2 mEq/L) + haloperidol (10 mg/day) + allopurinol (300 mg/day) (group A) or lithium (1–1.2 mEq/L) + haloperidol (10 mg/day) + placebo (group B) for an 8‐week, double‐blind, placebo‐controlled study. Patients were assessed by a third‐year resident of psychiatry at baseline and at 7, 14, 28, 42, and 56 days after the medication started. The mean decrease in the Young Mania Rating Scale score from baseline was used as the main outcome measure of response of mania to treatment. The extrapyramidal symptoms were assessed using the Extrapyramidal Symptoms Rating Scale (ESRS). Side effects were systematically recorded throughout the study and were assessed using a checklist.

Results:  Young Mania Rating Scale scores improved with allopurinol. The difference between the two protocols was significant as indicated by the effect of the group, the between‐subjects factor (F = 5.22, df = 1, p = 0.008). The mean ESRS scores for the placebo group were higher than the allopurinol group. However, the differences were not significant over the trial. The difference between the two groups in the frequency of side effects was not significant except for agitation that was more often in the placebo group.

Conclusions:  The efficacy of allopurinol to obtain a greater improvement in patients with mania seems to support the purinergic dysfunction in mania.
Rational approaches to the neurobiologic study of youth at risk for bipolar disorder and suicide
Authors: Elizabeth Sublette M , Oquendo Maria A , John Mann J
Published: October 2006

Objectives:  The aims of this paper are to provide an overview of neuroimaging findings specific to bipolar disorder and suicide, and to consider rational approaches to the design of future in vivo studies in youth at risk.

Methods:  Neuroimaging and related neurobiological literature pertaining to bipolar disorder and suicide in adult and pediatric samples was reviewed in a non‐quantitative manner.

Results:  Specific structural and functional brain findings in bipolar disorder are described, where possible in the context of relevant current neurobiological theories of etiology. Diagnostic and prognostic implications are discussed.

Conclusions:  The simultaneous use of complementary neurobiological approaches may be a powerful way of identifying and validating factors reliably associated with bipolar disorder and suicide. A profile of neurobiological markers with which to screen for bipolar disorder and suicide risk may provide for earlier and more accurate diagnosis, perhaps even in the pre‐ or subsyndromal stages in high‐risk youth.
A novel technique to evaluate fluctuations of mood: implications for evaluating course and treatment effects in bipolar/affective disorders
Authors: Sree Hari Rao V , Raghvendra Rao C , Yeragani Vikram K
Published: October 2006

Objectives:  Several psychiatric conditions are associated with frequent fluctuations of affect. In this study, we propose a new technique to uniformly score depression and mania objectively and use a new mathematical technique to model the frequent fluctuations in mood using simulated data. Our main aim is to examine the usefulness of this measure for evaluating treatment effects or course of illness, especially in bipolar or unipolar affective illness to quantify mood fluctuations.

Methods:  We use a prototypical model, which takes into account the mean, the standard deviation (SD) and the coefficient of variation (CV = SD*100/mean) of the mood scores of the subjects over a user‐defined period. We utilize simulated data of subjects for euthymia, minor depression, minor mania, severe depression, severe mania and cyclic bipolar illness (manic depression, MDP). We propose an objective method to quantify the mood of the subjects at weekly intervals (the interval can be user‐defined) using a scale of 1–9 (1–4 = degrees of depression, 5 = euthymia, 6–9 = degrees of mania). These scores can be sampled according to the convenience and feasibility of the measurements, which can be derived from various clinical scales or by observation of the subjects in hospitals or other environments. We derive a new mathematical technique to arrive at a normalized measure for each of these conditions of simulated data in addition to the mean, SD and approximate entropy (ApEn).

Results:  We utilize three sets of data, one to train the model to classify the condition of the subjects and the other two to test the reliability of the technique. We are able to successfully classify the condition of the subjects over a 52‐timepoint period (length can be days or weeks depending upon the sampling rate). The New Index (NI) correlates significantly only with the mean (r2 = 0.78), but not with the SD or ApEn score.

Conclusions:  These results indicate that it may be beneficial to reduce data according to the techniques we propose so that there is greater uniformity within which to compare future studies to evaluate treatment effects, not only in rapid‐cycling MDP but also in other affective disorders. This method may be suitable for the meta‐analysis of several studies, although different scales have been used in each of those studies. Our measure derived from simulated data has shown sufficient deviation of all the abnormal states from the euthymic state. The advantages and pitfalls of these techniques are further discussed to evaluate affect in various disorders. However, future prospective studies must address the importance of this measure in comparison with mean, SD and ApEn scores or other nonlinear measures of these time series. We are evaluating other nonlinear dynamic models, which may provide a continuous measure with which to identify different degrees of fluctuation of mood.
A comparison of the medical lethality of suicide attempts in bipolar and major depressive disorders
Authors: Zalsman Gil , Braun Melanie , Arendt Mikkel , Grunebaum Michael F , Sher Leo , Burke Ainsley K , Brent David A , Chaudhury Sadia R , John Mann J , Oquendo Maria A
Published: October 2006

Objectives:  Among mood disorders, bipolar disorder (BPD) is often noted to involve the highest rates of suicide attempts and possibly of completion. This study sought to determine whether suicide attempters with BPD exhibit suicide attempts with higher lethality than attempters with major depressive disorder (MDD) and to explore differences in clinical features associated with suicidal acts.

Methods:  Mood disordered suicide attempters were interviewed about Axis I and II diagnoses, lifetime history of suicide attempts, suicidal intent, suicidal ideation, the medical lethality of their most severe suicide attempt, severity of depression, hopelessness, lifetime aggression, and impulsivity.

Results:  The maximum lethality of suicidal acts tended to be higher among BPD attempters compared with those with MDD. However, there were no differences in the number of suicide attempts, intent to die or suicidal ideation. Suicide attempters with BPD reported higher levels of aggression and impulsivity but less hopelessness compared with MDD attempters. These differences could not be explained by Cluster B personality disorder comorbidity. Of note, within the BPD group, but not the MDD group, males reported suicidal acts with higher lethality. Multivariate analyses suggested that risk for more lethal suicide attempts is associated with BPD and male sex and that bipolar males appear to be especially vulnerable to these behaviors.

Conclusions:  Males with BPD make more lethal suicide attempts than females with BPD, an effect not observed among the MDD sample. Our findings suggest that higher rates of suicidal behavior in BPD may be due to a specific effect of BPD on males, leading to more dangerous suicidal behaviors. This effect, together with the larger proportion of males in the BPD group compared with the MDD group may lead to higher rates of reported attempted and completed suicide.
Social semantics: altruism, cooperation, mutualism, strong reciprocity and group selection
Authors: WEST S. A. , GRIFFIN A. S. , GARDNER A.
Published: October 2006

From an evolutionary perspective, social behaviours are those which have fitness consequences for both the individual that performs the behaviour, and another individual. Over the last 43 years, a huge theoretical and empirical literature has developed on this topic. However, progress is often hindered by poor communication between scientists, with different people using the same term to mean different things, or different terms to mean the same thing. This can obscure what is biologically important, and what is not. The potential for such semantic confusion is greatest with interdisciplinary research. Our aim here is to address issues of semantic confusion that have arisen with research on the problem of cooperation. In particular, we: (i) discuss confusion over the terms kin selection, mutualism, mutual benefit, cooperation, altruism, reciprocal altruism, weak altruism, altruistic punishment, strong reciprocity, group selection and direct fitness; (ii) emphasize the need to distinguish between proximate (mechanism) and ultimate (survival value) explanations of behaviours. We draw examples from all areas, but especially recent work on humans and microbes.
Selection on flowering time and floral display in an alpine and a lowland population of Arabidopsis lyrata
Authors: SANDRING S. , RIIHIMÄKI M.‐A. , SAVOLAINEN O. , ÅGREN J.
Published: October 2006

To determine whether population differentiation in flowering time is consistent with differences in current selection, we quantified phenotypic selection acting through female reproductive success on flowering phenology and floral display in two Scandinavian populations of the outcrossing, perennial herb Arabidopsis lyrata in two years. One population was located in an alpine environment strongly affected by grazing, whereas the other was close to sea level and only moderately affected by herbivory. Multiple regression models indicated directional selection for early end of flowering in one year in the lowland population, and directional selection for early start of flowering in one year in the alpine population. As expected, there was selection for more inflorescences in the lowland population. However, in the alpine population, plants with many inflorescences were selectively grazed and the number of inflorescences produced was negatively related to female fitness in one year and not significantly related to female fitness in the second year. The results are consistent with the hypothesis that genetic differentiation in flowering phenology between the study populations is adaptive, and indicate that interactions with selective grazers may strongly influence selection on floral display in A. lyrata.
Primary Hyperaldosteronism in a Dog with Concurrent Lymphoma
Authors: Johnson K. D. , Henry C. J. , McCaw D. L. , Turnquist S. E. , Stoll M. R. , Kiupel M. , Bondy P. J.
Published: October 2006

An 11‐year‐old, male castrated English springer spaniel was presented for muscle weakness, lethargy and anorexia while undergoing treatment of Stage IV lymphoma. Persistent hypokalemia prompted multiple diagnostic tests. Serum aldosterone levels, surgical exploration and histopathology confirmed primary hyperaldosteronism. Hyperaldosteronism is a rarely reported endocrinopathy in the dog. This report describes a case in which immunohistochemistry was utilized to confirm the diagnosis of an aldosterone‐secreting tumour.
ALTERING EXTRACELLULAR POTASSIUM CONCENTRATION DOES NOT MODULATE DRUG BLOCK OF HUMAN ETHER‐A‐GO‐GO‐RELATED GENE (hERG) CHANNELS
Authors: Limberis James T , Su Zhi , Cox Bryan F , Gintant Gary A , Martin Ruth L
Published: October 2006

Drug‐induced block of the rapidly activating delayed rectifier K+ current (IKr), encoded by human ether‐a‐go‐go‐related gene (hERG), has been linked to acquired long QT syndrome (aLQTS). Hypokalaemia is a recognized risk factor in aLQTS. To further understand why hypokalaemia is a risk factor in aLQTS, we examined the effect of [K+]o on drug block of the hERG potassium channel stably expressed in human embryonic kidney (HEK‐293) cells using whole‐cell voltage‐clamp techniques.

The effects of selected [K+]o (1–20 mmol/L) on hERG block with four structurally diverse compounds (dofetilide, mesoridazine, quinidine and terfenadine) from different therapeutic classes were evaluated. Reducing [K+]o from 20 to 1 mmol/L had little effect on IC50 values for hERG current block for all four compounds. For example, evaluating quinidine in external potassium concentrations of 20, 10, 5 and 1 mmol/L resulted in IC50 values of 1.82 ± 0.33, 2.04 ± 0.28, 1.57 ± 0.52 and 1.14 ± 0.21 mmol/L, respectively. No statistically significant difference (P > 0.35, anova) was observed between drug block of hERG in different external potassium concentrations. These data are in contrast with previously reported results examining hERG channel modulation expressed in AT‐1 cells under similar experimental conditions.

These results demonstrate that [K+]o does not directly modulate drug block of hERG channels expressed in an HEK‐293 cell line. The enhanced risk of Torsades de Pointes associated with hypokalaemia in aLQTS may be due to reduction of other (non‐hERG) potassium currents, further reducing the repolarization reserve, and not due to direct modulation of hERG block by [K+]o.
VOLTAGE AND IONIC REGULATION OF HUMAN SEROTONIN TRANSPORTER IN XENOPUS OOCYTES
Authors: Li Cizhen , Zhong Hua , Wang Yiyin , Wang Hongwei , Yang Zhifang , Zheng Yanqian , Liu Kai , Liu Yuanmou
Published: October 2006

The serotoninergic system is known to be involved in the control of multiple behavioural and physiological functions. The serotonin (5‐hydroxtryptamine; 5‐HT) transporter (SERT), which controls the synaptic 5‐HT concentration through re‐uptake of this neurotransmitter into presynaptic terminals, has been a primary therapeutic target for various psychiatric and peripheral disorders. The aim of the present study was to identify the regulatory mechanism(s) of the human SERT (hSERT) in heterologously expressed oocytes.

The hSERT cRNA was transcribed in vitro and injected into Xenopus oocytes. The 5‐HT‐induced transporter currents were measured by voltage clamp. The effects of extracellular sodium or chloride were studied by replacement perfusion with tetramethylammonium‐chloride (96 mmol/L) or sodium acetate (96 mmol/L). In addition, to alter the internal calcium concentration, CaCl2 (50 µmol/L) and inositol triphosphate (IP3; 50 µmol/L), with or without EGTA (2.5 mmol/L), were injected into oocytes. The specificity of 5‐HT‐sensitive currents was determined by the use of the SERT antagonist desipramine and niflumic acid to block background chloride currents.

The hSERT‐expressing oocytes displayed voltage‐dependent, 5‐HT‐induced currents that increased at negative potentials. Replacing extracellular sodium or chloride significantly decreased the hSERT currents by 89 and 45%, respectively (P < 0.05, n = 7 each). Injection of IP3 or CaCl2 increased the hSERT currents by approximately 65% (P < 0.05; n = 10 each) and the effect of IP3 was abolished by preinjection of EGTA.

These results demonstrate that hSERT activity is not only voltage dependent, but is also affected by intracellular calcium and extracellular sodium and chloride.
Introductory perspective on the COREF Project
Authors: Iryu Yasufumi , Matsuda Hiroki , Machiyama Hideaki , Piller Werner E. , Quinn Terrence M. , Mutti Maria
Published: October 2006

Abstract  Coral reefs are tropic to subtropic, coastal ecosystems comprising very diverse organisms. Late Quaternary reef deposits are fossil archives of environmental, tectonic and eustatic variations that can be used to reconstruct the paleoclimatic and paleoceanographic history of the tropic surface oceans. Reefs located at the latitudinal limits of coral‐reef ecosystems (i.e. those at coral‐reef fronts) are particularly sensitive to environmental changes – especially those associated with glacial–interglacial changes in climate and sealevel. We propose a land and ocean scientific drilling campaign in the Ryukyu Islands (the Ryukyus) in the northwestern Pacific Ocean to investigate the dynamic response of the corals and coral‐reef ecosystems in this region to Late Quaternary climate and sealevel change. Such a drilling campaign, which we call the COREF (coral‐reef front) Project, will allow the following three major questions to be evaluated: (i) What are the nature, magnitude and driving mechanisms of coral‐reef front migration in the Ryukyus? (ii) What is the ecosystem response of coral reefs in the Ryukyus to Quaternary climate changes? (iii) What is the role of coral reefs in the global carbon cycle? Subsidiary objectives include (i) the timing of coral‐reef initiation in the Ryukyus and its causes; (ii) the position of the Kuroshio current during glacial periods and its effects on coral‐reef formation; and (iii) early carbonate diagenetic responses as a function of compounded variations in climate, eustacy and depositional mineralogies (subtropic aragonitic to warm‐temperate calcitic). The geographic, climatic and oceanographic settings of the Ryukyu Islands provide an ideal natural laboratory to address each of these research questions.
Best candidates for capsule endoscopy for obscure gastrointestinal bleeding
Authors: Ge Zhi‐Zheng , Chen Hai‐Ying , Gao Yun‐Jie , Hu Yun‐Biao , Xiao Shu‐Dong
Published: October 2006

Background and Aim:  Capsule endoscopy (CE) has an important role in the diagnosis of patients with obscure gastrointestinal bleeding. However, there was still controversy regarding the best candidates for CE. The present retrospective study aimed to access the best candidates for CE.

Methods:  There were 91 consecutive patients referred to the present study for 94 CE examinations from May 2002 to January 2005. They were divided into two groups (41 with active bleeding, and 50 with previous bleeding).

Results:  The CE findings were positive in 74.7%, suspicious in 11% of cases and negative in 14.3% of cases, respectively. The positive and suspected positive yield of CE were 75.6% and 19.5% in the active bleeding group, 74% and 4% in the previous bleeding group (P = 0.01), 75.7% and 21.6% in the overt bleeding group, 75% and 0% in the occult bleeding group (P = 0.206), 89.7% and 3.4% in patients who bled 2 weeks previously, 52.38% and 4.76% in patients who bled >2 weeks previously (P = 0.003), 75.6% and 19.5% in active bleeding group, 89.7% and 3.4% in patients who bled 2 weeks ago (P = 0.128).

Conclusions:  The best candidates for the procedure are those with active bleeding, or active bleeding in the previous 2 weeks.
Prospective randomized trial of transnasal versus peroral endoscopy using an ultrathin videoendoscope in unsedated patients
Authors: Murata Atsuhiko , Akahoshi Kazuya , Sumida Yorinobu , Yamamoto Hidehiko , Nakamura Kazuhiko , Nawata Hajime
Published: October 2006

Aim:  The aim of this study was to compare the acceptance and tolerance of transnasal and peroral esophagogastroduodenoscopy (EGD) using an ultrathin videoendoscope in unsedated patients.

Methods:  A total of 124 patients referred for diagnostic endoscopy were assigned randomly to have an unsedated transnasal EGD (n = 64) or peroral EGD (n = 60) with local anesthesia. An ultrathin videoendoscope with a diameter of 5.9 mm was used in this study. A questionnaire for tolerance was completed by the patient (a validated 0–10 scale where ‘0’ represents no discomfort/well tolerated and ‘10’ represents severe discomfort/poorly tolerated).

Results:  Of the 64 transnasal EGD patients, 60 patients (94%) had a complete examination. Four transnasal EGD examinations failed for anatomical reasons; all four patients were successfully examined when switched to the peroral EGD. All 60 peroral EGD patients had a complete examination. Between the transnasal and peroral groups, there was a statistically significant difference in scores for discomfort during local anesthesia (1.5 ± 0.2 vs 2.6 ± 0.3, P = 0.003), discomfort during insertion (2.3 ± 0.3 vs 4.3 ± 0.3, P = 0.001), and overall tolerance during procedure (1.6 ± 0.2 vs 3.8 ± 0.2, P = 0.001). In all, 95% of transnasal EGD patients and 75% of peroral EGD patients (P = 0.002) were willing to undergo the same procedure in the future. Four patients in the transnasal EGD group experienced mild epistaxis.

Conclusion:  For unsedated endoscopy using an ultrathin videoendoscope, transnasal EGD is well tolerated and considerably reduces patient discomfort compared with peroral EGD.
Cloning and expression profile of FLT3 gene during progenitor cell‐dependent liver regeneration
Authors: Aydin Iraz T , Tokcaer Zeynep , Dalgic Aydin , Konu Ozlen , Akcali Kamil C
Published: October 2006

Background and Aim:  The liver has a unique capacity to regenerate upon exposure to viral infections, toxic reactions and cancer formation. Liver regeneration is a complex phenomenon in which several factors participate during its onset. Cellular proliferation is an important component of this process and the factors that regulate this proliferation have a vital role. FLT3, a well‐known hematopoietic stem cell and hepatic lineage surface marker, is involved in proliferative events of hematopoietic stem cells. However, its contribution to liver regeneration is not known. Therefore, the aim of this study was to clone and examine the role of FLT3 during liver regeneration in rats.

Methods:  Partial cDNA of rat homolog of FLT3 gene was cloned from thymus and the tissue specific expression of this gene at mRNA and protein levels was examined by RT‐PCR and Western blot. After treating with 2‐AAF and performing hepatectomy in rats to induce progenitor‐dependent liver regeneration, the mRNA and protein expression profile of FLT3 was investigated by real‐time PCR and Western blot during liver regeneration. In addition, cellular localization of FLT3 protein was determined by immunohistochemistry.

Results:  The results indicated that rat FLT3 cDNA has high homology with mouse and human FLT3 cDNA. It was also found that FLT3 is expressed in most of the rat tissues and during liver regeneration. In addition, its intracellular localization is altered during the late stages of liver regeneration.

Conclusion:  The FLT3 receptor is activated at the late stages of liver regeneration and participates in the proliferation response that is observed during progenitor‐dependent liver regeneration.
Comprehensive malnutrition inflammation score as a marker of nutritional status in Chinese peritoneal dialysis patients
Authors: CHAN JESSIE YING WING , CHE KIT I , LAM KARRY MAU CHU , CHOW KAI‐MING , CHUNG KWOK‐YI , LI PHILIP KAM‐TAO , SZETO CHEUK‐CHUN
Published: October 2006

Background:  Malnutrition is common among peritoneal dialysis (PD) patients. However, the ideal marker of nutritional status in PD patients remained controversial.

Methods:  We studied 165 unselected adult PD patients. We compared the comprehensive Malnutrition‐Inflammation Score (MIS) and the 7‐point Subjective Global Assessment (SGA) score.

Results:  The mean age was 59.2 ± 11.5 years. Seventy patients were male. MIS significantly correlated with the SGA score (r =−0.667, P < 0.001). Of the 165 patients, 132 (80.0%) had similar classification of nutritional status by SGA and MIS (Group I); 17 (10.3%) were classified as normal by SGA but moderately malnourished by MIS (Group II), while 16 (9.7%) were classified as normal by MIS but moderately malnourished by SGA (Group III). Group II had been dialysed longer than Group I (71.7 ± 50.3 vs 40.7 ± 37.5 months, P = 0.011). As compared with Group I, Group III was more likely to require helper for PD exchange (37.5%vs 9.7%, P = 0.004), marginally more likely to be diabetic (62.5%vs 35.6%, P = 0.085) and had a slightly higher Charlson’s comorbidity score (6.13 ± 1.78 vs 4.98 ± 2.1, P = 0.085), although the latter two were not statistically significant.

Conclusion:  MIS has a reasonable correlation with the conventional SGA score in PD patients. Patients with limited self‐care capability, diabetes and multiple comorbidities probably had worse score (i.e. worse nutrition) revealed by SGA than by MIS, while patients who had been dialysed longer had worse score revealed by MIS than by SGA.
Elevated levels of interferon γ‐inducible protein‐10 and epithelial neutrophil‐activating peptide‐78 in patients with pulmonary sarcoidosis
Authors: SUGIYAMA Kanako , MUKAE Hiroshi , ISHII Hiroshi , KAKUGAWA Tomoyuki , ISHIMOTO Hiroshi , NAKAYAMA Seiko , SHIRAI Ryo , FUJII Takeshi , MIZUTA Yohei , KOHNO Shigeru
Published: October 2006

Objective and background:  Interferon γ‐inducible protein (IP)‐10 and epithelial neutrophil‐activating peptide (ENA)‐78 belong to the CXC chemokine family and are important factors in inflammatory lung diseases. In sarcoidosis, the potential role of IP‐10 to regulate the migration and activation of T‐cells towards sites of sarcoid activity has been suggested.

Methods:  In this study, the concentrations of IP‐10 and ENA‐78 in the serum and BAL fluid of patients with different stages of active pulmonary sarcoidosis (n = 41) and healthy subjects (n = 12) were measured by enzyme‐linked immunosorbent assay to evaluate the contribution of these CXC chemokines to this disease.

Results:  Serum and BAL fluid concentrations of IP‐10 and BAL fluid levels of ENA‐78 in patients with sarcoidosis were significantly higher than those in control subjects. The serum levels of IP‐10 were significantly increased only in patients with stages I and II sarcoidosis, while BAL fluid levels of ENA‐78 were increased only in stage III sarcoidosis. In addition, serum concentrations of IP‐10 were elevated in patients with extrapulmonary lesions compared with those without such lesions. In patients with sarcoidosis, IP‐10 concentrations in BAL fluid correlated with lymphocyte proportions in BAL fluid.

Conclusion:  IP‐10 may play an important role in regulating lymphocytes into the lung and that ENA‐78 may be associated with lung parenchymal disease in pulmonary sarcoidosis.
PROSPECTIVE STUDY TO DEVELOP AN ALGORITHM FOR INVESTIGATION BY ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY OR MAGNETIC RESONANCE CHOLANGIOPANCREATOGRAPHY*
Authors: Jenkins John T. , Williamson Barry W. A.
Published: October 2006

Background:  Identifying cost‐efficient and patient‐friendly pathways for those who present with suspected pancreatico‐biliary disease remains a challenge. Algorithms must be tailored to improve decision‐making. We assessed suitable criteria from which an algorithm for selection for endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography could be developed.

Methods:  Data on clinical, ultrasound and liver function test findings and outcome were recorded for consecutive patients undergoing ERCP and patients were stratified into different indications and a therapeutic ratio (TR) obtained for each (TR = number of therapeutic ERCP/total number of ERCP).

Results:  One hundred and twenty ERCP were attempted with 112 cannulations (93.3%). Seventy‐one therapeutic procedures were attempted with 64 (90.1%) successes. Forty‐two (35%) investigations were normal. Seven (6%) patients suffered complications. Thirteen indications were used. The TR varied according to the indication. The TR for jaundice with biliary dilatation was 0.85. In contrast, asymptomatic patients with deranged liver function test and normal gall bladder on USS had a TR of 0.17. Gallstones with cholestatic liver function test yielded a TR of 0.54. A TR of 0.7 was considered an appropriate ‘cut‐off’ for triage to ERCP or magnetic resonance cholangiopancreatography. An algorithm was generated based on these data. From this cohort, 50 (42%) patients would have been more appropriately investigated by magnetic resonance cholangiopancreatography, although 20 (40%) would have required therapy afterwards.

Conclusions:  An algorithm that separates indications by TR (TR > 0.7) may provide a cost‐efficient, patient‐friendly pathway for investigation and improve the use of resources.
REM sleep changes in rats induced by siRNA‐mediated orexin knockdown
Authors: Chen Lichao , Thakkar Mahesh M. , Winston Stuart , Bolortuya Yunren , Basheer Radhika , McCarley Robert W.
Published: October 2006

Short interfering RNAs (siRNA) targeting prepro‐orexin mRNA were microinjected into the rat perifornical hypothalamus. Prepro‐orexin siRNA‐treated rats had a significant (59%) reduction in prepro‐orexin mRNA compared to scrambled siRNA‐treated rats 2 days postinjection, whereas prodynorphin mRNA was unaffected. The number of orexin‐A‐positive neurons on the siRNA‐treated side decreased significantly (23%) as compared to the contralateral control (scrambled siRNA‐treated) side. Neither the colocalized dynorphin nor the neighbouring melanin‐concentrating hormone neurons were affected. The number of orexin‐A‐positive neurons on the siRNA‐treated side did not differ from the number on the control side 4 or 6 days postinjection. Behaviourally, there was a persistent (∼ 60%) increase in the amount of time spent in rapid eye movement (REM) sleep during the dark (active) period for 4 nights postinjection, in rats treated with prepro‐orexin siRNA bilaterally. This increase occurred mainly because of an increased number of REM episodes and decrease in REM‐to‐REM interval. Cataplexy‐like episodes were also observed in some of these animals. Wakefulness and NREM sleep were unaffected. The siRNA‐induced increase in REM sleep during the dark cycle reverted to control values on the 5th day postinjection. In contrast, the scrambled siRNA‐treated animals only had a transient increase in REM sleep for the first postinjection night. Our results indicate that siRNA can be usefully employed in behavioural studies to complement other loss‐of‐function approaches. Moreover, these data suggest that the orexin system plays a role in the diurnal gating of REM sleep.
The neural substrates of amphetamine conditioned place preference: implications for the formation of conditioned stimulus–reward associations
Authors: Rademacher David J. , Kovacs Beatrix , Shen Fei , Napier T. Celeste , Meredith Gloria E.
Published: October 2006

Associations formed between conditioned stimuli and drug reward are major contributors in human drug addiction. To better understand the brain changes that accompany this process, we used immunohistochemistry for c‐Fos (a neuronal activity marker), synaptophysin (a marker for synaptogenesis) and tyrosine kinase B receptor (a neurotrophic factor receptor that mediates synaptic plasticity) to investigate the neural substrates of amphetamine‐induced conditioned place preference in rats. Conditioned place preference was induced by both 1.0 mg/kg and 0.3 mg/kg doses of amphetamine. Furthermore, amphetamine conditioning increased the density of c‐Fos‐immunoreactive cells and these cells were fully colocalized with the tyrosine kinase B receptor in the dentate gyrus, CA1 field and basolateral amygdala. Amphetamine conditioning increased the density of synaptophysin‐immunoreactive varicosities in all brain regions studied, except the nucleus accumbens shell and dorsolateral striatum. The degree of conditioned place preference was highly correlated with c‐Fos‐immunoreactive cell density in the basolateral amygdala and with the density of synaptophysin‐immunoreactive varicosities in all mesolimbic regions studied. The latter correlation was particularly impressive for the ventral pallidum and basolateral amygdala. The formation of conditioned stimulus–amphetamine reward associations is accompanied by tyrosine kinase B receptor expression in the basolateral amygdala and dentate gyrus, CA1 and CA3 fields of the hippocampus. These data therefore suggest that the formation of conditioned stimulus–reward associations requires, at least in part, activation of amygdalar–hippocampal circuits.
Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP‐32 striatal progenitors within the graft
Authors: Ferrari Daniela , Sanchez‐Pernaute Rosario , Lee Hyojin , Studer Lorenz , Isacson Ole
Published: October 2006

The correct identity and functional capacity of transplanted dopamine (DA) neurons derived in vitro from embryonic stem (ES) cells is a critical factor for the development of an ES cell‐based replacement therapy for Parkinson's disease. We transplanted primate Cyno‐1 ES cells differentiated in vitro for 4 (progenitor ES cells) or 6 (differentiated ES cells) weeks, or control fetal primate cells into the striatum of hemi‐parkinsonian rats. Partial behavioral recovery in amphetamine‐induced rotation was correlated with the number of ES‐derived tyrosine hydroxylase‐positive (TH +) neurons in the grafts (r = 0.5, P < 0.05). Post mortem analysis of ES‐derived grafts revealed TH + neurons with mature morphology, similar to fetal DA neurons, and expression of midbrain transcription factors, such as Engrailed (En) and Nurr‐1. While the total number of TH + neurons was not different between the two groups, TH/En co‐expression was significantly higher (> 90%) in grafts from differentiated ES cells than in grafts derived from progenitor cells (< 50%), reflecting a more heterogeneous cellular composition. Within the grafts there was an overlap between ES‐derived TH + axonal arbors and clusters of primate ES‐derived striatal neurons expressing brain factor 1 (Bf‐1, Foxg1) and DA and cAMP‐regulated phosphoprotein (DARPP‐32). Such overlap was never observed for other regional transcription factors that define neighboring forebrain domains in the developing brain, such as Nkx2.1 (medial ganglionic eminence), Nkx2.2 (pallidal and diencephalic progenitors) or Pax6 (dorsal telencephalic progenitors). Despite the heterogeneity of ES‐derived graft cell composition, these results demonstrate normal phenotypic specification, conserved natural axonal target selectivity and functionality of DA neurons derived from primate ES cells.
Preferential responses in amygdala and insula during presentation of facial contempt and disgust
Authors: Sambataro Fabio , Dimalta Savino , Di Giorgio Annabella , Taurisano Paolo , Blasi Giuseppe , Scarabino Tommaso , Giannatempo Giuseppe , Nardini Marcello , Bertolino Alessandro
Published: October 2006

Some authors consider contempt to be a basic emotion while others consider it a variant of disgust. The neural correlates of contempt have not so far been specifically contrasted with disgust. Using functional magnetic resonance imaging (fMRI), we investigated the neural networks involved in the processing of facial contempt and disgust in 24 healthy subjects. Facial recognition of contempt was lower than that of disgust and of neutral faces. The imaging data indicated significant activity in the amygdala and in globus pallidus and putamen during processing of contemptuous faces. Bilateral insula and caudate nuclei and left as well as right inferior frontal gyrus were engaged during processing of disgusted faces. Moreover, direct comparisons of contempt vs. disgust yielded significantly different activations in the amygdala. On the other hand, disgusted faces elicited greater activation than contemptuous faces in the right insula and caudate. Our findings suggest preferential involvement of different neural substrates in the processing of facial emotional expressions of contempt and disgust.
The role of exotic species in homogenizing the North American flora
Authors: Qian Hong , Ricklefs Robert E.
Published: October 2006

Exotic species have begun to homogenize the global biota, yet few data are available to assess the extent of this process or factors that constrain its advance at global or continental scales. We evaluate homogenization of vascular plants across America north of Mexico by comparing similarity in the complete native and exotic floras between states and provinces of the USA and Canada. Compared with native species, exotic plants are distributed haphazardly among areas but spread more widely, producing differentiation of floras among neighbouring areas but homogenization at greater distance. The number of exotic species is more closely associated with the size of the human population than with ecological conditions, as in the case of native species, and their distributions are less influenced by climate than those of native species.
Plasma homocysteine, oxidative stress and endothelial function in patients with Type 1 diabetes mellitus and microalbuminuria
Authors: Wotherspoon F. , Laight D. W. , Browne D. L. , Turner C. , Meeking D. R. , Allard S. E. , Munday L. J. , Shaw K. M. , Cummings M. H.
Published: October 2006

Aims  The purpose of this study was to examine the associations between endothelial function, plasma homocysteine and oxidative stress in patients with Type 1 diabetes mellitus (DM) and microalbuminuria compared with DM patients with normoalbuminuria and non‐diabetic control subjects. We wished to test the hypothesis that increased cardiovascular risk in patients with Type 1 diabetes and microalbuminuria may be in part as a result of hyperhomocysteinaemia‐mediated oxidative stress leading to impaired endothelial function.

Methods  We measured forearm blood flow, total plasma homocysteine, total antioxidant status (TAOS) and whole blood glutathione in 31 DM patients, 16 with microalbuminuria and 15 with normoalbuminuria, and 15 non‐diabetic control subjects.

Results  Plasma homocysteine levels were significantly higher in the microalbuminuric diabetic patients compared with the normoalbuminuric patients and the control subjects. TAOS was significantly lower in the micoalbuminuric and normoalbuminuric diabetic patients compared with the control subjects, although TAOS levels were similar in both groups of diabetic patients. There was no difference in forearm blood flow between the groups and no association between measured endothelial function and antioxidant defence/oxidative stress and homocysteine in each group. There was no association between plasma total homocysteine and TAOS or whole blood glutathione within the groups.

Conclusions  We have found mild hyperhomocysteinaemia in microalbuminuric DM patients compared with normoalbuminuric DM patients and non‐diabetic subjects and some evidence for reduced antioxidant defence in DM patients. These findings add to our understanding of the increased risk of vascular disease in patients with Type 1 diabetes.
Mortality in individuals with Type 2 diabetes and heart disease in a unique New Zealand population
Authors: Kerr G. D. , Gamble G. D. , Doughty R. N. , Simmons D. , Baker J.
Published: October 2006

Aims  To determine rate and predictors of mortality in patients with Type 2 diabetes living in a population with a large proportion of Maori and Pacific peoples who were admitted to hospital with myocardial infarction (MI) or congestive cardiac failure (CCF).

Methods  The study population included 4193 individuals with Type 2 diabetes who lived in South Auckland and who participated in a primary care audit between 1994 and 1999. We studied a subgroup of 319 patients who subsequently had a hospital admission for MI or CCF between 1999 and 2001. We examined their demographics, drug treatment, vascular risk factors and mortality up to 2003.

Results  Following discharge, the prescription of β‐blockers, angiotensin‐converting enzyme (ACE) inhibitors, aspirin and statins had all increased significantly. Vascular risk factors including total cholesterol, high‐density lipoprotein (HDL) cholesterol, systolic blood pressure and glycated haemoglobin (HbA1c) improved significantly. Nevertheless, mortality remained high with individuals admitted because of an MI 7.2‐fold more likely to die early and those with a CCF admission 5.9‐fold more likely to die early than other individuals with Type 2 diabetes. Maori patients have an 80% excess mortality.

Conclusions  Patients with past admission for MI and/or CCF remain at exceptionally high risk of death for at least 4 years after hospital admission, even with improvements in management of cardiovascular risk factors. Maori individuals are at particular risk.
HNF‐1α G574S is a functional variant with decreased transactivation activity
Authors: Navalón‐García K. , Mendoza‐Alcantar L. , Díaz‐Vargas M. E. , Martínez‐Godínez M. A. , Reyna‐Garfias H. , Aguilar‐Salinas C. A. , Riba L. , Canizales‐Quinteros S. , Villarreal‐Molina T. , González‐Chávez A. , Argueta‐Villamar V. , Tusié‐Luna M. T. , Miliar‐García A.
Published: October 2006

Aim  To assess the functional consequence of the hepatocyte nuclear factor 1α gene (HNF‐1α) G574S variant previously proposed as a diabetes susceptibility allele, in a group of Mexican Type 2 diabetic patients with end‐stage renal disease (ESRD).

Methods  The transcriptional activity of the HNF‐1α G574S recombinant protein on the human insulin promoter was assessed by transfection assays in RINm5f and HepG2 cell lines.

Results  Two unrelated Mexican diabetic patients with no known African ancestry were found to carry the G574S variant. This substitution was not found among unrelated healthy control subjects. Whereas the G574S HNF‐1α transcription activation of the human insulin promoter was 40% lower than that of the wild‐type protein in RINm5f β cells, no difference was found in a hepatic cell line (HepG2).

Conclusions  G574S affects the transactivation potential of HNF‐1α on the insulin promoter in pancreatic β‐cells. Although it has been difficult to prove its role in the development of diabetes in case–control association studies, this variant exhibits functional effects consistent with it being a potential diabetes susceptibility allele.