bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress hormones and abiotic stresses have different effects on antioxidants in maize lines with different sensitivity
Authors: Kellős T. , Tímár I. , Szilágyi V. , Szalai G. , Galiba G. , Kocsy G.
Published: June 2008

The effect of stress hormones and abiotic stress treatments on reactive oxygen species and on antioxidants was compared in two maize (Zea mays L.) lines (Penjalinan and Z7) having different stress tolerance. Following treatment with abscisic acid, salicylic acid or hydrogen peroxide, the amount of hydrogen peroxide and lipid peroxides increased, while after osmotic stress or cultivation in continuous darkness, the levels were unchanged or decreased. The higher amount of lipid peroxides in Penjalinan indicated its greater sensitivity compared to Z7. The level of the examined antioxidants was increased by nearly all treatments. Glutathione and cysteine contents were higher after salicylic acid, hydrogen peroxide and polyethylene glycol treatments and lower after application of abscisic acid, NaCl and growth in darkness in Z7 than in Penjalinan. The activity of glutathione reductase, ascorbate peroxidase, catalase and glutathione S‐transferase was higher after almost all treatments in Z7. The expression of the glutathione synthetase (EC 6.3.2.3) gene was not affected by the treatments, while the level of γ‐glutamylcysteine synthetase (EC 6.3.2.2) and glutathione reductase (EC 1.6.4.2) transcripts increased after most treatments. The two stress hormones and the stress treatments resulted in different changes in antioxidant levels in the two maize lines, which indicates the specific, stress tolerance‐dependent response of plants to the various growth regulators and adverse environmental effects that were examined.
Technical Restrictions of Computer‐Manipulated Visual Stimuli and Display Units for Studying Animal Behaviour
Authors: Baldauf Sebastian A. , Kullmann Harald , Bakker Theo C. M.
Published: June 2008

Computer‐manipulated visual stimuli are a well‐established tool to experimentally study animal behaviour. They provide the opportunity to manipulate single or combined visual stimuli selectively, while other potentially confounding variables remain constant. A wide array of different presentation methods of artificial stimuli has been used in recent research. Furthermore, a wide range of basic hardware and software has been used to conduct experiments. The outcomes of experimental trials using computer‐manipulated visual stimuli differed among studies. Failing or contradictory results were mostly discussed in a behavioural and ecological context. However, the results sometimes may be basically flawed due to methodological traps in the experimental design. Based on characteristics and restrictions of technical standards, we discuss which kinds of computer stimuli and visual display units are available today and their suitability for experimental trials when studying animal behaviour. A computer‐manipulated stimulus displayed by a certain visual display unit may be accurate to investigate behaviour in a specific species, if various preconditions are met. However, simply due to technical characteristics of the visual display unit, the set‐up may be unsuitable for other test species. Thus, future research should critically apply the included technique, with respect to both the intended kind of stimulus and the species under investigation. If these preconditions are met, computer‐manipulated stimuli provide a high degree of standardization and the potential to display visual signals without losing a crucial amount of information from the native data.
Size‐Dependent Mating Success at Various Nutritional States in the Yellow Dung Fly
Authors: Blanckenhorn Wolf U. , Birrer Maurus , Meier Christoph M. , Reim Constanze , Teuschl Yvonne , Weibel Denise
Published: June 2008

Mating success not only depends on genetic quality, but also equally on environmental factors, most prominently food availability. We investigated the interactive effects of nutritional state and body size on mating success and copula duration in yellow dung fly males (Scathophaga stercoraria; Diptera: Scathophagidae) of three body size selection lines in the laboratory in both non‐competitive (single) and competitive (group) situations. Adults require protein and lipids from prey to reproduce, as well as sugars as an energy source for reproductive activity. We expected mating success to decrease with time because of sperm depletion (sugar treatment) and/or energy shortage (water treatment) relative to the control, prey plus sugar treatment. Based on physiological scaling, we also expected large‐line males to become depleted either sooner because of their higher energy and sperm demands, or later because of their more efficient energy use. Average mating success indeed declined over a period of 5–7 d (or 5–15 potential copulations per male), but equally for all food treatments and body size classes. Surprisingly, water‐fed and small‐line males had the highest mating probability in the non‐competitive setting, while in the competitive setting large‐line males had the highest success. Energy‐depleted males showed apparent terminal investment. Small males acquired females more readily but eventually lost them to larger males in the competitive situation. As shown before, copula duration was inversely related to body size and increased with copulation number, independent of food treatment. We conclude that sugar or prey shortage has little effect on mating success in the short term, and does not differentially affect males of different sizes.
ALVEOLAR–ARTERIAL OXYGEN GRADIENT, PNEUMONIA SEVERITY INDEX AND OUTCOMES IN PATIENTS HOSPITALIZED WITH COMMUNITY ACQUIRED PNEUMONIA
Authors: Moammar Mahmoud Q , Azam Hamad M , Blamoun Adel I , Rashid Ashraf O , Ismail Medhat , Khan M Anees , DeBari Vincent A
Published: June 2008

The alveolar–arterial oxygen gradient (ΔA–a) provides a useful assessment of ventilation/perfusion (V/Q) abnormalities. The objectives of the present study were to: (i) examine the correlation between the ΔA–a and the pneumonia severity index (PSI); and (ii) determine whether these measures were comparable in predicting clinical outcomes.

The present study was conducted at a 750‐bed teaching hospital. It examined a retrospective cohort of 255 patients with community acquired pneumonia (CAP) over a 2 year period. Association between the CAP and ΔA–a was investigated by regression models and correlation, as well as two logistic models for subjects bifurcated by low‐risk/moderate‐to‐high risk. The decision levels (DL) for both PSI and ΔA–a were then compared as predictors of both length of stay (LOS) and survival.

The correlation between PSI and ΔA–a was strong (ρ = 0.76; P < 0.0001) and was best modelled by a curvilinear relationship. Both logistic models indicated a strong association (P < 0.001) between ΔA–a and PSI and yielded an optimal DL for the ΔA–a of < 89 mmHg. Inter‐test agreement of ΔA–a with PSI was 76.9% (κ = 0.60; 95% confidence interval 0.47–0.72; P < 0.0001). At < 89 mmHg, the odds ratios for LOS were similar to those at PSI = 90 in predicting LOS in the range 3–7 days, inclusive. There was no significant difference in the ability of ΔA–a and PSI to predict survival for either the low‐ or high‐risk group (P = 0.363 and P = 0.951, respectively).

The ΔA–a correlates well with PSI and performs comparably in predicting two major outcomes in subjects hospitalized with CAP.
SHORT‐TERM TREATMENT OF STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS WITH AN AT1 RECEPTOR BLOCKER PROTECTS AGAINST HYPERTENSIVE END‐ORGAN DAMAGE BY PROLONGED INHIBITION OF THE RENIN–ANGIOTENSIN SYSTEM
Authors: Hamaguchi Rika , Takemori Kumiko , Inoue Takao , Masuno Kouichi , Ito Hiroyuki
Published: June 2008

The aim of the present study was to investigate the effects of short‐term treatment with an AT1 receptor blocker (ARB) on amelioration of hypertensive end‐organ damage in stroke‐prone spontaneously hypertensive rats (SHRSP).

Male SHRSP were divided into two groups: (i) an ARB‐treated group; and (ii) a control group. Candesartan (1 mg/kg per day) was administered orally from 6 to 11 weeks of age. At 20 weeks of age, plasma renin activity (PRA), angiotensin II concentrations, angiotensin‐converting enzyme (ACE) activity and hydroperoxide content were measured. Expression of intercellular adhesion molecule (ICAM)‐1, renin, AT1 and AT2 receptors was investigated by reverse transcription–polymerase chain reaction.

Blood pressure in the ARB group was slightly lower at 7, 8, 11, 13–15 and 18 weeks of age, but no significant difference in blood pressure was found between the ARB and control groups at 20 weeks of age. All rats in the control group had cerebral oedema, whereas no lesions were found in the ARB group. In the ARB group, PRA, AII and hydroperoxide content were lower than in the control group. In the ARB‐treated group, lower ICAM‐1 expression was found in the cerebral cortex and slightly, albeit not significantly, lower expression of renin was found in the kidney. In contrast, AT1 receptor expression in the cerebrum and kidney was higher in the ARB group compared with the control group.

These results indicate that short‐term treatment of SHRSP with ARB at a young age is effective in preventing cerebral oedema after maturation. Such beneficial effects of ARB may be due, in part, to decreased blood pressure and is likely mainly due to inhibition of total circulating and local renin–angiotensin systems.
EFFECT OF INHIBITION OF NEURONAL NITRIC OXIDE SYNTHASE AND l‐ARGININE SUPPLEMENTATION ON RENAL ISCHAEMIA–REPERFUSION INJURY AND THE RENAL NITRIC OXIDE SYSTEM
Authors: Rusai Krisztina , Fekete Andrea , Szebeni Beáta , Vannay Ádám , Bokodi Géza , Müller Veronika , Viklicky Ondrej , Bloudickova Silvie , Rajnoch Jan , Heemann Uwe , Reusz György , Szabó András , Tulassay Tivadar , Szabó Attila J
Published: June 2008

The role of nitric oxide synthases (NOS) and the nitric oxide (NO) substrate l‐arginine in renal ischaemia–reperfusion (I/R) has been studied extensively. However, the results reported are often controversial. In the present study, we examined the effects of the neuronal (n) NOS inhibitor 7‐nitroindazole (7‐NI) and l‐arginine administration on renal I/R injury and the renal NO system in rats.

Following 7 days pretreatment with 7‐NI (50 mg/kg per day), l‐arginine (2 g/kg per day) or vehicle (dimethylsulphoxide : sesame oil, 1 : 9), the left renal vascular pedicles were clamped for 50 min in male Sprague‐Dawley rats and kidneys were removed 24 h after reperfusion (n = 7/group).

Neither 7‐NI nor l‐arginine had any effect on parameters of renal function, the grade of tissue injury or the number of terminal deoxyribonucleotidyl transferase‐mediated dUTP–digoxigenin nick end‐labelling (TUNEL)‐positive tubular cells compared with vehicle‐treated rats. 7‐Nitroindazole decreased nNOS mRNA expression and inducible (i) NOS protein levels, but had no effect on endothelial NOS expression. l‐Arginine supplementation increased mRNA expression of all NOS isoforms, but only increased protein expression of iNOS.

The results of the present study demonstrate that selective inhibition of nNOS has no effect on renal injury, indicating that nNOS does not play a central role in the pathophysiology of renal I/R. In addition, although l‐arginine has no effect on renal I/R injury in the model used in the present study, its administration increases the mRNA expression of NOS isoforms.
CENTRAL CHOLINE SUPPRESSES PLASMA RENIN RESPONSE TO GRADED HAEMORRHAGE IN RATS
Authors: Isbil‐Buyukcoskun Naciye , Ilcol Yesim O , Cansev Mehmet , Hamurtekin Emre , Ozluk Kasim , Ulus Ismail H
Published: June 2008

Central administration of choline increases blood pressure in normotensive and hypotensive states by increasing plasma concentrations of vasopressin and catecholamines. We hypothesized that choline could also modulate the renin–angiotensin pathway, the third main pressor system in the body.

Plasma renin activity (PRA), which serves as an index of the function of the peripheral renin–angiotensin system, was determined in rats subjected to graded haemorrhage following central choline administration.

Intracerebroventricular (i.c.v.) injection of choline (12.5–150 µg), a precursor of the neurotransmitter acetylcholine (ACh), inhibited the increase in PRA in rats subjected to graded haemorrhage by sequential removal of 0.55 mL blood/100 g bodyweight. Choline, in the range 50–150 µg, increased blood pressure.

Intraperitoneal (i.p.) administration of 150 µg choline failed to alter blood pressure and plasma renin responses to graded haemorrhage. Administration of a higher dose (90 mg/kg, i.p.) of choline decreased blood pressure and enhanced PRA in the first two blood samples obtained during the graded haemorrhage. Physostigmine (10 µg, i.c.v.), ACh (10 µg, i.c.v.), carbamylcholine (10 µg, i.c.v.) and cytidine 5′‐diphosphocholine (CDP‐choline; 250 µg, i.c.v.) increased blood pressure and attenuated plasma renin responses to graded haemorrhage.

Inhibition of PRA by i.c.v. choline was abolished by i.c.v. pretreatment with mecamylamine (50 µg), but not atropine (10 µg). Blood pressure responses to choline (150 µg) were attenuated by pretreatment with both mecamylamine and atropine.

Inhibition of PRA in response to central choline administration was associated with enhanced plasma vasopressin and catecholamine responses to graded haemorrhage. Pretreatment of rats with a vasopressin antagonist reversed central choline‐induced inhibition of plasma renin responses to graded haemorrhage without altering the blood pressure response.

In conclusion, central administration of choline inhibits the plasma renin response to graded haemorrhage. Nicotinic receptor activation and an increase in plasma vasopressin appear to be involved in this effect.
IDENTIFICATION OF A NOVEL REPRESSOR ELEMENT IN THE CYCLO‐OXYGENASE‐2 PROMOTER AND ITS NUCLEAR BINDING PROTEIN
Authors: Yang Xiaomin , Lin Ling , Zhang Xiongfei , Ji Yong , Lv Jinghuan , Zhu Yunxia , Yin Yongmei , Sun Yujie , Han Xiao
Published: June 2008

Cyclo‐oxygenase‐2 (COX‐2) has important functions in many diseases. Although its transcriptional regulation has been investigated in considerable detail, some important elements remain unknown. The aim of the present study was to demonstrate the existence of a novel repressor element in the mouse COX‐2 promoter and characterize some of its binding proteins.

In order to identify the repressor element, the activity of the mouse COX‐2 promoter was investigated in the pancreatic β‐cell line RINm5F using a series of deletion and mutant constructs. The ability of nuclear proteins to bind to this repressor element was then determined by an electrophoretic mobility shift assay and the proteins binding to this repressor element were purified and identified by mass spectrometry. One of the nuclear proteins identified was overexpressed to examine its inhibitory effect on COX‐2 promoter activity.

We found a novel repressor element located from nucleotides –655 to –632 of the mouse COX‐2 promoter region. Some proteins from RINm5F cell nuclear extracts bound to this element, one of which was identified as non‐POU‐domain‐containing, octamer‐binding protein (NonO). Overexpression of NonO significantly inhibited wild‐type COX‐2 promoter activity, but had no effect when the repressor element was mutated.

In conclusion, we have demonstrated that a regulatory ‘spot’ is present in the COX‐2 promoter. This provides additional data on COX‐2 gene regulation and may provide an insight into the clinical treatment of diseases where COX‐2 is highly expressed.
INHIBITION OF LEFT VENTRICULAR REMODELLING IN SPONTANEOUSLY HYPERTENSIVE RATS by Gαq‐PROTEIN CARBOXYL TERMINUS IMITATION POLYPEPTIDE GCIP‐27 IS NOT ENTIRELY DEPENDENT ON BLOOD PRESSURE
Authors: Wang Xiu‐Qin , Zhang Hai‐Gang , Cheng Yi‐Qun , Li Xiao‐Hui
Published: June 2008

The Gq‐protein is located at the convergent point in the signal transduction pathway that leads to ventricular remodelling. In G‐protein signalling pathways, the carboxyl terminus of the Gα‐subunit plays a vital role in G‐protein–receptor interaction. The aim of the present study was to explore the effects of a synthetic Gαq carboxyl terminus imitation peptide, namely GCIP‐27, on left ventricular (LV) remodelling and blood pressure in spontaneous hypertensive rats (SHR).

In the present study, 10, 30 or 90 µg/kg, i.p., GCIP‐27 was administered for 8 weeks to SHR. In addition, another two groups of SHR were treated with either 6 mg/kg losartan or vehicle (saline). Wistar‐Kyoto rats were used as controls. Systolic blood pressure (SBP) was measured using the standard tail‐cuff method once every 2 weeks. At the end of the experiment, the LV mass index (LVMI) was evaluated. In addition, LV structure and function, collagen content, microstructure and ultrastructure were examined using echocardiography, the hydroxyproline assay, routine light microscopy and transmission electron microscopy, respectively.

In the losartan‐ and GCIP‐27 (10, 30 and 90 µg/kg)‐treated groups, SBP was decreased significantly compared with that of the vehicle (saline) group. However, even at the highest concentration used, the hypotensive effect of GCIP‐27 was weaker than that of losartan. For example, after 8 weeks treatment, SBP had decreased by 30.4% in the losartan‐treated group compared with decreases of 10.5, 13.1 and 18.5% in the 10, 30 and 90 µg/kg GCIP‐27‐treated groups, respectively.

Both GCIP‐27 (10, 30 and 90 µg/kg) and losartan (6 mg/kg) significantly reduced LV posterior wall thickness, the thickness of the interventricular septum, collagen content and LVMI, with the effects of GCIP‐27 at all three concentrations tested being greater than those of losartan.

In conclusion, GCIP‐27 effectively attenuates LV remodelling in SHR and the antiremodelling effect may not be dependent entirely on decreases in blood pressure.
Influence of haemodialysis on early markers of atherosclerosis
Authors: KOVACIC VEDRAN , LJUTIC DRAGAN , DODIG JOSIPA , RADIC MISLAV , DUPLANCIC DARKO
Published: June 2008

Introduction: End‐stage renal disease (ESRD) patients treated by haemodialysis (HD) have impaired endothelium‐dependent vasodilatation and increased intima‐media thickness (IMT) of the carotid artery The aim of the study was to analyse the relationships between parameters of chronic HD treatment and non‐invasive assessments of preclinical atherosclerosis (endothelial dysfunction and carotid IMT) in ESRD patients on HD.

Methods: Fifty‐two (19 females, 33 males) adult patients on chronic maintenance (4.65 ± 3.29 years) HD aged 59.88 ± 15.49 years were investigated. Ultrasonographic studies were performed with a 7.5 MHz high‐resolution probe. The common carotid artery IMT was measured. Brachial artery diameter was analysed to the rest. In order to assess flow‐mediated dilatation (FMD), hyperaemia was induced by a pneumatic cuff, and an analysis of the diameter was performed 1, 2, 3 and 4 min after cuff deflation.

Results: Significant differences were found in the average carotid IMT value between subjects with delivered dialysis dose (Kt/V) ≥1.2 and <1.2 (0.89 ± 0.21 vs 1.04 ± 0.11,P = 0.0045). A correlation between Kt/V and IMT (r = 0.366,P = 0.004) was demonstrated. FMD values of the brachial artery did not correlate with Kt/V. A correlation between low molecular weight heparin per kg of body mass and maximal percent of FMD was demonstrated (r = −0.242,P = 0.049). The maximal percent of brachial FMD was correlated with absolute difference between pre‐ and postdialysis pulse pressure values (r = −0.265,P = 0.033). In a partial correlation with haemoglobin as control, a variable significant correlation between total erythropoietin dose and maximal carotid IMT (r = −0.262,P = 0.036) was found. In a multiple linear regression model, Kt/V was independently correlated with carotid IMT values (β = −0.227,P = 0.0335).

Conclusion: This study has demonstrated the association between HD procedure and early atherosclerosis markers. HD treatment has to be considered as potential modifying factor in atherosclerosis development.
Evaluation of the prognostic value of the risk, injury, failure, loss and end‐stage renal failure (RIFLE) criteria for acute kidney injury
Authors: PEREZ VALDIVIESO JOSE R , BES‐RASTROLLO MAIRA , MONEDERO PABLO , DE IRALA JOKIN , LAVILLA FRANCISCO J
Published: June 2008

Aim:  The experts have argued about the use of the risk, injury, failure, loss and end‐stage renal failure (RIFLE) criteria as a prognosis scoring system. We examined the association between in‐hospital mortality and the RIFLE criteria, and discussed its accuracy as a prognosis factor.

Methods:  In this prospective study, we analysed the data gathered from a cohort of 956 patients admitted in a Spanish tertiary hospital between January 1998 and April 2006. Hazard ratios for mortality, and survival curves within 60 days were calculated. Discrimination and calibration of the model were also assessed.

Results:  Excluding 53 patients, 903 patients were finally analysed. We classified them into groups according to the maximum RIFLE class reached during their admission. The RIFLE class was assessed by the glomerular filtration rate criterion. We found an increase in the in‐hospital mortality risk. Cox proportional hazard models showed that RIFLE classes risk, injury, and failure were significant predictive factors (hazard ratios were 2.77, 3.23 and 3.52, respectively; P for trend was 0.005). The multivariate analyses from the cross‐classification of the participants according to Liano score values (severity of illness) and RIFLE classes showed additive effects of the exposures on in‐hospital mortality.

Conclusion:  In this population, the risk of in‐hospital mortality during the acute kidney injury (AKI) episode was positively associated with RIFLE classes. We showed that the RIFLE classification system had discriminative power in predicting hospital mortality within 60 days in AKI patients, but not better than a specific AKI predictive model. However, a combined use of both may give a more robust prognosis system.
Effect of levamisole supplementation on hepatitis B virus vaccination response in hemodialysis patients
Authors: SALI SHAHNAZ , ALAVIAN SEYED M , HAJARIZADEH BEHZAD
Published: June 2008

Aim:  As an immune‐modulating agent, levamisole has been reported to stimulate depressed T‐cell activity, enhance B lymphocyte function and restore delayed hypersensitivity reactions in immune‐depressed patients. There are a number of recent studies claiming that levamisole can improve response rate to hepatitis B virus (HBV) vaccination in haemodialysis patients. The present study has examined this hypothesis amongst some Iranian patients, using double‐blind randomized clinical trial.

Methods:  During a 12 month period, 70 patients on maintenance haemodialysis with negative anti‐hepatitis B surface antibody (HBsAb) and HBV core antibody (HBcAb), from four different dialysis centres were enrolled into the study. The patients were randomized to two groups. The first group (levamisole group) received 40 μg doses of recombinant HBV vaccine i.m. at 0, 1 and 6 months, plus 100 mg levamisole p.o., after each haemodialysis session. The second group (placebo group) received the same vaccination protocol, except for the placebo instead of levamisole. The patients were followed on serum HBsAb level. Those with an HBsAb level of above 10 mIU/mL, 1 month after the third dose of vaccination, were considered as responders.

Results:  The levamisole group was comprised of 38 patients and the placebo group of 32 patients. Thirty‐one patients (81.6%) of levamisole group and 26 patients (81.3%) of placebo group responded to vaccination. The difference between two groups was not significant.

Conclusion:  This study indicated that in a haemodialysis population with high response to HBV vaccination, levamisole might have no significant effect in enhancing the response. Further studies with higher power can give more accurate results.
Overexpression of decorin induces apoptosis and cell growth arrest in cultured rat mesangial cells in vitro
Authors: WU HUIJUAN , WANG SUXIA , XUE AIMIN , LIU YUAN , LIU YE , WANG HUIJUN , CHEN QI , GUO MUYI , ZHANG ZHIGANG
Published: June 2008

Background:  Decorin (DCN) is a small leucine‐rich proteoglycan that plays an important role in the regulation of intercellular contact, cell migration and proliferation. DCN suppresses cell growth and induces apoptosis in various tumour cells. The aim of this study was to investigate whether overexpression of DCN could induce apoptosis and cell growth arrest in mesangial cells (MsCs) in vitro.

Methods:  PcDNA3.1A‐DCN plasmid was transfected into cultured rat MsCs, and positive clones stably expressing DCN (MsC/DCN) were selected. SiRNA was used for blocking DCN expression in MsC/DCN. Apoptosis and cell growth of MsCs were assayed by flow cytometry. Hoechst staining was used for observing apoptotic cells. Expressions of active Caspase‐3, epidermal growth factor receptor (EGFR), P21 and transforming growth factor‐β (TGF‐β1) were analyzed using Western blot.

Results:  Overexpression of DCN in MsCs induced apoptosis and arrested cells in the G0/G1 phase. The protein level of active Caspase‐3 was significantly elevated in MsC/DCN (P < 0.01). DCN transfection induced downregulation of EGFR and up‐expression of P21. In addition, the expression of TGF‐β1 was significantly inhibited. DCN‐siRNA transfection remarkably blocked the expression of DCN and reversed the downregulatory effects of DCN on MsC's proliferation.

Conclusion:  Overexpression of DCN could inhibit MsCs proliferation by inducing apoptosis and cell growth arrest in vitro and it also downregulates expression of TGF‐β1. These results suggest novel strategies for regulating the proliferation of MsC in glomerular diseases.
Hypothesis: A simple algorithm to distinguish between hypoaldosteronism and renal aldosterone resistance in patients with persistent hyperkalemia
Authors: ADAM WILLIAM R
Published: June 2008

Aim:  Many patients with hyperkalemia have a readily identifiable cause, which leads to appropriate management. In others, particularly those with a reduced glomerular filtration rate, differentiating between (relative) hypoaldosteronism (HA) and renal aldosterone resistance (RAR) can be problematic. The aim of this study was to see if a plasma aldosterone to potassium algorithm could be defined which would help identify patients with hyperkalemia owing to suboptimal levels of aldosterone, thereby validating treatment with 9‐alpha‐fluhydrocortisone, instead of cation exchange resins, if more conservative treatment fails.

Methods:  A literature search for, and analysis of, studies providing details of plasma aldosterone and plasma potassium in normals (made hyperkalemic)and patients with a plasma potassium >5.3 mmol/L, and a contemporaneous plasma aldosterone.

Results:  One study was found in which normals were made significantly hyperkalemic (to 6.3 mmol/L). These subjects, while on a high sodium, low potassium (western) diet (n = 5), provided an arbitrary definition of a simple aldosterone to potassium algorithm for diagnosis (factored aldosterone (FAldo) = plasma aldosterone/(plasma K – 4.2)). The limit for FAldo is set at 280(pmol/L) or 10(ng/dL): results below the limit suggest HA; above the limit, RAR. This algorithm was then tested against, and, when plasma potassium was greater than 5.3, found to be consistent with, reported patients with confirmed HA (n = 33) and pseudohypoaldosteronism (n = 23). The ratios in reported patients with renal failure (n = 43) were consistent with either HA (n = 30) or RAR(n = 13).

Hypothesis:  In hyperkalemic patients a plasma aldosterone to potassium algorithm may help distinguish HA from RAR, thereby guiding therapy.
Parathyroid hormone is inversely related to endothelin‐1 in patients on haemodialysis
Authors: PALERMO ALESSANDRO , MULÈ GIUSEPPE , GUARNERI MARCO , ARSENA ROSALIA , RICCOBENE RAFFAELLA , LORITO MARIA CARMELA , VACCARO FRANCESCO , CERASOLA GIOVANNI , COTTONE SANTINA
Published: June 2008

Aim:  Parathyroid hormone secretion is mainly influenced by hypocalcaemia, hyperphosphataemia and vitamin D deficiency. However, previous in vitro and in vivo studies showed that endothelin‐1 can influence parathyroid hormone secretion. This study was aimed at evaluating this relationship in vivo in uraemic patients.

Methods:  Parathyroid hormone and endothelin‐1 plasma concentrations were measured in 67 haemodialysed patients. Patients with history of cardiovascular diseases and those with parathyroid adenoma were excluded.

Results:  Plasma levels of endothelin‐1 were found to be inversely related to those of parathyroid hormone (P < 0.04) The multiple regression analysis, carried out considering parathyroid hormone as a dependent variable, and including age, sex, blood pressure, calcium × phosphorus product, and endothelin‐1, demonstrated that the independent correlates of parathyroid hormone were endothelin‐1 (β = −0.276; P = 0.015), and calcium × phosphorus product (β = 0.417; P < 0.0001).

Conclusion:  For the first time in vivo, we demonstrated an inverse independent relationship between endothelin‐1 and parathyroid hormone in haemodialysed patients. Because both endothelin‐1 and parathyroid hormone are endowed with well‐known harmful actions on cardiovascular apparatus, whether such inverse relation may really influence the natural history of cardiovascular damage due to secondary hyperparathyroidism remains to be elucidated.
Assigning Escherichia coli strains to phylogenetic groups: multi‐locus sequence typing versus the PCR triplex method
Authors: Gordon David M. , Clermont Olivier , Tolley Heather , Denamur Erick
Published: June 2008

It is well recognized that Escherichia coli consists of a number of distinct phylo‐groups and that strains of the different phylo‐groups vary in their ecological niches, life‐history characteristics and propensity to cause disease. Consequently, much can be learnt by assigning a strain of E. coli to one of the recognized phylo‐groups. A triplex PCR‐based method that enables strains of E. coli to be assigned to a phylo‐group using a dichotomous key approach based on the presence or absence of two genes (chuA and yjaA) and an anonymous DNA fragment (TSPE4.C2) has been developed. However, the accuracy with which this method assigns strains to their correct phylo‐group has not been adequately evaluated. Consequently, 662 strains of E. coli were characterized using a multi‐locus sequence typing approach. Unsupervised population assignment algorithms were used to assign strains to phylo‐groups based on the multi‐locus sequence typing data. The analyses revealed that 85–90% of E. coli strains can be assigned to a phylo‐group and that 80–85% of the phylo‐group memberships assigned using the Clermont method are correct. However, the accuracy with which strains are assigned to the correct phylo‐group depends on their Clermont genotype. For example, strains yielding a Clermont genotype consistent with phylo‐groups B1 and B2 are assigned correctly 95% of the time. Strains failing to yield any PCR products using the Clermont method are seldom members of phylo‐group A and strains with such a genotype should not be assigned to a phylo‐group.
The management and outcome of anastomotic leaks in colorectal surgery
Authors: Khan A. A. , Wheeler J. M. D. , Cunningham C. , George B. , Kettlewell M. , Mortensen N. J. McC.
Published: June 2008

Purpose  Anastomotic leaks in colorectal surgery are associated with significant morbidity and mortality and may result in poor functional and oncological outcomes. Diagnostic difficulties may delay identification and appropriate management of leaks. The aim of this study was to look at the diagnosis, clinical management and outcomes of anastamotic leaks in our department.

Method  A retrospective audit and case note review of all patients who underwent the formation of a colorectal anastomosis between January 1996 and December 2002 (n = 1421) was performed. An anastomotic leak was defined as sepsis identified to have arisen from an anastomosis that subsequently required surgery, radiological drainage or intravenous antibiotics. Forty‐one patients (25 male, 16 female) with a median age of 60 years (range 7–89 years) were identified as having suffered an anastomotic leak.

Results  The median time to diagnosis of an anastomotic leak following surgery was 7 days (range 3–29). At re‐operation, 21 patients (51%) underwent formation of a stoma, and any who required the anastomosis to be formally taken down have been left with a ‘permanent’ stoma. Currently only four of 12 patients (33%) who required a stoma for an anastomotic leak following anterior resection have undergone stoma reversal. Eleven of 16 patients (69%) who had received a stoma following another colorectal procedure had undergone stoma reversal. The mortality associated with an anastamotic leak in this series was 5% (n = 2).

Conclusion  Although anastomotic leaks following colorectal surgery are associated with significant morbidity and stoma formation, early and aggressive management should result in a low overall mortality. If an anastomosis is taken down following an anastomotic leak after anterior resection, this will usually result in a ‘permanent’ stoma.
Pathologic response assessed by Mandard grade is a better prognostic factor than down staging for disease‐free survival after preoperative radiochemotherapy for advanced rectal cancer
Authors: Suárez J. , Vera R. , Balén E. , Gómez M. , Arias F. , Lera J. M. , Herrera J. , Zazpe C.
Published: June 2008

Objective  The reduction in tumour stage induced by full course radiotherapy plus chemotherapy is apparent from histological changes. The purpose of this study was to determine the rate of complete pathological response and to evaluate the prognostic value for disease free survival (DFS) and disease specific survival (DSS) of the response. The relation between pretreatment variables (age, gender, stage, tumour height and [carcinoembryogenic antigen (CEA)] and postsurgical variables was compared to the pathological response.

Method  A total of 119 patients with stage II or III rectal cancer underwent surgery 6 weeks after neoadjuvant treatment. Group A included patients with a complete or good pathological response (Mandard grade I–II) and group B patients with a poor response (Mandard grade III–IV–V).The pretreatment endo‐rectal ultrasound scan stage was compared with histopathology stage of the resected specimen. DFS and DSS were compared using the log‐rank test.

Results  All 119 patients (mean age 67.9 years, 83 males) underwent resection. The tumour was located in the upper, middle and lower third of the rectum in 11, 51 and 57 patients. 88 patients had a low anterior resection, 28 patients abdomino‐perineal resection and three a Hartmann’s operation. There was no postoperative death. The circumferential margin (CM) was involved in 10%. A complete pathological response was observed in 17 (14.2%) patients. Thirty‐six (30.2%) patients had a group A and 83 a group B response. Group A showed DFS to be significantly higher than group B (log rank: P = 0.007). The DSS rate was not significantly different between the two groups (log rank P = 0.113). Down‐staging was not related with DFS. No relation was found between pretreatment variables and response. A good pathological response was related to a lower rate of permanent colostomy but not with CM involvement or the number of lymph nodes.

Conclusion  Tumour regression of grades I or II was a good indicator of DFS in locally advanced rectal cancer, treated by neoadjuvant chemotherapy and radiotherapy. Patients with a high regression grade were associated with a lower incidence of definitive stoma formation. The regression grade was shown to be a better prognostic factor than down‐staging.
Fibre supplementation in addition to loperamide for faecal incontinence in adults: a randomized trial
Authors: Lauti M. , Scott D. , Thompson‐Fawcett M. W.
Published: June 2008

Background and aims  Many patients with faecal incontinence (FI) are prescribed a constipating agent concurrently with either fibre supplementation or a low‐residue diet. Clinician opinion varies as to which initial approach is best. This study compared these treatments in routine clinical practice.

Method  Design: Double‐blind randomized cross‐over trial.

Participants: Patients referred for FI.

Intervention: Six weeks of low‐residue diet, placebo fibre supplement and loperamide followed by 6 weeks of fibre supplement, neutral diet and loperamide or the reverse order.

Results  Sixty‐three patients were randomized. At baseline the mean Faecal Incontinence Severity Index (FISI) was 31. After low‐residue diet, placebo fibre supplement and loperamide the FISI was 18.4 (standard deviation, SD 13.2). After fibre supplementation and loperamide the FISI was 18.8 (SD 14.1). The mean difference between the treatment arms was not significant (−0.8; 95% CI: −4.9 to 3.3). There was also no difference between the treatments for the SF‐36 and the Faecal Incontinence Quality of Life scale. There was marked variability in individual responses, some favouring more fibre and some less.

Conclusions  This study provides evidence that treatment with more or less fibre in addition to loperamide has similar clinical effectiveness overall, however individual tailoring of treatment seems important to achieve the best outcome.
Combination statin–fibrate therapy: safety aspects
Authors: Franssen R. , Vergeer M. , Stroes E. S. G. , Kastelein J. J. P.
Published: June 2008

Patients with type 2 diabetes or metabolic syndrome remain at high residual risk of cardiovascular events even after intensive statin therapy. While treatment guidelines recommend the addition of a fibrate to statin therapy in this setting, concerns about the potential for myopathy may limit the use of this combination in clinical practice. These concerns are certainly justified for gemfibrozil, which interferes with statin glucuronidation, leading to elevation in statin plasma concentrations and an increased risk of myotoxicity in combination with a range of commonly prescribed statins. However, the available evidence refutes suggestions that this is a class effect for fibrates. Fenofibrate does not adversely influence the metabolism or pharmacokinetics of any of the commonly prescribed statins. This in turn translates to a reduced potential for myotoxicity in combination with a statin. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the efficacy and safety of fenofibrate plus simvastatin combination therapy in type 2 diabetes patients.
Relationships between insulin secretion after intravenous and oral glucose administration in subjects with glucose tolerance ranging from normal to overt diabetes
Authors: Mari A. , Tura A. , Pacini G. , Kautzky‐Willer A. , Ferrannini E.
Published: June 2008

Aims  Acute insulin release (AIR) in response to intravenous glucose injection (IVGTT) can be abolished in diabetic subjects when their response to oral glucose is maintained. To elucidate this phenomenon, we examined the relationships between fasting plasma glucose (FPG) and the secretory responses to an IVGTT and an oral glucose test (OGTT).

Methods  We measured AIR and secretion after a 75‐g OGTT in 221 subjects [age 37 ± 11 years, body mass index (BMI) 28 ± 5 kg/m2; mean ± sd] with normal glucose tolerance (NGT, n = 147), impaired FPG/impaired glucose tolerance (IFG/IGT, n = 28) and Type 2 diabetes (n = 46). Insulin secretion was calculated by C‐peptide deconvolution; pancreatic B‐cell glucose sensitivity was obtained by OGTT modelling.

Results  Both AIR [186 (185), 142 (164) and 10 (16) pmol/l, median (interquartile range)] and B‐cell glucose sensitivity [98 (64), 66 (53) and 16 (20) pmol min−1 m−2 l mmol−1] decreased across glucose tolerance category (P < 0.0001). However, AIR became ~0 at ~7 mmol/l FPG, whereas B‐cell glucose sensitivity declined gradually throughout the FPG range. In addition, for FPG > 7 mmol/l, AIR was no longer related to FPG, whereas a strong relationship between FPG and B‐cell glucose sensitivity was preserved (ρ = −0.71, P < 0.0001). In a multivariate regression model, adjusting for sex, age and BMI, glucose sensitivity [standardized regression coefficient (std.r.) = −0.67, P < 0.0001], but not AIR (std.r. = 0.03, P = 0.55), was an independent predictor of FPG.

Conclusions  AIR vanishes at fasting or 2‐h glucose levels, at which levels some B‐cell glucose sensitivity is retained; therefore, AIR has a limited ability to quantify B‐cell function in hyperglycaemic states.
Variable phenotypic spectrum of diabetes mellitus in a family carrying a novel KCNJ11 gene mutation
Authors: D’Amato E. , Tammaro P. , Craig T. J. , Tosi A. , Giorgetti R. , Lorini R. , Ashcroft F. M.
Published: June 2008

Aims  Heterozygous activating mutations in KCNJ11, which encodes the Kir6.2 subunit of the pancreatic ATP‐sensitive potassium (KATP) channel, cause both permanent and transient neonatal diabetes. Identification of KCNJ11 mutations has important therapeutic implications, as many patients can replace insulin injections with sulphonylurea tablets. The aim was to determine if a KCNJ11 mutation was responsible for a dominantly inherited form of diabetes mellitus, showing variability in age at diagnosis, in an Italian family.

Methods  We sequenced KCNJ11 in members of a three‐generation family with variable phenotypes of dominantly inherited diabetes mellitus. One had transient early‐onset diabetes, one had impaired glucose tolerance during the second pregnancy, and two had young‐onset diabetes. None of the subjects showed permanent neonatal diabetes or neurological symptoms.

Results  A novel heterozygous mutation (c. 679C→G and c. 680A→T) was identified, resulting in a GAG→CTG (E227L) substitution in KCNJ11. Functional studies of recombinant heterozygous KATP channels revealed a small reduction in channel inhibition by ATP (IC50 of 15 µmol/l and 38 µmol/l for wild‐type and heterozygous channels, respectively) and an increase in the resting KATP current. This would be expected to impair insulin secretion. The results are in agreement with the mild phenotype of the patients.

Conclusions  Our results broaden the spectrum of diabetes phenotypes resulting from KCNJ11 mutations. They indicate testing for KCNJ11 mutations should be considered not only for neonatal diabetes but also for other forms of dominantly inherited diabetes with later onset, especially where these are associated with a low body mass index and low birth weight.
Notification of random hyperglycaemia to general practitioners by an emergency medicine team: impact of a simple intervention plan
Authors: Nicholls G. M. , Dissanayake A. M. , Hazell W.
Published: June 2008

Aim  To determine whether general practitioners (GPs) were being appropriately notified of patients’ elevated random glucose levels by emergency medicine (EM) staff, and to investigate whether two simple interventions improved the notification rate.

Methods  Patients were included if their random venous plasma glucose (RVPG) at presentation to the Emergency Department (ED) was ≥ 7.8 mmol/l and if they were discharged directly to their GP. Patients with known impaired glucose metabolism (IGM) were excluded. Patient discharge summaries were reviewed over a 5‐month period before and a 5‐week period after two simple interventions: first, a targeted educational session for EM staff and second, modifications to the automated message accompanying laboratory results.

Results  Before intervention, the GPs of 120 out of 178 patients received no notification of an elevated RVPG compared with 23 of 62 patients after intervention (P < 0.00001). Notification met a predefined standard in 25 of 178 patients before, and 34 of 62 patients after intervention (P < 0.01).

Conclusions  EM staff education, together with an automated laboratory message, significantly improved the rate and quality of notification of elevated RVPG levels to GPs. These simple measures have the potential to hasten implementation of preventive and therapeutic measures in patients with IGM.
Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene
Authors: Valéro R. , Bannwarth S. , Roman S. , Paquis‐Flucklinger V. , Vialettes B.
Published: June 2008

Aims  Mutations of the WFS1 gene have been implicated in autosomal dominant diseases, such as low‐frequency sensorineural hearing impairment (LFSNHI) and/or diabetes mellitus and/or optic atrophy. The aim was to investigate WFS1 gene sequences in a family with diabetes mellitus and hearing impairment.

Methods  Three members of a family with a maternally inherited combination of diabetes mellitus and hearing impairment, but no specific mutations in its mitochondrial genome, were investigated for mutations in the WFS1 gene.

Results  This pedigree, in which the proband had non‐insulin‐dependent diabetes mellitus and congenital hearing impairment and his mother a triple combination of diabetes mellitus, hearing impairment and optic atrophy, was found to be associated with autosomal dominant transmission of the E864K mutation of the WFS1 gene.

Conclusions  In the light of this confirmatory study, we recommend the systematic analysis of WFS1 gene sequences in patients with parentally inherited diabetes mellitus and deafness (± optic atrophy), in particular when diabetogenic mtDNA mutations have been excluded.
Continuous rise in incidence of childhood Type 1 diabetes in Germany
Authors: Ehehalt S. , Blumenstock G. , Willasch A. M. , Hub R. , Ranke M. B. , Neu A. ,   for the DIARY‐study Group Baden‐Württemberg
Published: June 2008

Aims  To assess the incidence and the trend in incidence of Type 1 diabetes (T1DM) in children and adolescents < 15 years of age in Baden‐Württemberg (BW), Germany.

Methods  BW is Germany's third largest federal state. All 31 paediatric departments in BW and one diabetes centre participated in the study. Case registration was done according to the EURODIAB criteria. The degree of ascertainment was 97.2%.

Results  From 1987 to 2003, the age‐ and sex‐standardized incidence rate was 14.1/100 000 per year [95% confidence interval (CI) 13.7, 14.6, n = 4017]. The estimated annual increase in incidence was 3.8% (95% CI 1.1, 6.6). Compared with the first years of our registry, the current mean number of new cases of T1DM has doubled (1987–1989, n = 153; 2000–2003, n = 302). Generally, the highest rise in incidence occurred in the youngest age group of 0–4‐year‐old patients (5.8%; 95% CI 2.5, 9.3), followed by the age groups 5–9 (3.4%; 95% CI 0.8, 6.0) and 10–14 (2.7%; 95% CI 0.3, 5.1).

Conclusions  In Germany, the number of children and adolescents with new‐onset T1DM has been rising at a faster pace than expected. A distinct shift to younger age at onset has been observed in Germany.