bluuebunny/crossref_metadata_2025 huggingface dataset:
Apoptosis: molecular mechanisms and implications for human disease
Authors: ORRENIUS STEN
Published: August 2009

Abstract. Apoptosis is a highly regulated process of cell death with characteristic morphological changes that are distinct from necrosis. The biochemical machinery responsible for apoptotic cell death appears to be constitutively expressed in most, if not all, cells and can be triggered by a variety of signals, including sustained increases in the intracellular Ca2+ level. Apoptosis is the main mechanism of cell deletion during development, normal cell turnover, hormone‐induced tissue atrophy, and pathological processes such as T‐cell depletion in HIV/AIDS and neurodegenerative disease. The aim of this review is to briefly summarize current knowledge of the molecular mechanisms of apoptosis and its role in human disease.
Fasting blood glucose in determining the prevalence of diabetes in a large, homogeneous population of Caucasian middle‐aged women
Authors: LARSSON H. , AHRÉN B. , LINDGÄRDE F. , BERGLUND G.
Published: August 2009

Abstract. Objectives. To determine the usefulness of a single, fasting blood glucose (FBG) value in measuring the prevalence of diabetes mellitus in a large, homogeneous population.

Design. Fasting blood glucose and 2‐h oral glucose tolerance test (OGTT) values were determined. Based on the results of the OGTT, the sensitivity and specificity of different cut‐off levels of FBG for the diagnosis of diabetes were assessed. ROC (receiver operating characteristic) analysis was performed on the data.

Setting. A health screening unit at the University Hospital in Malmö, Sweden.

Subjects. A total of 1843 Caucasian women without known diabetes aged 55–57 years.

Results. The prevalence of previously undiagnosed diabetes was 3.9% and the prevalence of impaired glucose tolerance (IGT) was 27.9% using the WHO cut‐off values for 2‐h blood glucose values after an OGTT. With an FBG cut‐off value of 6.7 mmol IT−1, the sensitivity of a single FBG value was 36.6%. Reducing the cut‐off value to 6.0 mmol L−1 increased the sensitivity to 53.4%. At a cut‐off level of 4.8 mmol L−1, the sensitivity reached the high value of 85.9%, but the specificity was only 45% and the predictive value of a positive test as low as 5.9%. ROC analysis showed that the optimal cut‐off value for FBG in this population was 5.3 mmol L−1, giving a sensitivity and specificity of 77% but a positive predictive value of only 11.9%.

Conclusions. This study has shown that in a large and homogeneous Caucasian population of women aged 55–57 years with a high prevalence of IGT, a single FBG value is not useful as a screening tool for diabetes mellitus.
Diterpene composition of oils from Arabica and Robusta coffee beans and their effects on serum lipids in man
Authors: MENSINK RONALD P. , LEBBINK W. JANET , LOBBEZOO IRENE E. , DER WOUW MARIANNE P. M. E. WEUSTEN‐VAN , ZOCK PETER L. , KATAN MARTIJN B.
Published: August 2009

Abstract. Objectives. The cholesterol‐raising effect of boiled coffee is caused by diterpenes from coffee oil. In order to identify the diterpene responsible, we analysed the diterpene composition of oils from Arabica (Coffea arabica) and Robusta (Coffea canephora robusta) beans and their effects on serum lipids and thyroid function.

Design, Subjects, and Intervention. During the first 3‐week period of a randomized, cross‐over trial, 11 healthy, normolipaemic volunteers received per day either 2 g of coffee oil (n = 5) or placebo oil (n = 6). After a 2‐week wash‐out, the reverse treatments were applied for another 3 weeks. Six subjects received Arabica oil, supplying 72 mg day−1 cafestol and 53 mg day−1 kahweol, and five received Robusta oil, which provided 40 mg of cafestol, 19 mg of 16‐O‐methyl‐cafestol, and 2 mg of kahweol per day. Background diets were constant.

Results. The average serum cholesterol levels rose by 0.65 mmol L−1 (13%) on Arabica oil (P < 0.025; 95% CI, 0.21–1.09 mmol L−1) and by 0.53 mmol L−1 (13%) on Robusta oil (NS; 95% CI –0.36–1.42 mmol L−1). The triglycerides levels rose by 0.54 mmol L−1 (71%) on Arabica (P < 0.005; 95% CI, 0.22–0.76 mmol L−1) and 0.49 mmol L−1 (61%) on Robusta oil (P < 0.005; 95% CI, 0.30–0.68 mmol L−1). None of the effects on serum lipids or lipoprotein cholesterol levels was significantly different between Arabica and Robusta oil. Concentrations of serum total and free thyroxine (T4), triiodothyronine (T3), and thyroid‐stimulating hormone (TSH) were largely unaffected.

Conclusions. Both Arabica and Robusta oil elevated serum lipid levels; therefore, cafestol must be involved and kahweol cannot be the sole cholesterol‐raising diterpene. The mode of action of coffee diterpenes does not involve induction of hypothyroidism.
Left ventricular thrombosis after anterior myocardial infarction with and without thrombolytic treatment
Authors: MOOE T. , TEIEN D. , KARP K. , ERIKSSON P.
Published: August 2009

Abstract. Objectives. To examine the incidence of left ventricular thrombus in patients with anterior myocardial infarction, with and without streptokinase treatment. To identify predictors of thrombus development.

Design. Consecutive patients prospectively studied during the hospitalized period. Echocardiography was performed within 3 days of admission and before discharge.

Setting. Umeå University Hospital, a teaching hospital in Northern Sweden.

Subjects. Ninety‐nine patients with anterior myocardial infarction of whom 74 were treated with streptokinase.

Main outcome measures. Left ventricular thrombus and left ventricular segmental myocardial function.

Results. During the hospital stay, a thrombus developed in 46% (95% confidence interval [CI], 35–57%) of the patients in the thrombolysis group and in 40% (95% CI, 21–59%) of the patients in the non‐thrombolysis group. No difference in left ventricular segmental myocardial function was found between the thrombolysis and non‐thrombolysis groups at hospital discharge. No embolic events were observed. The occurrence of a left ventricular thrombus at hospital discharge was significantly associated with previous myocardial infarction, peak enzyme levels, left ventricular global and segmental dysfunction and an increased dose of peroral diuretics or use of parenteral diuretics. In a multiple logistic regression model, left ventricular segmental dysfunction was the most important predictor of left ventricular thrombus.

Conclusion. Thrombolytic treatment with streptokinase does not prevent the development of a left ventricular thrombus but the risk of embolic complications is low. The left ventricular segmental myocardial score can be used to assess the risk of thrombus development, also, after thrombolysis.
The cost‐effectiveness of a cardiovascular multiple‐risk‐factor intervention programme in treated hypertensive men
Authors: JOHANNESSON M. , AGEWALL S. , HARTFORD M. , HEDNER T. , FAGERBERG B.
Published: August 2009

Abstract. Objectives. The aim of this study was to carry out a cost‐effectiveness analysis of a multifactorial intervention programme in treated hypertensive patients.

Design. A cost‐effectiveness analysis based on 3 years of follow‐up in an open, randomized, parallel‐group study with allocation either to a comprehensive, multiple‐risk‐factor modification programme or to conventional treatment.

Setting. An outpatient clinic of a city hospital.

Subjects. Inclusion criteria were: male sex, age 50–72 (mean 66.4) years, treated hypertension and at least one of the following: serum cholesterol ≥ 6.5 mmol L‐1, and/or smoking and/or diabetes mellitus. A total of 508 patients were included in the study.

Interventions. Advice given to individuals, and group meetings based on nutritional advice and behavioural treatment principles. If necessary, drug therapy could be instituted to achieve the treatment goals in the intervention group: serum total cholesterol of < 6.0 mmol L−1, no smoking, HbAlc < 6.0% and diastolic blood pressure < 90 mmHg in both groups.

Main outcome measure. Incremental cost per life‐year gained of the intervention programme.

Results. The cost per life‐year gained was SEK 4000 in an estimation based on the observed risk reduction and ranged between SEK 62 000 and SEK 163 000 in three estimations based on the risk factor changes.

Conclusions. The analysis indicates that the intervention programme is cost‐effective in the studied patient population.
Why do all drugs work in animals but none in stroke patients ? 1 Drugs promoting cerebral blood flow
Authors: DEL ZOPPO G. J.
Published: August 2009

Abstract.Medical treatments which presumably alter cerebral blood flow (CBF) have been quite unimpressive in their effect on stroke outcome. In considering experimental and clinical data from the use of haemodilution and of the antiplatelet agent prostacyclin in focal cerebral ischaemia, and the current work with fibrinolytic agents in acute stroke, several lessons are apparent. Often agents hypothesized to affect CBF receive an undeserved reputation based on sparse experimental evidence. Significant even unsuspected differences between species limit application to the clinical setting. Limitations of CBF measurements in experimental models and in humans raise questions about apparent responses to those agents. The failure to confirm a relationship between CBF enhancement and reduction in infarct development experimentally has plagued these approaches. The need for early application of agents which may modulate CBF during cerebral ischaemia is critical. Attention to these general issues and careful application of appropriate models are necessary so that a potentially useful therapeutic intervention is not overlooked.
Interventional neurovascular techniques in the treatment of stroke — state‐of‐the‐art therapy
Authors: HIGASHIDA R. T. , TSAI F. Y. , HALBACH V. V. , BARNWELL S. L. , DOWD C. F. , HIESHIMA G. B.
Published: August 2009

Abstract. Interventional neurovascular techniques for the treatment of patients presenting with symptoms of acute or impending stroke, are now being utilized with increasing frequency in three major areas. (i) For patients presenting with cerebrovascular ischaemic symptoms due to haemodynamically significant stenosis from atherosclerosis, vasculitis, intimal hyperplasia, and dissection, cerebral percutaneous transluminal angioplasty has been shown to be beneficial for both extracranial and intracranial disease. (ii) Patients with acute, embolic occlusion of the internal carotid, middle cerebral, distal vertebral, and basilar arteries have been successfully treated by placement of microcatheters directly into the thrombus with successful thrombolysis, recanalization, and reperfusion to the distal ischemic brain. (iii) Acute arterial vasospasm secondary to subarachnoid haemorrhage is now being managed by balloon angioplasty in those instances where conventional medical therapy has failed.

These techniques are altering our current management and broadening the therapeutic alternatives for patients who present with acute cerebrovascular insufficiency and stroke in evolution. As wider experience is gained in these techniques, the clinical indications for their use will also broaden.
Lowering of body iron stores by blood letting and oxidation resistance of serum lipoproteins: a randomized cross‐over trial in male smokers
Authors: SALONEN J. T. , KORPELA H. , NYYSSÖNEN K. , PORKKALA E. , TUOMAINEN T.‐P. , BELCHER J. D. , JACOBS D.R. , SALONEN R.
Published: August 2009

Abstract. Objectives. The purpose of this study was to test the hypothesis that the reduction of body iron stores by venesection (blood letting) would reduce the susceptibility to oxidation of atherogenic serum lipoproteins.

Design. This is a randomized, controlled cross‐over trial in 14 regularly smoking men with elevated serum ferritin concentration. The study design comprised two 14‐week study periods, with a 14‐week wash‐out period in between, with either blood donations or control.

Setting. The study site was the Research Institute of Public Health, University of Kuopio. Investigators from the Division of Epidemiology, University of Minnesota, Minneapolis, participated in the planning of the study.

Subjects. Fourteen volunteers who were heavy smokers and had previous experience in blood letting were recruited for the study.

Interventions. During the intervention periods, the subjects donated 450 mg (500 mL) of blood three times in 14 weeks.

Main outcome measurements. Oxidation resistance of very low density lipoprotein (VLDL)/low density lipoprotein (LDL) was measured after inducing oxidation with haemin and H2O2.

Results. Serum ferritin concentration was reduced by 44% [95% confidence interval (CI) 8–82%, P = 0.021] during the venesection periods, the maximal oxidation velocity was decreased by 20% (95% CI 3–30%, P = 0.032), and the lag time to start of oxidation was lengthened (oxidation resistance increased) by 33% (95% CI 1–64%, P = 0.036).

Conclusions. These observations indicate that the reduction of body iron stores by venesection can increase the oxidation resistance of serum VLDL/LDL in regularly smoking men.
Rapid detection and prevalence of the variants of the angiotensinogen gene in patients with essential hypertension
Authors: MORISE T. , TAKEUCHI Y. , TAKEDA R.
Published: August 2009

Abstract. Objectives. The angiotensinogen (AGT) gene has been implicated as a candidate gene of high blood pressure. However, because the variants of the AGT gene are point mutations, it is difficult to detect them in large scale population studies. The aims of this study were to develop a rapid screening method for the point mutations and, using this method, to determine the possible role of the AGT gene variant in high blood pressure in the Japanese population.

Design and subjects. A rapid screening method for the point mutations by means of primer‐specified restriction map modification is described here. Using this method, the distribution of two variants of the AGT gene, M235T and T174M, was determined in 80 patients with essential hypertension (EHT) and 100 normotensive controls (control).

Result. The hypertensive group showed a significantly (P < 0.05) higher frequency for the T174M variant but the same frequency for the M235T variant.

Conclusion. These data provide evidence in favour of an association between hypertension and a genetic variant of AGT in human EHT, and a marked ethnic difference in the AGT gene.
Diagnosis of acute intermittent porphyria in northern Sweden: an evaluation of mutation analysis and biochemical methods
Authors: ANDERSSON C. , THUNELL S. , FLODERUS Y. , FORSELL C. , LUNDIN G. , ANVRET M. , LANNFELT L. , WETTERBERG L. , LITHNER F.
Published: August 2009

Abstract. Objective. To validate the use of a recently observed guanine to adenine mutation in exon 10 in the porphobilinogen deaminase (PBGD) gene as a diagnostic marker of acute intermittent porphyria (AIP). To evaluate the efficiency of the traditional biochemical diagnostic methods.

Design. Matched and blinded case–control study (1:4).

Setting. A primary health care centre in Arjeplog, the National Porphyria Research Unit and a department of clinical genetics in Stockholm.

Subjects. A total of 48/49 (98%) patients over the age of 15 years living in Arjeplog with AIP, diagnosed according to standard clinical and biochemical criteria. For each AIP patient, four controls were matched for age, sex and geographical area and 164/196 (86%) participated. In the validity study, 35 patients were selected as indisputable AIP gene carriers, according to strict biochemical criteria, and 92 matched controls were selected with strict exclusion criteria.

Main outcome measures. Validity, specificity and sensitivity of DNA diagnosis for this AIP mutation. Specificity and sensitivity of traditional biochemical methods.

Results. Validity study: the mutation was found in all 35 individuals classified as carriers of AIP. None of the 92 controls had the mutation. Evaluation study: all 48 AIP gene carriers, diagnosed by traditional methods, had the mutation, as had one of the control persons. In an inconclusive group of five persons with heredity for AIP, two had a positive DNA test.

Conclusions. The PBGD mutation analysis was found to have full specificity and sensitivity and can be used as the sole diagnostic method in the family complex studied, representing the major AIP mutation in Sweden. The traditional diagnostic methods, used in optimal combinations, work in most cases, but they do not show high precision. However, they must be used when the specific mutation in the PBGD gene is not known.
Gastrointestinal motility: regulation and impact on metabolism
Authors: PM Hellström
Published: August 2009

Abstract. The function of the small intestine is to digest and absorb nutrients. Motility of the small intestine mixes nutrients with digestive enzymes and promotes absorption of the nutrients delivered to the gut. Gastrointestinal motility is organized in motor patterns that are dependent on the nutrient content. In the digestive phase, motility mixes nutrients with intestinal secretions by segmenting stationary contractions. Propulsion is caused by rapid propagated contractions, but also by stationary contractions if there is an aborally decreasing gradient of the number of contractions. Manometry of digestive motility requires closely spaced multiple recording points. In the interdigestive state, the small intestine is swept clear of secretions and debris through the action of the migrating motor complex (MMC) that occurs at variable intervals concomitant with episodes of gallbladder emptying and slowly propagates along the gut. Manometry of MMC is achieved using longer distances between the recording points. Immediately after food intake, nutrients rapidly flow through the intestine; later, digesta accumulates in the distal intestine through the action of inhibitory feedback mechanisms. The slowing of the transit as the nutrients pass down the gut is dependent on the motility pattern evoked in the digestive phase. Disturbance of these motility patterns may have metabolic effects as evidenced by the consequences of a deranged glucose metabolism in diabetes mellitus, in smooth muscle disease with secondary bacterial overgrowth, and in obesity.
Role of bile in regulation of gut motility
Authors: Hellström P. M. , NILSSON I. , SVENBERG T.
Published: August 2009

Abstract. Bile empties into the duodenum not only after a meal but also in the interdigestive state. In man, inter‐digestive biliary emptying is related to fasting motor activity, the migrating motor complex (MMC), in the stomach and small bowel and generally occurs during phase 2 preceding a gastroduodenal phase 3 activity (activity front). It seems that the main regulatory peptide to initiate phase 3 is motilin. During a period with 13 phase 3 activities of MMC, 18 episodes of gall‐bladder emptying and 19 motilin peaks were observed. Such a peak of plasma motilin usually took place 25 ± 11 min after onset of biliary emptying. In conclusion, data indicate that motilin is released to the circulation by the biliary output and induces phase 3 of MMC. The induced phase 3 propels bile acids along the gut to promote their absorption in the distal intestine. The choleretic action of recycling of bile acids may cause subsequent episodes of biliary emptying with motilin release by the action of the enterohepatic circulation of bile acids. In such a manner the MMC may be withheld as a recycling motility pattern.
Gastrointestinal motility in obesity
Authors: Wisén Olof , HELLSTRÖM P. M.
Published: August 2009

Abstract. Gastrointestinal motility is closely linked to the rate at which nutrients become systemically available. Regulation of gastric emptying represents the most important brake against delivery of nutrients to the intestine in excess of digestive and absorptive capacity. In man, gastric emptying is slowed in proportion to the energy density of the meal, which will level out the rate of energy delivery to the duodenum. Studies suggest a more rapid gastric emptying in obesity, although the opposite has been reported in some experimental settings. Moreover, gastric volume is larger in obese individuals and appropriate satiety signals are not triggered in response to gastric distension. Postprandial intestinal transit time in obesity is similar to that in normal‐weight subjects, however, despite this fact, intestinal absorption of nutrients is more efficient in obesity. Several regulatory mechanisms for gastrointestinal motility, such as the autonomous and enteric nervous systems and gastrointestinal regulatory peptides, are also of importance for feeding behaviour and metabolism. Dysfunction of the autonomous nervous system has been observed, the sensitivity to cholecystokinin is decreased in obesity, and plasma concentrations of somatostatin and neurotensin are lower than in normal‐weight subjects. These changes in regulatory mechanisms favour rapid gastrointestinal transit of ingested nutrients and promote rapid intestinal absorption in obesity and decreased satiety in response to ingested food. It is presently not known whether the observed changes in gastrointestinal motility in obesity represent a primary feature linked to the pathogenesis of such disease.
Gastrointestinal motility disorders and bacterial overgrowth
Authors: Husebye Einar
Published: August 2009

Abstract.Data on the relationship between small intestinal motility, absorption, and nutrition are sparse and incomplete. Yet, impaired motility is considered to be a plausible cause of bacterial overgrowth, which may have deleterious effects on digestion and absorption. This review discusses the scientific validity and clinical relevance of the concept that intestinal motor abnormalities are responsible for enteric bacterial overgrowth.

Disorders associated with intestinal dysmotility and bacterial overgrowth, are illuminated, and concurrent studies of intestinal motility and microflora are focused on in detail. Moreover, practical considerations are given with regard to the clinical management of patients with bacterial overgrowth.

Available data allow the conclusion to be drawn that impaired intestinal motility, as evidenced by attenuated migrating motor complex activity, results in bacterial overgrowth. The criteria for an intestinal motility disorder likely to result in bacterial overgrowth have been determined in patients with late radiation enteropathy, but studies in other clinical conditions are needed to establish general guidelines.
The Expression of Voltage‐Gated Ca2+ Channels in Pituicytes and the Up‐Regulation of L‐Type Ca2+ Channels During Water Deprivation
Authors: Wang D. , Yan B. , Rajapaksha W. R. A. K. J. S. , Fisher T. E.
Published: August 2009

The primary components of the neurohypophysis are the neuroendocrine terminals that release vasopressin and oxytocin, and pituicytes, which are astrocytes that normally surround and envelop these terminals. Pituicytes regulate neurohormone release by secreting the inhibitory modulator taurine in an osmotically‐regulated fashion and undergo a marked structural reorganisation in response to dehydration as well as during lactation and parturition. Because of these unique functions, and the possibility that Ca2+ influx could regulate their activity, we tested for the expression of voltage‐gated Ca2+ channel α1 subunits in pituicytes both in situ and in primary culture. Colocalisation studies in neurohypophysial slices show that pituicytes (identified by their expression of the glial marker S100β), are immunoreactive for antibodies directed against Ca2+ channel α1 subunits CaV2.2 and CaV2.3, which mediate N‐ and R‐type Ca2+ currents, respectively. Pituicytes in primary culture express immunoreactivity for CaV1.2, CaV2.1, CaV2.2, CaV2.3 and CaV3.1 (which mediate L‐, P/Q‐, N‐, R‐ and T‐type currents, respectively) and immunoblotting studies confirmed the expression of these Ca2+ channel α1 subunits. This increase in Ca2+ channel expression may occur only in pituicytes in culture, or may reflect an inherent capability of pituicytes to initiate the expression of multiple types of Ca2+ channels when stimulated to do so. We therefore performed immunohistochemistry studies on pituitaries obtained from rats that had been deprived of water for 24 h. Pituicytes in these preparations showed a significantly increased immunoreactivity to CaV1.2, suggesting that expression of these channels is up‐regulated during the adaptation to long‐lasting dehydration. Our results suggest that Ca2+ channels may play important roles in pituicyte function, including a contribution to the adaptation that occurs in pituicytes when the need for hormone release is elevated.
Mutation frequency of NS5A in patients vertically infected with HCV genotype 1 predicts sustained virological response to peginterferon alfa‐2b and ribavirin combination therapy
Authors: Jenke A. C. W. , Moser S. , Orth V. , Zilbauer M. , Gerner P. , Wirth S.
Published: August 2009

Summary.  Viral genome analyses performed in adult HCV‐patients yielded very inconsistent results and are not transferable to children who are often infected vertically during a state of high immune tolerance. We analysed the mutational frequency in the PKR‐binding domain (PKR‐BD) of NS5A and PePHD of E2 protein pre‐ and post‐treatment with peginterferon‐alfa‐2b and ribavirin in children chronically infected with HCV genotype 1. Amino acid sequences of NS5A (2 209–2 274) and E2 (618–681) were determined in serum samples using standard PCR procedures. Concerning the PKR‐BD a significant higher number of mutations was observed in vertically compared to horizontally infected patients (2.14 vs 1.24, P‐value = 0.03). This difference was exclusively based on the increased number of mutations in responders vs non‐responders in vertically infected patients (2.95 vs 1.33; P‐value = 0.02). While all patients with at least four mutations (n = 3) did respond to therapy, no other predictive parameters could be identified. In the PePHD no differences could be observed between either of these groups. These findings support the idea that viral properties, mode and therewith time of infection in terms of immune tolerance are equally important factors for predicting SVR in children. However given the low number of cases further studies are required to confirm this hypothesis.
Dynamic changes in the extracellular proteome caused by absence of a pleiotropic regulator AdpA in Streptomyces griseus
Authors: Akanuma Genki , Hara Hirofumi , Ohnishi Yasuo , Horinouchi Sueharu
Published: August 2009

In Streptomyces griseus, A‐factor (2‐isocapryloyl‐3R‐hydroxymethyl‐γ‐butyrolactone) triggers morphological development and secondary metabolism by inducing a pleiotropic transcriptional regulator AdpA. Extracellular proteome analysis of the wild‐type and ΔadpA strains grown to the end of the exponential phase in liquid minimal medium revealed that 38 secreted proteins, including many catabolic enzymes, such as protease, glycosyl hydrolase and esterase, were produced in an AdpA‐dependent manner. Transcriptome analysis showed that almost all of these AdpA‐dependent secreted proteins were regulated at the transcriptional level. In vitro AdpA‐binding assays and determination of transcriptional start sites led to identification of 11 promoters as novel targets of AdpA. Viability staining revealed that some hyphae lysed during the exponential growth phase, which could explain the detection of 3 and 23 cytoplasmic proteins in the culture media of the wild‐type and ΔadpA strains respectively. In the wild‐type strain, due to high protease activity in the culture medium, cytoplasmic proteins that leaked from dead cells seemed to be degraded and reused for the further growth. The existence of many AdpA‐dependent (i.e. A‐factor‐inducible) secreted catabolic enzymes, which are likely involved in the assimilation of material that leaked from dead cells, reemphasizes the importance of A‐factor in the morphological differentiation of S. griseus.
Enhancer of decapping proteins 1 and 2 are important for translation during heat stress in Saccharomyces cerevisiae
Authors: Neef Daniel W. , Thiele Dennis J.
Published: August 2009

In mammalian and Drosophila cells, heat stress strongly reduces general protein translation while activating cap‐independent translation mechanisms to promote the expression of stress‐response proteins. In contrast, in Saccharomyces cerevisiae general translation is only mildly and transiently reduced by heat stress and cap‐independent translation mechanisms have not been correlated with the heat stress response. Recently we have identified direct target genes of the heat shock transcription factor (HSF), including genes encoding proteins thought to be important for general translation. One gene activated by HSF during heat stress encodes the enhancer of decapping protein, Edc2, previously shown to enhance mRNA decapping under conditions when the decapping machinery is limited. In this report we show that strains lacking Edc2, as well as the paralogous protein Edc1, are compromised for growth under persistent heat stress. This growth deficiency can be rescued by expression of a mutant Edc1 protein deficient in mRNA decapping indicative of a decapping independent function during heat stress. Yeast strains lacking Edc1 and Edc2 are also sensitive to the pharmacological inhibitor of translation paromomycin and exposure to heat stress and paromomycin functions synergistically to reduce yeast viability, suggesting that in the absence of Edc1 and Edc2 translation is compromised under heat stress conditions. Strains lacking Edc1 and Edc2 have significantly reduced rates of protein translation during growth under heat stress conditions, but not under normal growth conditions. We propose that Edc1 and the stress responsive isoform Edc2 play important roles in protein translation during stress.
Vital role for the Plasmodium actin capping protein (CP) beta‐subunit in motility of malaria sporozoites
Authors: Ganter Markus , Schüler Herwig , Matuschewski Kai
Published: August 2009

Successful malaria transmission from the mosquito vector to the mammalian host depends crucially on active sporozoite motility. Sporozoite locomotion and host cell invasion are driven by the parasite's own actin/myosin motor. A unique feature of this motor machinery is the presence of very short subpellicular actin filaments. Therefore, F‐actin stabilizing proteins likely play a central role in parasite locomotion. Here, we investigated the role of the Plasmodium berghei actin capping protein (PbCP), an orthologue of the heterodimeric regulator of filament barbed end growth, by reverse genetics. Parasites containing a deletion of the CP beta‐subunit developed normally during the pathogenic erythrocytic cycle. However, due to reduced ookinete motility, mutant parasites form fewer oocysts and sporozoites in the Anopheles vector. These sporozoites display a vital deficiency in forward gliding motility and fail to colonize the mosquito salivary glands, resulting in complete attenuation of life cycle progression. Together, our results show that the CP beta‐subunit exerts an essential role in the insect vector before malaria transmission to the mammalian host. The vital role is restricted to fast locomotion, as displayed by Plasmodium sporozoites.
Two‐enzyme systems for glycolipid and polyglycerolphosphate lipoteichoic acid synthesis in Listeria monocytogenes
Authors: Webb Alexander J. , Karatsa‐Dodgson Maria , Gründling Angelika
Published: August 2009

Lipoteichoic acid (LTA) is an important cell wall polymer in Gram‐positive bacteria and often consists a polyglycerolphosphate backbone chain that is linked to the membrane by a glycolipid. In Listeria monocytogenes this glycolipid is Gal‐Glc‐DAG or Gal‐Ptd‐6Glc‐DAG. Using a bioinformatics approach, we have identified L. monocytogenes genes predicted to be involved in glycolipid (lmo2555 and lmo2554) and LTA backbone (lmo0644 and lmo0927) synthesis. LTA and glycolipid analysis of wild‐type and mutant strains confirmed the function of Lmo2555 and Lmo2554 as glycosyltransferases required for the formation of Glc‐DAG and Gal‐Glc‐DAG. Deletion of a third gene, lmo2553, located in the same operon resulted in the production of LTA with an altered structure. lmo0927 and lmo0644 encode proteins with high similarity to the staphylococcal LTA synthase LtaS, which is responsible for polyglycerolphosphate backbone synthesis. We show that both proteins are involved in LTA synthesis. Our data support a model whereby Lmo0644 acts as an LTA primase LtaP and transfers the initial glycerolphosphate onto the glycolipid anchor, and Lmo0927 functions as LTA synthase LtaS, which extends the glycerolphosphate backbone chain. Inactivation of LtaS leads to severe growth and cell division defects, underscoring the pivotal role of LTA in this Gram‐positive pathogen.
Quality of life of living kidney donors in Brazil: an evaluation by the short form‐36 and the WHOQOL‐bref questionnaires
Authors: Padrão Marta B. , Sens Yvoty A. S.
Published: August 2009

Abstract:  Introduction:  There are few studies that evaluate donors’ quality of life (QOL) following renal transplant in developing countries. This study was conducted to evaluate post‐donation QOL of Brazilian living kidney donors using SF‐36 and WHOQOL‐bref questionnaires.

Subjects and methods:  Demographic, socioeconomic and the QOL data were analyzed utilizing SF‐36 and WHOQOL‐bref questionnaires of 69 living kidney donors and compared with 68 non‐donor subjects from the same community.

Results:  The donors and controls were similar as for gender and ethnicity, predominating the female. There was no difference in the educational level or socioeconomic class between the groups, the lower income being more prevalent. The evaluation of the donors’ QOL was not significantly different from that of the control group. In some domains of the SF‐36 and of the WHOQOL‐bref questionnaires, donors scored higher than controls. Even the evaluation of the QOL of donors whose recipients had suffered loss of the graft or death following renal transplantation, showed in a general manner a similar QOL to the controls.

Conclusions:  Living kidney donors in a mainly low‐income segment of the Brazilian population present a post‐donation quality of life equal or superior to that of the non‐donor population with the same socioeconomic profile. The two generic instruments used to evaluate the quality of life presented similar results.
Validity and utility of bipolar spectrum models
Authors: Phelps James , Angst Jules , Katzow Jacob , Sadler John
Published: August 2009

The bipolar spectrum model suggests that several patient presentations not currently recognized by the DSM warrant consideration as part of a mood disorders continuum. These include hypomania or mania associated with antidepressants; manic symptoms which fall short of the current DSM threshold for hypomania; and depression attended by multiple non‐manic markers that are associated with bipolar course. Evidence supporting the inclusion of these groups within the realm of bipolar disorder (BP) is examined. Several diagnostic tools for detecting and characterizing these patient groups are described. Finally, options for altering DSM‐IV criteria to allow some of the above patient presentations to be recognized as bipolar are considered. More data on the validity and utility of these alterations would be useful, but limited changes appear warranted now. We describe an additional BP Not Otherwise Specified (BP NOS) example which creates a subthreshold hypomanic analogue to cyclothymia, consistent with existing BP NOS criteria. This change should be accompanied by additional requirements for the assessment and reporting of non‐manic bipolar markers.
The Mediterranean intercalibration exercise on soft‐bottom benthic invertebrates with special emphasis on the Italian situation
Authors: Occhipinti Ambrogi Anna , Forni Giulia , Silvestri Cecilia
Published: August 2009

The intercalibration exercise is an important step in the building process of the surface water ecological quality assessment, which is required by the Water Framework Directive (WFD). Its aim is to apply the water quality classification in a uniform manner to all the Member States belonging to the same eco‐region. Cyprus, France, Greece, Italy, Slovenia and Spain participated in the soft‐bottom benthic invertebrate subgroup for the Mediterranean coastal region. The methodologies proposed by Member States were applied and tested; the results were compared and harmonized to establish agreed and comparable boundaries for the benthic invertebrate ecological status classes. The national methods used in the intercalibration process were: for Cyprus and Greece, the Bentix Index; for Slovenia, a combination of AZTI Marine Biotic Index (AMBI), richness and diversity with the use of factor and discriminant analysis (Multimetric AMBI); for Spain, a new index, named MEDOCC, which is an adaptation of the AMBI index to the Western Mediterranean area. Italy and France tested different methods, none of which have been officially adopted. Final class boundary values for the different official classification systems were obtained and compared. Besides describing methods and results obtained by the different countries, the Italian situation is examined in more detail. All the above methods have been applied to Italian data, but the results were not conclusive. Major causes for concern are related to insufficient sites and data, to the lack of real non‐impacted reference sites, and to the difficulties in validating the ecological status classification in sites not showing a pollution gradient.
Melatonin prevents peritoneal adhesions in rats
Authors: Ersoz Nail , Ozler Mehmet , Altinel Ozcan , Sadir Serdar , Ozerhan Ismail Hakki , Uysal Bulent , Topal Turgut , Guven Ahmet , Korkmaz Ahmet
Published: August 2009

Background and Aim:  Intra‐abdominal adhesions are important postoperative complications following abdominal surgery. The adhesions that develop form the basis of more advanced pathology such as intestinal obstruction or infertility. Melatonin is secreted from the pineal gland in a circadian pattern; this molecule has potent antioxidant characteristics and has beneficial effects in many models of inflammation. The aim of this study was to evaluate the effects of melatonin on peritoneal adhesions created in rats.

Methods:  A total of 28 Sprague–Dawley male rats were used and divided into four groups. In the first phase of the study, pinealectomy (PINX) was performed on half the animals. An incision was made and sutured in the cecum of all experimental animals in all groups 15 days after the PINX procedure. Some animals were given melatonin orally at a dose of 5 mg/kg daily following the adhesion operation and continued for 15 days. The rats were anesthetized and the abdomen opened after the 15th day (on day 30 of the study). After adhesion scoring based on macroscopic inspection, tissue samples were obtained from the sutured region of the cecum to measure malondialdehyde and hydroxyproline.

Results:  Peritoneal adhesion density was significantly higher in the PINX group compared to the control animals; exogenously administered melatonin significantly reduced adhesion formation. The degree of adhesion was also significantly lower in the intact rats given melatonin compared to the control group.

Conclusion:  Antioxidant activity increases in the oxidative process. We conclude that melatonin may be an important molecule in preventing peritoneal adhesions.
Optimal dose of intravenous pantoprazole in patients with peptic ulcer bleeding requiring endoscopic hemostasis in Korea
Authors: Choi Kee Don , Kim Nayoung , Jang In‐Jin , Park Young Soo , Cho Joo Youn , Kim Jung‐Ryul , Shin Jai Moo , Jung Hyun Chae , Song In Sung
Published: August 2009

Background and Aim:  The lowest effective dose of proton pump inhibitors (PPI) for prevention of peptic ulcer rebleeding remains unclear. The objective of the present study was to evaluate whether low‐dose PPI has a similar efficacy to high‐dose i.v. administration for maintaining intragastric pH above 6.

Methods:  Sixty‐one patients with bleeding ulcers were randomized into one of three groups after endoscopic hemostasis: pantoprazole 80 mg bolus followed by 8 mg/h; 40 mg, 4 mg/h infusion; and bolus injection of 40 mg every 24 h. Intragastric pH values and rebleeding rates were measured. In addition, pharmacokinetic parameters and association with CYP2C19 polymorphisms and H. pylori infection were assessed.

Results:  Mean percentage of time with intragastric pH > 6, and the proportion of patients with pH > 6 for more than 60% of the time were significantly higher in the 40 mg, 4 mg/h infusion group compared to the 40 mg bolus injection. There was no significant difference between the 80 mg, 8 mg/h and the 40 mg, 4 mg/h groups. In the H. pylori (−) group, only 40% of patients that received continuous infusion reached the target pH > 6 for more than 60% of the time; this was significantly lower than the H. pylori (+) group, 87.5% (P = 0.026).

Conclusions:  A continuous infusion, regardless of high or low dose, was more effective for acid suppression than a 40 mg bolus PPI injection in Korea. H. pylori infection was an important factor for the maintenance of an intragastric pH > 6.
Risk factors for severe hand foot and mouth disease
Authors: Suzuki Yoko , Taya Keiko , Nakashima Kazutoshi , Ohyama Takaaki , Kobayashi John M. , Ohkusa Yasushi , Okabe Nobuhiko
Published: August 2009

Background:  Hand foot and mouth disease (HFMD) and herpangina are enteroviral infectious diseases caused mainly by Coxsackie virus A (CA) or enterovirus 71 (EV71). From 2000 to 2002, many complicated cases were reported in Japan, therefore a nationwide questionnaire survey was carried out to assess the situation. The subjects were patients with HFMD or herpangina, or other enterovirus infection from 2000 to 2002, who were either hospitalized over 24 h or who died. The response rates were 41.3% in 2000 and 2001 and 31.6% in 2002. The survey period included the year 2000, when HFMD epidemics due to EV71 occurred. To examine risk factors causing complications of enterovirus infection, severe cases of HFMD were focused on.

Methods:  HFMD cases in 2000 were divided into two groups according to severity: ‘more severe’ and ‘less severe’. ‘More severe’ was defined as ‘fatal, involving sequelae, or involving hospitalization for 7 days or longer’. Statistical analyses were conducted with Epi info version 3.3 and the association between risk factors and severity was estimated.

Results:  The number of patients with more severe and less severe cases was 96 and 103, respectively. There was no difference in sex, age, having siblings and family history between the two groups. There was a significant association between attending child care center and severe HFMD.

Conclusions:  It is not clear why attending child care centers was associated with HFMD severity. Further study is needed.
Increased Fos expression among midbrain dopaminergic cell groups during birdsong tutoring
Authors: Nordeen E.J. , Holtzman D.A. , Nordeen K.W.
Published: August 2009

During avian vocal learning, birds memorize conspecific song patterns and then use auditory feedback to match their vocal output to this acquired template. Some models of song learning posit that during tutoring, conspecific visual, social and/or auditory cues activate neuromodulatory systems that encourage acquisition of the tutor’s song and attach incentive value to that specific acoustic pattern. This hypothesis predicts that stimuli experienced during social tutoring activate cell populations capable of signaling reward. Using immunocytochemistry for the protein product of the immediate early gene c‐Fos, we found that brief exposure of juvenile male zebra finches to a live familiar male tutor increased the density of Fos+ cells within two brain regions implicated in reward processing: the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). This activation of Fos appears to involve both dopaminergic and non‐dopaminergic VTA/SNc neurons. Intriguingly, a familiar tutor was more effective than a novel tutor in stimulating Fos expression within these regions. In the periaqueductal gray, a dopamine‐enriched cell population that has been implicated in emotional processing, Fos labeling also was increased after tutoring, with a familiar tutor again being more effective than a novel conspecific. As several neural regions implicated in song acquisition receive strong dopaminergic projections from these midbrain nuclei, their activation in conjunction with hearing the tutor’s song could help to establish sensory representations that later guide motor sequence learning.
Neuron synchronization in the rat gracilis nucleus facilitates sensory transmission in the somatosensory pathway
Authors: Malmierca Eduardo , Castellanos Nazareth P. , Nuñez‐Medina Alberto , Makarov Valeri A. , Nuñez Angel
Published: August 2009

We have studied the role of the temporal correlation of multiple cell discharges in the facilitation of the somatosensory information transmission from the gracilis nucleus to the primary somatosensory (SI) cortex in anesthetized rats. Pairs of gracilis neurons or gracilis–SI cortical neurons were recorded during application of 20‐ms tactile stimuli in control conditions and after electrical corticofugal stimulation. Cross‐correlation of neural spike trains showed significant changes in synchronization of the neuron firing provoked by the corticofugal stimulation. To quantify the time–frequency alterations in the functional association within neuron pairs we used the wavelet coherence measure. We show that electrical stimulation of the SI cortex induces a short‐lasting facilitation of tactile responses of projecting gracilis neurons if their receptive fields (RFs) overlap with the RF of the stimulated cortical area (matching condition). Moreover, synchronization of discharges of gracilis neurons with a common RF is increased by activation of the corticofugal projection. Synchronization is favored by a stimulus induced synchronous oscillatory activity of projecting neurons in the range 3–10 Hz. In the matching condition synchronous discharges in the gracilis increment the number of spikes elicited in the SI cortex. Thus the efficacy of the sensory transmission from the gracilis nucleus to the SI cortex is modulated by the corticofugal projection through two complementary mechanisms: (i) by changing the responsiveness (number of elicited spikes) of individual gracilis neurons; and (ii) by a dynamic consolidation of gracilis neurons with a common RF into microcircuits generating synchronous spikes.
Health‐related quality of life predicts hospital admission within 1 year in people with diabetes: a nationwide study from Taiwan
Authors: Li C. L. , Chang H. Y. , Lu J. R.
Published: August 2009

Aims  To investigate whether health‐related quality of life (HRQOL) predicts hospital admission in a nationally representative sample of adults with diabetes.

Methods  We conducted a prospective study on persons aged ≥ 18 years with self‐reported physician‐diagnosed diabetes (n = 797) who participated in the National Health Interview Survey in Taiwan, 2001. Of these potential participants, 674 provided consent for data linkage and were successfully linked to the National Health Insurance claims data. We analysed the associations between the Short Form 36 (SF‐36) subscales and summaries and the occurrence of hospital admission for any cause during 2002.

Results  Approximately 23% of participants with diabetes had at least one hospital admission during 2002. After adjusting for demographic characteristics, co‐morbidities and diabetics‐related attributes, those who had been admitted to hospital had significantly poorer mean scores on each of the physical dimensions, physical components summary (PCS) and social functioning domain of the SF‐36 at baseline. In logistic regression models, poorer scores on the PCS [odds ratio (OR) = 1.80; 95% confidence interval (CI) = (1.14–2.86)], duration of diabetes ≥ 10 years [OR = 2.10; 95% CI = (1.14–3.89)] and the presence of heart disease [OR = 1.63; 95% CI = (1.01–2.63)] were significantly associated with an increased risk of hospital admission.

Conclusion  In people with diabetes, poorer scores on the PCS of the SF‐36 at baseline may provide additional information for assessment of hospital admission risk, independent of other measures of health outcomes.