bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification of Cylindrocarpon destructans f. sp. panacis in soils by real‐time PCR
Authors: Kernaghan G. , Reeleder R. D. , Hoke S. M. T.
Published: December 2006

Ginseng (Panax quinquefolius) is an important cash crop in various regions of North America, but yields are often reduced by various root pathogens. A quantitative real‐time PCR (qPCR) assay for Cylindrocarpon destructans f. sp. panacis (CDP), the cause of a root rot and replant disease which discourages successive cropping of ginseng on the same site, was developed to quantify the levels of this pathogen in soils previously cropped with ginseng. DNA was extracted from 5‐g samples of soil. In pasteurized soils which were re‐infested with varying levels of the pathogen, qPCR estimates of pathogen DNA were significantly correlated with disease severity (r = 0·494) and with counts of colony‐forming units (r = 0·620) obtained with an agar medium. In several naturally infested field soils, qPCR estimates of CDP‐DNA concentration were significantly correlated with disease severity (r = 0·765) and these concentrations were estimated to range from 0 to 1·48 ng g−1 dried soil. A principal components analysis did not show any strong relationships between soil chemistry factors and the concentration of pathogen DNA. The approach outlined here allows the quantification of current populations of CDP in soil many years after ginseng cultivation and the prediction of disease severity in future crops. The method should be generally applicable to root diseases of many crops.
Incidence of five viruses infecting sweetpotatoes in Uganda; the first evidence of Sweet potato caulimo‐like virus in Africa
Authors: Aritua V. , Bua B. , Barg E. , Vetten H. J. , Adipala E. , Gibson R. W.
Published: December 2006

In a survey of most sweetpotato‐growing areas of Uganda, virus‐like diseases were observed in all districts surveyed. Out of 338 fields sampled in 35 of the then 42 districts, 219 (65%) had some plants with symptoms. The most common symptoms included vein clearing, mottling, leaf distortion, yellowing, stunting and leaf strapping. Particularly high virus‐like disease incidences (means of 34–86%) were encountered in districts around Lake Victoria and in the Rift Valley in southern and western parts of Uganda; particularly low incidences were encountered in the east and north of Uganda. Using four formats of enzyme‐linked immunosorbent assay in combination with immunoelectron microscopy and polymerase chain reaction assays, five viruses were identified. Sweet potato feathery mottle virus (SPFMV) and Sweet potato chlorotic stunt virus (SPCSV) were most commonly detected, being found in about 90% of samples. Sweet potato mild mottle virus at 10%, Sweet potato chlorotic fleck virus (SPCFV) at 8% and Sweet potato caulimo‐like virus (SPCaLV) at 0·07% were more rarely detected. Most infections were multiple, SPCSV + SPFMV constituting > 90% of all double infections. Triple infections, involving mainly SPFMV, SPCSV and either SPMMV or SPCFV, and quadruple infections of SPFMV + SPCSV + SPMMV + SPCFV were observed in < 10% of the diseased samples. The identification of SPCaLV is the first evidence of its occurrence in Africa.
Use of terminal restriction fragment length polymorphism (T‐RFLP) for identification of phytoplasmas in plants
Authors: Hodgetts J. , Ball T. , Boonham N. , Mumford R. , Dickinson M.
Published: December 2006

A terminal restriction fragment analysis (T‐RFLP) technique was developed for the simple and rapid detection and diagnosis of phytoplasmas in plants. The selected primers amplified part of the 23S rRNA gene to provide improved resolution between the taxonomic groups compared to conventional restriction enzyme analysis of the 16S rRNA. Using the restriction enzymes Bsh12361 and MseI on the PCR products, and fragment analysis in the range 68–640 bp, the technique was tested on 37 isolates from 10 of the 16Sr groups. Distinct and unambiguous T‐RFLP profiles were produced for nine of the 10 taxonomic groups, such that almost all isolates within a group shared the same profile and could be distinguished from isolates in other groups. The technique also identified the presence of mixtures of phytoplasmas from different groups in samples. Furthermore, the primers were devised to amplify a terminal restriction fragment (TRF) product of a specific defined size (461 bp) from the host plant chloroplast DNA, so that there was a built‐in internal control in the procedure to show that the absence of a phytoplasma peak in a sample was the result of no detectable phytoplasma being present, not the result of PCR inhibition. This method offers the possibility of simultaneously detecting and providing a taxonomic grouping for phytoplasmas in test samples using a single PCR reaction.
Red colouration in apple fruit is due to the activity of the MYB transcription factor, MdMYB10
Authors: Espley Richard V. , Hellens Roger P. , Putterill Jo , Stevenson David E. , Kutty‐Amma Sumathi , Allan Andrew C.
Published: December 2006

Anthocyanin concentration is an important determinant of the colour of many fruits. In apple (Malus × domestica), centuries of breeding have produced numerous varieties in which levels of anthocyanin pigment vary widely and change in response to environmental and developmental stimuli. The apple fruit cortex is usually colourless, although germplasm does exist where the cortex is highly pigmented due to the accumulation of either anthocyanins or carotenoids. From studies in a diverse array of plant species, it is apparent that anthocyanin biosynthesis is controlled at the level of transcription. Here we report the transcript levels of the anthocyanin biosynthetic genes in a red‐fleshed apple compared with a white‐fleshed cultivar. We also describe an apple MYB transcription factor, MdMYB10, that is similar in sequence to known anthocyanin regulators in other species. We further show that this transcription factor can induce anthocyanin accumulation in both heterologous and homologous systems, generating pigmented patches in transient assays in tobacco leaves and highly pigmented apple plants following stable transformation with constitutively expressed MdMYB10. Efficient induction of anthocyanin biosynthesis in transient assays by MdMYB10 was dependent on the co‐expression of two distinct bHLH proteins from apple, MdbHLH3 and MdbHLH33. The strong correlation between the expression of MdMYB10 and apple anthocyanin levels during fruit development suggests that this transcription factor is responsible for controlling anthocyanin biosynthesis in apple fruit; in the red‐fleshed cultivar and in the skin of other varieties, there is an induction of MdMYB10 expression concurrent with colour formation during development. Characterization of MdMYB10 has implications for the development of new varieties through classical breeding or a biotechnological approach.
Human MHC region harbors both susceptibility and protective haplotypes for coronary artery disease
Authors: Palikhe A. , Sinisalo J. , Seppänen M. , Valtonen V. , Nieminen M. S. , Lokki M. L.
Published: December 2006

Aiming to study the role of human major histocompatibility complex (MHC) region on coronary artery disease (CAD), we enrolled two separate patient materials and controls. First, heart transplantation recipients (n= 276) were divided into three subgroups according to the severity of atherosclerosis. The human leukocyte antigen (HLA)‐A–B–DR haplotype and gene frequencies were compared between groups. Second, patients with acute coronary syndrome (ACS) (n= 100) and healthy controls (n= 74) were assessed by nine genetic MHC markers (HLA‐A, HLA‐B, HLA‐DRB1, LTA+253(a/g), LTA+496(C/T), LTA+633(c/g), LTA+724(C/A), C4A and C4B), and the frequencies were compared. In the heart transplantation recipients, HLA‐DR1 was strongly associated with CAD [severe vs no evidence, odds ratio (OR) 2.37; 95% confidence interval (CI) 1.33–4.25; P= 0.003]. Similarly, in the patients with ACS, HLA‐DRB1*01 was associated with CAD (patients vs controls, OR 2.36; 95% CI 1.25–4.44; P= 0.007). HLA‐DRB1*01 was associated with low‐density‐lipoprotein cholesterol (OR 5.32; 95% CI 1.64–17.26; P= 0.005) and smoking habit (OR 3.13; 95% CI 1.09–9.03; P= 0.035) as risk factors. The strongest protective gene was HLA‐B*07 alone (OR 0.46; 95% CI 0.24–0.88; P= 0.02) or together with the haplotype LTA+253a−LTA+633g−C4A3−C4B1 (OR 0.36; 95% CI 0.22–0.57; P= 0.00001). In conclusion, human MHC region harbors genes that protect from and predispose to CAD.
An anther‐specific lipid transfer protein gene in sugar beet: its expression is strongly reduced in male‐sterile plants with Owen cytoplasm
Authors: Matsuhira Hiroaki , Shinada Hiroshi , Yui‐Kurino Rika , Hamato Naonori , Umeda Mitsuhiro , Mikami Tetsuo , Kubo Tomohiko
Published: December 2006

Differential screening of a sugar beet (normal cytoplasm line TK81‐O) cDNA library made with anther tissues of various stages resulted in the isolation of a clone (#74‐29) that hybridized to flower bud RNA but did not hybridize to RNA of vegetative organs. The clone contained an open reading frame (ORF) (designated bvLTP‐1) that encoded a putative lipid transfer protein. We also identified a second copy (bvLTP‐2) of the gene. In situ hybridization analysis demonstrated that expression of bvLTP‐1 was confined to the tapetal cells of the anthers at the young microspore stage. Flower bud RNA was prepared from male‐sterile sugar beet with Owen cytoplasm and fertility‐restored plants and used for northern hybridization with the bvLTP‐1 probe. Interestingly, bvLTP‐1 was found to be expressed in the flower buds from the restored plants producing 30% or more stainable pollen, but not in the flower buds from completely sterile or poorly fertility‐restored plants. These results lead us to suppose that the expression of bvLTP‐1 is strongly reduced in the tapetum in response to mitochondrial dysfunction and subsequent physiological changes caused by the Owen cytoplasm.
Application of the comet assay to measure DNA damage induced by UV radiation in the hydrophyte, Spirodela polyrhiza
Authors: Jiang Lei , Wang Yan , Li Shaoshan
Published: December 2006

The single‐cell gel electrophoresis or comet assay is now widely used to detect DNA damage in animal cells induced by radiation or chemicals. Here, we apply the comet assay to measure ultraviolet (UV)‐B‐induced DNA damage in plant cells. The accepted animal cell protocol for the comet assay was modified to adapt it to plant cells. The major modifications were conversion of the plant cells to protoplasts and the use of T4 endonuclease V. As a positive control hydrogen peroxide was applied. Significant DNA damage was detected at 100 μM H2O2. This type of DNA damage was not affected by T4 endonuclease V treatment, which implies that the mechanism of H2O2‐induced DNA damage was different from UV‐B‐induced DNA damage. Our results also indicate that both UV‐A and UV‐B radiation can induce DNA single‐strand breaks in plant cells, while UV‐B was more effective than UV‐A for inducing pyrimidine dimer formation.
Blood conservation strategies in cardiac surgery
Authors: Van der Linden P. , Dierick A.
Published: December 2006

Despite the continuous efforts to increase the safety of blood components, red blood cell transfusions remain associated with some risks and side effects. Therefore, numerous techniques have been developed to decrease blood use, but they also carry risks and bear costs. Most of them are frequently used in cardiac surgery, which still consumes a large part of the available blood supply. Among western countries the use of alternative techniques, but also transfusion practice, has been shown to vary markedly. ‘Blood conservation’ is a global concept engulfing all possible strategies aimed at reducing patients’ exposure to allogeneic blood components. The development of the ‘best strategy’ consists of the selection of those techniques that are most appropriate to the local specific situation. It implies the establishment of a reliable system, collecting data both at the surgical team and at the medical level.
Rationalizing blood transfusion in cardiac surgery: preliminary findings with a red cell volume‐based model
Authors: Slight R. D. , Fung A. K. Y. , Alonzi C. , Bappu N. J. , McClelland D. B. L. , Mankad P. S.
Published: December 2006

Background and Objectives  Cardiac surgery, utilizing extracorporeal circulation, is associated with a heavy fluid load that may significantly depress haemoglobin concentration. Thus, considering haemoglobin alone may be an inaccurate method of replacing red cell volume loss. This study was designed to examine the impact on red cell transfusion of a red cell volume‐based guideline.

Materials and Methods  Patients were randomized to receive red cells as dictated by the red cell volume‐based guideline or a haemoglobin‐based protocol. End‐points considered were red cell transfusion and clinical outcome.

Results  Patients transfused as per the red cell volume‐based guideline received significantly less red cells with no associated difference in clinical outcome.

Conclusion  Considering haemoglobin concentration alone may significantly overestimate the requirement for red cell transfusion in elective cardiac surgery patients.
Normal levels of ADAMTS13 and factor H are present in the pharmaceutically licensed plasma for transfusion (Octaplas®) and in the universally applicable plasma (Uniplas) in development
Authors: Heger A. , Kannicht C. , Römisch J. , Svae T.‐E.
Published: December 2006

Background and Objectives  The pathomechanism of thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS) is associated with a severe deficiency of ADAMTS13 and factor H. The aim of this study was to quantify the levels of ADAMTS13 and factor H in the pharmaceutically licensed plasma for transfusion, Octaplas®, and the universally applicable plasma, Uniplas (development product, working title). Furthermore, Octaplas® batches of blood groups A, B, O, AB, and plasmas derived from different sources were compared.

Materials and Methods  Twenty‐four Octaplas® and three Uniplas batches were selected for the study. ADAMTS13 activities were measured by fluorescence resonance energy transfer assay, ADAMTS13 antigen levels were quantified using enzyme‐linked immunosorbent assay test kit, while factor H antigen levels were detected using radial immunodiffusion (RID) methods. In addition, von Willebrand factor (vWF) multimeric analyses were performed.

Results  Both Octaplas®, produced from US and European plasma of different blood groups, and Uniplas contain ADAMTS13 antigen and activity levels as well as factor H concentrations at normal levels without significant differences. In addition, Octaplas® and Uniplas show a vWF multimeric pattern comparable to normal plasma.

Conclusion  The study revealed that Octaplas® and Uniplas contain normal levels of ADAMTS13 at low batch‐to‐batch variations. Therefore, both products can substitute the missing or neutralized protease activity in TTP patients and thereby limit vWF‐dependent (platelet‐related) thrombosis. In addition, both plasma products contain factor H at a physiological level, and, thus can be used efficiently in the treatment of aHUS patients, which have been shown to benefit from plasma administration.
Ovarian Cysts in MRL/MpJ Mice Originate from Rete Ovarii
Authors: Kon Y. , Konno A. , Hashimoto Y. , Endoh D.
Published: December 2006

In MRL mice aged more than 1 year, but not in C57BL/6 mice, ovaries had grossly visible cysts presenting unilaterally or bilaterally. Postnatally, all MRL mice developed ovarian cysts by 8 months of age. Observations by light microscopy, including lectin histochemistry, indicated that the cysts sometimes included papillomatous tissues located at the hilar region and were similar to the rete ovarii system, but not to follicles. Two types of epithelial cells, ciliated and non‐ciliated, were arranged on the cysts, in which both cell types had many microvilli projecting in various directions and random ramifications in the cystic lumen. These characteristics suggest that ovarian cysts developing in MRL mice originate mostly from the rete ovarii. Cysts derived from the rete ovarii at 8 months of age were histologically detected in all C3H mice as well as MRL mice, with variable incidence in ICR, AKR, CBA/N and ddY, and none in C57L/6, DBA/2, BALB and A/J mice. However, measurement of the maximum diameters of the ovarian cysts indicated that MRL mice regularly possessed the largest cysts visible to the naked eye. This is the first report of ovarian cysts in this inbred strain, suggesting that ovarian cysts in MRL mice appear with stable incidence and development.
Development of the Chick Pancreas with Regard to Estimation of the Relative Occurrence and Growth of Endocrine Tissue
Authors: Maňáková E. , Titlbach M.
Published: December 2006

Endocrine cells in chick pancreas were observed to map their distribution during development and to perform morphometric studies starting on embryonic day 5. The ratio of exocrine to endocrine tissues first prevailed in favour of the endocrine ones, and changed abruptly after day 9 when rapid growth of exocrine tissue began. Endocrine tissue was formed of two types of islets. The ‘light’ (or B) islets were composed of insulin‐immunoreactive cells, completed perhaps by a few somatostatin‐immunoreactive cells occurring on the periphery. The majority of the somatostatin‐ and glucagon‐immunoreactive cells were present in the ‘dark’ (or A) islets. Endocrine elements were also scattered as single cells over the pancreas. Sporadically, the endocrine cells established contacts with exocrine ducts. In morphometric analysis, volume density of insulin‐, glucagon‐, and somatostatin‐immunoreactive cells was measured, and ratios were calculated between particular components. The volume density of endocrine cells and their ratio appeared stable in individual lobes but varied significantly between each other. Increase of the glucagon volume density is exponential, whereas insulin increases almost linearly especially in splenic lobe. The process results in the increase of the hormone‐immunoreactive cell volume density in favour of glucagon‐immunoreactive cells typical for birds.
Topography of Arterial Circle of the Brain in Egyptian Spiny Mouse (Acomys cahirinus, Desmarest)
Authors: Szczurkowski A. , Kuchinka J. , Nowak E. , Kuder T.
Published: December 2006

Using stained acryl latex‐injected techniques, the arterial circle of the brain in Acomys cahirinus Desmarest was studied. Results revealed an important individual variability of investigated structure. Three morphological variants were found: (1) the lack of typical arterial circle – opened in front and the back side, (2) partial opened at the back side, (3) completely closed arterial circle. This finding is opposed to many species of mammals, including rodents, and especially laboratory mouse. In our point of view, it seems to be a specific character.
Growth and Yield of Sweet Corn Following Green Manure in a Warm Temperate Environment on Sandy Soil
Authors: Cherr C. M. , Scholberg J. M. S. , McSorley R. , Mbuya O. S.
Published: December 2006

Legumes used as green manure (GMN) may provide on‐farm sources of N for subsequent crops. In warm‐humid climates on sandy soils, however, there is a need to evaluate effects on growth and yield of subsequent crops when GMN substitutes for chemical N fertilizer. We collected time‐series data for 2 years to evaluate growth and ear yield response of sweet corn (Zea mays L. var. Rugosa) in annual rotation with GMN (summer, winter or summer plus winter GMN) and supplemented with 0, 67 or 133 kg chemical N ha−1. Control treatments receiving 0, 67, 133, 200 or 267 kg chemical N ha−1 were used for comparison. Rotation with summer plus winter GMN resulted in more growth and yield benefit for sweet corn than did the other GMN rotations. Compared with control treatments receiving the same chemical N rates, rotation with summer plus winter GMN increased sweet corn ear yield, leaf area index and total plant dry weight and N content by 15–30 %. Despite these benefits, use of high chemical N rate (267 kg chemical N ha−1) resulted in ear yields at least 20 % greater than sweet corn rotated with any GMN and fertilized with reduced N rates. Largest increases in sweet corn dry weight and N content occurred between 4 and 6 weeks after emergence in all treatments. After this period of rapid growth, sweet corn fertilized with 267 kg chemical N ha−1 showed higher N content than all other treatments. Prior to this period of rapid growth, multiple rainfall events in excess of 30 mm may have resulted in leaching of N from GMN residue. Considering the high rainfall levels, low water and N retention capability of sandy soils and rapid N release from GMN during decomposition, future research of GMN in this environment should evaluate options to better match GMN termination with time of greatest potential N uptake from a subsequent crop.
Heterosis and genetic analysis of iron concentration in grains and leaves of maize
Authors: Chen F. , Chun L. , Song J. , Mi G.
Published: December 2006

Iron (Fe) is a major micronutrient affecting animal and plant health. Maize (Zea mays L.) is an important crop for both food and fodders. The concentration of Fe in grains and vegetative organs, therefore, may exert a direct or indirect influence on human nutrition. Improving Fe nutrition by breeding is a promising way, but little is known about the genetics and heterosis of Fe nutrition in maize. In the present study, nine inbred lines were used to analyse the heterosis, combining ability and genetic ability of Fe concentration in grain and in the leaves supporting the cobs (ear‐leaf) of maize by a diallel mating design. It was showed that heterosis of Fe concentration in grains was very low, indicating that traditional hybrid breeding may not be efficient for improving this trait. Iron concentration of the ear‐leaf was controlled by additive gene effects and heterosis was high, indicating that hybrid breeding can be used to improve Fe nutrition of the vegetative organs of maize.
Quantitative trait loci for agronomic traits in soybean
Authors: Panthee D. R. , Pantalone V. R. , Saxton A. M. , West D. R. , Sams C. E.
Published: December 2006

There continues to be improvement in seed yields of soybean by conventional breeding, but molecular techniques may provide faster genetic gains. The objective of this study was to identify quantitative trait loci (QTL) associated with the agronomic traits seed yield, lodging, plant height, seed filling period and plant maturity in soybean. To achieve this objective, 101 F6‐derived recombinant inbred lines (RIL) from a population developed from a cross of N87‐984‐16 × TN93‐99 were used. Experiments were conducted in six environments during 2002–2003. Heritability estimates on an entry mean basis from data combined across environments ranged from 0.12 to 0.65 for seed yield and seed filling period, respectively. Composite interval mapping detected one QTL for yield (near Satt076), two for lodging (near Satt225 and Satt593) and four for maturity (near Satt263, Satt292, Satt293 and Satt591) in this population. Additional environmentally sensitive QTL for these traits, and for seed filling period and plant height are also reported. The QTL associated with agronomic traits that we report and the recently released germplasm (PI 636460) from this population may be useful in soybean breeding programmes.
Identification and characterization of sources of resistance to Erysiphe pisi Syd. in Pisum spp.
Authors: Fondevilla S. , Carver T. L. W. , Moreno M. T. , Rubiales D.
Published: December 2006

A collection of 67 accessions of Pisum species originating from different countries was screened in a glasshouse test for resistance to Erysiphe pisi. All Pisum fulvum accessions were completely resistant. Incomplete resistance was identified in some accessions of P. sativum subsp. sativum var. arvense and P. sativum subsp. elatius and abyssinicum. Microscopy revealed several distinct cellular mechanisms governing resistance. In P. fulvum, it was mainly due to a high frequency of cell death that occurred both as a rapid response to attempted infection and a delayed response that followed colony establishment. Cell death following colony establishment was also key to the incomplete resistance in some accessions of P. sativum subsp. sativum var. arvense. In addition, impaired spore germination, and to a lesser extent appressorium formation, contributed to pre‐penetration resistance in some accessions. In some cases, resistance also retarded colony growth, possibly through effects on haustorial development or function in cells that survived the attack. Thus, these wild pea accessions offer diverse resistances that could be introduced to cultivated peas to increase the efficacy of powdery mildew resistance.
2··, a new high molecular weight glutenin subunit coded by Glu‐A1: its predicted structure and its impact on bread‐making quality
Authors: Gobaa S. , Kleijer G. , Stamp P.
Published: December 2006

The suitability of wheat varieties for bread‐making depends on their glutenin subunits. The amino acid composition of these gluten building‐blocks have a strong influence on the rheology of the dough and, thus, on the suitability of the variety for bread‐making. This study reports a new x‐type high molecular weight glutenin subunit coded by the locus Glu‐A1 and named 2··. To investigate the impact of this allele on 10 quality parameters, a doubled haploid (DH) population of Triticum aestivum, segregating for Glu‐A1, was created. The statistical analysis demonstrates that, at Glu‐A1, the subunit 2·· is as favourable for quality as the subunit 2*. This is in accordance with results showing that the 2·· open reading frame still has the same number of cysteines as 2*. The small differences in the length of the central domain had no detectable effect on the elasticity, tenacity and baking quality, of the dough.
Production and molecular characterization of Citrus intergeneric somatic hybrids between red tangerine and citrange
Authors: Guo W. W. , Wu R. C. , Cheng Y. J. , Deng X. X.
Published: December 2006

Somatic hybridization has been an effective and successful technique for plant improvement. In this paper, embryogenic callus protoplasts of red tangerine (Citrus reticulata Blanco) were electrically fused with mesophyll protoplasts from citrange (C. sinensis × P. trifoliata, a Chinese local strain) in an effort to produce complementary tetraploid citrus rootstocks. Regenerated embryoids grew slowly and were vulnerable to browning. Twelve plants were finally regenerated, rooted and transplanted into a greenhouse. Root‐tip chromosome counting of five randomly‐selected plants revealed most cells were tetraploid (2n = 4x = 36), but aneuploid cells also existed. Flow cytometry analysis further confirmed their tetraploid nature. Nuclear simple sequence repeat (SSR) analysis verified their hybridity. Further mitochondrial genome analysis by restriction fragment length polymorphism and cleaved amplified polymorphic sequence revealed their mtDNA banding pattern was identical to that of red tangerine, the embryogenic callus parent; while their chloroplast DNA inheritance was random as revealed by chloroplast SSR analysis, in addition to cpDNA co‐existence detected in one plant. Cytological and molecular analysis indicated that somatic hybrid plants between red tangerine and citrange had been successfully obtained.
STATINS REDUCE MACROPHAGE INFLAMMATORY PROTEIN‐1α EXPRESSION IN HUMAN ACTIVATED MONOCYTES
Authors: Bruegel Mathias , Teupser Daniel , Haffner Ivonne , Mueller Marc , Thiery Joachim
Published: December 2006

3‐Hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors (statins) exhibit a wide variety of anti‐atherogenic effects that may be independent of their property to lower plasma cholesterol.

In order to systematically investigate these effects at a cellular level, we investigated gene expression in phorbol myristate acetate (PMA)‐activated and non‐activated human THP‐1 monocytes in response to statins using cDNA arrays.

Of 588 genes tested, 26 were differentially expressed in the presence of statins. A marked reduction was found for the chemokine macrophage inflammatory protein‐1α (MIP‐1α). The decrease in MIP‐1α mRNA expression after incubation with statins was confirmed by quantitative reverse transcription–polymerase chain reaction in THP‐1 monocytes and human freshly isolated monocytes. Macrophage inflammatory protein‐1α protein in THP‐1 monocytes was reduced from 377 to 299 and 305 pg/mL by 0.1 µmol/L simvastatin and 0.01 µmol/L cerivastatin, respectively. The reduction in MIP‐1α expression by statins was due, at least in part, to transcriptional inhibition of MIP‐1α promoter activity.

The CC receptor ligand MIP‐1α is a chemokine that has been implicated in atherosclerotic lesion formation. The present findings suggest that statin‐mediated immunomodulation by inhibiting MIP‐1α could contribute to the beneficial effects of statin therapy independent of lowering plasma cholesterol.
TISSUE‐SPECIFIC REGULATION OF INSULIN‐LIKE GROWTH FACTORS AND INSULIN‐LIKE GROWTH FACTOR BINDING PROTEINS IN MALE DIABETIC RATS IN VIVO AND IN VITRO
Authors: Han Ho Jae , Kang Chang Won , Park Soo Hyun
Published: December 2006

Insulin‐like growth factors (IGFs) are associated with the development of diabetes mellitus. The liver, kidney and heart have been implicated as important organs in the onset of diabetes mellitus. However, the effect of diabetes on the IGF system in these organs has not been fully described. Thus, we investigated changes in IGF‐I, IGF‐II and IGF binding proteins (IGFBPs) in male steptozotocin‐induced diabetic rats, as well as in a high glucose‐induced in vitro model.

Serum levels of IGF‐I were decreased, but the levels of IGF‐II were increased, in diabetic rats compared with controls. The expression of IGFBP‐3 in the serum was markedly decreased; in contrast, the expression of IGFBP‐1 and ‐2 was increased in diabetic rats. The expression of IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐2, IGFBP‐3 and IGFBP‐4 in the liver of the diabetic group was similar to that in the serum of diabetic rats.

In heart tissue of the diabetic group, IGF‐I levels were decreased, but IGF‐II levels were increased. In addition, the expression of IGFBP‐3, IGFBP‐1 and IGFBP‐2 was decreased in diabetic rats.

In the kidney of the diabetic group, IGF‐I and IGF‐II levels were increased. There was only slight expression of IGFBP‐3 in the kidney and this was not altered in diabetic rats. Levels of IGFBP‐1 and ‐2 were markedly increased in the kidney of diabetic rats.

Insulin treatment recovered the changes in expression of IGF‐I, IGF‐II and IGFBPs in the serum, liver, heart and kidney. In the liver, heart and kidney, the expression of the insulin receptor was increased in male diabetic rats.

In conclusion, diabetes tissue‐specifically alters the IGF system in the liver, heart and kidney in rats; this effect can be recovered by insulin treatment.
CHANGES IN THE VISCERAL FUNCTIONS OF PLASMODIUM BERGHEI‐INFECTED AND ‐UNINFECTED RATS FOLLOWING ADMINISTRATION OF ARTEMETHER
Authors: Akomolafe RO , Adeoshun IO , Fakunle JB , Iwalewa EO , Ayoka AO , Akanji BO
Published: December 2006

The effects of artemether (12.5, 25.0 and 50.0 mg/kg per day, i.m.), administered to different groups of Plasmodium berghei‐infected and ‐uninfected adult Wistar rats for 1 week, were investigated.

The parameters evaluated were the feeding, drinking and urinating patterns of the rats and these were compared with those of rats that received normal saline.

Artemether caused a significant dose‐dependent reduction in food consumption of both P. berghei‐infected and ‐uninfected rats (P < 0.05). Food intake in infected rats was reduced by approximately 7 g/24 h. This reduction in food intake was further reduced during drug treatment with artemether. Artermether also reduced food intake in uninfected rats. The food consumption of rats that received 12.5 and 25.0 mg/kg artemether was restored after stopping treatment, in contrast with rats that received 50.0 mg/kg, in which the significant reduction in food consumption persisted 1 week after drug administration.

During treatment with artemether, the water intake of infected rats was significantly lower than that of uninfected rats in the 12.5 mg/kg artemether‐treated group, but was significantly higher in infected rats than in uninfected rats dosed with 25.0 and 50.0 mg/kg artemether.

For all doses of artemether tested, a significant increase in urine output was observed in infected rats during treatment and 1 week after treatment, whereas in uninfected rats a significant increase in urine output was observed only following 25.0 and 50.0 mg/kg artemether 1 week after drug administration.

The present study confirms the anorexic activity of a high dose of artemether in both P. berghei‐infected and ‐uninfected rats. It also indicates that high doses of the drug could cause impaired renal function in rats and that the significant increase in urine output could also be due to other effects of artemether, namely those on thirst, anti‐diuretic hormone output and the osmotic pressure of the blood.
PERSONAL DIGITAL VIDEO: A METHOD TO MONITOR DRUG REGIMEN ADHERENCE DURING HUMAN CLINICAL INVESTIGATIONS
Authors: Carroll Chad C , Trappe Todd A
Published: December 2006

Maintaining patient adherence to a drug regimen has proven to be difficult. Missed doses can impact drug efficacy and disease control, leading to increased health‐care costs.

During clinical drug trials, poor adherence could lead to false conclusions regarding drug efficacy. Therefore, the purpose of the present study was to determine the feasibility of using personal digital video cameras to monitor adherence to a medication regimen during a clinical investigation.

Older men and women (60–78 years) participated in a double‐blind, placebo‐controlled trial to determine the effect of ibuprofen or paracetamol on skeletal muscle adaptations to chronic resistance exercise training. Patients took three daily doses of either a placebo or the maximal daily over‐the‐counter dose of ibuprofen (1.2 g/day) or paracetamol (4.0 g/day) for 12 weeks. Prior to beginning the study, subjects were trained to use a personal digital video camera to record their drug consumption.

Subjects correctly recorded 4956 of 5375 doses, resulting in an average camera compliance rate of 92% (71–100%).

We describe a method of monitoring adherence to a prescribed drug regimen during a clinical investigation. Camera compliance rates, which directly confirm drug consumption, were higher than what is typically obtained with other methods of monitoring adherence. This camera compliance method provides the investigator with a simple and convenient means to generate direct evidence of drug consumption.
ELECTROPHYSIOLOGICAL EVIDENCE FOR THE INTERACTION OF SUBSTANCE P AND GLUTAMATE ON Aδ AND C AFFERENT FIBRE ACTIVITY IN RAT HAIRY SKIN
Authors: Zhang Qi , Zhao Yan , Guo Yuan , Cao Dong‐Yuan , Tian Yu‐Ling , Yao Fan‐Rong , Wang Hui‐Sheng
Published: December 2006

The purpose of the present study was to investigate whether there was a cooperative interaction between substance P (SP) and glutamate (GLU) administered subcutaneously on Aδ and C primary afferent fibre activity in dorsal hairy skin of the rat in vivo. The single unit activities of Aδ and C afferent fibres were recorded by isolation of fibre filaments from the dorsal cutaneous nerve branches and the effects of subcutaneous injections of low doses of SP, GLU and SP + GLU on activity were determined.

Sub‐threshold doses of SP (1 µmol/L, 10 µL) administered subcutaneously into the dorsal hairy skin had no effect on the afferent discharges of either Aδ or C units.

The afferent discharges of 35% (11/31) of Aδ fibres and 33% (6/18) of C fibres were increased by local injection of the submaximal doses of GLU (10 µmol/L, 10 µL) into the receptive fields.

The GLU‐induced excitatory response was significantly enhanced by coinjection of subthreshold doses of SP. The mean discharge rates of Aδ fibres and C fibres were increased from 5.84 ± 1.54 and 5.02 ± 2.65 impulses/min to 19.91 ± 4.35 and 17.58 ± 5.59 impulses/min, respectively, whereas the excitatory proportions of Aδ and C fibres were increased from 35 and 33% to 84 and 83%, respectively. The duration of the excitation for Aδ fibres and C fibres was also significantly increased after coinjection of SP + GLU compared with that observed when either substance was given alone.

The present study provides electrophysiological evidence for an interaction between receptors for SP and GLU on the fine fibres activities in rat hairy skin, which may be involved in the mechanisms of hyperalgesia.
BIOCHEMICAL EVALUATION OF ANTIDIABETOGENIC PROPERTIES OF SOME COMMONLY USED INDIAN PLANTS ON STREPTOZOTOCIN‐INDUCED DIABETES IN EXPERIMENTAL RATS
Authors: Narendhirakannan RT , Subramanian S , Kandaswamy M
Published: December 2006

Diabetes mellitus is a serious metabolic disorder with micro‐ and macrovascular complications that results in significant morbidity and mortality.

The aim of the present study was to evaluate the hypoglycaemic efficacy of commonly used traditional Indian plants, such as Murraya koenigii, Mentha piperitae, Ocimum sanctum and Aegle marmelos, in streptozotocin (STZ)‐induced experimental rats.

Oral administration of the ethanolic extract of these plants resulted in a significant decrease in the levels of blood glucose, glycosylated haemoglobin and urea, with a concomitant increase in glycogen, haemoglobin and protein, in diabetic rats. Treatment with these plant extracts also resulted in an increase in insulin and C‐peptide levels and glucose tolerance.

The decreased activities of carbohydrate‐metabolising enzymes, such as hexokinase, glucose‐6‐phosphate dehydrogenase and glycogen synthase, in diabetic rats were significantly elevated towards near normal in rats treated with extracts of M. koenigii, O. sanctum and A. marmelos; the increased activities of lactate dehydrogenase, fructose‐1,6‐bisphosphatase, glucose‐6‐phosphatase and glycogen phosphorylase in STZ diabetic rats were significantly reduced following treatment with the plant extracts.

Elevated specific binding of [125I]‐labelled insulin to the receptor found in diabetic rats was markedly decreased in extract‐treated groups. However, treatment of diabetic rats with M. piperitae did not result in any significant modification in all parameters.

Phytochemical screening conducted by us revealed the presence of biologically active ingredients in the ethanolic extracts of M. koenigii, O. sanctum and A. marmelos, which may readily account for the observed hypoglycaemic activity.
CHARACTERIZATION OF THE ACUTE CARDIOVASCULAR EFFECTS OF INTRAVENOUSLY ADMINISTERED INSULIN‐LIKE GROWTH FACTOR‐I IN CONSCIOUS SPRAGUE‐DAWLEY RATS
Authors: Cao Nga , Lau Shannen , Nguyen Tien Thuy , White Paul J
Published: December 2006

Insulin‐like growth factor (IGF)‐I has acute effects on cardiovascular function, including a well‐characterized vasodilator response in isolated arteries. In addition to increasing the release of nitric oxide, IGF‐I also has effects on a variety of other signalling pathways that affect vascular tone, in particular interactions with the sympathetic nervous system and the renin–angiotensin–aldosterone system. We sought to characterize the effects of intravenous IGF‐I on blood pressure and on responses to noradrenaline (NA), angiotensin II, acetylcholine and dobutamine.

Administration of IGF‐I administration caused small decreases in mean arterial pressure (5.4 ± 1.5%) and responsiveness to the prazosin‐sensitive vasoconstrictor effects of NA (a 2.1 ± 0.6‐fold increase in ED50; n = 40; P < 0.01) and both effects were maximal at 200 µg/kg IGF‐I. In addition, IGF‐I significantly increased pulse pressure increases induced by low doses of dobutamine (from an increase in pulse pressure of 9.9 ± 1.2 to 13.4 ± 1.9 mmHg; n = 39; P < 0.05). Administration of IGF‐I had no significant effect on responses to AngII or ACh.

Intravenous administration of IGF‐I receptor antisense oligonucleotides (400 µg/kg) abolished the effects of IGF‐I on NA‐induced vasoconstriction (n = 11; P < 0.05), whereas administration of a mismatch oligonucleotide did not.

These data indicate that the maximal effects of exogenously administered IGF‐I include modest direct vasodilation and inhibition of constrictor responses to NA and an increase in the effect of dobutamine on pulse pressure. The magnitude of these effects was less than what previous in vitro studies and those performed in anaesthetized animals may have indicated likely.

The modest magnitude of the dilator effects of IGF‐I observed in conscious rats in vivo in the present study suggests that IGF‐I is unlikely to be a major player in regulating vascular tone in normotensive animals.
REFLEXLY EVOKED COACTIVATION OF CARDIAC VAGAL AND SYMPATHETIC MOTOR OUTFLOWS: OBSERVATIONS AND FUNCTIONAL IMPLICATIONS
Authors: Paton Julian FR , Nalivaiko Eugene , Boscan Pedro , Pickering Anthony E
Published: December 2006

The purpose of the present review is to highlight the pattern of activity in the parasympathetic and sympathetic nerves innervating the heart during their reflex activation.

We describe the well‐known reciprocal control of cardiac vagal and sympathetic activity during the baroreceptor reflex, but point out that this appears to be the exception rather than the rule and that many other reflexes reviewed herein (e.g. peripheral chemoreceptor, nociceptor, diving response and oculocardiac) involve simultaneous coactivation of both autonomic limbs.

The heart rate response during simultaneous activation of cardiac autonomic outflows is unpredictable because it does not simply reflect the summation of opposing influences. Indeed, it can result in bradycardia (peripheral chemoreceptor, diving and corneal), tachycardia (nociceptor) and, in some circumstances, can predispose to malignant arrhythmias.

We propose that this cardiac autonomic coactivation may allow greater cardiac output during bradycardia (increased ventricular filling time and stronger contraction) than activation of the sympathetic limb alone. This may be important when pumping blood into a constricted vascular tree, such as is the case during the peripheral chemoreceptor reflex and the diving response.
DUAL ACTIVATION OF CARDIAC SYMPATHETIC AND PARASYMPATHETIC COMPONENTS DURING CONDITIONED FEAR TO CONTEXT IN THE RAT
Authors: Carrive Pascal
Published: December 2006

The present study investigates the contribution of the sympathetic and vagal parasympathetic systems to the tachycardic response of long‐lasting (40 min) conditioned fear responses to context.

The conditioned fear response evoked by re‐exposure to a footshock chamber was tested 10 min after intravenous injection of the β‐adrenoceptor antagonist propranolol (2 mg/kg) or the muscarinic antagonist atropine methyl nitrate (2 mg/kg) in rats implanted with radiotelemetric probes.

Compared with saline controls, the drugs did not change the behavioural component of the response (freezing, 22 kHz ultrasonic vocalizations) or its pressor component (+28 mmHg).

Propranolol abolished the tachycardic response of fear, whereas atropine more than doubled it (from +75 to +175 b.p.m. above resting baseline).

The results demonstrate that both sympathetic and vagal parasympathetic outflows to the heart are strongly activated during conditioned fear. The vagal activation may act to hold back cardiac acceleration while the animal waits for the aversive stimulus to come.
DIFFERENTIAL CONTROL OF CARDIAC FUNCTIONS BY THE BRAIN
Authors: Salo Lauren M , Campos Ruy R , McAllen Robin M
Published: December 2006

The idea is introduced that cardiac rate, contractility or atrioventricular (A‐V) conduction spread may be controlled independently by the brain. Limited data from reflex studies are cited to support this view.

Evidence is presented that individual autonomic post‐ and preganglionic neurons have quite specific actions on the heart. Premotor and other central neurons can have preferential actions on heart rate, contractility or A‐V conduction.

The functional implications of selective cardiac control are discussed.
5‐HT1ARECEPTORS IN STRESS‐INDUCED CARDIAC CHANGES: A POSSIBLE LINK BETWEEN MENTAL AND CARDIAC DISORDERS
Authors: Nalivaiko Eugene
Published: December 2006

Mental disorders associated with chronic stressors are established risk factors for cardiac morbidity and mortality, but there is no satisfactory explanation of the mechanistic link between mental and cardiac disorders.

The present article presents the hypothesis suggesting that abnormal functioning of serotonin 5‐HT1Areceptors in the lower brain stem may represent this missing link. Currently available data suggest that there may be a global downregulation of 5‐HT1Areceptors in depressive and panic patients.

Recent animal results indicate that 5‐HT1Areceptors, located in the medullary raphe, possibly on the raphe–spinal presympathetic cardiomotor neurons, reduce stress‐elicited activation of these neurons.

Decreased density/function of 5‐H1Areceptors in the raphe area (possibly occurring during chronic stress/depression) may lead to increased sympathetic outflow to the heart and, consequently, to the increase in noradrenalin release from the cardiac sympathetic nerve terminals.
MECHANISMS OF SYMPATHETIC ACTIVATION IN HEART FAILURE
Authors: Watson AMD , Hood SG , May CN
Published: December 2006

Heart Failure (HF) is a serious, debilitating condition with poor survival rates and an increasing level of prevalence. A characteristic of HF is a compensatory neurohumoral activation that increases with the severity of the condition.

The increase in sympathetic activity may be beneficial initially, providing inotropic support to the heart and peripheral vasoconstriction, but in the longer term it promotes disease progression and worsens prognosis. This is particularly true for the increase in cardiac sympathetic nerve activity, as shown by the strong inverse correlation between cardiac noradrenaline spillover and prognosis and by the beneficial effect of β‐adrenoceptor antagonists.

Possible causes for the raised level of sympathetic activity in HF include altered neural reflexes, such as those from baroreceptors and chemoreceptors, raised levels of hormones, such as angiotensin II, acting on circumventricular organs, and changes in central mechanisms that may amplify the responses to these inputs.

The control of sympathetic activity to different organs is regionally heterogeneous, as demonstrated by a lack of concordance in burst patterns, different responses to reflexes, opposite responses of cardiac and renal sympathetic nerves to central angiotensin and organ‐specific increases in sympathetic activity in HF. These observations indicate that, in HF, it is essential to study the factors causing sympathetic activation in individual outflows, in particular those that powerfully, and perhaps preferentially, increase cardiac sympathetic nerve activity.