bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial extraction from grapevine and detection of Xylophilus ampelinus by a PCR and Microwell plate detection system*
Authors: Manceau C. , Grall S. , Brin C. , Guillaumes J.
Published: May 2005

Xylophilus ampelinus is listed as a quarantine pest in Annex II/A2 of EU Directive 2000/29. Grapevine cuttings used either as rooting or grafting material represent a primary source of inoculum because of the systemic nature of bacterial colonization. We describe a PCR‐based method for the specific detection of X. ampelinus from various plant materials (trunks, woody branches, growing shoots, leaves and bleeding sap), making the detection of X. ampelinus reliable throughout the year. Bacterial cells were extracted by crushing the plant tissues and soaking them in sterile distilled water for 30–120 min at 4 °C. Bacterial cells were harvested by centrifugation at 13 000 g for 10 min through sterile paper discs, and lysed in SDS buffer. DNA was extracted by a silica‐based procedure. Specific DNA amplifications were performed with a pair of primers, of which one was labelled with biotin. A digoxygenin‐labelled oligonucleotide with a sequence specific for the amplicon was used as the probe. Finally, amplicons were immobilized in microplate wells coated with streptavidine, and hybridization of the digoxygenin‐labelled probe was detected with alkaline phosphatase‐conjugated antibiodies in a colorimetric assay. This method was sensitive, specific and allowed experiments with high throughput.
On the non‐occurrence of Ditylenchus dipsaci in India
Authors: Rajan  , Lal Arjun
Published: May 2005

On the basis of results of surveys, examination of materials collected through exploration trips for gene banks and research, phytosanitary inspection of germplasm material meant for export (in 1976/2003), published literature and crop protection databases, it is reported that, though congenial climatic conditions prevail and host crops are under regular production in the area, the important pest Ditylenchus dipsaci does not occur in India.
Connecting seas: western Palaearctic continental flyway for water birds in the perspective of changing land use and climate
Authors: Van Eerden Mennobart R. , Drent Rudolf H. , Stahl Julia , Bakker Jan P.
Published: May 2005

The western Palaearctic continental flyway that connects the tundra and taiga belts of Russia with north‐west Europe is the major migratory avenue for an estimated 9.3 million herbivorous water birds (swans, geese and ducks). Agricultural practices together with protection measures subsidize the carrying capacity of winter habitats of the birds. Densities of these birds are highest in the Netherlands, where nitrogen (N) inputs to farmland have increased during the last 70 years and became the highest in Europe (>250 kg manure and fertilizer ha−1 yr−1). A comparison of population trends of 13 species of avian herbivores reveals generally expanding populations in the past 50 years, with the greatest increases from 1970 to 1990. Populations of the smallest avian herbivores, such as ducks, are either stable or have peaked and are now in decline, whereas numbers of larger herbivores (geese and swans) continue to increase and barnacle and greylag geese now breed in the Netherlands, in addition to northern sites.

During the northerly spring migration, stop‐over sites, mostly in the agricultural regions of eastern Europe and Scandinavia, lie between the 3 and 6°C mean daily temperature isotherms in April, temperatures at which grasses start to grow, where flooding of riparian wetlands frequently occurs and fertilizers are applied to farmland. However, the restructuring of agricultural practices in an enlarged EU is likely to affect water bird populations and their migration routes. The reduced use of N in the Netherlands is predicted to constrain population growth, especially of the smallest avian herbivores with their high basal metabolic rates, because of the declining food quality of grass leaves. The introduction of large‐scale farming of oilseed rape, winter cereals, sugar beet and potatoes at the expense of grassland also will adversely affect these birds, whereas larger species are likely to continue exploiting these crops.
Interactions between land use, habitat use, and population increase in greater snow geese: what are the consequences for natural wetlands?
Authors: Gauthier Gilles , Giroux Jean‐François , Reed Austin , Béchet Arnaud , Bélanger Luc
Published: May 2005

The North American greater snow goose population has increased dramatically during the last 40 years. We evaluated whether refuge creation, changes in land use on the wintering and staging grounds, and climate warming have contributed to this expansion by affecting the distribution, habitat use, body condition, and migration phenology of birds. We also reviewed the effects of the increasing population on marshes on the wintering grounds, along the migratory routes and on the tundra in summer. Refuges established before 1970 may have contributed to the initial demographic increase. The most important change, however, was the switch from a diet entirely based on marsh plants in spring and winter (rhizomes ofScirpus/Spartina) to one dominated by crops (corn/young grass shoots) during the 1970s and 1980s. Geese now winter further north along the US Atlantic coast, leading to reduced hunting mortality. Their migratory routes now include portions of southwestern Québec where corn production has increased exponentially. Since the mid‐1960s, average temperatures have increased by 1–2.4°C throughout the geographic range of geese, which may have contributed to the northward shift in wintering range and an earlier migration in spring. Access to spilled corn in spring improved fat reserves upon departure for the Arctic and may have contributed to a high fecundity. The population increase has led to intense grazing of natural wetlands used by geese although these habitats are still largely undamaged. The foraging in fields allowed the population to exceed limits imposed by natural marshes in winter and spring, but also prevented permanent damage because of their overgrazing.
TCP10L is expressed specifically in spermatogenic cells and binds to death associated protein kinase‐3
Authors: YU HONGXIU , JIANG DAOJUN , GUO ZEKUN , SAIYIN HEXIGE , GUO JINHU , WANG XIANG , YU LONG
Published: May 2005

The human transcriptional factor T‐complex protein 10 like (TCP10L) gene is expressed exclusively in the liver and testis. However, the function of TCP10L in the testis remains unknown. We examined the expression of TCP10L in human testis and found that TCP10L was expressed specifically in the nucleus of spermatogenic cells during spermatogenesis. In addition, we identified death associated protein kinase 3 (DAPK‐3/ZIP kinase) as a binding partner for TCP10L by yeast two‐hybrid screening, followed with immunoprecipitation and subcellular localization experiments. Mutagenesis study revealed that this interaction was dependant on the leucine zipper motif‐containing region. The specific expression pattern of TCP10L and interaction with DAPK‐3 implies that TCP10L might play crucially important roles in spermatogenesis through its interaction with DAPK‐3.
A two‐stage convective air and vacuum freeze‐drying technique for bamboo shoots
Authors: Xu Yanyang , Zhang Min , Tu Dingyu , Sun Jincai , Zhou Lequn , Mujumdar Arun S.
Published: May 2005

To obtain dehydrated bamboo shoot slices of high quality, a two‐stage hybrid method of drying was tested to see if it could be cost‐effective. While freeze‐drying provides the best quality bamboo shoot it is a very expensive process. In this study, the drying techniques (a) hot airflow drying followed by vacuum freeze drying and (b) the reverse of the process (a) were examined. The quality of bamboo shoots dried by process (b) was found to be approximately equal to that of freeze‐dried bamboo shoots but at a significantly lower cost. This paper reports results comparing the two processes in terms of energy consumption and the physico‐chemical properties of the dried bamboo.
The impact of roasting on the ochratoxin A content of coffee
Authors: Suárez‐Quiroz Mirna , Louise Béatrice De , Gonzalez‐Rios Oscar , Barel Michel , Guyot Bernard , Schorr‐Galindo Sabine , Guiraud Joseph‐Pierre
Published: May 2005

Roasting coffee led to a drop in the ochratoxin A (OTA) concentration, as measured by the reference method, especially for dark type roasts. The way the beverage was prepared also affected the OTA content, which could paradoxically be higher than that of the initial roasted coffee. Assays on the thermal stability of pure OTA showed that it ought to be found in larger quantities in roasted coffee. This suggested that OTA was masked by reactions with the substrate during roasting. The absence of OTA in green coffee is therefore the best guarantee of safety.
Stress and crack prediction during drying of Japanese noodle (udon)
Authors: Inazu Tadao , Iwasaki Ken‐ichi , Furuta Takeshi
Published: May 2005

The distribution of stress during drying of fresh Japanese noodle (udon) was investigated by mathematically modelling the changes in shrinkage and other mechanical properties, this allowed crack formation to be predicted. It was observed that the shrinkage coefficients were nearly the same in all three directions with changing moisture content, and the degree of shrinkage was independent of the temperature. The Young's modulus, yield stress and fracture stress could be expressed as exponential functions of moisture content. Changes in stress distribution during drying were calculated by coupling the moisture transfer equation with the constitutive equation using a finite element method. The calculated stress distribution indicated that a rapid drying rate causes extensive internal tensile stress in udon. The scheme used in the present study was found to effectively represent the potential for crack formation along the central axis, this was shown to be consistent with the actual cracking pattern.
Correlating instrumental measurements of texture and flavour release with human perception
Authors: Cook David J. , Hollowood Tracey A. , Linforth Robert S. T. , Taylor Andrew J.
Published: May 2005

Attempts to correlate sensory perception with analytical measurement of the physical or chemical properties of a food are widespread in both industry and academia. Reasons for this are discussed, along with some of the techniques employed. The inter‐relationship between instrumental analysis and sensory evaluation in the development and quality control of food products is emphasized. Three examples are drawn from the field of flavour research, where a combination of instrumental and sensory techniques was used for different purposes. Instrumental measures may be used to predict sensory quality within a known design space, provided this has first been validated with appropriate sensory methodology. It is true, however, that a significant correlation between analytical and sensory data does not necessarily imply that a causal relationship exists between the two.
The physico‐chemical properties of commercial canola protein isolate‐guar gum gels
Authors: Uruakpa Florence O. , Arntfield Susan D.
Published: May 2005

Biopolymer mixtures impart desirable texture to foods. Dynamic rheology was used to characterize canola protein isolate (CPI)‐guar gum gels. The effects of pH, salt, guar gum and protein concentrations on the gelling ability of CPI were evaluated. Factorial and response surface optimization models were used to identify the optimum conditions (20%, w/v CPI; pH 10; 1.5%, w/v guar gum; 0.05 m NaCl) that would simultaneously maximize G′ (≥28 000 Pa) and minimize tan δ (<0.17) values of CPI‐guar gum gels. Although pH > 8 is unconventional in food systems, strong and elastic CPI‐guar gum gels (G′ =56 440 Pa; tan δ = 0.18) were produced at pH 10, whereas gels prepared at pH 6 were less elastic (G′ = 2726 Pa; tan δ = 0.2). Under the optimum conditions, CPI alone formed a stronger gel (G′ = 64 575 Pa; tan δ = 0.15) than CPI‐guar gum mixture, suggesting that guar gum interfered with protein gelation.
The effects of 1‐methylcyclopropene treatment on the shelf life and quality of cherry tomato (Lycopersicon esculentum var. cerasiforme) fruit
Authors: Opiyo Arnold M. , Ying Tie‐Jin
Published: May 2005

The use of 1‐methylcyclopropene (1‐MCP) to extend the shelf life of cherry tomato (Lycopersicon esculentum var. cerasiforme) was investigated. Higher concentrations of 1‐MCP delayed the ethylene induced climacteric peaks in mature green (MG) and breaker (BR) fruits. Thirteen days after treatment, control fruits were 55% as firm as fruit treated with 0.11 μL L−1 1‐MCP. The initiation of fruit softening, chlorophyll degradation and accumulation of lycopene and carotenoids was delayed in treated fruits. Higher 1‐MCP concentrations inhibited the accumulation of lycopene and carotene such that the colour of the fruit did not reach that of control fruit. Treatment of MG cherry tomatoes with 1‐MCP enhanced shelf life optimally, while treatment of BR fruits was beneficial where full colour and high content of lycopene and carotenoids is important. Differentiation of the different stages of ripening before application of 1‐MCP is needed in order to succeed in accomplishing different postharvest objectives.
A computer based system for matching colours during the monitoring of tea fermentation
Authors: Borah Surajit , Bhuyan Manabendra
Published: May 2005

The design and development of a personal computer (PC) based system for monitoring changes in colour during the fermentation process that is used to produce tea is described. The technique is based on imaging the fermenting tea at different intervals of time and processing the colour images. A digital camera, together with a special lighting arrangement, was used to capture colour images during the fermentation process. The RGB colour model was used so that histogram dissimilarity measurements matched the colour of test images to a standard image colour. This dissimilarity measurement was represented by difference from the Manhattan norm (L1). The technique was compared with the visual methods used by expert tea tasters.
The quality and sensory attributes of cookies supplemented with fluted pumpkin (Telfairia occidentalis Hook) seed flour
Authors: Giami Sunday Y. , Achinewhu Simeon C. , Ibaakee Christiana
Published: May 2005

Replacing wheatflour (WHF) with defatted fluted pumpkin (Telfairia occidentalis Hook) seed flour (FPF) at levels of 0–25% was investigated for its effect on chemical, physical, sensory and nutritional properties of cookies (biscuits). Protein quality was evaluated by using weanling albino rats fed a diet of cookies, which were formulated to supply 10% protein, with a casein diet as a control. Up to 15% substitution of WHF with FPF produced acceptable cookies with spread ratio, hardness, colour and flavour similar to the control (100% WHF) cookies. Use of higher levels (20–25%), however, resulted in reduction in these quality attributes. When WHF was replaced with 15% FPF, there was an increase of 84.6% in crude protein, 62.9% in calcium, 131.0% in potassium and 61.6% in phosphorus contents of composite cookies. There were no significant (P > 0.05) differences between the values obtained for protein efficiency ratio, net protein ratio and true digestibility of cookie diets containing 15–20% FPF, and casein when fed to rats.
Possible mechanisms underlying age‐related resistance to bovine babesiosis
Authors: Zintl Annetta , Gray Jeremy S. , Skerrett Helen E. , Mulcahy Grace
Published: May 2005

Calves infected with the tick‐borne parasites Babesia spp. do not develop severe clinical babesiosis. Instead they display persistent low parasitaemias without any apparent ill‐effects. This age‐related resistance not only benefits the host, but also furthers parasite transmission. Both calves and adult animals respond with a Th I immune response to primary infection. Here we hypothesize that the difference in the outcome of infection may at least partly be explained by the localization and timing of the inflammatory response: in calves NO production occurs early and appears to be concentrated in the spleen. On the other hand, there is evidence that a delayed and systemic inflammatory response occurs in adult animals that is ineffectual and probably contributes to the pathogenesis. An improved understanding of the possible mechanisms that underlie this phenomenon may lead to new approaches for the treatment and immune prophylaxis of the disease.
Galectins as immunoregulators during infectious processes: from microbial invasion to the resolution of the disease
Authors: Rabinovich G. A. , Gruppi A.
Published: May 2005

Recent evidence has implicated galectins, a family of evolutionarily conserved carbohydrate‐binding proteins, as regulators of immune cell homeostasis and host–pathogen interactions. Galectins operate at different levels of innate and adaptive immune responses, by modulating cell survival and cell activation or by influencing the Th1/Th2 cytokine balance. Furthermore, galectins may contribute to host–pathogen recognition and may serve as receptors for specific interactions of pathogens with their insect vectors. Here we will explore the influence of galectins in immunological processes relevant to microbial infection and will summarize exciting recent work related to the specific interactions between galectins and their glycoconjugate ligands as critical determinants of pathogen recognition. Understanding the role of galectin–sugar interactions during the course of microbial infections might contribute to defining novel targets for disease prevention and immune intervention.
Protection induced by vaccinating sheep with a thiol‐binding extract ofHaemonchus contortusmembranes is associated with its protease components
Authors: Knox D. P. , Smith S. K. , Redmond D. L. , Smith W. D.
Published: May 2005

Previous work has shown that a protein extract enriched for cysteine protease activity (TSBP) prepared from adultHaemonchus contortususing thiol sepharose affinity chromatography confers substantial protection against a single challenge infection. TSBP comprised proteases and other proteins. Here, TSBP were further fractionated using anion‐exchange chromatography and fractions pooled on the basis of containing (1) protease activity, (2) a prominent non‐protease peptide and (3) material which did not bind to the column. A protection trial showed that only the protease‐enriched material conferred protective immunity and this was comparable to that observed in a TSBP‐immunized positive control group. Immunization stimulated a marked IgG response with the IgG2 isotype predominating.
The innate immune response to Entamoeba histolytica lipopeptidophosphoglycan is mediated by toll‐like receptors 2 and 4
Authors: Maldonado‐Bernal C. , Kirschning C. J. , Rosenstein Y. , Rocha L. M. , Rios‐Sarabia N. , Espinosa‐Cantellano M. , Becker I. , Estrada I. , Salazar‐González R. M. , López‐Macías C. , Wagner H. , Sánchez J. , Isibasi A.
Published: May 2005

Entamoeba histolytica is a human pathogen that may invade the intestinal mucosa, causing amoebic colitis or hepatic abscesses when the trophozoites travel through the portal circulation to the liver. Lipopeptidophosphoglycan (LPPG) is a molecular pattern of E. histolytica recognized by the human immune system. Here we report that LPPG is exposed on the cell surface of E. histolytica trophozoites, and is recognized by the host through toll‐like receptor (TLR) 2 and TLR4. Correspondingly, human embryonic kidney (HEK)‐293 cells were rendered LPPG responsive through overexpression of TLR2 or TLR4/MD2. Moreover, co‐expression of CD14 enhanced LPPG signal transmission through TLR2 and TLR4. The interaction of LPPG with TLR2 and TLR4 resulted in activation of NF‐κB and release of interleukin (IL)‐10, IL‐12p40, tumour necrosis factor (TNF)‐α, and IL‐8 from human monocytes. Consistent with these findings, responsiveness of mouse macrophages lacking TLR2 expression (TLR2–/–) or functional TLR4 (TLR4d/d) to E. histolytica LPPG challenge was impaired while double deficient macrophages were unresponsive. In contrast to wild‐type control and TLR2–/–animals succumbing to lethal shock syndrome, TLR4d/dmice were resistant to systemic LPPG challenge‐induced pathology.
ES‐62 is unable to modulate Toxoplasma gondii‐driven Th1 responses and pathology
Authors: Couper K. N. , Chen W. , Houston K. M. , Harnett W. , Johnson L. L.
Published: May 2005

ES‐62, a filarial nematode‐derived anti‐inflammatory immunomodulator, was administered to mice in an attempt to prevent pathology associated with Toxoplasma gondii infection. The nematode product was shown to elevate mitogen and T. gondii‐specific IL‐10 production but was unable to inhibit Th1 responses. Consequently ES‐62 could not prevent Th1 generated immunopathology.
The assessment of hookworm calreticulin as a potential vaccine for necatoriasis
Authors: Winter J. A. , Davies O. R. , Brown A. P. , Garnett M. C. , Stolnik S. , Pritchard D. I.
Published: May 2005

A vaccine against the human hookworm Necator americanus is urgently required to reduce hookworm‐induced morbidity in endemic areas. In the present study, recombinant hookworm calreticulin, a nominated vaccine candidate, has been tested in mice. Mice given calreticulin had 43–49% fewer worms in their lungs, compared to non‐vaccinated controls, following challenge infection with infective hookworm larvae. These levels of protection were achieved in the absence of adjuvant following intraperitoneal administration of three doses of 15 µg antigen. Antigen was also encapsulated in PLG microparticles. Encapsulated calreticulin elicited higher levels of anti‐calreticulin IgG1 than free antigen but failed to induce protective immunity. The protection induced by free calreticulin was associated with low levels of serum IgE and moderate lung eosinophilia whilst administration of calreticulin‐loaded microparticles was associated with high levels of serum IgE and higher lung eosinophil activity, suggesting that the classical Th2 phenotype may not always be associated with protective immunity, albeit in experimental necatoriasis.
Successful treatment of Bacillus cereus meningitis following allogenic stem cell transplantation
Authors: Haase Roland , Sauer Harald , Dagwadordsch Urantschimeg , Foell Jürgen , Lieser Ulla
Published: May 2005

Abstract:  We report the case of a 19‐yr‐old boy, who received an allogeneic stem cell transplantation for the second relapse of Hodgkin's disease. The patient developed seizures and flaccid hemiparesis on day +10. Meningoencephalitis induced by Bacillus cereus was diagnosed. The treatment consisted of appropriate antibiotics, G‐CSF and removal of the central venous line. Infection control and nearly full neurological recovery was achieved. Immunocompromised patients susceptible to B. cereus infection, indicated by the isolation of B. cereus in prior cultures, should receive antibiotic treatment covering B. cereus.
Gynecologic health care for the adolescent solid organ transplant recipient
Authors: Sucato Gina S. , Murray Pamela J.
Published: May 2005

Abstract:  The improved survival of pediatric recipients of solid organ transplants has prompted increased attention to quality of life issues. These include attainment of normal growth, involvement in romantic relationships, and the desire to control fertility. As an increasing number of adolescent transplant recipients are involved in normal social and sexual relationships, they require careful attention to their gynecologic and reproductive health care needs. Anticipating the onset of sexual activity before it occurs may help to prevent a mistimed pregnancy by providing or prescribing condoms and emergency contraception in advance. In addition, many transplant recipients can safely use the currently available methods of hormonal contraception provided there is careful attention to organ function, other medical problems, and concurrently prescribed medications. In adolescent patients, issues such as pubertal development and menstruation, contraception, and routine gynecologic health care are typically addressed by the patient's primary care provider. However, the complexity of the adolescent transplant recipient's medical care necessitates close collaboration among all health care providers caring for the patient. This review is intended to help the transplant team better understand the gynecologic health care needs and treatment options of their adolescent patients.
Elevated blood concentrations of calcineurin inhibitors during diarrheal episode in pediatric liver transplant recipients: Involvement of the suppression of intestinal cytochrome P450 3A and P‐glycoprotein
Authors: Maezono Sachiko , Sugimoto Koh‐ichi , Sakamoto Koh‐ichi , Ohmori Masami , Hishikawa Shuji , Mizuta Koichi , Kawarasaki Hideo , Watanabe Yoshiteru , Fujimura Akio
Published: May 2005

Abstract:  We encountered two cases of pediatric living‐related liver transplant recipients who showed increases in blood concentration of cyclosporine or tacrolimus, a dual substrate for cytochrome P450 (CYP) 3A and P‐glycoprotein (P‐gp), during a diarrheal episode. To investigate the effect of intestinal inflammation on the metabolic and efflux pump activities, we conducted the experiments using the lipopolysaccharide (LPS)‐induced intestinal damage model.

Intestinal epithelial CYP3A activity was assessed by nifedipine oxidation using intestinal epithelial microsomes in rat. Drug efflux by P‐gp was tested using digoxin flux with the excised intestine perfusion system in rats. Intraperitoneal injection of LPS (0.3 mg/kg) significantly reduced the intestinal epithelial CYP3A activity by 41% (p < 0.01). In the proximal jejunal segment of the rats treated with LPS, mucosal to serosal flux of digoxin was significantly enhanced compared to that of control (p < 0.05). Efflux of digoxin, which was taken up by intestinal epithelium, to mucosal perfusate was significantly blunted in the jejunum treated with LPS (p < 0.05), which indicates that the LPS treatment reduced the P‐gp activity in rat small intestine.

These findings suggest that the suppression of CYP3A and P‐gp activities may be involved in the mechanism of elevated blood concentrations of cyclosporine and tacrolimus during enteritis‐induced diarrhea. To prevent a drug‐induced adverse effect, dose of a drug, which is a substrate of CYP3A or P‐gp, should be reduced during such an episode.
C0 or C2 driven cyclosporine monitoring in long‐term pediatric kidney transplant recipients: Is there any threat for chronic rejection development?
Authors: Ferraresso Mariano , Ghio Luciana , Edefonti Alberto , Vigano Sarà , Boschiero Luigi , Berardinelli Luisa
Published: May 2005

Abstract:  The clinical management of cyclosporine has evolved greatly during the last decade thanks to the use of pharmacokinetic (PK) studies which confirmed the dose relationship between drug exposure and its biological effects. Therefore, cyclosporine PK monitoring during the early phase of the post‐transplant period became essential to avoid over or underexposure to the drug thus preventing the risk of nephrotoxicity or acute rejection episodes. More recently, a simple PK determination based on cyclosporine blood concentration measured 2 h after the morning dose, has proven to be very effective for monitoring cyclosporine exposure in the early postoperative period. In this paper, the authors present a set of PK profiles obtained from a stable, long‐term pediatric kidney transplant population and correlate these parameters with the risk of chronic rejection development. The study shows how cyclosporine monitoring based on the sole trough level determination misled a correct therapeutic behavior, as revealed by the PK parameters that were constantly below the therapeutic threshold in a small patient cohort who eventually developed chronic rejection. The C2 determination should be considered as the gold standard for cyclosporine monitoring in long‐term pediatric recipients.
Chronic alcohol exposure reduces hippocampal neurogenesis and dendritic growth of newborn neurons
Authors: He Jun , Nixon Kimberly , Shetty Ashok K. , Crews Fulton T.
Published: May 2005

Hippocampal neurogenesis is known as the formation of new neurons from the proliferating neural progenitor cells (NPC) at the dentate gyrus. Cell proliferation, survival, differentiation and maturation are critical stages leading to the generation of healthy neurons. As all of these stages can be influenced by alcohol exposure, we studied the effects of chronic alcohol on each process by immunocytochemistry for stage‐specific antigens and prelabelling newborn cells with bromodeoxyuridine (BrdU). Rats were administered alcohol liquid diet or control diet for one, two or four weeks. We found that cell proliferation was inhibited as proliferating cell nuclear antigen (PCNA) expression was reduced by approximately 50% in alcohol‐treated animals at all time points. Doublecortin (DCX), a microtubule protein expressed early in differentiating neurons, was progressively decreased over the duration of exposure and significantly reduced after two and four weeks of drinking. Morphological analyses of DCX‐positive cells revealed that four weeks of alcohol treatment reduced the size of the dendritic tree including the total length of apical dendrites, number of nodes and endings. Furthermore, BrdU labelling demonstrated a dramatic decrease in cell survival after four weeks of drinking, while cell death was increased by such treatment. Confocal analysis indicated that over 80% of BrdU+ cells colabelled with NeuN suggesting that alcohol reduced neurogenesis. In conclusion, chronic alcohol exposure disrupts neurogenesis by decreasing NPC proliferation, inhibiting cell survival and altering morphological maturation of newborn neurons. These data implicate impaired hippocampal neurogenesis with the cognitive and affective dysfunction associated with chronic alcoholism.
Decreased firing frequency of midbrain dopamine neurons in mice lacking mu opioid receptors
Authors: Mathon Daniel S. , Ramakers Geert M. J. , Pintar John E. , Marinelli Michela
Published: May 2005

Dopamine neurons originating in the midbrain and projecting to cortico‐limbic and motor structures are one of the major neuronal substrates implicated in the reinforcing properties of drugs of abuse. The output of this system is largely determined by its impulse activity (amount and pattern of firing activity). Several intrinsic and synaptic factors can influence dopamine neuronal activity and, consequently, addiction liability. Pharmacological studies indicate that µ‐opioid receptors and their activation by endogenous opioids may play an important role. In the present study, we use a genetic approach to better understand the role of µ‐opioid receptors in modulating dopamine neuronal activity in vivo. Using in vivo extracellular single‐unit recordings, we show that mice lacking µ‐opioid receptors exhibit lower firing rates of dopamine neurons compared with their wild‐type littermates. Although we observed no overall changes in bursting activity compared with wild‐type mice, animals lacking µ‐opioid receptors exhibited a higher proportion of regular‐spiking cells that lacked bursting activity. These findings are the first to emphasize the critical role of µ‐opioid receptors in modulating action potential output of dopamine neurons in vivo using a genetic approach. They also provide a possible underlying mechanism for the decreased reinforcing properties of drugs of abuse that was previously observed in mice lacking µ‐opioid receptors.
Risk of specific congenital abnormalities in offspring of women with diabetes
Authors: Nielsen G. L. , Nørgard B. , Puho E. , Rothman K. J. , Sørensen H. T. , Czeizel A. E.
Published: May 2005

Aims  To assess the extent to which the increased risk of congenital abnormalities seen in women with pre‐gestational insulin‐treated diabetes mellitus is unspecific or related to the embryology of specific organs.

Methods  Cases with congenital abnormalities were identified in the population‐based Hungarian Congenital Abnormality Registry from 1980 to 1996 with two newborn children without congenital abnormality selected from the National Birth Registry as controls. We adjusted for parity, maternal age, and use of antipsychotic drugs.

Results  Among cases we found 63/22 843 babies with maternal diabetes compared with 50/38 151 in the control group [adjusted prevalence odds ratio (POR) 2.1; 95% CI 1.5–3.1]. The association was strongest for the following congenital abnormalities: renal agenesis (POR: 14.8; 95% CI, 3.5–62.1), obstructive congenital abnormalities of the urinary tract (POR: 4.3; 95% CI, 1.3–13.9), cardiovascular congenital abnormalities (POR: 3.4; 95% CI, 2.0–5.7), and multiple congenital abnormalities (POR: 5.0; 95% CI, 2.4–10.2).

Conclusions  These data indicate that pre‐gestational maternal diabetes is associated with strong teratogenic effects on the kidney, urinary tract, and heart, and strongly associated with multiple congenital abnormalities. We found no material association between diabetes and spinal congenital abnormalities and limb deficiencies.
Association analysis of the variant in the regulatory subunit of phosphoinositide 3‐kinase (p85α) with Type 2 diabetes mellitus and hypertension in the Chinese Han population
Authors: Chen S. , Yan W. , Huang J. , Ge D. , Yao Z. , Gu D.
Published: May 2005

Aims  To determine whether variants in the gene for the regulatory subunit of phosphoinositide 3‐kinase (p85α) are associated with Type 2 diabetes mellitus (Type 2 DM) and hypertension in a Chinese population.

Methods  We performed a case‐control study genotyping the Met326Ile and IVS4+82A>G polymorphisms in 494 patients with Type 2 DM and hypertension and 557 normal controls from the north of China. Individual genotypes were identified by the polymerase chain reaction—restriction fragment length polymorphism (PCR–RFLP) method. The IVS4+82A>G polymorphism was further confirmed by direct sequencing in 20 randomly selected cases.

Results  The IVS4+82A>G polymorphism that is common in Caucasians was not detected in our population. Frequencies of genotypes and alleles of Met326Ile polymorphism were not significantly different between cases and controls in whole samples by univariate analysis. Logistic regression analysis demonstrated that Ile326Ile genotype was associated with a 2.085‐fold (95% CI, 1.043–4.168, P = 0.0377) relative risk of diabetes and hypertension. After stratification by obesity, the frequency of Ile326Ile genotype in cases was higher than that in controls (18/304 vs. 13/510, P = 0.015) among non‐obese individuals (BMI < 28 kg/m2). We did not find that this missense mutation was associated with blood pressure, glucose and blood lipids in the control group.

Conclusion  Our data indicate that the Met326Ile variation in the gene encoding the p85α protein might contribute to the increased risk of Type 2 DM and hypertension in Chinese.
Pre‐gestational maternal body mass index predicts an increased risk of congenital malformations in infants of mothers with gestational diabetes
Authors: Martínez‐Frías M. L. , Frías J. P. , Bermejo E. , Rodríguez‐Pinilla E. , Prieto L. , Frías J. L.
Published: May 2005

Aims  The aim of the present study was to identify characteristics in women diagnosed with gestational diabetes mellitus (GDM) that could be predictive of congenital malformations in their infants.

Methods  Using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), a hospital‐based case‐control study and surveillance system, we assessed the relationship between a number of maternal variables, including pre‐gestational body mass index (BMI), and specific congenital malformations in their infants.

Results  The overall risk for a selected group of congenital malformations in an infant of an obese mother with GDM compared with an obese mother with normal glucose tolerance (NGT) was 2.78 (1.38–5.55, P < 0.001). Within the group of mothers with GDM, obesity (BMI ≥ 30 kg/m2) was associated with a significantly increased risk of cardiovascular defects compared with non‐obese women [OR = 2.82 (1.31–7.04), P < 0.01]. In mothers with NGT, pre‐gestational BMI was not associated with congenital malformations.

Conclusion  Pre‐gestational obesity is a predictive variable for congenital malformations in infants of mothers with GDM. The greater their BMI, the higher the risk for congenital malformations in their offspring. Given the blastogenic origin of the congenital defects identified, and the relationship between obesity and Type 2 diabetes, it is probable that this increased risk is as a result of previously unidentified pre‐gestational diabetes mellitus (PGD). It is important that overweight and obese women planning a pregnancy be evaluated for the presence of diabetes.
Setting and negotiating targets in people with Type 2 diabetes in primary care J. Stewart & D. Kendrick
Authors: Stewart J. , Kendrick D. ,   the Nottingham Diabetes Blood Pressure Study Group
Published: May 2005

Aims  To investigate the provision of diabetes care, the frequency of practices setting targets for their diabetic population, the targets set and the frequency of targets being negotiated with people with diabetes.

Methods  Cross‐sectional study using a survey of 123 general practices within four Primary Care Trusts in Nottingham UK.

Results  Eighty per‐cent (99) of practices responded. Of these, 88 and 89%, respectively, had set glycosolated haemoglobin (HbA1c) and blood pressure targets for people with Type 2 diabetes. Twenty‐five per‐cent (24) of practices reported negotiating targets with almost all people with Type 2 diabetes for HbA1c and 31% (30) for blood pressure. In 46% (45) of practices, the annual diabetic review for some or all of the people with Type 2 diabetes was carried out by the practice nurse alone. In these practices, targets were negotiated with a smaller proportion of people than those where the doctor was involved in the annual review for both blood pressure [43 vs. 64% negotiated blood pressure targets with almost all or many people odds ratio (OR) 0.42 (95% CI 0.19, 0.96), P = 0.04] and HbA1c[39 vs. 60% negotiated HbA1c targets with almost all or many people, OR 0.41 (95% CI 0.18, 0.94), P = 0.03].

Conclusions  Negotiating targets with people with Type 2 diabetes does not routinely occur in primary care. Targets are negotiated less often in practices where nurses undertake reviews alone and further work is needed to explore the reasons for this.
Left ventricular diastolic dysfunction in patients with chronic renal failure: impact of diabetes mellitus
Authors: Miyazato J. , Horio T. , Takiuchi S. , Kamide K. , Sasaki O. , Nakamura S. , Nakahama H. , Inenaga T. , Takishita S. , Kawano Y.
Published: May 2005

Aims  Left ventricular (LV) hypertrophy and LV diastolic dysfunction are cardiac changes commonly observed in patients with chronic renal failure (CRF) as well as hypertension. Although the impairment of LV diastolic function in patients with diabetes mellitus has been shown, little is known about the specific effect of diabetes on LV diastolic function in patients with CRF. The present study was designed to investigate the impact of diabetic nephropathy on LV diastolic dysfunction, independent of LV hypertrophy, in CRF patients.

Methods  In 67 patients with non‐dialysis CRF as a result of chronic glomerulonephritis (n = 33) or diabetic nephropathy (n = 34), and 134 hypertensive patients with normal renal function, two‐dimensional and Doppler echocardiographic examinations were performed, and LV dimension, mass, systolic function, and diastolic function were evaluated.

Results  LV mass was increased and LV diastolic dysfunction was advanced in subjects with CRF compared with hypertensive controls. In the comparison of echocardiographic parameters between the two groups of CRF patients, i.e. chronic glomerulonephritis and diabetic nephropathy groups, all indices of LV diastolic function were more deteriorated in the diabetic nephropathy group than in the chronic glomerulonephritis group, although LV structure including hypertrophy and systolic function did not differ between the groups. In a multiple regression analysis, the presence of diabetes (i.e. diabetic nephropathy group) was a significant predictor of LV diastolic dysfunction in CRF subjects, independent of other influencing factors such as age, blood pressure, renal function, anaemia and LV hypertrophy.

Conclusion  The present findings suggest that LV diastolic dysfunction, independent of LV hypertrophy, is specifically and markedly progressed in patients with CRF as a result of diabetic nephropathy.
Quality assurance for diabetic retinopathy telescreening
Authors: Schneider S. , Aldington S. J. , Kohner E. M. , Luzio S. , Owens D. R. , Schmidt V. , Schuell H. , Zahlmann G.
Published: May 2005

Aims  TOSCA was an EU‐Commission supported international research project designed to develop telescreening services in diabetic retinopathy and glaucoma. This paper describes the quality assurance methods developed for the diabetic retinopathy telescreening service within the TOSCA project.

Setting  The study was performed in 1895 patients with diabetes between 2000 and 2002 at diabetic retinopathy screening sites in five European countries. Data were analysed centrally.

Methods  Patients attending each clinic's diabetic retinopathy screening service received standardized retinal photography. The images and associated data were transferred electronically to a remote location for grading. Each photographer uploading images and each grader downloading images for assessment was controlled by a systematic quality management approach. The quality assurance measures defined were image quality, intragrader reliability. A cockpit chart was developed for the management and presentation of relevant results and quality measures. For the intragrader reliability tests, 10% of the images were processed for a second grading. An algorithm for calculating differences between repeated gradings was developed.

Results  The assessment of image quality for the different sites showed that only 0–0.7% were unassessable. One hundred per cent agreement for both gradings was achieved in 50–85% of graded cases, depending on site and grader, and an agreement better than 95% in 71–100% of cases.

Conclusions  A telemedicine‐supported quality assurance process is practical and advantageous. The cockpit charts have proven to be useful tools when monitoring the performance of a telescreening service. Grader feedback showed high satisfaction with the quality assurance process.
The SPINK1 N34S mutation is not associated with Type 2 diabetes mellitus in a population of the USA
Authors: Schneider A. , Lawrence E. C. , Barmada M. M. , Norris J. M. , Hamman R. F. , Marshall J. A. , Ferrell R. E. , Whitcomb D. C.
Published: May 2005

Aims  Mutations in the serine protease inhibitor (SPINK1) gene have been associated with all forms of chronic pancreatitis. Recently, an association of SPINK1 mutations with early‐onset Type 2 diabetes mellitus has been reported in patients from Bangladesh. Therefore, we determined the frequency of SPINK1 N34S mutations in patients with Type 2 diabetes mellitus from the USA.

Methods  The study population of Hispanic and non‐Hispanic white people consisted of 387 patients with Type 2 diabetes and familial clustering of the disease, 232 family members without diabetes, 259 patients with Type 2 diabetes without a family history, and 302 ethnically matched healthy controls as part of the San Luis Valley Diabetes Study. We performed linkage‐ and association‐analysis in 82 multiplex families with Type 2 diabetes mellitus.

Results  No significant linkage or allele sharing was detected between Type 2 diabetes mellitus and the SPINK1 locus. The frequency of the N34S mutation was determined by fluorescence polarization and was similar between patients (n = 14/387 patients with familial clustering; n = 2/259 patients without family history) and controls (n = 5/232 family members without diabetes; n = 10/302 individuals). Variables such as ethnicity, age of diabetes onset and percentage of individuals with impaired glucose tolerance did not differ significantly between carriers and homozygous normal individuals.

Conclusion  The SPINK1 N34S mutation appears not to predispose Hispanic or non‐Hispanic white people from the USA to the development of Type 2 diabetes mellitus.
Association between MspI polymorphism of the APO AI gene and Type 2 diabetes mellitus
Authors: Morcillo S. , Cardona F. , Rojo‐Martínez G. , Esteva I. , Ruíz‐de‐Adana M. S. , Tinahones F. , Gómez‐Zumaquero J. M. , Soriguer F.
Published: May 2005

Aims  Genes of the Apo AI/CIII/AIV cluster on chromosome 11 have been related to plasma lipid patterns. The close relationship between carbohydrate metabolism and lipid metabolism warrants investigation of the association between this cluster and Type 2 diabetes mellitus. We therefore examined the possible association between polymorphisms of this cluster and Type 2 diabetes mellitus as part of a study of the prevalence of diabetes and the metabolic syndrome in southern Spain.

Methods  A total of 1224 persons were selected randomly from the town of Pizarra in the province of Malaga, southern Spain. The sample errors for the prevalence of Type 2 diabetes mellitus and the three polymorphisms studied were all ≤ 4%. All subjects underwent phenotyping after an oral glucose tolerance test (75 g) (WHO 1998 criteria) and the XmnI and MspI polymorphisms of Apo AI and the SstI polymorphism of Apo CIII were genotyped.

Results  Those subjects with the mutated AA genotype of the MspI polymorphism (−75 G→A) of Apo AI had a greater risk of impaired glucose tolerance [odds ratio (OR) = 1.95, CI = 1.02–3.8, P = 0.05], Type 2 diabetes mellitus, both known (OR = 7.38, CI = 1.3–39.7, P = 0.02) and unknown (OR = 3.7, CI = 1.4–9.9, P = 0.009). This risk was independent of age, sex, obesity, triglyceride level, HDL cholesterol and pattern of insulin resistance.

Conclusions  Pending confirmation in prospective studies, the AA genotype of the MspI polymorphism of the Apo AI gene, within the Apo A‐I/C‐III/A‐IV cluster, seems to be a risk factor for Type 2 diabetes mellitus.
Prevalence of undiagnosed Type 2 diabetes and impaired fasting glucose in older B ritish men and women
Authors: Thomas M. C. , Walker M. K. , Emberson J. R. , Thomson A. G. , Lawlor D. A. , Ebrahim S. , Whincup P. H.
Published: May 2005

Aim  To estimate the prevalence of undiagnosed diabetes and impaired fasting glucose in older British men and women, using the 1999 World Health Organization (WHO) thresholds based on fasting glucose measurements.

Methods  Participants in the British Regional Heart Study and the British Women's Heart and Health Study were selected from one socially representative general practice in 24 British towns. Included in this analysis were 3736 men and 3642 women aged 60–79 years (predominantly white), who provided a single fasting blood sample at a clinical examination between 1998 and 2001, and who had no previous diagnosis of diabetes.

Results  Two hundred and eleven men (5.7%) and 190 women (5.2%) had a fasting blood glucose level consistent with the WHO threshold for a diagnosis of diabetes (≥ 7.0 mmol/l), whilst a further 667 men (17.9%) and 642 women (17.6%) had impaired fasting glucose levels (6.1 ≤ 7 mmol/l). When analyses were restricted to subjects who had fasted for at least 8 h, and whose blood sample was taken before 12.00 h, the predicted prevalence of undiagnosed diabetes (based on two separate measurements) was 6.7% in men and 6.0% in women. The predicted prevalence of impaired fasting glucose (based on two separate measurements) was approximately 20% in both sexes.

Conclusions  More than one‐fifth of older white British men and women have either undiagnosed diabetes or impaired fasting glucose according to new WHO criteria. Strategies for the primary and secondary prevention of Type 2 diabetes among older individuals are urgently needed.