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Additive concentration effects on enantioselective separations in supercritical fluid chromatography.

Polar additive concentration effects in supercritical fluid chromatography were studied on chiral stationary phases having either a macrocyclic glycopeptide or a derivatized polysaccharide as the chiral selector. Two basic additives, isopropylamine and triethylamine, were incorporated into the methanol modifier at various concentrations and the effects on retention, selectivity, and resolution were monitored. Many of the analytes failed to elute from the macrocyclic glycopeptide stationary phase in the absence of an additive and the most noticeable effect of increasing additive concentration was a significant decrease in retention. On the derivatized polysaccharide stationary phase the additives had little effect on retention, but they did foster significant improvements in peak shape and resolution.

Journal Article↗

Additive value of low-dose dobutamine to technetium-99m sestamibi-gated single-photon emission computed tomography for prediction of wall motion improvement in patients undergoing coronary artery bypass graft.

BACKGROUND: The two most useful methods for myocardial viability assessment are perfusion imaging and dobutamine echocardiography. HYPOTHESIS: The present study investigated the additive value of a new method, dobutamine technetium 99m (99mTc)-sestamibi-gated single-photon emission computed tomography (SPECT), which combines these two modalities, to the prediction of wall motion improvement after revascularization. METHODS: Fifty-five consecutive patients with ischemic cardiomyopathy, who were referred for viability evaluation, underwent resting and dobutamine (dose, 5-10 microkg/kg/min) gated SPECT with 99mTc-sestamibi. Of these patients, 36 underwent coronary artery bypass graft (CABG) within 1 month of the study and 32 had repeat resting gated SPECT within 1 year. Global and regional wall motion, wall thickness, and perfusion were simultaneously analyzed at rest and after dobutamine using the 20-segment model; the sestamibi uptake and wall motion response to dobutamine of each segment were rated quantitatively. Based on these findings, the segments were categorized as normal, viable, or nonviable. The predictive values for wall motion improvement were assessed by perfusion, using cutoffs of 50 and 60% of sestamibi uptake, and thereafter by the addition of dobutamine response in the segments that were rated nonviable. RESULTS: Of the 1,080 myocardial segments studied, 906 (84%) had abnormal wall motion and were analyzed for viability. Concordance between perfusion and wall motion response to dobutamine was 60% with the 50% cutoff of sestamibi uptake, and increased to 65% with the 60% sestamibi cutoff (p < 0.04). The respective predictive values of wall motion improvement using the 50 and 60% cutoff points were as follows: sensitivity 93 and 70%, respectively, (p < 0.01); specificity 59 and 86% (p < 0.001), respectively; accuracy 77% for both. The addition of the wall motion response to dobutamine to the assessment of the nonviable segments by perfusion (60% cutoff) increased the sensitivity from 70 to 85% (p = 0.001) and the negative predictive value from 70 to 81% (p = 0.009); the positive predictive value remained high (86 vs. 82%). No additive value of wall motion response to dobutamine was demonstrated for nonviable segments by perfusion with a 50% cutoff. CONCLUSION: Dobutamine sestamibi-gated SPECT is a feasible method for the analysis of myocardial perfusion, function, and contractile reserve of individual myocardial segments in patients with ischemic cardiomyopathy. Viability assessment based on a threshold of 60% uptake of sestamibi, with the addition of the wall motion response to dobutamine in the nonviable segments, seems to yield better predictive values for wall motion improvement after CABG.

Aged↗

Variation in the mode of receptor cell addition in the electrosensory system of gymnotiform fish.

Age-related changes in ampullary and tuberous receptor organ morphology were studied in six species of gymnotiform weakly electric fish. Cheek skin was silver-stained, whole-mounted, and viewed under Nomarski differential interference contrast optics. The ampullary receptor units of all species show an increasing number of receptor organs per afferent fiber with fish size, presumably the result of addition of newly formed receptor organs. Ampullary units composing over a dozen organs were observed in large specimens of a few species. Receptor cells were also added in the tuberous receptor system of all species, but in different ways. As previously reported for Sternopygus, small specimens of Eigenmannia had only a single tuberous receptor organ per afferent. Fish of increasing size retained a population of afferents that innervated only a single receptor organ and, in addition, had a population of afferents that innervated a cluster of receptor organs. The mean number of receptor organs per cluster increased in fish of increasing size. In addition, the mean number of sensory receptor cells per organ increased. New organs presumably derive from older ones, which divide under the stimulus of continued addition of new receptor cells. Apteronotus, Adontosternarchus, and Hypopomus all added more receptor cells to their tuberous organs. In these species, every afferent innervated only a single tuberous organ and there was no indication of division of receptor organs. Gymnorhamphichthys and Gymnotus were intermediate in that they added new receptor cells to each receptor organ, and, in larger fish, these were segregated into discrete patches within a single receptor organ. It is likely that the addition of new receptor cells aids in increasing sensitivity of both ampullary and tuberous receptors as fish grow.

Animals↗

Molecular analysis of the V kappa III-J kappa junctional diversity of polyclonal rheumatoid factors during rheumatoid arthritis frequently reveals N addition.

Much interest was stirred in recent years by the evidence that rheumatoid factors (RF) variable regions are encoded by a restricted set of V genes, with little or no somatic mutations, that are often overexpressed in the fetal repertoire. This is reminiscent of what has been observed for natural autoantibodies. However, these data come from studies of monoclonal RF (mRF) isolated from patients with lymphoproliferative disorders who usually do not present autoimmune symptoms. The molecular characterization of RF during autoimmune diseases such as rheumatoid arthritis (RA) has been hampered for some time because of their polyclonality; recently using the polymerase chain reaction method, we have demonstrated that RF kappa variable regions from a patient with RA were encoded by V kappa III genes known to code for mRF but that these genes had undergone somatic mutations with a pattern suggesting an antigen-driven maturation. Because an important role of the light chain third complementarity-determining region (CDR3) in anti-IgG reactivity and idiotype expression has already been suspected for RF, we now report the molecular characterization of the junction regions of these rearranged V kappa gens. Surprisingly, our data show that in 55% of the cases there is addition of a proline and/or glycine amino acid residue at the recombination site between V kappa and J kappa. The sequence analysis of our patients' germ-line Vg and J kappa 4 genes segments and their flanking regions demonstrates that the additional codons are not readily explicable by recombination between germ-line sequences and probably result from an N addition process. Since we could not find such an additional codon in 15 previously published mRF kappa chains we suggest that "pathogenic" RF during RA and mRF derive from different, although overlapping, B cell subsets. Moreover, since additional codons at the recombination site of V kappa and J kappa seem exceptional in expressed human kappa chains and because the resulting amino acid residue is a proline in most cases, we think that RF kappa chain CDR3 is under a very strong selective pressure during RA.

Amino Acid Sequence↗

Effect of silver addition on the properties of nickel-titanium alloys for dental application.

Equiatomic and near-equiatomic nickel-titanium alloys exhibit a shape-memory effect and superelasticity. However, the properties of such alloys are extremely sensitive to the precise nickel-titanium ratio and the addition of alloying elements. High corrosion resistance is necessary for biomedical applications, especially orthodontic. The purpose of this study was to investigate the effect of silver addition to nickel-titanium alloys for dental and medical application. Arc melting, homogenization, hot rolling, and solution heat treatment were performed to prepare the nickel-titanium-silver (NiTi-Ag) specimens. The properties of the ternary NiTi-Ag alloys such as phase-transformation temperature, microstructure, microhardness, corrosion resistance, and cytotoxicity were investigated. The NiTi-Ag alloys showed low silver recovery rate for the cast alloy, due to silver's low evaporation temperature, and low silver solubility in nickel-titanium. Silver addition to nickel-titanium increased the transition temperature range to 100 degrees C and stabilized the martensitic phase (monoclinic structure) at room temperature, because the martensitic transformation starting temperature (Ms) was above room temperature. Martensitic and austenitic phases existed in X-ray diffraction patterns of solution-annealed NiTi-Ag alloys. The silver addition was considered to improve the corrosion resistance and form a stable passive film. Significantly, the mechanical properties of the silver-added alloys were dependent upon the amount of alloying addition. There was no toxicity in the NiTi-Ag alloys, as the response index showed none or mild levels.

Animals↗

The generation of leukemic dendritic cells from acute myeloid leukemia cells is potentiated by the addition of CD40L at the terminal maturation stage.

Leukemic dendritic cells (DCs) that are derived from acute myeloid leukemia (AML) cells display low-level expression of several key molecules. We investigated the optimal combination of cytokines needed to generate potent leukemic DCs from AML cells in vitro. AML cells were cultured in the presence of the following combinations of cytokines: Group A, granulocyte-macrophage colony-stimulating factor (GM-CSF) + interleukin-4 (IL-4) + tumor necrosis factor-alpha (TNF-alpha); Group B, GM-CSF + IL-4 + CD40L; and Group C, CD40L addition at the terminal maturation point of cells that were grown as for Group A. The AML cells showed clear upregulation of CD80, CD83, CD86, CD40, and HLA-DR expression under all culture conditions, without significant differences between these groups. However, the addition of CD40L (as in Group C) showed a slight upregulation in the expression of CD83 and CD86 on leukemic DCs. The leukemic DCs in Groups A and B had higher allogeneic T-cell stimulatory capacities than untreated AML cells, and the addition of CD40L (Group C) enhanced this effect. The function of the cytotoxicity-stimulating autologous T cells was also augmented by the addition of CD40L (Group C). These results suggest that AML cells may be used to generate leukemic DCs using various cytokine combinations, and that the most potent, mature leukemic DCs are generated by the addition of CD40L to terminal-stage AML cultures that are grown in the presence of conventional cytokine combinations.

Adolescent↗

Effect of polymer additives on hydrodynamics and oxygen transfer in a bubble column bioreactor.

The influence of polymer additives (polyethylene oxide and polyacrylamide) on the hydrodynamics and oxygen transfer in a bubble column bioreactor was examined. The addition of small amounts of these polymers has been known to cause significant drag reduction in turbulent flow circumstances. The gas hold-up was slightly decreased and the liquid-phase mixing was somewhat enhanced due to the addition of the polymers. The addition of polymer additives brought about a reduction of the volumetric oxygen transfer coefficient by about 40%. In dilute polymer solutions, large bubbles formed by bubble coalescence moved with high rise velocities in the presence of many small bubbles and the bubble size distributions were less uniform compared with those in water. The complicated changes in bubble hydrodynamic characteristics were examined to give possible explanations for oxygen transfer reduction.

Acrylic Resins↗

Stable and general-purpose chemiluminescent detection system for horseradish peroxidase employing a thiazole compound enhancer and some additives.

A stable and highly sensitive chemiluminescent detection system for horseradish peroxidase (HRP)/luminol/hydrogen peroxide using a newly designed thiazole compound enhancer has been established. Some additives for the chemiluminescent reaction were explored to overcome some defects of the reaction such as rapid decay and high background of light emission. Recrystallization of luminol and the addition of several detergents into the reacting solution were effective to increase specific light emissions. The addition of skim milk into the reacting solution reduced the background. Consequently, skim milk combined with a detergent increased the signal to noise ratio about 20 times compared with the reactions in the absence of both additives. The optimal concentration of enhancer and the addition of egg albumin stabilized the emission. In the new method, 6x 10(-18) mol of HRP was detectable. This would be the most sensitive enhanced chemiluminescent detection system for HRP. Furthermore, we could detect picogram per milliliter (10(-17) mol) concentrations of a trace component in biological materials such as endothelin-1 by employing this reaction.

Endothelins↗

A production task evaluation of individual differences in mental addition skill development: internal and external validation of chronometric models.

A production task paradigm for obtaining reaction times to mental addition stimuli was used for internal and external validation of chronometric models of mental addition processing. The first analysis explored the internal validity of extant chronometric models and found that three models, (a) a tabular memory network retrieval strategy (PRODUCT), (b) a nontabular memory network retrieval strategy (ERROR RATE), and (c) a computational strategy (MIN), were able to encompass individual differences in strategy choice for 155 individuals from Grades 2 to 8 and 111 college students. Patterns of convergent and discriminant validity for these models were also demonstrated. The second analysis explored the external validity of relations among (a) two traditionally measured factor analytic dimensions of ability, Numerical Facility and Perceptual Speed; (b) two information processing dimensions presumed to underlie mental addition. Addition Efficiency and Speediness; and (c) a digit-span measure of Short-Term Memory. We specified a series of two-group (grade school and college) structural equation models to represent the relations among all measures and showed that individual differences in the apparently calculative processes that underlie the traditionally defined ability dimension of Numerical Facility are highly related to individual differences in Addition Efficiency and Speediness of information processing.

Adolescent↗

Kindergartners' understanding of additive commutativity within the context of word problems.

Baroody and Gannon (1984) proposed that children's understanding of additive commutativity progresses through several levels of understanding based on a unary view of addition (change meaning) before developing a "true" level of understanding based on a binary conception (part-whole meaning). Resnick (1992) implied that children have both a unary and a binary conception of additive commutativity from the earliest stages of development. Fifty-three 5- and 6-year-old (M = 6-0) kindergartners' unary and binary understanding of additive commutativity was investigated using performance on tasks involving change-add-to and part-part-whole word problems, respectively. The data were inconsistent with the predictions of both models and suggest three alternate theoretical explanations. Moreover, the data indicate that success on a task involving change-add-to problems may be a more rigorous test of understanding of additive commutativity than that involving part-part-whole problems.

Analysis of Variance↗

On the Complexity of Additive Clustering Models.

Additive clustering provides a conceptually simple and potentially powerful approach to modeling the similarity relationships between stimuli. The ability of additive clustering models to accommodate similarity data, however, typically arises through the incorporation of large numbers of parameterized clusters. Accordingly, for the purposes of both model generation and model comparison, it is necessary to develop quantitative evaluative measures of additive clustering models that take into account both data-fit and complexity. Using a previously developed probabilistic formulation of additive clustering, the Bayesian Information Criterion is proposed for this role, and its application demonstrated. Limitations inherent in this approach, including the assumption that model complexity is equivalent to cluster cardinality, are discussed. These limitations are addressed by applying the Laplacian approximation of a marginal probability density, from which a measure of cluster structure complexity is derived. Using this measure, a preliminary investigation is made of the various properties of cluster structures that affect additive clustering model complexity. Among other things, these investigations show that, for a fixed number of clusters, a model with a strictly nested cluster structure is the least complicated, while a model with a partitioning cluster structure is the most complicated. Copyright 2001 Academic Press.

Journal Article↗

Additive estrogenic activities of a binary mixture of 2',4',6'-trichloro- and 2',3',4',5'-tetrachloro-4-biphenylol.

The estrogenic activity of 2',4',6'-trichloro-4-biphenylol (HO-PCB3), 2',3',4',5'-tetrachloro-4-biphenylol (HO-PCB4), and an equimolar mixture of both compounds (HO-PCB3/HO-PCB4) was investigated in the 21-day-old B6C3F1 mouse uterus, MCF-7 and MDA-MB-231 human breast cancer cells, HepG2 cells, and in a yeast-based reporter gene assay. Treatment of the animals with 17beta-estradiol (E2) (0.02 microg/kg/day x3) resulted in increased uterine wet weight, peroxidase activity and progesterone receptor binding. Treatment with 18, 73, 183 or 366 micromol/kg (x3) doses of HO-PCB3, HO-PCB4, or HO-PCB3/HO-PCB4 (equimolar) caused a dose-dependent increase in estrogenic activity; a maximal-induced response was not observed at any dose and the activity of the mixture was additive. Binding of E2, HO-PCB3, HO-PCB4, and HO-PCB3/HO-PCB4 to the mouse uterine estrogen receptor (ER) was determined in a competitive binding assay using [3H]E2 as the radioligand. The IC50 values were 1.1 x 10(-8), 3.4 x 10(-6), 9.9 x 10(-7), and 4.25 x 10(-6) m, respectively. HO-PCB3 and HO-PCB4 maximally induced MCF-7 cell proliferation, rat creatine kinase, and human complement C3 (C3-LUC) reporter gene activity at concentrations of 10(-5) to 10(-6) m, and these compounds were 10(3) to 10(4) less potent than E2. The HO-PCB3/HO-PCB4 mixture was active at the high concentration (10(-5) m) and was additive for these responses. HO-PCB3 and HO-PCB4 also exhibited estrogenic activity in human HepG2 cells cotransfected with C3-LUC and an ER expression plasmid, and the estrogenic activity of the HO-PCB mixture was additive. Similar results were obtained in yeast transformed with the human ER and a double estrogen responsive element upstream of the beta-gal reporter gene. The effects of variable ER expression on the potential synergistic interactions of HO-PCB3/HO-PCB4 were investigated in HepG2 cells cotransfected with C3-LUC (405 ng/well) and variable amounts of ER expression plasmid (270, 27, 2.7, or 0.27 ng/well). The results show that as ER levels decreased, the magnitude of the induction response by E2, HO-PCB3, HO-PCB4, and HO-PCB3/HO-PCB4 also decreased. However, the activities of the HO-PCB mixture were additive at high and low levels of ER. Similar results were obtained in MDA-MB-231 cells cotransfected with C3-LUC and variable amounts of ER expression plasmid. The results of this study demonstrate that for several estrogen-responsive assays in the mouse uterus; MCF-7, HepG2, and MDA-MBA-231 human cancer cells; and a yeast based-reporter gene assay, both HO-PCB3 and HO-PCB4 exhibited estrogenic activity. The estrogenic activity of an equimolar mixture of these compounds was additive at high and low levels of ER expression.

Animals↗

Additional lactate dehydrogenase (LDH) isoenzymes in normal testis and spermatozoa of adult man.

Adult human testicular tissue contains up to six previously undescribed lactate dehydrogenase (LDH) isoenzymes in addition to the five LDH isoenzymes normally found and the sixth found in spermatogenic cells and spermatozoa, LDH-X. Additional LDH isoenzymes were also found in spermatozoa but not in seminal fluid or in serum. After electrophoresis one additional LDH isoenzyme of testicular tissue was localized between LDH-1 and LDH-2, two between LDH-2 and LDH-3, two between LDH-3 and LDH-4, and two between LDH-4 and LDH-5. These localizations indicate that the additional LDH isoenzymes are tetramers combining the A and B subunits of the five normal LDH isoenzymes and the C subunit of LDH-X. The additional LDH isoenzymes may be important in the metabolism of spermatogenic germ cells and spermatozoa.

Adult↗

In vitro availability of iron from cereal meal with the addition of protein isolates and fenugreek leaves (Trigonella foenum-graecum).

In vitro iron availability was determined from a standard cereal meal (C) with and without the addition of protein isolates from bovine milk (BP), groundnut milk (GP) and soybean milk (SP). A second set of studies were done to investigate the potentially available iron from fenugreek leaves per se and the effect of their addition on the available iron from the cereal meal. The potentially available iron from the meal increased from 4.91% to 6.73% on the addition of BP. The next best enhancer was GP (4.91% to 6.17%). Although the addition of SP increased the total iron content of the cereal meal significantly, the percent available iron decreased compared to the other milk proteins. The addition of fenugreek leaves (100 g/meal) to the meal increased the total iron content of the meal significantly (3.24 mg to 9.12 mg) (p < .001), however, the available iron was observed to decrease (4.91% vs 4.34%).

Biological Availability↗

[Repeated addition of fentanyl to bupivacaine peridural analgesia in labor. Clinical action and fentanyl plasma level].

A combination of epidural opioids with local anaesthetics has been used to improve pain relief during labor and to reduce side effects, such as muscle weakness, usually seen when local anaesthetics are used alone. The addition of epidural fentanyl (F) produces highly effective analgesia, the only side effect being mild itching. Initial trials investigated the improvement in analgesia after a single administration of F during first- but not during second-stage labor. Even though pain perception during second-stage labor under epidural analgesia with local anaesthetics can be severe, the addition of opioids was avoided for fear of neonatal or maternal depression. A recent report found maternal and umbilical plasma concentrations following injection of 100 micrograms F to be safe and the investigators speculated that repeated addition of epidural/F to injection of local anaesthetic may prove beneficial for the parturient without exposing the mother or fetus to risk. We therefore studied maternal analgesia, maternal and umbilical plasma levels and associated side effects following repeated addition of 100 micrograms F to bupivacaine epidural analgesia during labor. METHODS. Following institutional and governmental approval 53 parturients were randomly assigned to receive either 8 ml bupivacaine 0.25% + 0.1 mg fentanyl (B + F group; n = 28) or 8 ml bupivacaine 0.25% + 2 ml saline (BUP group; n = 25) in an epidural catheter at L2/3. The same dose was reinjected upon the patients' request regardless of the degree of cervical dilatation. Blood pressure, heart rate, respiratory rate and the incidence of side effects were recorded before and following each epidural injection. Pain relief was determined at each injection and following cord clamping using the visual analogue pain scale (VAS; 0-100 mm). Maternal venous blood samples were collected to measure plasma F concentrations before and 20 and 40 min after each injection and at birth when umbilical venous and arterial blood was obtained. After centrifugation the samples were maintained at -20 degrees C and then analyzed by radioimmunoassay. At delivery, Apgar scores and umbilical venous and arterial blood gas values were determined. RESULTS. Both groups were comparable for age, weight, height, gestational age and parity. A total of 48 epidural injections were evaluated in the B + F group, 43 in the BUP group. No statistically significant group difference was found between the frequency of injections per delivery (B + F: 2.2; BUP: 1.8); regarding the time between the initial and the first top-up dose (B + F: 144 min; BUP: 140 min) or regarding the interval between the last injection and birth (B + F: 94 min; BUP; 90 min). However, the quality of pain relief during labor and particularly at birth was significantly improved by F (mean VAS in B + F group: 6 mm; mean VAS in BUP group: 42 mm). Mild itching was observed in 43% of patients receiving F, moderate shivering in 13% versus 40% in patients not receiving F. At control mean maternal F plasma levels were not zero but 0.25 ng/ml. After the initial injection and following the first and second top-up dose mean maximum maternal F plasma concentrations were 0.54 ng/ml (+/-0.32; +/-SD), 0.88 ng/ml (+/-0.62) and 1.06 ng/ml (+/-0.4) (range 0.18-2.76 ng/ml), respectively. The increase in maternal F concentrations with increasing injection frequency was statistically significant (P < 0.02). Mean umbilical venous and arterial F concentrations at birth were 0.72 ng/ml (+/-1.16) and 0.62 ng/ml (+/-0.52). No significant group differences were found regarding Apgar scores or umbilical blood gas analyses. In one newborn, radioimmunoassay resulted in unexplainably high umbilical F concentrations without any clinical signs of sedation, depressed vigilance and without any sequellae. DISCUSSION. Repeated addition of 100 micrograms F to epidural anaesthesia with bupivacaine significantly improves analgesia and provides pain relief not only during the fir

Adult↗

Production of wheat-Leymus racemosus chromosome addition lines.

We produced ten wheat-Leymus racemosus chromosome addition lines. Eight chromosomes (A, C, F, H, I, J, k, and l) were recovered as disomic additions and two (E and n) as monosomic. Screening of the addition lines was done by fluorescence in situ hybridization using several repetitive sequences as probes, which allowed us to identify different L. racemosus chromosomes and find many aberrant L. racemosus chromosomes. RFLP analysis revealed partial conservation of homology between L. racemosus and wheat chromosomes, depending on the homologous groups. Chromosomes A and l belonged to group 2, chromosomes C and I to group 5, and chromosome k to group 6. Chromosomes H and J were a mixture of groups 1, 3, and 7, chromosome n of groups 3 and 7, and chromosomes E and F were of group 4 and others. Comparison of our addition lines with other addition lines showed large cytological differences.

Blotting, Southern↗

Molecular cytogenetic analysis of Brassica rapa-Brassica oleracea var. alboglabra monosomic addition lines.

Interspecific alien chromosome addition lines can be very useful for gene mapping and studying chromosome homoeology between closely related species. In this study we demonstrate a simple but robust manner of identifying individual C-genome chromosomes (C5, C8 and C9) in the A-genome background through the simultaneous use of 5S and 25S ribosomal probes on mitotic and meiotic chromosomes of three different Brassica rapa-B. oleracea var. alboglabra monosomic addition lines. Sequential silver staining and fluorescence in situ hybridisation indicated that 18S-5.8S-25S rRNA genes on the additional chromosome C9 are expressed in the A-genome background. Meiotic behaviour of the additional chromosomes was studied in pollen mother cells at diakinesis and metaphase I. In all of the addition lines the alien chromosome was most frequently observed as a univalent. The alien chromosome C5, which carries an intercalary 5S rDNA locus, occasionally formed trivalents that involved either rDNA- or non rDNA-carrying chromosomes from the A genome. In the case of chromosomes C8 and C9, the most frequently observed intergenomic associations involved the regions occupied by 18S-5.8S-25S ribosomal RNA genes. It is possible that not all such associations represent true pairing but are remnants of nucleolar associations from the preceding interphase. Variations in the numbers and distribution of 5S and 25S rDNA sites between cultivars of B. oleracea, B. oleracea var. alboglabra and B. rapa are discussed.

Brassica↗

Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this analysis was to examine the long-term effects of pioglitazone or gliclazide addition to failing metformin monotherapy and pioglitazone or metformin addition to failing sulphonylurea monotherapy in patients with type 2 diabetes. METHODS: Two 2-year, randomised, multicentre trials were performed in patients with inadequately controlled type 2 diabetes (HbA1c 7.5-11% inclusive), who were receiving either metformin or a sulphonylurea at > or = 50% of the maximum recommended dose or at the maximum tolerated dose. In the first study, patients on metformin received add-on therapy with pioglitazone (15-45 mg/day, n = 317) or gliclazide (80-320 mg/day, n = 313). In the second study, patients on sulphonylurea therapy were randomised to receive add-on therapy with either pioglitazone (15-45 mg/day, n = 319) or metformin (850-2,550 mg/day, n = 320). HbA(1)c, fasting plasma glucose, insulin and lipids were investigated. RESULTS: At week 104, the mean reduction from baseline in HbA(1)c was 0.89% for pioglitazone and 0.77% for gliclazide addition to metformin (p = 0.200). There was a statistically significant between-group difference for the change in mean fasting plasma glucose at week 104 (-1.8 mmol/l for pioglitazone vs -1.1 mmol/l for gliclazide, p < 0.001). There were no significant differences in changes from baseline in glycaemic parameters for pioglitazone compared with metformin addition to sulphonylurea therapy. Whether added to metformin or sulphonylurea, pioglitazone caused significantly greater decreases in triglycerides and significantly greater increases in HDL cholesterol than the comparator regimens (p < or = 0.001). There were decreases in LDL cholesterol in the comparator groups and these were significantly different from the small changes observed with pioglitazone (p < 0.001). All treatment regimens were well tolerated. There were weight increases of 2.5 kg and 3.7 kg in the pioglitazone and 1.2 kg in the gliclazide add-on groups, and there was a mean decrease of 1.7 kg in the metformin add-on group. CONCLUSIONS/INTERPRETATION: As add-on therapy to existing sulphonylurea or metformin therapy, pioglitazone improved glycaemic control and this improvement was sustained over 2 years. Furthermore, there were potential benefits in terms of improvements in specific lipid abnormalities. This could offer an advantage over the addition of other oral agents in the long-term treatment of diabetes.

Adult↗