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PubMed1993

Alternative methods of selection for litter size in mice: III. Response to 21 generations of selection.

Alternative methods of selection to increase litter size in mice have been practiced for 21 generations followed by six generations of relaxed selection. Three replicates were used with four selection criteria: index of components (IX:I = 1.21 x total ovulation rate + 9.05 x ova success), uterine capacity (UT), litter size (LS), and an unselected control (LC). In IX, ovulation rate and ova success were measured by number of corpora lutea and number of pups born/number of corpora lutea, respectively. In UT, uterine capacity was measured and defined as number of pups born to unilaterally ovariectomized (right ovary excised) females. Selection in LS was based on number born to unaltered dams. In all cases, number born was fully formed, live or dead pups. Pups from 16 randomly chosen LC dams and from the top 16 dams in IX, UT, and LS were selected to produce the next generation in each criterion-replicate line. Response in number born, selected criteria deviated from control, was regressed on generation number over the 21 generations of selection. Responses for the IX and LS criteria were quite similar (.14 +/- .01 and .16 +/- .01 pups per generation, respectively), whereas response in UT, with only one functional horn, was slightly lower (.09 +/- .01). The average cumulative selection differentials for IX, LS, and UT at Generation 21 were 32.78 index units, 36.38 pups, and 28.53 pups, respectively. The LC criterion had an unintentional cumulative selection differential of 3.3 pups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Inhibition of neutrophil-superoxide generation by alpha-tocopherol and coenzyme Q.

Effects of various derivatives of alpha-tocopherol (VE) and coenzyme Q (CoQ) on superoxide (O2.-) generation of neutrophils and protein kinase C (PKC) activity were examined. VE and CoQ8 inhibited O2.- generation of neutrophils stimulated by a protein kinase C mediated process monitored by cytochrome c reduction and spin trapping methods. The inhibitory action was observed not only with alpha-tocopherol, but also with beta-, gamma-, delta-tocopherols and with tocol which is a chemical similar to VE but lacking methyl groups on the chromanol ring structure and which is not a radical scavenger. By contrast, no inhibition was observed with 2-carboxy-2, 5, 7, 8-tetramethyl-6-chromanol (CTMC, trolox) or 2, 2, 5, 7, 8,-pentamethyl-6-chromanol (PMC) which are water soluble VE derivatives having radical scavenging activity. Compounds having a similar isoprenoid chain, such as CoQ, also have inhibitory activity on PKC-dependent O2.- generation of neutrophils. The inhibitory activity of CoQ derivatives is dependent on the length of the unsaturated isoprenoid chain. CoQ derivatives having 16, 24 and 32 carbon isoprenoid chains corresponding to CoQ4, 6, and 8 inhibited O2.- generation but 4 and 40 carbon isoprenoid chains corresponding to CoQ2 and 10 had no inhibitory activity on O2.- generation. Alpha-tocopherol and CoQ inhibited PKC activity but the ID50 for O2.- generation and PKC activity was different for each compound. However, no direct relationship between VE content and O2.- generation of neutrophils was observed. These results suggest that isoprenoids of VE and CoQ participate in the inhibition of the NADPH oxidase activation system through modulation of the neutrophil membrane probably by the inhibition of PKC.

Animals↗
PubMed1995

Oxyradical generation after resuscitation of hemorrhagic shock with blood or stroma-free hemoglobin solution.

Hypovolemic states are characterized by inadequate tissue perfusion; when this state is reversed, the reintroduction of oxygen is accompanied by the excess generation of oxyradicals and these, in turn, may cause "reperfusion injury" in susceptible tissues. When hemoglobin solution is used to resuscitate the hypovolemic state, the generation of oxyradicals may be enhanced by catalytic means. The generation of oxyradicals was estimated in dogs subjected to the acute removal of 35 ml/Kg blood, and resuscitated 45 mins thereafter with an equal volume of either autologous blood (Group I, n = 6) or 6% stromafree hemoglobin solution (S.F.H.S.) (Group II, n = 6). Hepatic and pancreatic enzymes were measured in blood drawn at intervals. The hypovolemic state was characterized by profound hypotension which was reversed by resuscitation. Oxyradical generation in arterial blood samples, drawn at various times, was estimated by the generation of oxidation products (2,3- and 2,5-dihydroxybenzoic acid) of exogenously administered sodium salicylate, determined by HPLC in plasma samples extracted with diethyl ether. Salicylate oxidation products rose significantly above the baseline value in Group I dogs, whereas they rose 5-6-fold higher than the baseline values in those of Group II. The actual values attained and the increments were significantly (p < .05) greater in Group II than in Group I. In the group resuscitated with S.F.H.S., catalytically active iron concentration in plasma also rose 10-12-fold higher and was associated with spuriously elevated levels of gamma-glutamyl transferase due to interference with the assay. These findings are consistent with the hypothesis that blood-resuscitation of hypovolemic shock is accompanied by oxyradical generation of a modest degree; in contrast, S.F.H.S.-resuscitation introduces catalytically active iron and is accompanied by oxyradical generation of a significantly greater degree.

Animals↗
PubMed2006

Effect of cis-urocanic acid on bovine neutrophil generation of reactive oxygen species.

Neutrophils play a fundamental role in the host innate immune response during mastitis and other bacterial-mediated diseases of cattle. One of the critical mechanisms by which neutrophils contribute to host innate immune defenses is through their ability to phagocytose and kill bacteria. The ability of neutrophils to kill bacteria is mediated through the generation of reactive oxygen species (ROS). However, the extracellular release of ROS can be deleterious to the host because ROS induce tissue injury. Thus, in diseases such as mastitis that are accompanied by the influx of neutrophils, the generation of large quantities of ROS may result in significant injury to the mammary epithelium. cis-Urocanic acid (cis-UCA), which is formed from the UV photoisomerization of the trans isoform found naturally in human and animal skin, is an immunosuppressive molecule with anti-inflammatory properties. Little is known about the effect of cis-UCA on neutrophils, although one report demonstrated that it inhibits human neutrophil respiratory burst activity. However, the nature of this inhibition remains unknown. Because of the potential therapeutic use that a molecule such as cis-UCA may have in blocking excessive respiratory burst activity that may be deleterious to the host, the ability of cis-UCA to inhibit bovine neutrophil production of ROS was studied. Further, because neutrophil generation of ROS is necessary for optimal neutrophil bactericidal activity, a response which is critical for the host innate immune defense against infection, the effects of cis-UCA on bovine neutrophil phagocytosis and bacterial killing were assayed. cis-Urocanic acid dose-dependently inhibited the respiratory burst activity of bovine neutrophils as measured by luminol chemiluminescence. Subsequently, the effect of cis-UCA on the production of specific oxygen radicals was investigated using more selective assays. Using 2 distinct assays, we established that cis-UCA inhibited the generation of extracellular superoxide. In contrast, cis-UCA had no effect on the generation of intracellular levels of superoxide or other ROS. At concentrations that inhibited generation of extracellular superoxide, bovine neutrophil phagocytosis and bacterial activity remained intact. Together, these data suggest that cis-UCA inhibits the tissue-damaging generation of extracellular ROS while preserving neutrophil bactericidal activity.

Animals↗
PubMed1983

Eight generations of selection for duration of fertility of frozen-thawed semen in the chicken.

The response to eight generations of selection for duration of fertility of frozen-thawed chicken semen, the correlated responses of other fertility parameters of frozen-thawed semen and the fertility of fresh semen, and the heritabilities of frozen-thawed and fresh semen were studied. The selected and control lines were derived from a base meat-type control male population developed at Peel's Poultry Farm Ltd., Port Perry, Ontario. Selection has improved duration of fertility of frozen-thawed semen significantly (P less than .01) with the mean increasing from 1 day in Generation 1 to 5 days in Generation 8 and an average improvement per generation of .29 day since Generation 3. There were significant (P less than .01) correlated increases in percent fertility for 2 to 8 days postinsemination and percent fertility for the duration of fertility of frozen-thawed semen as well as the fertility of fresh semen. Percent hatchability of fertile eggs of frozen-thawed semen did not change. In Generation 8, means and standard errors of fertility parameters of frozen-thawed semen in the selected and control lines, respectively, were: 38.54 +/- 1.39 and 25.58 +/- 1.77 for percent fertility for 2 to 8 days postinsemination, 47.73 +/- 3.54 and 32.02 +/- 2.17 for percent fertility for the duration of fertility, and 78.21 +/- 1.56 and 79.27 +/- 2.53 for percent hatchability of fertile eggs. For fertility of fresh semen, means and standard errors were: 12.69 +/- .20 and 11.54 +/- .42 for duration of fertility, 82.91 +/- 1.45 and 75.71 +/- 2.83 for percent fertility for 2 to 8 days postinsemination, and 71.89 +/- 1.25 and 69.22 +/- 2.06 for percent fertility for the duration of fertility. The means of the heritability estimates of the fertility of frozen-thawed and fresh semen, respectively, ranged from .01 to .31 and -.01 to .21. The realized heritability of duration of fertility of frozen-thawed semen, based on five generations, was .17 +/- .05. The phenotypic correlations of duration of fertility of frozen-thawed semen with percent fertility for 2 to 8 days postinsemination and percent fertility for the duration of fertility of frozen-thawed semen were high and positive and correlations between fertility of frozen-thawed and fresh semen were low but positive.

Animals↗
PubMed1984

Plasma constituents and body weights of Japanese quail (Coturnix coturnix japonica) selected for twelve generations for plasma cholesterol responses to adrenocorticotropin.

Japanese quail were selected bidirectionally over 12 generations for plasma cholesterol (PC) responses to adrenocorticotropin (ACTH). In addition to the selected trait, plasma corticosteroids (PCS), triglycerides (PT), and glucose (PG) were measured before and after 3 daily injections of ACTH. The quail were also weighed at 31 days of age. By the 12th generation of selection, when measurements were expressed as deviations from the randombred control (C) line from which the selected lines had been derived, there was a difference in PC of approximately 55% between the high response (HR) and the low-response (LR) lines. Pre-ACTH PCS levels increased in all three lines over generations; however, relative to the C line, there was no difference between selected lines. The 3 days of ACTH injection depressed PCS levels. Relative to the C line, pre- and post-ACTH levels of PT were higher in the HR line than in the LR line, and the LR line declined linearly over generations. Levels of PG did not change over generation in the selected lines; however, pre-ACTH levels of PG tended to be higher in the LR line than in the HR line in all generations. Body weights of the HR line at 31 days remained almost exactly the same as the C line, but those of the LR line declined linearly over the 12 generations of selection. These studies demonstrated that the PC response to ACTH was moderately heritable (h2 approximately equal to .20).

Adrenal Cortex Hormones↗
PubMed2006

Release from generation failure: the role of study list structure.

Three experiments, using the original encoding-specificity paradigm, investigated the role of study list structure in producing Higham and Tam's (2005) generation failure effect. Generation failure occurs when cued recall performance for strong, extralist cues is worse than target production in a control group that is given no study list but is instead required merely to generate responses to the same test cues. In the present study, generation failure was replicated in Experiment 1, and Experiment 2 demonstrated that strong, extralist cues were more likely to elicit targets in pure generation groups when participants had studied a list of strong associates than when they had studied a list of weak ones. In Experiment 3, participants were released from generation failure when a study list of moderate associates was used and the cue-to-target associative strength was equated between the reinstated- and extralist-cue conditions. Together, these results suggest that generation failure is partly attributable to participants' searching inappropriate domains that, though consistent with the study list structure, are unlikely to contain targets.

Cues↗
PubMed2002

The generation effect: dissociating enhanced item memory and disrupted order memory.

Generating stimuli at encoding typically improves memory for occurrence (item memory) but might disrupt memory for order. In three experiments, the relationship between generation and order memory was examined by using familiar stimuli, which give rise to the standard generation advantage in item memory, and unfamiliar stimuli, which do not. The participants generated or read words and non-words in Experiments 1 and 2 and familiar and unfamiliar word compounds in Experiment 3. For the familiar stimuli, generation enhanced item memory (as measured by recognition) but disrupted performance on the order-reconstruction test. For the unfamiliar stimuli, generation produced no recognition advantage and yet persisted in disrupting order reconstruction. Thus, the positive effects of generation on item memory were dissociated from its negative impact on order memory.

Association↗
PubMed2026

Trans-Mitochondrial Cybrid Generation from mtDNA Patient Platelets: An Efficient Protocol Optimizing Colony Selection and Functional Validation.

Trans-mitochondrial cybrid cell line generation represents the gold-standard method for determining pathogenicity by enabling biochemical analyses of a specific mitochondrial DNA (mtDNA) variant of interest at high and low percentages (heteroplasmy levels) within an otherwise identical mtDNA and nuclear genome background. Historically, the cybrid generation process has been tedious and poorly efficient. Here, we describe a highly efficient and effective protocol for generating trans-mitochondrial cybrid cell lines by fusing human platelets with a standard osteosarcoma 143B cell line to provide an isogenic nuclear background depleted of mtDNA (Rho0 cells). Cell isolates capture a given mtDNA genome of interest to establish stable cell lines harboring different degrees of heteroplasmy, or to compare divergent effects of distinct mitochondrial haplogroups. Because cybrids from mitochondrial patients may be more difficult to establish with standard protocols, this current methodology focuses on isolating mtDNA variants where the electron transport chain activity is affected. We here demonstrate that colony selection techniques reduce time and improve the yield of generating high-level heteroplasmy mtDNA mutant cybrid lines. A case study is provided of cybrid generation for a variant of unknown significance in MT-ND1, m.3985G>A (p.E227K). We analyze the efficiency of the cybrid generation process using this protocol and run functional studies performed by high-resolution respirometry. High-level heteroplasmy MT-ND1 m.3985G>A cybrid mutants generated by this protocol are shown to have impaired complex I-dependent mitochondrial respiration relative to wild-type control, demonstrating m.3985G>A is likely pathogenic.

Humans↗
PubMed2006

A modified tyrosinase-related protein 2 epitope generates high-affinity tumor-specific T cells but does not mediate therapeutic efficacy in an intradermal tumor model.

The generation of tumor-specific T cells is hampered by the presentation of poorly immunogenic tumor-specific epitopes by the tumor. Here, we demonstrate that, although CD8+ T cells specific for the self/tumor Ag tyrosinase-related protein 2 (TRP2) are readily detected in tumor-bearing hosts, vaccination of either tumor-bearing or naive mice with an epitope derived from TRP2 fails to generate significant numbers of tetramer-staining TRP2-specific T cells or antitumor immunity. We identified an altered peptide epitope, called deltaV, which elicits T cell responses that are cross-reactive to the wild-type TRP2 epitope. Immunization with deltaV generates T cells with increased affinity for TRP2 compared with immunization with the wild-type TRP2 epitope, although TRP2 immunization often generates a greater number of TRP2-specific T cells based on intracellular IFN-gamma analysis. Despite generating higher affinity responses, deltaV immunization alone fails to provide any greater therapeutic efficacy against tumor growth than TRP2 immunization. This lack of tumor protection is most likely a result of both the deletion of high affinity and functional tolerance induction of lower affinity TRP2-specific T cells. Our data contribute to a growing literature demonstrating the ability of variant peptide epitopes to generate higher affinity T cell responses against tumor-specific Ags. However, consistent with most clinical data, simple generation of higher affinity T cells is insufficient to mediate tumor immunity.

Animals↗
PubMed2004

Growth inhibition dependent on reactive oxygen species generated by C9-UK-2A, a derivative of the antifungal antibiotic UK-2A, in Saccharomyces cerevisiae.

UK-2A is a potent antifungal antibiotic and its structure is highly similar to that of antimycin A3 (AA). UK-2A and AA inhibit mitochondrial electron transport at complex III. C9-UK-2A, which has been prepared to improve the duration of the antifungal activity of UK-2A, shows durable fungicidal activities against various species of fungi and induces both membrane injury and the generation of cellular reactive oxygen species (ROS) against Rhodotorula mucilaginosa IFO 0001 cells. We found that C9-UK-2A inhibited the vegetative growth of Saccharomyces cerevisiae IFO 0203 cells accompanying cellular ROS generation in Sabouraud dextrose (SD) medium, which contained a fermentable carbon source. The ROS generation was completely restricted by pretreatment with a lipophilic antioxidant alpha-tocopherol. In addition, the pretreatment with the antioxidant protected against the growth inhibition induced by C9-UK-2A. C9-UK-2A also induced ROS generation in isolated mitochondria of the S. cerevisiae cells. The addition of both a complex I inhibitor rotenone and a complex II inhibitor thenoyltrifluoroacetone reduced ROS generation induced by C9-UK-2A in the whole cells and the isolated mitochondria. The addition of the inhibitors of complex III, AA or myxothiazol, or of complex IV, KCN, did not reduce ROS generation. These results suggest that C9-UK-2A induces ROS generation due to the blockade of electron flow at complex III, thereby inhibiting the growth of S. cerevisiae in SD medium.

Lactones↗
PubMed1992

A new methyl bromide gas generator for inhalation toxicity studies.

A simple generator for methyl bromide gas has been newly developed by us. For inhalation toxicity studies, until now, there have been few generators capable of producing a constant and stable concentration of methyl bromide gas easily because of its high volatility. The principle of this new generator is based on gas-liquid equilibrium. The gas is generated from the surface of liquid methyl bromide in an evaporator made of a Teflon tube. The generator can produce up to 10,000 ppm of methyl bromide gas in a 0.1 m3 exposure chamber, and the concentration of this generated gas is able to be kept within +/- 0.8% over a long period of time. The generator has proved to be useful for investigating the effects of methyl bromide on health in inhalation toxicity studies.

Administration, Inhalation↗
PubMed1999

Dictated versus database-generated discharge summaries: a randomized clinical trial.

BACKGROUND: Hospital discharge summaries communicate information necessary for continuing patient care. They are most commonly generated by voice dictation and are often of poor quality. The objective of this study was to compare discharge summaries created by voice dictation with those generated from a clinical database. METHODS: A randomized clinical trial was performed in which discharge summaries for patients discharged from a general internal medicine service at a tertiary care teaching hospital in Ottawa were created by voice dictation (151 patients) or from a database (142 patients). Patients had been admitted between September 1996 and June 1997. The trial was preceded by a baseline cohort study in which all summaries were created by dictation. For the database group, information on forms completed by housestaff was entered into a database and collated into a discharge summary. For the dictation group, housestaff dictated narrative letters. The proportion of patients for whom a summary was generated within 4 weeks of discharge was recorded. Physicians receiving the summary rated its quality, completeness, organization and timeliness on a 100-mm visual analogue scale. Housestaff preference was also determined. RESULTS: Patients in the database group and the dictation group were similar. A summary was much more likely to be generated within 4 weeks of discharge for patients in the database group than for those in the dictation group (113 [79.6%] v. 86 [57.0%]; p < 0.001). Summary quality was similar (mean rating 72.7 [standard deviation (SD) 19.3] v. 74.9 [SD 16.6]), as were assessments of completeness (73.4 [SD 19.8] v. 78.2 [SD 14.9]), organization (77.4 [SD 16.3] v. 79.3 [SD 17.2]) and timeliness (70.3 [SD 21.9] v. 66.2 [SD 25.6]). Many information items of interest were more likely to be included in the database-generated summaries. The database system created summaries faster and was preferred by housestaff. Dictated summaries in the baseline and randomized studies were similar, which indicated that the control group was not substantially different from the baseline cohort. INTERPRETATION: The database system significantly increased the likelihood that a discharge summary was created. Housestaff preferred the database system for summary generation. Physicians thought that the quality of summaries generated by the 2 methods was similar. The use of computer databases to create hospital discharge summaries is promising and merits further study and refinement.

Abstracting and Indexing↗
PubMedDate not supplied

[The behavioral effects of a single adverse exposure in a number of rat generations: the role of maternal glucocorticoids].

The ionizing irradiation of rat fetuses during the last third of intrauterine development increased blood corticosterone level adulthood and decreased the open field locomotion of their adult offsprings of the next first nonirradiated generation. Treatment of the pregnant rats with glucocorticoids also decreased the offspring locomotion. Irradiation of fetuses in the middle of embryogenesis decreased blood corticosterone level in adulthood and shortened the open-field freezing reaction of their adult offsprings of the next first nonirradiated generation. Adrenalectomy of females before mating decreasing the blood corticosterone level had a similar effect on freezing duration of their adult offsprings. Irradiation of the ancestors within the last third of their intrauterine development had no effect on blood corticosterone level of their adult offsprings of the first generation and produced no behavioral alterations in their descendants of the next second nonirradiated generation. Irradiation of the ancestors in the middle of their embryogenesis decreased the stress-induced corticosterone response in their adult offsprings of the first generation and increased rearings and locomotion in their descendants of the next second nonirradiated generation. The data suggest that a single noxious treatment may have behavioral effects throughout two consequent generations of rats. Mother's glucocorticoid hormones may be one of the factors which transmit the effect.

Adrenalectomy↗
PubMedDate not supplied

Suppression of N(epsilon)-(carboxymethyl)lysine generation by the antioxidant N-acetylcysteine.

OBJECTIVE: Accumulated evidence suggests that N(epsilon)-(carboxymethyl)lysine (CML), which is a dominant antigen of advanced glycation end-products (AGEs), is generated in the peritoneal cavity of patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and that this process may be involved in the pathophysiology of the peritoneal injury found with CAPD treatment. Since CML is a sequential product of glycation and oxidation processes, CML generation could be suppressed by antioxidants. The aim of this in vitro study was to clarify the effect of N-acetylcysteine (NAC), an antioxidant, on CML generation from proteins under high glucose settings mimicking peritoneal dialysis solutions. DESIGN: Test proteins (bovine serum albumin/type I collagen) were incubated continuously for 16 weeks in glucose solutions (200 mmol/L) with or without NAC (2 mmol/L), and the generation time courses (8 and 16 weeks) of CML and furosine (the biomarker of the glycation products of the early Maillard reaction) were determined. RESULTS: In both proteins, furosine and CML were progressively generated in accordance with the duration of the incubation period. No apparent differences were found between solutions with and without NAC in furosine levels at the 8th and 16th weeks. However, the generation of CML was lower in the solution with NAC throughout the test periods. CONCLUSION: The results showed that NAC could suppress the generation of CML. This indicates the therapeutic potential of antioxidants for the glycoxidative stress-related peritoneal injury occurring during CAPD.

Acetylcysteine↗
PubMed2000

Inhibition of thrombin generation by the zymogen factor VII: implications for the treatment of hemophilia A by factor VIIa.

Factor VII circulates as a single chain inactive zymogen (10 nmol/L) and a trace ( approximately 10-100 pmol/L) circulates as the 2-chain form, factor VIIa. Factor VII and factor VIIa were studied in a coagulation model using plasma concentrations of purified coagulation factors with reactions initiated with relipidated tissue factor (TF). Factor VII (10 nmol/L) extended the lag phase of thrombin generation initiated by 100 pmol/L factor VIIa and low TF. With the coagulation inhibitors TFPI and AT-III present, factor VII both extended the lag phase of the reaction and depressed the rate of thrombin generation. The inhibition of factor Xa generation by factor VII is consistent with its competition with factor VIIa for TF. Thrombin generation with TF concentrations >100 pmol/L was not inhibited by factor VII. At low tissue factor concentrations (<25 pmol/L) thrombin generation becomes sensitive to the absence of factor VIII. In the absence of factor VIII, factor VII significantly inhibits TF-initiated thrombin generation by 100 pmol/L factor VIIa. In this hemophilia A model, approximately 2 nmol/L factor VIIa is needed to overcome the inhibition of physiologic (10 nmol/L) factor VII. At 10 nmol/L, factor VIIa provided a thrombin generation response in the hemophilia model (0% factor VIII, 10 nmol/L factor VII) equivalent to that observed with normal plasma, (100% factor VIII, 10 nmol/L factor VII, 100 pmol/L factor VIIa). These results suggest that the therapeutic efficacy of factor VIIa in the medical treatment of hemophiliacs with inhibitors is, in part, based on overcoming the factor VII inhibitory effect. (Blood. 2000;95:1330-1335)

Anticoagulants↗
PubMed2000

The relationship between elution time and eluate volume using the Ultra-TechneKow DTE technetium-99m generator.

OBJECTIVE: The new Ultra-TechneKow Dry Ship Top Elute 99mTc generator (UTK-DTE generator; Mallinckrodt Medical, Inc., St. Louis, MO) was devised to facilitate fractionated elution with an ergonomically designed elution shield. Fractionation is accomplished traditionally by visually observing the eluted volume through 2 layers of leaded glass windows located in a lighted elution shield and generator auxiliary shield. The goal of our study was to use elution time to determine the endpoint for obtaining the required volume of 99mTc-eluate from a UTK-DTE generator. METHODS: After triplicate elution at several predetermined elution times, the initial weight of the evacuated collecting vial was subtracted from the total weight after elution to determine the elution volume. RESULTS: A quadratic relationship was established between the eluate volume (v, mL) and elution time (t, s) (v = 0.3594 + 0.1889 t - 0.0009 t2). This equation is suitable for use with the 10-mL elution vial. This formula may not be accurate for the first elution since the UTK-DTE generator is a dry-column generator when shipped. The following elution times were calculated for some commonly eluted volumes: 2 mL (9 s), 4 mL (22 s), 5 mL (28 s), 7 mL (45 s), and 10 mL (88 s). CONCLUSION: Our calculated elution time method can be used to predict the eluate volume from a UTK-DTE generator.

Algorithms↗
PubMedDate not supplied

Hypercoagulable state in hypercholesterolemic subjects assessed by platelet-dependent thrombin generation: in vitro effect of cerivastatin.

BACKGROUND: Hypercholesterolemia is an important risk factor to develop acute thrombotic complications of atherosclerosis like to myocardial infarction and ischemic stroke. Platelets and coagulation factors are strictly involved in the genesis of such thrombotic events and their hyperactivity in hypercholesterolemic patients has been previously reported. Moreover some cholesterol-lowering molecules (statins) seem to be able of reducing platelet activity. METHODS: We performed platelet-dependent thrombin generation (colorimetric method) to assess the coagulative potential of 40 caucasian hypercholesterolemic subjects with respect to normal controls and to the grade of hypercholesterolemia. Moreover we observed the effect of platelets from hypercholesterolemics on thrombin generation in plasma from normal subjects. The effect of Cerivastatin on thrombin generation was evaluated too. RESULTS: Our data show an increased thrombin generation both in mild and high hypercholesterolemic subjects with respect to controls (424.6+/-30.5 vs. 197.1+/-27.4 mIU/ml). No significant difference in the amount of thrombin generation was found between mild and high hypercholesterolemics (399.6+/-20.7 vs. 440.2+/-21.4 mIU/ml). Platelets directly influence thrombin generation and they present an intrinsic hyperactivity that can be modulated by Cerivastatin (223.6+/-24.8 vs. 424.6+/-30.5 mIU/ml). CONCLUSIONS: Mild hypercholesterolemia is associated with an increased thrombinic potential that may be considered an added risk factor to develop thrombotic events. Platelets directly influences this hypercoagulative state and Cerivastatin is able to reduce thrombin generation by way of a direct interaction with platelets.

Blood Coagulation Disorders↗