An imidazopyridine anxiolytic alters glucose tolerance in patients: a pilot investigation.

PubMed

Bottaï, T; Cartault, F; Pouget, R; Blayac, J P; Petit, P

1995-02-01

We have recently shown that compounds with high affinity for peripheral-type benzodiazepine receptors inhibited glucose-induced insulin secretion in vitro. We therefore performed an oral glucose tolerance test in anxious inpatients treated with the imidazopyridine derivative alpidem, which has been shown to display high affinity for these binding sites. The test was performed before and after 1 week of daily administration of the drug. As compared with pretreatment values, a significant alteration of the insulin response to glucose was observed. It is suggested that daily administration of alpidem, at therapeutically effective doses for the treatment of anxiety, may alter glucose tolerance.

Anti-hyperglycemic effect and glucose tolerance of guajava (Psidium guajava L.) leaf ethanol extract in diabetic rats

NASA Astrophysics Data System (ADS)

Yanis Musdja, Muhammad; Mahendra, Feizar; Musir, Ahmad

2017-12-01

Traditionally guava (Psidium guajava L) leaf is used for treatment of various ailments like diarrhea, wounds, rheumatism, anti-allergy, ant-spasmodic, etc, as folk medicine. The aim of this research is to know the effect of hypoglycemia and glucose tolerance of ethanol extract of guava leaf against male white rat. The guajava leaf was obtained from Balitro Bogor. Preparation of guajava leaf extract was done by cold maceration extraction technique using ethanol 70%. Male albino rats were made into diabetics using the alloxan method. Rats were divided into 6 groups, as a comparative drug for anti-hyperglycemic used glibenclamid and as a comparative drug for glucose tolerance used acarbose. The result of blood glucometer test showed that ethanol extract 70% of guajava leaf had effect as anti-hyperglycemic and glucose tolerance with no significant difference with glibenclamid drug as anti-hyperglycemic and acarbose as glucose tolerance drug.

A study on nonlinear estimation of submaximal effort tolerance based on the generalized MET concept and the 6MWT in pulmonary rehabilitation

PubMed Central

Szczegielniak, Jan; Łuniewski, Jacek; Stanisławski, Rafał; Bogacz, Katarzyna; Krajczy, Marcin; Rydel, Marek

2018-01-01

Background The six-minute walk test (6MWT) is considered to be a simple and inexpensive tool for the assessment of functional tolerance of submaximal effort. The aim of this work was 1) to background the nonlinear nature of the energy expenditure process due to physical activity, 2) to compare the results/scores of the submaximal treadmill exercise test and those of 6MWT in pulmonary patients and 3) to develop nonlinear mathematical models relating the two. Methods The study group included patients with the COPD. All patients were subjected to a submaximal exercise test and a 6MWT. To develop an optimal mathematical solution and compare the results of the exercise test and the 6MWT, the least squares and genetic algorithms were employed to estimate parameters of polynomial expansion and piecewise linear models. Results Mathematical analysis enabled to construct nonlinear models for estimating the MET result of submaximal exercise test based on average walk velocity (or distance) in the 6MWT. Conclusions Submaximal effort tolerance in COPD patients can be effectively estimated from new, rehabilitation-oriented, nonlinear models based on the generalized MET concept and the 6MWT. PMID:29425213

Self testing for diabetes mellitus.

PubMed Central

Davies, M; Alban-Davies, H; Cook, C; Day, J

1991-01-01

OBJECTIVE--To develop a simple, economically viable, and effective means of population screening for diabetes mellitus. DESIGN--A postal request system for self testing for glycosuria with foil wrapped dipsticks. Preprandial and postprandial tests were compared with a single postprandial test. The subjects were instructed how to test, and a result card was supplied on which to record and return the result. All those recording a positive test result and 50 people recording a negative result were invited for an oral glucose tolerance test. SETTING--General practice in east Suffolk, list size 11534. PATIENTS--All subjects aged 45-70 years registered with the practice were identified by Suffolk Family Health Services Authority (n = 3057). The 73 subjects known to have diabetes from the practice's register were excluded, leaving 2984 subjects, 2363 (79.2%) of whom responded. 1167 subjects completed the single test and 1196 the two tests. MAIN OUTCOME MEASURES--Response rate and number of patients with glycosuria. Sensitivity, specificity, and positive predictive value of a single postprandial test and preprandial and postprandial tests. Number of new cases of diabetes identified and cost of screening. RESULTS--Of the patients completing the single postprandial test, 29 had a positive result, an oral glucose tolerance test showed that eight (28%) had diabetes, six (21%) impaired glucose tolerance, and 14 (48%) normal glucose tolerance. 44 of the group who tested before and after eating had a positive result; nine (20%) had diabetes, five (11%) impaired tolerance, and 26 (11%) normal tolerance. Screening cost 59p per subject and 81 pounds per case detected. Of the 17 people with previously undiagnosed diabetes, eight were asymptomatic and 11 had not visited their general practitioner in the past three months. CONCLUSIONS--A postal request system for self testing for postprandial glycosuria in people aged 45-70 is a simple and effective method of population screening for diabetes mellitus. PMID:1912918

Autogenic-feedback training exercise is superior to promethazine for control of motion sickness symptoms

NASA Technical Reports Server (NTRS)

Cowings, P. S.; Toscano, W. B.

2000-01-01

Motion sickness symptoms affect approximately 50% of the crew during space travel and are commonly treated with intramuscular injections of promethazine. The purpose of this paper is to compare the effectiveness of three treatments for motion sickness: intramuscular injections (i.m.) of promethazine, a physiological training method (autogenic-feedback training exercise [AFTE]), and a no-treatment control. An earlier study tested the effects of promethazine on cognitive and psychomotor performance and motion sickness tolerance in a rotating chair. For the present paper, motion sickness tolerance, symptom reports, and physiological responses of these subjects were compared to matched subjects selected from an existing database who received either AFTE or no treatment. Three groups of 11 men, between the ages of 33 and 40 years, were matched on the number of rotations tolerated during their initial rotating-chair motion sickness test. The motion sickness test procedures and the 7-day interval between tests were the same for all subjects. The drug group was tested under four treatment conditions: baseline (no injections), a 25 mg dose of promethazine, a 50 mg dose of promethazine, and a placebo of sterile saline. AFTE subjects were given four 30-minute AFTE sessions before their second, third, and fourth motion sickness tests (6 hours total). The no-treatment control subjects were only given the four rotating-chair tests. Motion sickness tolerance was significantly increased after 4 hours of AFTE when compared to either 25 mg (p < 0.00003) or 50 mg (p < 0.00001) of promethazine. The control and promethazine groups did not differ. AFTE subjects reported fewer or no symptoms at higher rotational velocities than subjects in the control or promethazine groups. The primary physiological effect of promethazine was an inhibition of skin conductance level. The AFTE group showed significantly less heart rate and skin conductance variability during motion sickness tests administered after training.

Autogenic-feedback training exercise is superior to promethazine for control of motion sickness symptoms.

PubMed

Cowings, P S; Toscano, W B

2000-10-01

Motion sickness symptoms affect approximately 50% of the crew during space travel and are commonly treated with intramuscular injections of promethazine. The purpose of this paper is to compare the effectiveness of three treatments for motion sickness: intramuscular injections (i.m.) of promethazine, a physiological training method (autogenic-feedback training exercise [AFTE]), and a no-treatment control. An earlier study tested the effects of promethazine on cognitive and psychomotor performance and motion sickness tolerance in a rotating chair. For the present paper, motion sickness tolerance, symptom reports, and physiological responses of these subjects were compared to matched subjects selected from an existing database who received either AFTE or no treatment. Three groups of 11 men, between the ages of 33 and 40 years, were matched on the number of rotations tolerated during their initial rotating-chair motion sickness test. The motion sickness test procedures and the 7-day interval between tests were the same for all subjects. The drug group was tested under four treatment conditions: baseline (no injections), a 25 mg dose of promethazine, a 50 mg dose of promethazine, and a placebo of sterile saline. AFTE subjects were given four 30-minute AFTE sessions before their second, third, and fourth motion sickness tests (6 hours total). The no-treatment control subjects were only given the four rotating-chair tests. Motion sickness tolerance was significantly increased after 4 hours of AFTE when compared to either 25 mg (p < 0.00003) or 50 mg (p < 0.00001) of promethazine. The control and promethazine groups did not differ. AFTE subjects reported fewer or no symptoms at higher rotational velocities than subjects in the control or promethazine groups. The primary physiological effect of promethazine was an inhibition of skin conductance level. The AFTE group showed significantly less heart rate and skin conductance variability during motion sickness tests administered after training.

Standardized Mixed-Meal Tolerance and Arginine Stimulation Tests Provide Reproducible and Complementary Measures of β-Cell Function: Results From the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series

PubMed Central

Shankar, Sudha S.; Vella, Adrian; Raymond, Ralph H.; Staten, Myrlene A.; Calle, Roberto A.; Bergman, Richard N.; Cao, Charlie; Chen, Danny; Cobelli, Claudio; Dalla Man, Chiara; Deeg, Mark; Dong, Jennifer Q.; Lee, Douglas S.; Polidori, David; Robertson, R. Paul; Ruetten, Hartmut; Stefanovski, Darko; Vassileva, Maria T.; Weir, Gordon C.

2016-01-01

OBJECTIVE Standardized, reproducible, and feasible quantification of β-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states. RESEARCH DESIGN AND METHODS Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT). RESULTS From the MMTT, insulin secretion in T2DM was >86% lower compared with NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (∼50%) to T2DM (93% lower [P < 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (>58%; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from ∼0.3 to ∼0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values >0.8 across all variables and populations. CONCLUSIONS Standardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use. PMID:27407117

Standardized Mixed-Meal Tolerance and Arginine Stimulation Tests Provide Reproducible and Complementary Measures of β-Cell Function: Results From the Foundation for the National Institutes of Health Biomarkers Consortium Investigative Series.

PubMed

Shankar, Sudha S; Vella, Adrian; Raymond, Ralph H; Staten, Myrlene A; Calle, Roberto A; Bergman, Richard N; Cao, Charlie; Chen, Danny; Cobelli, Claudio; Dalla Man, Chiara; Deeg, Mark; Dong, Jennifer Q; Lee, Douglas S; Polidori, David; Robertson, R Paul; Ruetten, Hartmut; Stefanovski, Darko; Vassileva, Maria T; Weir, Gordon C; Fryburg, David A

2016-09-01

Standardized, reproducible, and feasible quantification of β-cell function (BCF) is necessary for the evaluation of interventions to improve insulin secretion and important for comparison across studies. We therefore characterized the responses to, and reproducibility of, standardized methods of in vivo BCF across different glucose tolerance states. Participants classified as having normal glucose tolerance (NGT; n = 23), prediabetes (PDM; n = 17), and type 2 diabetes mellitus (T2DM; n = 22) underwent two standardized mixed-meal tolerance tests (MMTT) and two standardized arginine stimulation tests (AST) in a test-retest paradigm and one frequently sampled intravenous glucose tolerance test (FSIGT). From the MMTT, insulin secretion in T2DM was >86% lower compared with NGT or PDM (P < 0.001). Insulin sensitivity (Si) decreased from NGT to PDM (∼50%) to T2DM (93% lower [P < 0.001]). In the AST, insulin secretory response to arginine at basal glucose and during hyperglycemia was lower in T2DM compared with NGT and PDM (>58%; all P < 0.001). FSIGT showed decreases in both insulin secretion and Si across populations (P < 0.001), although Si did not differ significantly between PDM and T2DM populations. Reproducibility was generally good for the MMTT, with intraclass correlation coefficients (ICCs) ranging from ∼0.3 to ∼0.8 depending on population and variable. Reproducibility for the AST was very good, with ICC values >0.8 across all variables and populations. Standardized MMTT and AST provide reproducible and complementary measures of BCF with characteristics favorable for longitudinal interventional trials use. © 2016 by the American Diabetes Association.

Regulatory Focus Affects Physician Risk Tolerance

PubMed Central

Veazie, Peter J.; McIntosh, Scott; Chapman, Benjamin P.; Dolan, James G.

2014-01-01

Risk tolerance is a source of variation in physician decision-making. This variation, if independent of clinical concerns, can result in mistaken utilization of health services. To address such problems, it will be helpful to identify nonclinical factors of risk tolerance, particularly those amendable to intervention – regulatory focus theory suggests such a factor. This study tested whether regulatory focus affects risk tolerance among primary care physicians. Twenty-seven primary care physicians were assigned to promotion-focused or prevention-focused manipulations and compared on the Risk Taking Attitudes in Medical Decision Making scale using a randomization test. Results provide evidence that physicians assigned to the promotion-focus manipulation adopted an attitude of greater risk tolerance than the physicians assigned to the prevention-focused manipulation (P=0.01). The Cohen’s d statistic was conventionally large at 0.92. Results imply that situational regulatory focus in primary care physicians affects risk tolerance and may thereby be a nonclinical source of practice variation. Results also provide marginal evidence that chronic regulatory focus is associated with risk tolerance (P=0.05), but the mechanism remains unclear. Research and intervention targeting physician risk tolerance may benefit by considering situational regulatory focus as an explanatory factor. PMID:25431799

Abnormal glucose tolerance post-gestational diabetes mellitus as defined by the International Association of Diabetes and Pregnancy Study Groups criteria.

PubMed

Noctor, Eoin; Crowe, Catherine; Carmody, Louise A; Saunders, Jean A; Kirwan, Breda; O'Dea, Angela; Gillespie, Paddy; Glynn, Liam G; McGuire, Brian E; O'Neill, Ciarán; O'Shea, P M; Dunne, F P

2016-10-01

An increase in gestational diabetes mellitus (GDM) prevalence has been demonstrated across many countries with adoption of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria. Here, we determine the cumulative incidence of abnormal glucose tolerance among women with previous GDM, and identify clinical risk factors predicting this. Two hundred and seventy women with previous IADPSG-defined GDM were prospectively followed up for 5years (mean 2.6) post-index pregnancy, and compared with 388 women with normal glucose tolerance (NGT) in pregnancy. Cumulative incidence of abnormal glucose tolerance (using American Diabetes Association criteria for impaired fasting glucose, impaired glucose tolerance and diabetes) was determined using the Kaplan-Meier method of survival analysis. Cox regression models were constructed to test for factors predicting abnormal glucose tolerance. Twenty-six percent of women with previous GDM had abnormal glucose tolerance vs 4% with NGT, with the log-rank test demonstrating significantly different survival curves (P<0.001). Women meeting IADPSG, but not the World Health Organization (WHO) 1999 criteria, had a lower cumulative incidence than women meeting both sets of criteria, both in the early post-partum period (4.2% vs 21.7%, P<0.001) and at longer-term follow-up (13.7% vs 32.6%, P<0.001). Predictive factors were glucose levels on the pregnancy oral glucose tolerance test, family history of diabetes, gestational week at testing, and BMI at follow-up. The proportion of women developing abnormal glucose tolerance remains high among those with IADPSG-defined GDM. This demonstrates the need for continued close follow-up, although the optimal frequency and method needs further study. © 2016 European Society of Endocrinology.

[Objective evaluation of arterial intermittent claudication by the walking tolerance test. Comparative study of physiological walking and walking on a conveyor belt (author's transl)].

PubMed

Bouchet, J Y; Franco, A; Morzol, B; Beani, J C

1980-01-01

Two methods are used to evaluate the walking distance: physiological walking along a standard path (0% - 6 mk/h) and walking on a tread mill (10% - 3 km/h). In both tests, four data are checked: -- initial trouble distance, -- cramp or walking-distance, -- localisation of pain, -- recovery time. These tests are dependable for the diagnosis of arterial claudication, reproducible and well tolerated. Their results have been compared: there is no correlation between the initial trouble distance and the cramp distance. However there is a correlation between the cramp distance by physiological walking and on treadmill. Recovery time, if long, is a criteria of gravity. Interests of both methods are discussed.

Glucose tolerance test - non-pregnant

MedlinePlus

Oral glucose tolerance test - non-pregnant; OGTT - non-pregnant; Diabetes - glucose tolerance test; Diabetic - glucose tolerance test ... The most common glucose tolerance test is the oral glucose ... the test begins, a sample of blood will be taken. You will then ...

Skin surface cooling improves orthostatic tolerance following prolonged head-down bed rest

PubMed Central

Keller, David M.; Low, David A.; Davis, Scott L.; Hastings, Jeff

2011-01-01

Prolonged exposure to microgravity, as well as its ground-based analog, head-down bed rest (HDBR), reduces orthostatic tolerance in humans. While skin surface cooling improves orthostatic tolerance, it remains unknown whether this could be an effective countermeasure to preserve orthostatic tolerance following HDBR. We therefore tested the hypothesis that skin surface cooling improves orthostatic tolerance after prolonged HDBR. Eight subjects (six men and two women) participated in the investigation. Orthostatic tolerance was determined using a progressive lower-body negative pressure (LBNP) tolerance test before HDBR during normothermic conditions and on day 16 or day 18 of 6° HDBR during normothermic and skin surface cooling conditions (randomized order post-HDBR). The thermal conditions were achieved by perfusing water (normothermia ∼34°C and skin surface cooling ∼12–15°C) through a tube-lined suit worn by each subject. Tolerance tests were performed after ∼30 min of the respective thermal stimulus. A cumulative stress index (CSI; mmHg LBNP·min) was determined for each LBNP protocol by summing the product of the applied negative pressure and the duration of LBNP at each stage. HDBR reduced normothermic orthostatic tolerance as indexed by a reduction in the CSI from 1,037 ± 96 mmHg·min to 574 ± 63 mmHg·min (P < 0.05). After HDBR, skin surface cooling increased orthostatic tolerance (797 ± 77 mmHg·min) compared with normothermia (P < 0.05). While the reduction in orthostatic tolerance following prolonged HDBR was not completely reversed by acute skin surface cooling, the identified improvements may serve as an important and effective countermeasure for individuals exposed to microgravity, as well as immobilized and bed-stricken individuals. PMID:21454746

Sex differences in antinociceptive response to Δ-9-tetrahydrocannabinol and CP 55,940 in the mouse formalin test.

PubMed

LaFleur, Rebecca A; Wilson, Ronald P; Morgan, Daniel J; Henderson-Redmond, Angela N

2018-04-11

Cannabinoids have shown promise for the treatment of intractable pain states and may represent an alternative pharmacotherapy for pain management. A growing body of clinical evidence suggests a role for sex in pain perception and in cannabinoid response. We examined cannabinoid sensitivity and tolerance in male and female mice expressing a desensitization-resistant form (S426A/S430A) of the cannabinoid type 1 receptor (CB1R). Mice were assessed for acute and inflammatory nociceptive behaviors in the formalin test following pretreatment with either vehicle or mixed CB1R/CB2R agonists, Δ-9-tetrahydrocannabinol ([INCREMENT]-THC) (1-6 mg/kg) or CP 55,940 (0.06-0.2 mg/kg). Tolerance to the effects of 6 mg/kg [INCREMENT]-THC or 0.1 mg/kg CP 55,940 was examined by the formalin test following chronic daily dosing. Female mice showed decreased sensitivity to the effects of [INCREMENT]-THC and CP 55,940 compared with male mice. The S426A/S430A mutation increased the attenuation of nociceptive behaviors for both agonists in both sexes. Female mice displayed delayed tolerance to [INCREMENT]-THC compared with male mice, whereas the S426A/S430A mutation conferred a delay in tolerance to [INCREMENT]-THC in both sexes. Male S426A/S430A mutant mice also display resistance to tolerance to CP 55,940 compared with wild-type controls. This study demonstrates sex and genotype differences in response for two different cannabinoid agonists. The results underscore the importance of including both male and female mice in preclinical studies of pain and cannabinoid pharmacology.

[A comparative study of the effectiveness and tolerability of a procedure involving slow dose-escalation of rivastigmine in patients with mild or moderate Alzheimer-type dementia: the SCALEX study].

PubMed

Agüera-Ortiz, L F; Ramos-García, M; Gobartt, A L

To determine and to compare the tolerability and effectiveness of a slow escalation of the dose of rivastigmine in patients with Alzheimer's disease with respect to using it with a faster escalation. We conducted a multi-centre, naturalistic, open-label, randomised trial with 429 hospital outpatients diagnosed with Alzheimer-type dementia (according to DSM-IV and NINCDS-ADRA criteria) and in whom treatment with rivastigmine was clinically indicated. Two study groups were established: slow escalation and fast escalation (in accordance with usual clinical practice); effectiveness and tolerability variables were analysed in the two groups, as was the proportion of patients who reached therapeutic doses (> 6 mg/day). The scores obtained on the CGI, MMSE, NPI and Barthel index scales were analysed, together with adverse events and reactions concerning spontaneous communication, and scores on the UKU scale. The slow escalation group displayed slightly higher percentages of sub-therapeutic anticipated interruptions than the fast escalation group (chi-square test; p < 0.05). On comparing the two treatment groups, no statistically significant differences were observed for the evolution of the scores on the different scales of effectiveness; no statistically significant differences were found between the two groups in the safety and tolerability analyses (chi-square test, exact test; p > 0.05) for most of the parameters that were studied (adverse reactions in spontaneous communication and the modified UKU scale). Slow escalation of the dose of rivastigmine did not display greater effectiveness or tolerability in comparison to an escalation applied in accordance with usual clinical practice.

Efficacy and local tolerability of povidone iodine and octenidine hydrochloride solution for the antiseptic preparation of the orificium urethrae.

PubMed

Rudolph, P; Fritze, F; Reimer, K; Klebingat, K J; Kramer, A

1999-01-01

In a randomized clinical study, 61 hospitalized men were examined to test the local tolerability and antimicrobial efficacy of antiseptic treatment of the genitals with povidone iodine versus octenidine hydrochloride solution. Antibacterial efficacy was established by comparing the total aerobic bacterial colony count from standardized swabs from the orificium urethrae externum before, immediately after, and 30 and 60 min after antisepsis. Tolerability was assessed by dermatoscopy, applying a scale to rate the criteria of reddening, erosions and microbleeding. pH-value was taken and the nitracin yellow test carried out at several intervals. Patients assessed sensations (itching, burning, warmth, cold tension) in visual analogue scales. The test for equivalence in efficacy of both antiseptic agents produced no significant result (P = 0.3). The sum score of tolerability produced a better result for povidone iodine. In addition, the drop in the pH value after observed antisepsis with povidone iodine provides an additional protective mechanism against bacterial colonization.

Validation of SILVAH for tolerant hardwoods in Ontario

Treesearch

Jacek Bankowski; Daniel C. Dey; Rice Jim; Eric Boysen; Roj Miller

1995-01-01

SILVAH, a stand growth simulator commonly used in the northeastern United States, has been evaluated by comparing predicted and actual growth of tolerant hardwoods in southern Ontario. The data came from 139 stands, unmanaged or managed (thinned), even-aged or uneven-aged. The data were used to test the accuracy of diameter distribution, basal area, mean quadratic DBH...

Evaluation of Analgesia, Tolerance, and the Mechanism of Action of Morphine-6-O-Sulfate Across Multiple Pain Modalities in Sprague-Dawley Rats.

PubMed

Yadlapalli, Jai Shankar K; Dogra, Navdeep; Walbaum, Anqi W; Wessinger, William D; Prather, Paul L; Crooks, Peter A; Dobretsov, Maxim

2017-09-01

Morphine-6-O-sulfate (M6S) is a mixed μ/δ-opioid receptor (OR) agonist and potential alternative to morphine for treatment of chronic multimodal pain. To provide more support for this hypothesis, the antinociceptive effects of M6S and morphine were compared in tests that access a range of pain modalities, including hot plate threshold (HPT), pinprick sensitivity threshold (PST) and paw pressure threshold tests. Acutely, M6S was 2- to 3-fold more potent than morphine in HPT and PST tests, specifically, derived from best-fit analysis of dose-response relationships of morphine/M6S half-effective dose (ED50) ratios (lower, upper 95% confidence interval [CI]) were 2.8 (2.0-5.8) in HPT and 2.2 (2.1, 2.4) in PST tests. No differences in analgesic drug potencies were detected in the PPT test (morphine/M6S ED50 ratio 1.2 (95% CI, 0.8-1.4). After 7 to 9 days of chronic treatment, tolerance developed to the antinociceptive effects of morphine, but not to M6S, in all 3 pain tests. Morphine-tolerant rats were not crosstolerant to M6S. The antinociceptive effects of M6S were not sensitive to κ-OR antagonists. However, the δ-OR antagonist, naltrindole, blocked M6S-induced antinociception by 55% ± 4% (95% CI, 39-75) in the HPT test, 94% ± 4% (95% CI, 84-105) in the PST test, and 5% ± 17% (95% CI, -47 to 59) or 51% ± 14% (95% CI, 14-84; 6 rats per each group) in the paw pressure threshold test when examined acutely or after 7 days of chronic treatment, respectively. Activity via δ-ORs thus appears to be an important determinant of M6S action. M6S also exhibited favorable antinociceptive and tolerance profiles compared with morphine in 3 different antinociceptive assays, indicating that M6S may serve as a useful alternative for rotation in morphine-tolerant subjects.

Sensitivity and specificity of different methods for cystic fibrosis-related diabetes screening: is the oral glucose tolerance test still the standard?

PubMed

Mainguy, Catherine; Bellon, Gabriel; Delaup, Véronique; Ginoux, Tiphanie; Kassai-Koupai, Behrouz; Mazur, Stéphane; Rabilloud, Muriel; Remontet, Laurent; Reix, Philippe

2017-01-01

Cystic fibrosis-related diabetes (CFRD) is a late cystic fibrosis (CF)-associated comorbidity whose prevalence is increasing sharply lifelong. Guidelines for glucose metabolism (GM) monitoring rely on the oral glucose tolerance test (OGTT). However, this test is neither sensitive nor specific. The aim of this study was to compare sensitivity and specificity of different methods for GM monitoring in children and adolescents with CF. Continuous glucose monitoring system (CGMS), used as the reference method, was compared with the OGTT, intravenous glucose tolerance test (IGTT), homeostasis model assessment index of insulin resistance (HOMA-IR), homeostasis model assessment index of β-cell function (HOMA-%B) and glycated haemoglobin A1C. Patients were classified into three groups according to CGMS: normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes mellitus (DM). Twenty-nine patients (median age: 13.1 years) were recruited. According to CGMS, 11 had DM, 12 IGT and six NGT, whereas OGTT identified three patients with DM and five with IGT. While 13 of 27 had insulin deficiency according to IGTT, there was 19 of 28 according to HOMA-%B. According to HOMA-IR, 12 of 28 had insulin resistance. HOMA-%B was the most sensitive method for CFRD screening [sensitivity 91% (95% CI), specificity 47% (95% CI) and negative predictive value 89% (95% CI)]. OGTT showed the weak capacity to diagnose DM in CF and should no longer be considered as the reference method for CFRD screening in patients with CF. In our study, HOMA-%B showed promising metrics for CFRD screening. Finally, CGMS revealed that pathological glucose excursions were frequent even early in life.

[A study on training method for increasing adaptability to blood redistribution in human].

PubMed

Wu, Bin; You, Guang-xing; Wu, Ping; Xue, Yue-ying; Liu, Xing-hua; Su, Shuang-ning

2003-01-01

To verify validity of the increase in adaptability of blood redistribution in human body with repeated body position change training and to find preferable training method for increasing astronaut's adaptability of blood redistribution. Twelve subjects were randomly divided into group A and B. Six subjects in each group were trained with mode A and B repeated position change (9 times in 11 d) respectively. Their head-down tilt (HDT -30 degrees/30 min) tolerance and orthostatic tolerance were determined before and after training to verify training effects. 1) Two kinds of repeated body position change training modes increased all subjects' HDT tolerance. Compared with pre-training, during HDT test subjects' symptom scores in group B were significantly lower than those in group A (P<0.05) and after training decreasing magnitude of heart rate in group B increased significantly (P<0.01). Then mode B to be preferable training method in increasing HDT tolerance was suggested. 2) Two kinds of training modes improved all subjects' orthostatic tolerance. Compared with pre-training, during orthostatic tolerance test increasing magnitude of mean arterial blood pressure in group B increased significantly (P<0.05) and a trend of increasing magnitude of heart rate in group B was appeared smaller than in group A (P<0.10). Mode B to be preferable training method in increasing orthostatic tolerance was suggested too. Repeated body position change training could increase adaptability to blood redistribution in human body. Mode B was preferable training method and would be hopeful to be used in astronaut training.

Advancing our understanding of plant adaptation to metal polluted environments - new insights from Biscutella laevigata

NASA Astrophysics Data System (ADS)

Babst-Kostecka, Alicja; Waldmann, Patrik; Frérot, Hélène; Vollenweider, Pierre

2016-04-01

The legacy of industrial pollution alters ecosystems, particularly at post-mining sites where metal trace elements have created toxic conditions that trigger rapid plant adaptation. Apart from the purely scientific merits, in-depth knowledge of the mechanisms underlying plant adaptation to metal contamination is beneficial for the economic and societal sectors because of its application in bioengineering (e.g. phytoremediation or biofortification). An important process is the evolution and/or enhancement of metal tolerance, a trait that has predominantly been studied by applying acute metal stress on species that allocate large quantities of certain metals to their foliage (so-called hyperaccumulators). As the vast majority of vascular plants does not hyperaccumulate metals, more efforts are needed to investigate non-hyperaccumulating species and thereby broaden understanding of biological mechanisms underlying metal tolerance. The pseudometallophyte Biscutella laevigata has shown potential in this respect, but its characteristics are insufficiently understood. We determined the zinc tolerance level and various plant responses to environmentally relevant zinc concentrations in ten metallicolous and non-metallicolous B. laevigata populations. In a two-phase hydroponic experiment, we scored multiple morphological and physiological traits (e.g. biomass, visible stress symptoms, element content in foliage) and assessed phenotypic variability within plant families. The structure of these quantitative traits was compared to that of neutral molecular markers to test, whether natural selection caused population differentiation in zinc tolerance. While all genotypes were tolerant compared to a zinc sensitive reference species, we found congruent trends toward higher tolerance in metallicolous compared to non-metallicolous plants. We identified the most indicative parameters for these differences and find that enhanced zinc tolerance in metallicolous populations is driven by divergent selection in response to metal contamination. These findings promote B. laevigata as constitutively zinc tolerant but non-hyperaccumulating organism to study plant adaptation to contaminated environments. Remarkably, tolerance differences between edaphic types emerged already at an environmentally relevant zinc concentration. This opens an unusual perspective on plant adaptation that should be tested in other non-hyperaccumulating species.

Comparative evaluation of the efficacy and tolerability of itopride hydrochloride and domperidone in patients with non-ulcer dyspepsia.

PubMed

Sawant, Prabha; Das, H S; Desai, Nutan; Kalokhe, S; Patil, S

2004-08-01

Prokinetic drugs are widely used for treatment of non-ulcer dyspepsia (NUD). To assess the efficacy and tolerability of a new prokinetic agent, itopride hydrochloride in patients of NUD and compare it with domperidone. Fifty-six patients who fulfilled the inclusion and exclusion criteria were enrolled in the study. Patients underwent upper gastrointestinal endoscopy to rule out organic pathology as a cause for their symptoms. The patient's symptoms were graded on a 4-point scale (0 to 3) at the beginning of treatment and at the end of Week-one and Week-two Patients were randomly allocated to receive either one tablet of itopride hydrochloride 50mg three times daily or one tablet of domperidone 10mg three times daily for two weeks. Pre-treatment and post-treatment hemogram, liver function and renal function tests, prolactin level and ECG were done in all patients. The response to therapy was evaluated by assessing the relief of symptoms at the end of two weeks on a 5-point scale. Statistical analysis was done using two-tailed paired t-test; Wilcoxon matched pairs ranks sum test, Mann-Whitney-U test and chi-square test as applicable. Of the fifty-five patients enrolled in the study (age range of 18-60 yrs, median age of 35yrs), 26 were males and twenty nine were females. They had a median duration of symptoms for 4 weeks. Twenty-seven patients received itopride and 28 received domperidone. One patient did not follow up in the domperidone group, thus 54 patients were evaluable for analysis. Moderate to complete symptomatic relief was observed in 22 (81%) patients in the itopride group and 19 patients (70%) in the domperidone group (p > 0.05, NS). Both the drugs were well tolerated and neither caused prolongation of QT interval nor any abnormality in any serum biochemistry values. Therapy with itopride resulted in good symptomatic relief, was safe, well tolerated and comparable in efficacy to domperidone in relieving the symptoms of NUD. By virtue of its efficacy and tolerability, it could be an ideal choice for providing symptomatic relief to patients suffering from non-ulcer dyspepsia.

The tolerance efficiency of Panicum maximum and Helianthus annuus in TNT-contaminated soil and nZVI-contaminated soil.

PubMed

Jiamjitrpanich, Waraporn; Parkpian, Preeda; Polprasert, Chongrak; Laurent, François; Kosanlavit, Rachain

2012-01-01

This study was designed to compare the initial method for phytoremediation involving germination and transplantation. The study was also to determine the tolerance efficiency of Panicum maximum (Purple guinea grass) and Helianthus annuus (Sunflower) in TNT-contaminated soil and nZVI-contaminated soil. It was found that the transplantation of Panicum maximum and Helianthus annuus was more suitable than germination as the initiate method of nano-phytoremediation potting test. The study also showed that Panicum maximum was more tolerance than Helianthus annuus in TNT and nZVI-contaminated soil. Therefore, Panicum maximum in the transplantation method should be selected as a hyperaccumulated plant for nano-phytoremediation potting tests. Maximum tolerance dosage of Panicum maximum to TNT-concentration soil was 320 mg/kg and nZVI-contaminated soil was 1000 mg/kg in the transplantation method.

Assessing tolerance for wildlife: Clarifying relations between concepts and measures

USGS Publications Warehouse

Bruskotter, Jeremy T.; Singh, Ajay; Fulton, David C.; Slagle, Kristina

2015-01-01

Two parallel lines of inquiry, tolerance for and acceptance of wildlife populations, have arisen in the applied literature on wildlife conservation to assess probability of successfully establishing or increasing populations of controversial species. Neither of these lines is well grounded in social science theory, and diverse measures have been employed to assess tolerance, which inhibits comparability across studies. We empirically tested behavioral measures of tolerance against self-reports of previous policy-relevant behavior and behavioral intentions. Both composite behavioral measures were strongly correlated (r > .70) with two attitudinal measures of tolerance commonly employed in the literature. The strong correlation between attitudinal and behavioral measures suggests existing attitudinal measures represent valid, parsimonious measures of tolerance that may be useful when behavioral measures are too cumbersome or misreporting of behavior is anticipated. Our results demonstrate how behavioral measures of tolerance provide additional, useful information beyond general attitudinal measures.

Using Ice Cream for Diagnosis of Diabetes Mellitus and Impaired Glucose Tolerance: An Alternative to the Oral Glucose Tolerance Test.

PubMed

Chanprasertpinyo, Wandee; Bhirommuang, Nattapimon; Surawattanawiset, Titiporn; Tangsermwong, Thanwarin; Phanachet, Pariya; Sriphrapradang, Chutintorn

2017-12-01

Oral glucose tolerance test (OGTT) is a sensitive and reliable test for diabetes mellitus and impaired glucose tolerance (IGT). However, poor patient tolerance of glucose solutions is common. We aim to compare the diagnostic value of an ice cream test with a standard OGTT. A total of 104 healthy adults were randomly assigned to either 75-g OGTT or ice cream, followed by a crossover to the other test. Most patients were females (71%). Mean age was 37 ± 12 years, and body mass index was 24.2 ± 3.9kg/m 2 . Diabetes mellitus and IGT, as diagnosed by 75-g OGTT, were 4.8% and 6.7%, respectively. The 2-hour plasma glucose levels were 110 ± 55.5mg/dL with 75-g glucose and 97.52 ± 40.7mg/dL with ice cream. The correlation coefficient of 2-hour plasma glucose for the 2 tests was 0.82 (95% CI: 0.75-0.87; P < 0.001). Discordant diagnostic results, based on 2-hour plasma glucose levels, were 9.61%. By using a combination of fasting plasma glucose and 2-hour plasma glucose values, the ice cream test would have missed 5.76% of those at high risk for diabetes mellitus (impaired fasting glucose and IGT) or diabetes. An ice cream test may serve as an alternative to a 75-g OGTT. Before applying this test in clinical practice, it needs to be validated in a larger population. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

The Effect of Four Herbicides on the Survival and Growth of Nine Hardwood Species

Treesearch

Robert D. Williams; John E. Krajicek

1976-01-01

To learn more about the tolerance of hardwoods to herbicides, the survival and growth on nine hardwood species were compared in plots eitehr cultivated or treated with various herbicides applied at different rates, on prepared and unprepared ground, and before and after planting. Black walnut and white oak were very tolerant to all herbicides tested but American...

Development and Event-specific Detection of Transgenic Glyphosate-resistant Rice Expressing the G2-EPSPS Gene

PubMed Central

Dong, Yufeng; Jin, Xi; Tang, Qiaoling; Zhang, Xin; Yang, Jiangtao; Liu, Xiaojing; Cai, Junfeng; Zhang, Xiaobing; Wang, Xujing; Wang, Zhixing

2017-01-01

Glyphosate is a widely used herbicide, due to its broad spectrum, low cost, low toxicity, high efficiency, and non-selective characteristics. Rice farmers rarely use glyphosate as a herbicide, because the crop is sensitive to this chemical. The development of transgenic glyphosate-tolerant rice could greatly improve the economics of rice production. Here, we transformed the Pseudomonas fluorescens G2 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS) gene G2-EPSPS, which conferred tolerance to glyphosate herbicide into a widely used japonica rice cultivar, Zhonghua 11 (ZH11), to develop two highly glyphosate-tolerant transgenic rice lines, G2-6 and G2-7, with one exogenous gene integration. Seed germination tests and glyphosate-tolerance assays of plants grown in a greenhouse showed that the two transgenic lines could greatly improve glyphosate-tolerance compared with the wild-type; The glyphosate-tolerance field test indicated that both transgenic lines could grow at concentrations of 20,000 ppm glyphosate, which is more than 20-times the recommended concentration in the field. Isolation of the flanking sequence of transgenic rice G2-6 indicated that the 5′-terminal of T-DNA was inserted into chromosome 8 of the rice genome. An event-specific PCR test system was established and the limit of detection of the primers reached five copies. Overall, the G2-EPSPS gene significantly improved glyphosate-tolerance in transgenic rice; furthermore, it is a useful candidate gene for the future development of commercial transgenic rice. PMID:28611804

Determination of industrial color tolerance limits: case studies in the textile industry

NASA Astrophysics Data System (ADS)

Gay, Jennifer; Hirschler, Robert

2002-06-01

The approach and findings during the application of instrumental color quality control in industry are described, where the best tolerance formulae and tolerance limits were determined by correlating visual and instrumental evaluations. A panel of previously tested observers evaluated a collection of samples taken from production and color measurements are then compared to these assessments, according to different color difference formulae. T he formula and the limit giving the best agreement with visual evaluations were determined with two different methods. For a large variety of textile substrates, processes and market situations the CMC(2:1) formula was always the best or one of the bests, but the limits varied widely, according to the individual application. Additional shade sorting, based on the tolerance limit, was also applied in several companies. The ideal box size was also determined by comparing visual and instrumental evaluations. The application as logistical tools was established according to individual necessities.

Comparison of the pattern, efficacy, and tolerability of self-medicated drugs in primary dysmenorrhea: a questionnaire based survey.

PubMed

Sugumar, Ramya; Krishnaiah, Vasundara; Channaveera, Gokul Shetty; Mruthyunjaya, Shilpa

2013-01-01

To compare the pattern, efficacy, and tolerability of self-medicated drugs and to assess the adequacy of their dose in primary dysmenorrhea (PD). A survey using a self-developed, validated, objective, and structured questionnaire as a tool was conducted among subjects with PD. Statistical analysis was carried out using Chi-square test and ANOVA with post-hoc Tuckey's test. Out of 641 respondents, 42% were self-medicated. The pattern of drugs used was: Dicyclomine, an unknown drug, mefenamic acid, mefenamic acid + dicyclomine, and metamizole by 35%, 29%, 26%, 9%, and 1% of respondents, respectively. Mefenamic acid + dicyclomine, the combination was the most efficacious in comparison to other drugs in moderate to severe dysmenorrhea. There was better tolerability with mefenamic acid + dicyclomine group compared to other drugs. Sub-therapeutic doses were used by 86% of self-medicating respondents. The prevailing self-medication practices were inappropriate in a substantial proportion of women with inadequate knowledge regarding appropriate drug choice, therapeutic doses, and their associated side effects.

A comparative study on the immunogenicity, safety and tolerance of purified duck embryo vaccine (PDEV) manufactured in India (Vaxirab) and Switzerland (Lyssavac-N): a randomized simulated post-exposure study in healthy volunteers.

PubMed

Mahendra, Bangalore Jayakrishnappa; Madhusudana, Shampur Narayan; Ashwathnarayana, Doddabele Hanumanthaiah; Sampath, Gadey; datta, Soma Subhra; Sudarshan, Mysore Kalappa; Venkatesh, Gonibeedu Manjunatah; Muhamuda, Kader; Bilagumba, Gangaboraiah; Shamanna, Manjula

2007-12-05

Purified duck embryo vaccine (PDEV, Vaxirab) for rabies prophylaxis is now indigenously manufactured in India under technology transfer from Berna Biotech who made the original PDEV (Lyssavac). In the present study we have compared the two vaccines in terms of safety, immunogenicity and tolerance. The study was conducted in 220 adult healthy volunteers. It was observed that both vaccines produced neutralizing antibody titers (as determined by rapid fluorescent focus inhibition test, RFFIT) more than 0.5 IU/mL (minimum level for seroconversion) on all days tested but the titers on days 90 and 180 were significantly higher with Lyssavac. The adverse reactions produced were slightly more with Lysssavac but both vaccines were well tolerated. In conclusion, the indigenously produced PDEV (Vaxirab) was found to be equally safe and immunogenic as the original PDEV (Lyssavac) manufactured at Switzerland.

Thermocouple Calibration and Accuracy in a Materials Testing Laboratory

NASA Technical Reports Server (NTRS)

Lerch, B. A.; Nathal, M. V.; Keller, D. J.

2002-01-01

A consolidation of information has been provided that can be used to define procedures for enhancing and maintaining accuracy in temperature measurements in materials testing laboratories. These studies were restricted to type R and K thermocouples (TCs) tested in air. Thermocouple accuracies, as influenced by calibration methods, thermocouple stability, and manufacturer's tolerances were all quantified in terms of statistical confidence intervals. By calibrating specific TCs the benefits in accuracy can be as great as 6 C or 5X better compared to relying on manufacturer's tolerances. The results emphasize strict reliance on the defined testing protocol and on the need to establish recalibration frequencies in order to maintain these levels of accuracy.

Six-minute stepper test: a valid clinical exercise tolerance test for COPD patients

PubMed Central

Grosbois, JM; Riquier, C; Chehere, B; Coquart, J; Béhal, H; Bart, F; Wallaert, B; Chenivesse, C

2016-01-01

Introduction Exercise tolerance testing is an integral part of the pulmonary rehabilitation (PR) management of patients with chronic obstructive pulmonary disease (COPD). The 6-minute stepper test (6MST) is a new, well-tolerated, reproducible exercise test, which can be performed without any spatial constraints. Objective The aim of this study was to compare the results of the 6MST to those obtained during a 6-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) in a cohort of COPD patients. Methods Ninety-one COPD patients managed by outpatient PR and assessed by 6MST, 6MWT, and CPET were retrospectively included in this study. Correlations between the number of steps on the 6MST, the distance covered on the 6MWT, oxygen consumption, and power at the ventilatory threshold and at maximum effort during CPET were analyzed before starting PR, and the improvement on the 6MST and 6MWT was compared after PR. Results The number of steps on the 6MST was significantly correlated with the distance covered on the 6MWT (r=0.56; P<0.0001), the power at maximum effort (r=0.46; P<0.0001), and oxygen consumption at maximum effort (r=0.39; P<0.005). Performances on the 6MST and 6MWT were significantly improved after PR (570 vs 488 steps, P=0.001 and 448 vs 406 m, respectively; P<0.0001). Improvements of the 6MST and 6MWT after PR were significantly correlated (r=0.34; P=0.03). Conclusion The results of this study show that the 6MST is a valid test to evaluate exercise tolerance in COPD patients. The use of this test in clinical practice appears to be particularly relevant for the assessment of patients managed by home PR. PMID:27099483

Comparative analysis of the cold acclimation and freezing tolerance capacities of seven diploid Brachypodium distachyon accessions

PubMed Central

Colton-Gagnon, Katia; Ali-Benali, Mohamed Ali; Mayer, Boris F.; Dionne, Rachel; Bertrand, Annick; Do Carmo, Sonia; Charron, Jean-Benoit

2014-01-01

Background and Aims Cold is a major constraint for cereal cultivation under temperate climates. Winter-hardy plants interpret seasonal changes and can acquire the ability to resist sub-zero temperatures. This cold acclimation process is associated with physiological, biochemical and molecular alterations in cereals. Brachypodium distachyon is considered a powerful model system to study the response of temperate cereals to adverse environmental conditions. To date, little is known about the cold acclimation and freezing tolerance capacities of Brachypodium. The main objective of this study was to evaluate the cold hardiness of seven diploid Brachypodium accessions. Methods An integrated approach, involving monitoring of phenological indicators along with expression profiling of the major vernalization regulator VRN1 orthologue, was followed. In parallel, soluble sugars and proline contents were determined along with expression profiles of two COR genes in plants exposed to low temperatures. Finally, whole-plant freezing tests were performed to evaluate the freezing tolerance capacity of Brachypodium. Key Results Cold treatment accelerated the transition from the vegetative to the reproductive phase in all diploid Brachypodium accessions tested. In addition, low temperature exposure triggered the gradual accumulation of BradiVRN1 transcripts in all accessions tested. These accessions exhibited a clear cold acclimation response by progressively accumulating proline, sugars and COR gene transcripts. However, whole-plant freezing tests revealed that these seven diploid accessions only have a limited capacity to develop freezing tolerance when compared with winter varieties of temperate cereals such as wheat and barley. Furthermore, little difference in terms of survival was observed among the accessions tested despite their previous classification as either spring or winter genotypes. Conclusions This study is the first to characterize the freezing tolerance capacities of B. distachyon and provides strong evidence that some diploid accessions such as Bd21 have a facultative growth habit. PMID:24323247

Some changes of the heart bioelectric activity at the cosmonauts under the influence of LBNP in the long duration flights.

PubMed

Shelepnevich, S O; Alferova, I V; Golybchicova, Z A

2004-07-01

There was selected the group of the cosmonauts, who carry out long duration flights on the orbital complex "Mir", in which the tolerance of LBNP test was evaluated as poor (by hemodynamic indices--heart rate, arterial pressure, rheoencephalographic indices). The in-depth analysis of the electrocardiogram (in DS leads) indices was carry oiled on possible disturbances of conductivity and dynamics of temporary or amplitude characteristics. Furthermore is carry oiled the comparative estimation of these indices with the results of ECG analysis at the cosmonauts, who tolerance test good. Studies showed that the most informative ECG indices are the R, T-amplitudes and QT-interval. Under the influence of LBNP, especially during rarefactions on 45 and 50 mm Hg was noted reduction in the R, T-amplitude and the relative extension of QT-interval. The directivity of changes in these indices are identical for the cosmonauts with good and poor tolerance of the test; however in flight manifestation of the changes is more significant for the cosmonauts with poor tolerance of LBNP test. Thus, in the formation of orthostatic stability together with the hemodynamic influences take part the bioelectric processes, which are formed in the myocardium.

Opioid tolerance and urine drug testing among initiates of extended-release or long-acting opioids in Food and Drug Administration's Sentinel System.

PubMed

Larochelle, Marc R; Cocoros, Noelle M; Popovic, Jennifer; Dee, Elizabeth C; Kornegay, Cynthia; Ju, Jing; Racoosin, Judith A

A risk evaluation and mitigation strategy for extended-release and long-acting (ER/LA) opioid analgesics was approved by the Food and Drug Administration in 2012. Our objective was to assess frequency of opioid tolerance and urine drug testing for individuals initiating ER/LA opioid analgesics. Retrospective cohort study. Sentinel, a distributed database with electronic healthcare data on >190 million predominantly commercially insured members. Members under age 65 initiating ER/LA opioid analgesics between January 2009 and December 2013. We examined the proportion of opioid-tolerant-only ER/LA opioid analgesic initiates meeting tolerance criteria: receipt of ≥30 mg oxycodone equivalents per day in 7 days prior to the first opioid-tolerant-only dispensing. We separately examined the proportion of new users of extended-release oxycodone (ERO) and other ER/LA opioid analgesics with a claim for a urine drug test in the 30 days prior to, and separately for the 183 days after, dispensing. We identified 79,824 ERO, 7,343 extended-release hydromorphone, and 91,778 transdermal fentanyl opi-oid-tolerant-only episodes. Tolerance criteria were met in 64 percent of ERO, 64 percent of extended-release hydromorphone and 40 percent of transdermal fentanyl episodes. We identified 210,581 incident ERO and 311,660 other ER/LA opioid analgesic episodes. Use of urine drug testing for ERO compared with other ER/LA opioid analgesics was: 4 percent vs 14 percent respectively in the 30 days prior to initiation and 9 percent vs 23 percent respectively in the 183 days following initiation. These results suggest potential areas for improving appropriate ER/LA opioid analgesic prescribing practices.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Young-Ho; Byun, Thak Sang

Accident-tolerant fuels are expected to have considerably longer coping time to respond to the loss of active cooling under severe accidents and, at the same time, have comparable or improved fuel performance during normal operation. The wear resistance of accident tolerant fuels, therefore, needs to be examined to determine the applicability of these cladding candidates to the current operating PWRs because the most common failure of nuclear fuel claddings is still caused by grid-to-rod fretting during normal operations. In this study, reciprocating sliding wear tests on three kinds of cladding candidates for accident-tolerant fuels have been performed to investigate themore » tribological compatibilities of selfmated cladding candidates and to determine the direct applicability of conventional Zirconium-based alloys as supporting structural materials. The friction coefficients of the cladding candidates are strongly influenced by the test environments and coupled materials. The wear test results under water lubrication conditions indicate that the supporting structural materials for the cladding candidates of accident-tolerant fuels need to be replaced with the same cladding materials instead of using conventional Zirconium-based alloys.« less

Evaluation of a Reverse Gradient Garment for prevention of bed-rest deconditioning

NASA Technical Reports Server (NTRS)

Sandler, H.; Dolkas, D.; Newsom, B.; Webb, P.; Annis, J.; Pace, N.; Grunbaum, B. W.

1983-01-01

A Reverse Gradient Garment (RGG) was used to intermittently induce venous pooling in the extremities of a magnitude similar to that seen in going from a lying to standing position during the course of a 15-d period of horizontal bed rest. Venous pooling failed to improve bed-rest-induced losses in +2.5 Gz and +3.0 Gz centrifugation tolerance or to prevent increased heart-rate responses to lower-body negative pressure (LBNP). Four subjects served as controls, four were treated. Tests during the 7-d recovery period showed fluid/electrolyte and body composition values to have returned to pre-bed-rest levels with continued depression of acceleration tolerance times (56% decreased at +2.5 Gz and 74% decreased at +3.0 Gz compared to pre-bed-rest levels) and exaggerated blood insulin response on glucose tolerance testing (blood insulin for treated group increased 95% at 1 h before bed rest and 465% during recovery). This study demonstrates that the physiologic changes after bed rest persist for significant periods of time. Acceleration tolerance time proved to be a sensitive test for the deconditioning process.

Total and free cortisol levels during 1 μg, 25 μg, and 250 μg cosyntropin stimulation tests compared to insulin tolerance test: results of a randomized, prospective, pilot study.

PubMed

Peechakara, Seenia; Bena, James; Clarke, Nigel J; McPhaul, Michael J; Reitz, Richard E; Weil, Robert J; Recinos, Pablo; Kennedy, Laurence; Hamrahian, Amir H

2017-09-01

The appropriate cosyntropin dose during cosyntropin stimulation tests remains uncertain. We conducted a prospective, randomized pilot study to compare 1 μg IV low dose cosyntropin test, 25 μg IM medium dose cosyntropin test, and 250 μg IM standard dose cosyntropin test to evaluate secondary adrenal insufficiency. Insulin tolerance test was used as the gold standard. The study included patients with hypothalamic/pituitary disease (n  = 10) with at least one pituitary axis deficiency other than ACTH deficiency and controls (n  = 12). All tests were done in random order. Sensitivity and specificity were calculated for total cortisol and serum free cortisol cut-off levels during cosyntropin stimulation tests. The median (range) age and F/M sex ratios for patients and controls were 54 years (23-62), 2/8, and 33 years (21-51), 6/6, respectively. The best total cortisol cut-off during low dose cosyntropin test, medium dose cosyntropin test, 30 min and 60 min standard dose cosyntropin test were 14.6 μg/dL (100% sensitivity & specificity), 18.7 μg/dL (100% sensitivity, 88% specificity), 16.1 (100% sensitivity & specificity), and 19.5 μg/dL (100% sensitivity & specificity), respectively. There was no difference in the ROC curve for cortisol values between the cosyntropin stimulation tests (p  > 0.41). Using a cortisol cut-off of 18 μg/dL during cosyntropin stimulation tests, only cortisol level at 30 min during standard dose cosyntropin test provided discrimination similar to insulin tolerance test. The best peak free cortisol cut-off levels were 1 μg/dL for insulin tolerance test, 0.9 μg/dL for low dose cosyntropin test, 0.9 μg/dL for medium dose cosyntropin test, and 0.9 μg/dL and 1.3 μg/dL for 30 min and 60 min standard dose cosyntropin test, respectively. All cosyntropin stimulation tests had excellent correlations with insulin tolerance test, when appropriate cut-offs were used. This pilot study does not suggest an advantage in using 25 μg cosyntropin dose during the cosyntropin stimulation test. A serum free cortisol cut-off of 0.9 μg/dL may be used as pass criterion during low dose cosyntropin test, standard dose cosyntropin test cosyntropin test, and 30 min standard dose cosyntropin test.

A methodology for testing fault-tolerant software

NASA Technical Reports Server (NTRS)

Andrews, D. M.; Mahmood, A.; Mccluskey, E. J.

1985-01-01

A methodology for testing fault tolerant software is presented. There are problems associated with testing fault tolerant software because many errors are masked or corrected by voters, limiter, or automatic channel synchronization. This methodology illustrates how the same strategies used for testing fault tolerant hardware can be applied to testing fault tolerant software. For example, one strategy used in testing fault tolerant hardware is to disable the redundancy during testing. A similar testing strategy is proposed for software, namely, to move the major emphasis on testing earlier in the development cycle (before the redundancy is in place) thus reducing the possibility that undetected errors will be masked when limiters and voters are added.

Identification of a B cell signature associated with renal transplant tolerance in humans

PubMed Central

Newell, Kenneth A.; Asare, Adam; Kirk, Allan D.; Gisler, Trang D.; Bourcier, Kasia; Suthanthiran, Manikkam; Burlingham, William J.; Marks, William H.; Sanz, Ignacio; Lechler, Robert I.; Hernandez-Fuentes, Maria P.; Turka, Laurence A.; Seyfert-Margolis, Vicki L.

2010-01-01

Establishing long-term allograft acceptance without the requirement for continuous immunosuppression, a condition known as allograft tolerance, is a highly desirable therapeutic goal in solid organ transplantation. Determining which recipients would benefit from withdrawal or minimization of immunosuppression would be greatly facilitated by biomarkers predictive of tolerance. In this study, we identified the largest reported cohort to our knowledge of tolerant renal transplant recipients, as defined by stable graft function and receiving no immunosuppression for more than 1 year, and compared their gene expression profiles and peripheral blood lymphocyte subsets with those of subjects with stable graft function who are receiving immunosuppressive drugs as well as healthy controls. In addition to being associated with clinical and phenotypic parameters, renal allograft tolerance was strongly associated with a B cell signature using several assays. Tolerant subjects showed increased expression of multiple B cell differentiation genes, and a set of just 3 of these genes distinguished tolerant from nontolerant recipients in a unique test set of samples. This B cell signature was associated with upregulation of CD20 mRNA in urine sediment cells and elevated numbers of peripheral blood naive and transitional B cells in tolerant participants compared with those receiving immunosuppression. These results point to a critical role for B cells in regulating alloimmunity and provide a candidate set of genes for wider-scale screening of renal transplant recipients. PMID:20501946

Diagnostic value of tolerance-related gene expression measured in the recipient alloantigen-reactive T cell fraction.

PubMed

Lim, Dong-Gyun; Park, Youn-Hee; Kim, Sung-Eun; Jeong, Seong-Hee; Kim, Song-Cheol

2013-08-01

The efficient development of tolerance-inducing therapies and safe reduction of immunosuppression should be supported by early diagnosis and prediction of tolerance in transplantation. Using mouse models of donor-specific tolerance to allogeneic skin and islet grafts we tested whether measurement of tolerance-related gene expression in their alloantigen-reactive peripheral T cell fraction efficiently reflected the tolerance status of recipients. We found that Foxp3, Nrn1, and Klrg1 were preferentially expressed in conditions of tolerance compared with rejection or unmanipulated controls if their expression is measured in CD69(+) T cells prepared from coculture of recipient peripheral T cells and donor antigen-presenting cells. The same pattern of gene expression was observed in recipients grafted with either skin or islets, recipients of different genetic origins, and even those taking immunosuppressive drugs. These findings suggest that the expression of tolerance-related genes in the alloantigen-reactive T cell fraction could be used to detect tolerance in the clinic. Copyright © 2013 Elsevier Inc. All rights reserved.

Prospects for improving the salt tolerance of forest trees: A review

USGS Publications Warehouse

Allen, J.A.; Chambers, J.L.; Stine, M.

1994-01-01

Three major themes related to the improvement of salt tolerance in forest tree species are examined. First, evidence demonstrating that substantial intraspecific variation in salt tolerance exists in many species is presented. This evidence is important because it suggests that efforts to improve salt tolerance through conventional plant breeding techniques are justified. Second, the physiological and genetic mechanisms controlling salt tolerance are discussed briefly. Although salt tolerance involves the integration of numerous physiological processes, there is considerable evidence that differences in the ability to exclude Na+ and Cl- from leaves are the most important factors underlying intraspecific differences in tolerance. It is also becoming apparent that, although salt tolerance is a multigenic trait, major genes play an important role. Third, progress to date in improving salt tolerance of forest tree species is assessed. Compared with agricultural crops, relatively little progress has been made with either conventional or biotechnological methods, but field trials designed to test clones identified as salt tolerant in screening trials are underway now in several countries. We conclude that there is justification for cautious optimism about the prospects for improving salt tolerance in forest tree species.

Increased prevalence of abnormal glucose tolerance among obese siblings of children with type 2 diabetes.

PubMed

Magge, Sheela N; Stettler, Nicolas; Jawad, Abbas F; Levitt Katz, Lorraine E

2009-04-01

To test the hypothesis that overweight siblings of children with type 2 diabetes mellitus (T2DM) have a higher prevalence of abnormal glucose tolerance (AGT) compared with other overweight children. This was a cross-sectional study of overweight (body mass index [BMI] >or= 95(th) percentile) subjects, age 8 to 17 years, with at least 1 sibling age >or= 12 years. The primary outcome was AGT, as assessed by the oral glucose tolerance test (2-hour glucose >or= 140 mg/dL). The secondary outcome was insulin resistance by homeostasis model assessment (HOMA). The sibling (n=20) and control (n=42) groups were similar in terms of age, sex, racial distribution (largely African American), pubertal status, and BMI. The prevalence of AGT in the sibling group was 40.0% (n=8), compared with 14.3% (n=6) in controls (P= .048, Fisher exact test; unadjusted odds ratio=4.0; 95% confidence interval=1.2 to 13.5). Univariate analysis did not identify confounders for either outcome. There were no significant differences in HOMA or hemoglobin A1c between the 2 groups. Overweight siblings of children with T2DM had 4 times greater odds of having AGT compared with other overweight children. This group may represent a particularly high-risk population to target for screening and pediatric T2DM prevention.

Mouse handling limits the impact of stress on metabolic endpoints.

PubMed

Ghosal, Sriparna; Nunley, Amanda; Mahbod, Parinaz; Lewis, Alfor G; Smith, Eric P; Tong, Jenny; D'Alessio, David A; Herman, James P

2015-10-15

Studies focused on end-points that are confounded by stress are best performed under minimally stressful conditions. The objective of this study was to demonstrate the impact of handling designed to reduce animal stress on measurements of glucose tolerance. A cohort of mice (CD1.C57BL/6) naïve to any specific handling was subjected to either a previously described "cup" handling method, or a "tail-picked" method in which the animals were picked up by the tail (as is common for metabolic studies). Following training, an elevated plus maze (EPM) test was performed followed by measurement of blood glucose and plasma corticosterone. A second cohort (CD1.C57BL/6) was rendered obese by exposure to a high fat diet, handled with either the tail-picked or cup method and subjected to an intraperitoneal glucose tolerance test. A third cohort of C57BL/6 mice was exposed to a cup regimen that included a component of massage and was subjected to tests of anxiety-like behavior, glucose homeostasis, and corticosterone secretion. We found that the cup mice showed reduced anxiety-like behaviors in the EPM coupled with a reduction in blood glucose levels compared to mice handled by the tail-picked method. Additionally, cup mice on the high fat diet exhibited improved glucose tolerance compared to tail-picked controls. Finally, we found that the cup/massage group showed lower glucose levels following an overnight fast, and decreased anxiety-like behaviors associated with lower stress-induced plasma corticosterone concentration compared to tail-picked controls. These data demonstrate that application of handling methods that reduce anxiety-like behaviors in mice mitigates the confounding contribution of stress to interpretation of metabolic endpoints (such as glucose tolerance). Copyright © 2015 Elsevier Inc. All rights reserved.

Mouse Handling Limits the Impact of Stress on Metabolic Endpoints

PubMed Central

Ghosal, Sriparna; Nunley, Amanda; Mahbod, Parinaz; Lewis, Alfor G.; Smith, Eric P.; Tong, Jenny; D’Alessio, David A.; Herman, James P.

2015-01-01

Studies focused on end-points that are confounded by stress are best performed under minimally stressful conditions. The objective of this study was to demonstrate the impact of handling designed to reduce animal stress on measurements of glucose tolerance. A cohort of mice (CD1.C57BL/6) naïve to any specific handling were subjected to either a previously described “cup” handling method, or a “tail-picked” method in which the animals were picked up by the tail (as is common for metabolic studies). Following training, an elevated plus maze (EPM) test was performed followed by measurement of blood glucose and plasma corticosterone. A second cohort (CD1.C57BL/6) was rendered obese by exposure to a high fat diet, handled with either the tail-picked or cup method and subjected to an intraperitoneal glucose tolerance test. A third cohort of C57BL/6 mice was exposed to a cup regimen that included a component of massage and was subjected to tests of anxiety-like behavior, glucose homeostasis, and corticosterone secretion. We found that the cup mice showed reduced anxiety-like behaviors in the EPM coupled with a reduction in blood glucose levels compared to mice handled by the tail-picked method. Additionally, cup mice on the high fat diet exhibited improved glucose tolerance compared to tail-picked controls. Finally, we found that the cup/massage group showed lower glucose levels following an overnight fast, and decreased anxiety-like behaviors associated with lower stress-induced plasma corticosterone concentration compared to tail-picked controls. These data demonstrate that application of handling methods that reduce anxiety-like behaviors in mice mitigates the confounding contribution of stress to interpretation of metabolic endpoints (such as glucose tolerance). PMID:26079207

Comparison of efficacies of a dipeptidyl peptidase IV inhibitor and alpha-glucosidase inhibitors in oral carbohydrate and meal tolerance tests and the effects of their combination in mice.

PubMed

Yamazaki, Kazuto; Inoue, Takashi; Yasuda, Nobuyuki; Sato, Yoshiaki; Nagakura, Tadashi; Takenaka, Osamu; Clark, Richard; Saeki, Takao; Tanaka, Isao

2007-05-01

E3024 (3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate) is a dipeptidyl peptidase IV (DPP-IV) inhibitor. Since the target of both DPP-IV inhibitors and alpha-glucosidase inhibitors is the lowering of postprandial hyperglycemia, we compared antihyperglycemic effects for E3024 and alpha-glucosidase inhibitors in various oral carbohydrate and meal tolerance tests using normal mice. In addition, we investigated the combination effects of E3024 and voglibose on blood glucose levels in a meal tolerance test using mice fed a high-fat diet. ER-235516-15 (the trifluoroacetate salt form of E3024, 1 mg/kg) lowered glucose excursions consistently, regardless of the kind of carbohydrate loaded. However, the efficacy of acarbose (10 mg/kg) and of voglibose (0.1 mg/kg) varied with the type of carbohydrate administered. The combination of E3024 (3 mg/kg) and voglibose (0.3 mg/kg) improved glucose tolerance additively, with the highest plasma active glucagon-like peptide-1 levels. This study shows that compared to alpha-glucosidase inhibitors, DPP-IV inhibitors may have more consistent efficacy to reduce postprandial hyperglycemia, independent of the types of carbohydrate contained in a meal, and that the combination of a DPP-IV inhibitor and an alpha-glucosidase inhibitor is expected to be a promising option for lowering postprandial hyperglycemia.

Directional selection on cold tolerance does not constrain plastic capacity in a butterfly.

PubMed

Franke, Kristin; Dierks, Anneke; Fischer, Klaus

2012-12-05

Organisms may respond to environmental change by means of genetic adaptation, phenotypic plasticity or both, which may result in genotype-environment interactions (G x E) if genotypes differ in their phenotypic response. We here specifically target the latter source of variation (i.e. G x E) by comparing plastic responses among lines of the tropical butterfly Bicyclus anynana that had been selected for increased cold tolerance and according controls. Our main aim here was to test the hypothesis that directional selection on cold tolerance will interfere with plastic capacities. Plastic responses to temperature and feeding treatments were strong, with e.g. higher compared to lower temperatures reducing cold tolerance, longevity, pupal mass, and development time. We report a number of statistically significant genotype-environment interactions (i.e. interactions between selection regime and environmental variables), but most of these were not consistent across treatment groups. We found some evidence though for larger plastic responses to different rearing temperatures in the selection compared to the control lines, while plastic responses to different adult temperatures and feeding treatments were overall very similar across selection regimes. Our results indicate that plastic capacities are not always constrained by directional selection (on cold tolerance) and therefore genetic changes in trait means, but may operate independently.

Efficacy and tolerability of short-term specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A (MPL) for children and adolescents.

PubMed

Drachenberg, K J; Heinzkill, M; Urban, E; Woroniecki, S R

2003-01-01

Specific immunotherapy (SIT) with pollen allergoids formulated with the Th1-inducing adjuvant 3-deacylated monophosphoryl lipid A (MPL adjuvant, Corixa) has shown good efficacy and tolerability in the treatment of pollen allergies in adults. The aim of this study was to evaluate this treatment in children and adolescents aged 6-17 years old who were sensitive to grass/rye or tree pollens. An open, multicenter study was performed using 90 children and adolescents. The patients received four subcutaneous injections of grass/rye (n = 64) or tree pollen allergoids (n = 26) adsorbed to L-tyrosine and containing MPL adjuvant. Efficacy was measured by symptom and medication scoring, skin prick test reactivity and IgG/IgE antibody responses. Tolerability was monitored by recording adverse events. Both grass/rye and tree pollen treatment groups showed significant reductions in symptom scores and anti-allergic medication use compared with the previous pollen seasons (p < 0.01 in all cases). After therapy, skin prick test reactivity was significantly reduced in both groups and pollen-specific IgG was significantly increased in both groups whereas little change was apparent in pollen-specific IgE. Overall tolerability was similar to results obtained in previous studies in adults. Short-term SIT using four injections of grass/rye or tree pollen allergoids adsorbed to L-tyrosine and with MPL adjuvant was shown to be effective with good tolerability. The treatment compared favorably with previous studies in adults.

Neck injury tolerance under inertial loads in side impacts.

PubMed

McIntosh, Andrew S; Kallieris, Dimitrios; Frechede, Bertrand

2007-03-01

Neck injury remains a major issue in road safety. Current side impact dummies and side impact crashworthiness assessments do not assess the risk of neck injury. These assessments are limited by biofidelity and knowledge regarding neck injury criteria and tolerance levels in side impacts. Side impact tests with PMHS were performed at the Heidelberg University in the 1980s and 1990s to improve primarily the understanding of trunk dynamics, injury mechanisms and criteria. In order to contribute to the definition of human tolerances at neck level, this study presents an analysis of the head/neck biomechanical parameters that were measured in these tests and their relationship to neck injury severity. Data from 15 impact tests were analysed. Head accelerations, and neck forces and moments were calculated from 9-accelerometer array head data, X-rays and anthropometric data. Statistically significant relationships were observed between resultant head acceleration and neck force and neck injury severity. The average resultant head acceleration for AIS 2 neck injuries was 112 g, while resultant neck force was 4925 N and moment 241 Nm. The data compared well to other test data on cadavers and volunteers. It is hoped that the paper will assist in the understanding of neck injuries and the development of tolerance criteria.

Unmasking glucose metabolism alterations in stable renal transplant recipients: a multicenter study.

PubMed

Delgado, Patricia; Diaz, Juan Manuel; Silva, Irene; Osorio, José M; Osuna, Antonio; Bayés, Beatriz; Lauzurica, Ricardo; Arellano, Edgar; Campistol, Jose Maria; Dominguez, Rosa; Gómez-Alamillo, Carlos; Ibernon, Meritxell; Moreso, Francisco; Benitez, Rocio; Lampreave, Ildefonso; Porrini, Esteban; Torres, Armando

2008-05-01

Emerging information indicates that glucose metabolism alterations are common after renal transplantation and are associated with carotid atheromatosis. The aims of this study were to investigate the prevalence of different glucose metabolism alterations in stable recipients as well as the factors related to the condition. A multicenter, cross-sectional study was conducted of 374 renal transplant recipients without pre- or posttransplantation diabetes. A standard 75-g oral glucose tolerance test was performed. Glucose metabolism alterations were present in 119 (31.8%) recipients: 92 (24.6%) with an abnormal oral glucose tolerance test and 27 (7.2%) with isolated impaired fasting glucose. The most common disorder was impaired glucose tolerance (17.9%), and an abnormal oral glucose tolerance test was observed for 21.5% of recipients with a normal fasting glucose. By multivariate analysis, age, prednisone dosage, triglyceride/high-density lipoprotein cholesterol ratio, and beta blocker use were shown to be factors related to glucose metabolism alterations. Remarkably, triglyceride levels, triglyceride/high-density lipoprotein cholesterol ratio, and the proportion of recipients with impaired fasting glucose were already higher throughout the first posttransplantation year in recipients with a current glucose metabolism alteration as compared with those without the condition. Glucose metabolism alterations are common in stable renal transplant recipients, and an oral glucose tolerance test is required for its detection. They are associated with a worse metabolic profile, which is already present during the first posttransplantation year. These findings may help planning strategies for early detection and intervention.

7 CFR 801.9 - Tolerances for test weight apparatuses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... PERFORMANCE REQUIREMENTS FOR GRAIN INSPECTION EQUIPMENT § 801.9 Tolerances for test weight apparatuses. The maintenance tolerances for test weight per bushel apparatuses used in performing official inspection services... 7 Agriculture 7 2011-01-01 2011-01-01 false Tolerances for test weight apparatuses. 801.9 Section...

7 CFR 801.9 - Tolerances for test weight apparatuses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... PERFORMANCE REQUIREMENTS FOR GRAIN INSPECTION EQUIPMENT § 801.9 Tolerances for test weight apparatuses. The maintenance tolerances for test weight per bushel apparatuses used in performing official inspection services... 7 Agriculture 7 2010-01-01 2010-01-01 false Tolerances for test weight apparatuses. 801.9 Section...

Effects of linagliptin monotherapy compared with voglibose on postprandial blood glucose responses in Japanese patients with type 2 diabetes: Linagliptin Study of Effects on Postprandial blood glucose (L-STEP).

PubMed

Fujitani, Yoshio; Fujimoto, Shimpei; Takahashi, Kiyohito; Satoh, Hiroaki; Hirose, Takahisa; Hiyoshi, Toru; Ai, Masumi; Okada, Yosuke; Gosho, Masahiko; Mita, Tomoya; Watada, Hirotaka

2016-11-01

To compare the efficacy on glycemic parameters between a 12-week administration of once-daily linagliptin and thrice-daily voglibose in Japanese patients with type 2 diabetes. In a multi-center, randomized, parallel-group study, 382 patients with diabetes were randomized to the linagliptin group (n=192) or the voglibose group (n=190). A meal tolerance test was performed at weeks 0 and 12. Primary outcomes were the change from baseline to week 12 in serum glucose levels at 2h during the meal tolerance test, HbA1c levels, and serum fasting glucose levels, which were compared between the 2 groups. Whereas changes in serum glucose levels at 2h during the meal tolerance test did not differ between the groups, the mean change in HbA1c levels from baseline to week 12 in the linagliptin group (-0.5±0.5% [-5.1±5.4mmol/mol]) was significantly larger than in the voglibose group (-0.2±0.5% [-2.7±5.4mmol/mol]). In addition, there was significant difference in changes in serum fasting glucose levels (-0.51±0.95mmol/L in the linagliptin group vs. -0.18±0.92mmol/L in the voglibose group, P<0.001). The incidences of hypoglycemia, serious adverse events (AEs), and discontinuations due to AEs were low and similar in both groups. However, gastrointestinal AEs were significantly lower in the linagliptin group (1.05% vs. 5.85%; P=0.01). These data suggested that linagliptin monotherapy had a stronger glucose-lowering effect than voglibose monotherapy with respect to HbA1c and serum fasting glucose levels, but not serum glucose levels 2h after the start of the meal tolerance test. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Anti-nociceptive interactions between opioids and a cannabinoid receptor 2 agonist in inflammatory pain

PubMed Central

Hale, David E; Guindon, Josée; Morgan, Daniel J

2017-01-01

The cannabinoid 1 receptor and cannabinoid 2 receptor can both be targeted in the treatment of pain; yet, they have some important differences. Cannabinoid 1 receptor is expressed at high levels in the central nervous system, whereas cannabinoid 2 receptor is found predominantly, although not exclusively, outside the central nervous system. The objective of this study was to investigate potential interactions between cannabinoid 2 receptor and the mu-opioid receptor in pathological pain. The low level of adverse side effects and lack of tolerance for cannabinoid 2 receptor agonists are attractive pharmacotherapeutic traits. This study assessed the anti-nociceptive effects of a selective cannabinoid 2 receptor agonist (JWH-133) in pathological pain using mice subjected to inflammatory pain using the formalin test. Furthermore, we examined several ways in which JWH-133 may interact with morphine. JWH-133 produces dose-dependent anti-nociception during both the acute and inflammatory phases of the formalin test. This was observed in both male and female mice. However, a maximally efficacious dose of JWH-133 (1 mg/kg) was not associated with somatic withdrawal symptoms, motor impairment, or hypothermia. After eleven once-daily injections of 1 mg/JWH-133, no tolerance was observed in the formalin test. Cross-tolerance for the anti-nociceptive effects of JWH-133 and morphine were assessed to gain insight into physiologically relevant cannabinoid 2 receptor and mu-opioid receptor interaction. Mice made tolerant to the effects of morphine exhibited a lower JWH-133 response in both phases of the formalin test compared to vehicle-treated morphine-naïve animals. However, repeated daily JWH-133 administration did not cause cross-tolerance for morphine, suggesting opioid and cannabinoid 2 receptor cross-tolerance is unidirectional. However, preliminary data suggest co-administration of JWH-133 with morphine modestly attenuates morphine tolerance. Isobolographic analysis revealed that co-administration of JWH-133 and morphine has an additive effect on anti-nociception in the formalin test. Overall these findings show that cannabinoid 2 receptor may functionally interact with mu-opioid receptor to modulate anti-nociception in the formalin test. PMID:28879802

Comparison of the pattern, efficacy, and tolerability of self-medicated drugs in primary dysmenorrhea: A questionnaire based survey

PubMed Central

Sugumar, Ramya; Krishnaiah, Vasundara; Channaveera, Gokul Shetty; Mruthyunjaya, Shilpa

2013-01-01

Objective: To compare the pattern, efficacy, and tolerability of self-medicated drugs and to assess the adequacy of their dose in primary dysmenorrhea (PD). Materials and Methods: A survey using a self-developed, validated, objective, and structured questionnaire as a tool was conducted among subjects with PD. Statistical analysis was carried out using Chi-square test and ANOVA with post-hoc Tuckey's test. Results: Out of 641 respondents, 42% were self-medicated. The pattern of drugs used was: Dicyclomine, an unknown drug, mefenamic acid, mefenamic acid + dicyclomine, and metamizole by 35%, 29%, 26%, 9%, and 1% of respondents, respectively. Mefenamic acid + dicyclomine, the combination was the most efficacious in comparison to other drugs in moderate to severe dysmenorrhea. There was better tolerability with mefenamic acid + dicyclomine group compared to other drugs. Sub-therapeutic doses were used by 86% of self-medicating respondents. Conclusions: The prevailing self-medication practices were inappropriate in a substantial proportion of women with inadequate knowledge regarding appropriate drug choice, therapeutic doses, and their associated side effects. PMID:23716896

Dietary chromium tripicolinate supplementation reduces glucose concentrations and improves glucose tolerance in normal-weight cats.

PubMed

Appleton, D J; Rand, J S; Sunvold, G D; Priest, J

2002-03-01

The effect of dietary chromium supplementation on glucose and insulin metabolism in healthy, non-obese cats was evaluated. Thirty-two cats were randomly divided into four groups and fed experimental diets consisting of a standard diet with 0 ppb (control), 150 ppb, 300 ppb, or 600 ppb added chromium as chromium tripicolinate. Intravenous glucose tolerance, insulin tolerance and insulin sensitivity tests with minimal model analysis were performed before and after 6 weeks of feeding the test diets. During the glucose tolerance test, glucose concentrations, area under the glucose concentration-time curve, and glucose half-life (300 ppb only), were significantly lower after the trial in cats supplemented with 300 ppb and 600 ppb chromium, compared with values before the trial. Fasting glucose concentrations measured on a different day in the biochemistry profile were also significantly lower after supplementation with 600 ppb chromium. There were no significant differences in insulin concentrations or indices in either the glucose or insulin tolerance tests following chromium supplementation, nor were there any differences between groups before or after the dietary trial.Importantly, this study has shown a small but significant, dose-dependent improvement in glucose tolerance in healthy, non-obese cats supplemented with dietary chromium. Further long-term studies are warranted to determine if the addition of chromium to feline diets is advantageous. Cats most likely to benefit are those with glucose intolerance and insulin resistance from lack of exercise, obesity and old age. Healthy cats at risk of glucose intolerance and diabetes from underlying low insulin sensitivity or genetic factors may also benefit from long-term chromium supplementation. Copyright 2002 ESFM and AAFP.

Plant Distribution Data Show Broader Climatic Limits than Expert-Based Climatic Tolerance Estimates

PubMed Central

Curtis, Caroline A.; Bradley, Bethany A.

2016-01-01

Background Although increasingly sophisticated environmental measures are being applied to species distributions models, the focus remains on using climatic data to provide estimates of habitat suitability. Climatic tolerance estimates based on expert knowledge are available for a wide range of plants via the USDA PLANTS database. We aim to test how climatic tolerance inferred from plant distribution records relates to tolerance estimated by experts. Further, we use this information to identify circumstances when species distributions are more likely to approximate climatic tolerance. Methods We compiled expert knowledge estimates of minimum and maximum precipitation and minimum temperature tolerance for over 1800 conservation plant species from the ‘plant characteristics’ information in the USDA PLANTS database. We derived climatic tolerance from distribution data downloaded from the Global Biodiversity and Information Facility (GBIF) and corresponding climate from WorldClim. We compared expert-derived climatic tolerance to empirical estimates to find the difference between their inferred climate niches (ΔCN), and tested whether ΔCN was influenced by growth form or range size. Results Climate niches calculated from distribution data were significantly broader than expert-based tolerance estimates (Mann-Whitney p values << 0.001). The average plant could tolerate 24 mm lower minimum precipitation, 14 mm higher maximum precipitation, and 7° C lower minimum temperatures based on distribution data relative to expert-based tolerance estimates. Species with larger ranges had greater ΔCN for minimum precipitation and minimum temperature. For maximum precipitation and minimum temperature, forbs and grasses tended to have larger ΔCN while grasses and trees had larger ΔCN for minimum precipitation. Conclusion Our results show that distribution data are consistently broader than USDA PLANTS experts’ knowledge and likely provide more robust estimates of climatic tolerance, especially for widespread forbs and grasses. These findings suggest that widely available expert-based climatic tolerance estimates underrepresent species’ fundamental niche and likely fail to capture the realized niche. PMID:27870859

Cardiopulmonary exercise testing is well tolerated in people with Alzheimer-related cognitive impairment.

PubMed

Billinger, Sandra A; Vidoni, Eric D; Greer, Colby S; Graves, Rasinio S; Mattlage, Anna E; Burns, Jeffrey M

2014-09-01

To retrospectively assess whether cardiopulmonary exercise testing would be well tolerated in individuals with Alzheimer disease (AD) compared with a nondemented peer group. We retrospectively reviewed 575 cardiopulmonary exercise tests (CPETs) in individuals with and without cognitive impairment caused by AD. University medical center. Exercise tests (N=575) were reviewed for nondemented individuals (n=340) and those with AD-related cognitive impairment (n=235). Not applicable. The main outcome measure for this study was reporting the reason for CPET termination. The hypothesis reported was formulated after data collection. We found that in cognitively impaired individuals, CPETs were terminated because of fall risk more often, but that overall test termination was infrequent-5.5% versus 2.1% (P=.04) in peers without cognitive impairment. We recorded 6 cardiovascular and 7 fall risk events in those with AD, compared with 7 cardiovascular and 0 fall risk events in those without cognitive impairment. Our findings support using CPETs to assess peak oxygen consumption in older adults with cognitive impairment caused by AD. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Graded Aerobic Treadmill Testing in Adolescent Traumatic Brain Injury Patients.

PubMed

Cordingley, Dean M; Girardin, Richard; Morissette, Marc P; Reimer, Karen; Leiter, Jeff; Russell, Kelly; Ellis, Michael J

2017-11-01

To examine the safety and tolerability of clinical graded aerobic treadmill testing in recovering adolescent moderate and severe traumatic brain injury (TBI) patients referred to a multidisciplinary pediatric concussion program. We completed a retrospective case series of two moderate and five severe TBI patients (mean age, 17.3 years) who underwent initial Buffalo Concussion Treadmill Testing at a mean time of 71.6 days (range, 55-87) postinjury. Six patients completed one graded aerobic treadmill test each and one patient underwent initial and repeat testing. There were no complications. Five initial treadmill tests were completely tolerated and allowed an accurate assessment of exercise tolerance. Two initial tests were terminated early by the treatment team because of neurological and cardiorespiratory limitations. As a result of testing, two patients were cleared for aerobic exercise as tolerated and four patients were treated with individually tailored submaximal aerobic exercise programs resulting in subjective improvement in residual symptoms and/or exercise tolerance. Repeat treadmill testing in one patient performed after 1 month of treatment with submaximal aerobic exercise prescription was suggestive of improved exercise tolerance. One patient was able to tolerate aerobic exercise following surgery for posterior glottic stenosis. Preliminary results suggest that graded aerobic treadmill testing is a safe, well tolerated, and clinically useful tool to assess exercise tolerance in appropriately selected adolescent patients with TBI. Future prospective studies are needed to evaluate the effect of tailored submaximal aerobic exercise prescription on exercise tolerance and patient outcomes in recovering adolescent moderate and severe TBI patients.

Testing the myth: tolerant dogs and aggressive wolves.

PubMed

Range, Friederike; Ritter, Caroline; Virányi, Zsófia

2015-05-22

Cooperation is thought to be highly dependent on tolerance. For example, it has been suggested that dog-human cooperation has been enabled by selecting dogs for increased tolerance and reduced aggression during the course of domestication ('emotional reactivity hypothesis'). However, based on observations of social interactions among members of captive packs, a few dog-wolf comparisons found contradictory results. In this study, we compared intraspecies aggression and tolerance of dogs and wolves raised and kept under identical conditions by investigating their agonistic behaviours and cofeeding during pair-wise food competition tests, a situation that has been directly linked to cooperation. We found that in wolves, dominant and subordinate members of the dyads monopolized the food and showed agonistic behaviours to a similar extent, whereas in dogs these behaviours were privileges of the high-ranking individuals. The fact that subordinate dogs rarely challenged their higher-ranking partners suggests a steeper dominance hierarchy in dogs than in wolves. Finally, wolves as well as dogs showed only rare and weak aggression towards each other. Therefore, we suggest that wolves are sufficiently tolerant to enable wolf-wolf cooperation, which in turn might have been the basis for the evolution of dog-human cooperation (canine cooperation hypothesis).

Testing the myth: tolerant dogs and aggressive wolves

PubMed Central

Range, Friederike; Ritter, Caroline; Virányi, Zsófia

2015-01-01

Cooperation is thought to be highly dependent on tolerance. For example, it has been suggested that dog–human cooperation has been enabled by selecting dogs for increased tolerance and reduced aggression during the course of domestication (‘emotional reactivity hypothesis’). However, based on observations of social interactions among members of captive packs, a few dog–wolf comparisons found contradictory results. In this study, we compared intraspecies aggression and tolerance of dogs and wolves raised and kept under identical conditions by investigating their agonistic behaviours and cofeeding during pair-wise food competition tests, a situation that has been directly linked to cooperation. We found that in wolves, dominant and subordinate members of the dyads monopolized the food and showed agonistic behaviours to a similar extent, whereas in dogs these behaviours were privileges of the high-ranking individuals. The fact that subordinate dogs rarely challenged their higher-ranking partners suggests a steeper dominance hierarchy in dogs than in wolves. Finally, wolves as well as dogs showed only rare and weak aggression towards each other. Therefore, we suggest that wolves are sufficiently tolerant to enable wolf–wolf cooperation, which in turn might have been the basis for the evolution of dog–human cooperation (canine cooperation hypothesis). PMID:25904666

Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat

PubMed Central

Bobeck, Erin N.; Haseman, Rachel A.; Hong, Dana; Ingram, Susan L.; Morgan, Michael M.

2012-01-01

Systemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists, such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception. In contrast to systemic administration of morphine and fentanyl, microinjection of these drugs into the vlPAG had similar efficacy as measured by similar reductions in maximal antinociception following β-FNA administration. Analysis of tolerance revealed a rightward shift in the dose-response curve to a single pretreatment with morphine, but not fentanyl. Moreover, the magnitude of tolerance to morphine was comparable following one, four, or eight pretreatments. Tolerance to fentanyl also was evident following four or eight microinjections. These data are surprising in that antinociceptive efficacy appears to vary depending on the site of administration. Moreover, the similar efficacy following microinjection of morphine and fentanyl into the vlPAG was associated with comparable tolerance, with the one exception of no tolerance to acute administration of fentanyl. Perspective These data reveal that antinociceptive tolerance following vlPAG administration of opioids develops rapidly, is evident with both morphine and fentanyl, and the magnitude is relatively consistent regardless of the number of pretreatments. PMID:22766006

Exercise Tolerance Testing in a Prospective Cohort of Adolescents with Chronic Fatigue Syndrome and Recovered Controls Following Infectious Mononucleosis

PubMed Central

Katz, Ben Z.; Boas, Steven; Shiraishi, Yukiko; Mears, Cynthia J.; Taylor, Renee

2010-01-01

Objective Six months following acute infectious mononucleosis (IM), 13%, of adolescents meet criteria for chronic fatigue syndrome (CFS). We measured exercise tolerance in adolescents with CFS and controls 6 months following IM. Study design 21 adolescents with CFS 6 months following IM and 21 recovered controls performed a maximal incremental exercise tolerance test with breath-by-breath gas analysis. Values expressed are mean ± standard deviation. Results The adolescents diagnosed with CFS and controls did not differ in age, weight, body-mass index or peak work capacity. Lower VO2 (oxygen consumption) peak percent of predicted was seen in adolescents with CFS compared with controls (CFS 99.3 ± 16.6 vs control 110.7 ± 19.9, p = 0.05). Peak oxygen pulse also was lower in adolescents with CFS compared with recovered controls (CFS 12.4 ± 2.9 vs controls 14.9 ± 4.3, p = 0.03). Conclusions Adolescents with CFS 6 months following IM have a lower degree of fitness and efficiency of exercise than recovered adolescents. Whether these abnormal exercise findings are a cause or effect of CFS is unknown. IM can lead to both fatigue and measurable changes in exercise testing in a subset of adolescents. PMID:20447647

Ultrareliable fault-tolerant control systems

NASA Technical Reports Server (NTRS)

Webster, L. D.; Slykhouse, R. A.; Booth, L. A., Jr.; Carson, T. M.; Davis, G. J.; Howard, J. C.

1984-01-01

It is demonstrated that fault-tolerant computer systems, such as on the Shuttles, based on redundant, independent operation are a viable alternative in fault tolerant system designs. The ultrareliable fault-tolerant control system (UFTCS) was developed and tested in laboratory simulations of an UH-1H helicopter. UFTCS includes asymptotically stable independent control elements in a parallel, cross-linked system environment. Static redundancy provides the fault tolerance. A polling is performed among the computers, with results allowing for time-delay channel variations with tight bounds. When compared with the laboratory and actual flight data for the helicopter, the probability of a fault was, for the first 10 hr of flight given a quintuple computer redundancy, found to be 1 in 290 billion. Two weeks of untended Space Station operations would experience a fault probability of 1 in 24 million. Techniques for avoiding channel divergence problems are identified.

Effect of longitudinal physical training and water immersion on orthostatic tolerance in men

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Dunn, E. R.; Nesvig, C.; Keil, L. C.; Harrison, M. H.

1988-01-01

The effect of six months of moderately intense aerobic training on 60-deg head-up tilt tolerance was assessed before and after 6 hrs of water-immersion deconditioning by comparing the orthostatic and fluid-electrolyte-endocrine responses of five male subjects before and after these tests. It was found that six months of training has no significant effect on 60-deg head-up tilt tolerance. Thus, during pretraining, the water immersion tilt-tolerance was found to decrease from about 74 min before to 34 min after water immersion, while during posttraining, water immersion tilt tolerance decreased from 74 min to 44 min. Fluid-electrolyte-endocrine responses were also essentially the same during all four tilts. Plasma volume decreased by 9.0 to 12.6 percent; plasma sodium and osmotic concentrations were unchanged; and serum protein and plasma renin activity increased.

Computer-Delivered Social Norm Message Increases Pain Tolerance

PubMed Central

Pulvers, Kim; Schroeder, Jacquelyn; Limas, Eleuterio F.; Zhu, Shu-Hong

2013-01-01

Background Few experimental studies have been conducted on social determinants of pain tolerance. Purpose This study tests a brief, computer-delivered social norm message for increasing pain tolerance. Methods Healthy young adults (N=260; 44 % Caucasian; 27 % Hispanic) were randomly assigned into a 2 (social norm)×2 (challenge) cold pressor study, stratified by gender. They received standard instructions or standard instructions plus a message that contained artifically elevated information about typical performance of others. Results Those receiving a social norm message displayed significantly higher pain tolerance, F(1, 255)=26.95, p<.001, ηp2=.10 and pain threshold F(1, 244)=9.81, p=.002, ηp2=.04, but comparable pain intensity, p>.05. There were no interactions between condition and gender on any outcome variables, p>.05. Conclusions Social norms can significantly increase pain tolerance, even with a brief verbal message delivered by a video. PMID:24146086

Adipocytokines and insulin resistance across various degrees of glucose tolerance in pregnancy.

PubMed

Skvarca, A; Tomazic, M; Krhin, B; Blagus, R; Janez, A

2012-01-01

Gestational diabetes mellitus is characterized by progressive insulin resistance. Adipocytokines are thought to be associated with insulin resistance. This cross-sectional study evaluated the associations between serum concentrations of several adipocytokines and insulin resistance at different stages of glucose tolerance in pregnancy, using the homeostasis model assessment of insulin resistance (HOMA-IR) as a reference. According to oral glucose tolerance test results, 74 pregnant women were divided into three groups: normal glucose tolerance (n = 25); intermediate glucose tolerance (n = 19); gestational diabetes mellitus (n = 30). Adiponectin, leptin, resistin, visfatin and retinol-binding protein 4 (RBP4) concentrations were measured using enzyme-linked immuno sorbent assays. Groups were comparable regarding age, week of gestation and body mass index before gestation. There were statistically significant between-group differences in HOMA-IR, but no significant differences regarding serum adipocytokine concentrations. Adipo nectin, leptin, resistin, visfatin and RBP4 were not associated with the degree of glucose tolerance in pregnancy. Concentrations of these adipocytokines are not sufficiently sensitive to replace HOMA- IR in pregnancy.

COHORT CHANGES IN THE SOCIAL DISTRIBUTION OF TOLERANT SEXUAL ATTITUDES

PubMed Central

Pampel, Fred C.

2017-01-01

Though many studies have described societal-wide changes in tolerance for sexual behaviors outside marriage, few have examined how the social distribution of tolerant attitudes has changed. A diffusion-of-innovations approach predicts nonlinear change in the distribution: high SES groups adopt the attitudes first, which produces a positive relationship, but diffusion to other SES groups subsequently weakens the association with SES. I test this argument using the General Social Survey from 1973 to 2014 to compare the SES determinants of attitudes toward premarital sex, extramarital sex, same-gender sex, and teenage sex across 86 cohorts born from around 1900 to 1985. Multilevel age, period, and cohort models support diffusion arguments concerning tolerance of premarital sex by demonstrating that the effects of indicators of SES first strengthen and then weaken across cohorts. Little support emerges for diffusion arguments concerning tolerance of extramarital sex and teenage sex, and preliminary but suggestive support emerges concerning tolerance of same-gender sex. PMID:28533566

Many tests of significance: new methods for controlling type I errors.

PubMed

Keselman, H J; Miller, Charles W; Holland, Burt

2011-12-01

There have been many discussions of how Type I errors should be controlled when many hypotheses are tested (e.g., all possible comparisons of means, correlations, proportions, the coefficients in hierarchical models, etc.). By and large, researchers have adopted familywise (FWER) control, though this practice certainly is not universal. Familywise control is intended to deal with the multiplicity issue of computing many tests of significance, yet such control is conservative--that is, less powerful--compared to per test/hypothesis control. The purpose of our article is to introduce the readership, particularly those readers familiar with issues related to controlling Type I errors when many tests of significance are computed, to newer methods that provide protection from the effects of multiple testing, yet are more powerful than familywise controlling methods. Specifically, we introduce a number of procedures that control the k-FWER. These methods--say, 2-FWER instead of 1-FWER (i.e., FWER)--are equivalent to specifying that the probability of 2 or more false rejections is controlled at .05, whereas FWER controls the probability of any (i.e., 1 or more) false rejections at .05. 2-FWER implicitly tolerates 1 false rejection and makes no explicit attempt to control the probability of its occurrence, unlike FWER, which tolerates no false rejections at all. More generally, k-FWER tolerates k - 1 false rejections, but controls the probability of k or more false rejections at α =.05. We demonstrate with two published data sets how more hypotheses can be rejected with k-FWER methods compared to FWER control.

Intraspecific competition facilitates the evolution of tolerance to insect damage in the perennial plant Solanum carolinense.

PubMed

McNutt, David W; Halpern, Stacey L; Barrows, Kahaili; Underwood, Nora

2012-12-01

Tolerance to herbivory (the degree to which plants maintain fitness after damage) is a key component of plant defense, so understanding how natural selection and evolutionary constraints act on tolerance traits is important to general theories of plant-herbivore interactions. These factors may be affected by plant competition, which often interacts with damage to influence trait expression and fitness. However, few studies have manipulated competitor density to examine the evolutionary effects of competition on tolerance. In this study, we tested whether intraspecific competition affects four aspects of the evolution of tolerance to herbivory in the perennial plant Solanum carolinense: phenotypic expression, expression of genetic variation, the adaptive value of tolerance, and costs of tolerance. We manipulated insect damage and intraspecific competition for clonal lines of S. carolinense in a greenhouse experiment, and measured tolerance in terms of sexual and asexual fitness components. Compared to plants growing at low density, plants growing at high density had greater expression of and genetic variation in tolerance, and experienced greater fitness benefits from tolerance when damaged. Tolerance was not costly for plants growing at either density, and only plants growing at low density benefited from tolerance when undamaged, perhaps due to greater intrinsic growth rates of more tolerant genotypes. These results suggest that competition is likely to facilitate the evolution of tolerance in S. carolinense, and perhaps in other plants that regularly experience competition, while spatio-temporal variation in density may maintain genetic variation in tolerance.

Value of the intravenous and oral glucose tolerance tests for detecting subtle impairments in insulin sensitivity and beta-cell function in former gestational diabetes.

PubMed

Tura, A; Mari, A; Prikoszovich, T; Pacini, G; Kautzky-Willer, A

2008-08-01

Women with former gestational diabetes mellitus (fGDM) often show defects in both insulin sensitivity and beta-cell function but it is not clear which defect plays the major role or which appears first. This might be because fGDM women are often studied as a unique group and not divided according to their glucose tolerance. Different findings might also be the result of using different tests. Our aim was to study insulin sensitivity and beta-cell function with two independent glucose tolerance tests in fGDM women divided according to their glucose tolerance. A total of 108 fGDM women divided into normal glucose tolerance (IGT; N = 82), impaired glucose metabolism (IGM; N = 20) and overt type 2 diabetes (T2DM; N = 6) groups, and 38 healthy control women (CNT) underwent intravenous (IVGTT) and oral glucose tolerance tests (OGTT). Measurements Insulin sensitivity and beta-cell function were assessed by both the IVGTT and the OGTT. Both tests revealed impaired insulin sensitivity in the normotolerant group compared to controls (IVGTT: 4.2 +/- 0.3 vs. 5.4 +/- 0.4 10(-4) min(-1) (microU/ml)(-1); OGTT: 440 +/- 7 vs. 472 +/- 9 ml min(-1) m(-2)). Conversely, no difference was found in beta-cell function from the IVGTT. However, some parameters of beta-cell function by OGTT modelling analysis were found to be impaired: glucose sensitivity (106 +/- 5 vs. 124 +/- 7 pmol min(-1) m(-2) mm(-1), P = 0.0407) and insulin secretion at 5 mm glucose (168 +/- 9 vs. 206 +/- 10 pmol min(-1) m(-2), P = 0.003). Both insulin sensitivity and beta-cell function are impaired in normotolerant fGDM but the subtle defect in beta-cell function is disclosed only by OGTT modelling analysis.

New insights on diabetes in Turner syndrome: results from an observational study in adulthood.

PubMed

Ibarra-Gasparini, Daniela; Altieri, Paola; Scarano, Emanuela; Perri, Annamaria; Morselli-Labate, Antonio M; Pagotto, Uberto; Mazzanti, Laura; Pasquali, Renato; Gambineri, Alessandra

2018-03-01

To explore the characteristics of diabetes mellitus in adults with Turner syndrome. Observational study consisting of a prospective phase after the access of adults with Turner syndrome to the Endocrinology Unit (median period of follow-up 15.6, interquartile range: 12.0-24.5 months) and a retrospective collection of data from the diagnosis of Turner syndrome until the time of access to the Endocrinology Unit. A total of 113 Italian Turner syndrome patients were included in the study. During the prospective phase of the study, each patient underwent physical examination, fasting blood sampling, and an oral glucose tolerance test on a yearly basis. Oral glucose tolerance test was used to perform the diagnosis of diabetes mellitus. Before access to the Endocrinology Unit, diabetes mellitus was diagnosed in two Turner syndrome patients. Another five cases of diabetes mellitus were diagnosed at the first access to the Endocrinology Unit, whereas seven new cases of diabetes mellitus were diagnosed during the prospective phase of the study. At the diagnosis of diabetes mellitus, only one patient had fasting glucose above 126 mg/dL, and only two had an HbA1c value >6.5% (48 mmol/mol). When compared to normo-glucose tolerant patients, the diabetic patients had a significantly lower insulin-to-glucose ratio at 30 and 60 min of the oral glucose tolerance test. In the regression analyses, only age was associated with the development of diabetes mellitus. This study confirms that diabetes mellitus is frequent in Turner syndrome and suggests that it is specific to the syndrome. In addition, this study demonstrates that oral glucose tolerance test is a more sensitive test than HbA1c for the diagnosis of diabetes mellitus in Turner syndrome.

In vitro testing of commercial and potential probiotic lactic acid bacteria.

PubMed

Jensen, Hanne; Grimmer, Stine; Naterstad, Kristine; Axelsson, Lars

2012-02-01

Probiotics are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host. The objective of this study was to investigate the diversity of selected commercial and potential probiotic lactic acid bacteria using common in vitro screening assays such as transit tolerance in the upper human gastrointestinal tract, adhesion capacity to human intestinal cell lines and effect on epithelial barrier function. The selected bacteria include strains of Lactobacillus plantarum, Lactobacillus pentosus, Lactobacillus farciminis, Lactobacillus sakei, Lactobacillus gasseri, Lactobacillus rhamnosus, Lactobacillus reuteri and Pediococcus pentosaceus. Viable counts after simulated gastric transit tolerance showed that L. reuteri strains and P. pentosaceus tolerate gastric juice well, with no reduction of viability, whereas L. pentosus, L. farciminis and L. sakei strains lost viability over 180min. All strains tested tolerate the simulated small intestinal juice well. The bacterial adhesion capacity to human intestinal cells revealed major species and strain differences. Overall, L. plantarum MF1298 and three L. reuteri strains had a significant higher adhesion capacity compared to the other strains tested. All strains, both living and UV-inactivated, had little effect on the epithelial barrier function. However, living L. reuteri strains revealed a tendency to increase the transepithelial electrical resistance (TER) from 6 to 24h. This work demonstrates the diversity of 18 potential probiotic bacteria, with major species and strain specific effects in the in vitro screening assays applied. Overall, L. reuteri strains reveal some interesting characteristics compared to the other strains investigated. Copyright © 2011 Elsevier B.V. All rights reserved.

Contamination avoidance devices for poppettype shutoff valves

NASA Technical Reports Server (NTRS)

Endicott, D. L.

1973-01-01

The determination of the cycle life is reported of the scal closure of a typical poppet-type shutoff valve in an uncontaminated GH2 environment and then compared this component performance with simulated operation with GN2 and LN2 containing controlled amounts of AL2O3 contaminant particles. The original valve design was tested for contamination damage tolerance characteristics under full-flow and cyclic-operating conditions, redesigned to improve the damage tolerance to contaminants, and then retested. The redesigned valve was found to have acceptable tolerance characteristics under all full-flow conditions and cyclic operation with small (25-75 microns) particulate contamination. The tolerance characteristics of the valve under cyclic conditions with large (75-250 microns) particulate contamination was improved but was not found to be completely satisfactory.

Mercury toxicity in the aquatic oligochaete Sparganophilus pearsei. II: Autotomy as a novel form of protection.

PubMed

Vidal, D E; Horne, A J

2003-11-01

Aquatic oligochaetes are commonly used for toxicity testing and for assessment of sediment impairment; some species can be relatively tolerant of sediment contaminants. However, there have been few studies of tolerance mechanisms; most work has focused on behavioral changes. The aquatic oligochaete worm, Sparganophilus pearsei, can be extremely tolerant to mercury in sediments depending on its prior history of exposure. Three S. pearsei populations, differing in their history of mercury exposure and in their tolerance to mercury, were assessed to determine tolerance mechanisms. In mercury-contaminated sediments, tolerant worms accumulated this contaminant in their caudal segments (i.e., their tails), which were then jettisoned via the process of autotomy, thus providing a mechanism of detoxification. This detoxification process appears to require a certain level of tolerance and may represent a novel exposure route for other organisms via feeding on discarded tails or release of accumulated contaminants as the tails decompose. Measurements of tissue mercury concentrations as contaminant body residues for this species (CBRs) are compared to other aquatic invertebrates.

Comparison of tizanidine and morphine with regard to tolerance-developing ability to antinociceptive action.

PubMed

Nabeshima, T; Yamada, S; Sugimoto, A; Matsuno, K; Kameyama, T

1986-10-01

The antinociceptive, tolerance-developing and anti-withdrawal activities of tizanidine [5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzo-thiadiazole] were investigated by comparing its effects with those of morphine and clonidine in tail-flick-, hot plate-, acetic acid-induced writhing-, and naloxone-precipitated withdrawal jumping-tests. The antinociceptive action of tizanidine was not altered by naloxone, while that of morphine was antagonized. Tolerance to the tizanidine-induced antinociceptive action and to motor incoordination was developed by successive administration of tizanidine. In the tizanidine-tolerant mice, the antinociceptive action of morphine was significantly decreased, but not sleeping time induced by pentobarbital. The action of tizanidine was not modified in the morphine-tolerant mice. Tizanidine failed to induce morphine-withdrawal jumping and to inhibit naloxone-precipitated withdrawal jumping in the morphine-dependent mice. Cross tolerance to the antinociceptive action induced by tizanidine and clonidine was developed. These results suggest that alpha 2-adrenoreceptors may be involved in the action mechanism of tizanidine, but not opioid receptors. Functional tolerance to tizanidine action may be developed by successive administration of tizanidine.

Time-dependent relation between smoking cessation and improved exercise tolerance in apparently healthy middle-age men and women.

PubMed

Berkovitch, Anat; Kivity, Shaye; Klempfner, Robert; Segev, Shlomo; Milwidsky, Assi; Goldenberg, Ilan; Sidi, Yechezkel; Maor, Elad

2015-06-01

Smoking is an independent cardiovascular risk factor and correlates with reduced exercise tolerance. However, data on the time dependent effect of smoking cessation on exercise tolerance are limited. We investigated 17,115 men and women who were annually screened at the Institute for Medical Screening of the Chaim Sheba Medical Centre. All subjects had their smoking status documented and performed an exercise stress testing (EST) according to Bruce protocol at each visit. Subjects were divided at baseline into four groups: active smokers (N = 2858), recent quitters (smoking cessation ≤2 years before baseline EST; N = 861), remote quitters (smoking cessation >2 years before the baseline EST; N = 3856) and never smokers (N = 9810). Baseline and follow up EST duration were compared among the four groups. Recent quitters demonstrated a 2.4-fold improvement in their EST duration compared with active smokers (improvement of 24 ± 157 vs. 10 ± 157 s, respectively, p = 0.02). Multivariate logistic regression showed that recent quitters were 26% more likely to improve their exercise tolerance compared with active smokers (95% confidence interval (CI) 1.08-1.47, p = 0.003). Assessing smoking status as a time-dependent covariate during four consecutive visits demonstrated that recent quitters were 17% more likely to improve their exercise tolerance compared with active smokers (95% CI 1.02-1.34, p = 0.02), with a less pronounced benefit among remote quitters (hazard ratio = 1.11, 95% CI 1.02-1.21; p = 0.01). Smoking cessation is independently associated with improved exercise tolerance. The benefits of smoking cessation are evident within the first two years of abstinence. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Experience with the high-intensity sweetener saccharin impairs glucose homeostasis and GLP-1 release in rats

PubMed Central

Swithers, Susan E.; Laboy, Alycia F.; Clark, Kiely; Cooper, Stephanie; Davidson, T.L.

2012-01-01

Previous work from our lab has demonstrated that experience with high-intensity sweeteners in rats leads to increased food intake, body weight gain and adiposity, along with diminished caloric compensation and decreased thermic effect of food. These changes may occur as a result of interfering with learned relations between the sweet taste of food and the caloric or nutritive consequences of consuming those foods. The present experiments determined whether experience with the high-intensity sweetener saccharin versus the caloric sweetener glucose affected blood glucose homeostasis. The results demonstrated that during oral glucose tolerance tests, blood glucose levels were more elevated in animals that had previously consumed the saccharin-sweetened supplements. In contrast, during glucose tolerance tests when a glucose solution was delivered directly into the stomach, no differences in blood glucose levels between the groups were observed. Differences in oral glucose tolerance responses were not accompanied by differences in insulin release; insulin release was similar in animals previously exposed to saccharin and those previously exposed to glucose. However, release of GLP-1 in response to an oral glucose tolerance test, but not to glucose tolerance tests delivered by gavage, was significantly lower in saccharin-exposed animals compared to glucose-exposed animals. Differences in both blood glucose and GLP-1 release in saccharin animals were rapid and transient, and suggest that one mechanism by which exposure to high-intensity sweeteners that interfere with a predictive relation between sweet tastes and calories may impair energy balance is by suppressing GLP-1 release, which could alter glucose homeostasis and reduce satiety. PMID:22561130

Unmasking Glucose Metabolism Alterations in Stable Renal Transplant Recipients: A Multicenter Study

PubMed Central

Delgado, Patricia; Diaz, Juan Manuel; Silva, Irene; Osorio, José M.; Osuna, Antonio; Bayés, Beatriz; Lauzurica, Ricardo; Arellano, Edgar; Campistol, Jose Maria; Dominguez, Rosa; Gómez-Alamillo, Carlos; Ibernon, Meritxell; Moreso, Francisco; Benitez, Rocio; Lampreave, Ildefonso; Porrini, Esteban; Torres, Armando

2008-01-01

Background and objectives: Emerging information indicates that glucose metabolism alterations are common after renal transplantation and are associated with carotid atheromatosis. The aims of this study were to investigate the prevalence of different glucose metabolism alterations in stable recipients as well as the factors related to the condition. Design, setting, participants, & measurements: A multicenter, cross-sectional study was conducted of 374 renal transplant recipients without pre- or posttransplantation diabetes. A standard 75-g oral glucose tolerance test was performed. Results: Glucose metabolism alterations were present in 119 (31.8%) recipients: 92 (24.6%) with an abnormal oral glucose tolerance test and 27 (7.2%) with isolated impaired fasting glucose. The most common disorder was impaired glucose tolerance (17.9%), and an abnormal oral glucose tolerance test was observed for 21.5% of recipients with a normal fasting glucose. By multivariate analysis, age, prednisone dosage, triglyceride/high-density lipoprotein cholesterol ratio, and β blocker use were shown to be factors related to glucose metabolism alterations. Remarkably, triglyceride levels, triglyceride/high-density lipoprotein cholesterol ratio, and the proportion of recipients with impaired fasting glucose were already higher throughout the first posttransplantation year in recipients with a current glucose metabolism alteration as compared with those without the condition. Conclusions: Glucose metabolism alterations are common in stable renal transplant recipients, and an oral glucose tolerance test is required for its detection. They are associated with a worse metabolic profile, which is already present during the first posttransplantation year. These findings may help planning strategies for early detection and intervention. PMID:18322043

Extraversion and pain.

PubMed

Barnes, G E

1975-09-01

According to Eysenck's (1957, 1960, 1967) theory of personality, extroverts are posited as having higher pain thresholds and greater pain tolerance than introverts. The evidence for these hypothesized relationships is reviewed. Findings appear inconclusive in both cases. Probability pooling (Mosteller & Bush, 1954) is therefore performed, grouping the comparable studies and carrying out overall tests of significance. Results support the hypothesized relationships between extraversion and pain threshold and between extraversion and pain tolerance. Possible reasons why certain studies failed to find these results are discussed.

The Evolution of Sulfide Tolerance in the Cyanobacteria

NASA Technical Reports Server (NTRS)

Miller, Scott R.; Bebout, Brad M.; DeVincenzi, Donald L. (Technical Monitor)

2000-01-01

Understanding how the function of extant microorganisms has recorded both their evolutionary histories and their past interactions with the environment is a stated goal of astrobiology. We are taking a multidisciplinary approach to investigate the diversification of sulfide tolerance mechanisms in the cyanobacteria, which vary both in their degree of exposure to sulfide and in their capacity to tolerate this inhibitor of photosynthetic electron transport. Since conditions were very reducing during the first part of Earth's history and detrital sulfides have been found in Archean sediments, mechanisms conferring sulfide tolerance may have been important for the evolutionary success of the ancestors of extant cyanobacteria. Two tolerance mechanisms have been identified in this group: (1) resistance of photosystem II, the principal target of sulfide toxicity; and (2) maintenance of the ability to fix carbon despite photosystem II inhibition by utilizing sulfide as an electron donor in photosystem I - dependent, anoxygenic photosynthesis. We are presently collecting comparative data on aspects of sulfide physiology for laboratory clones isolated from a variety of habitats. These data will be analyzed within a phylogenetic framework inferred from molecular sequence data collected for these clones to test how frequently different mechanisms of tolerance have evolved and which tolerance mechanism evolved first. In addition, by analyzing these physiological data together with environmental sulfide data collected from our research sites using microelectrodes, we can also test whether the breadth of an organism's sulfide tolerance can be predicted from the magnitude of variation in environmental sulfide concentration it has experienced in its recent evolutionary past and whether greater average sulfide concentration and/or temporal variability in sulfide favors the evolution of a particular mechanism of sulfide tolerance.

Effect of saturated fatty acid-rich dietary vegetable oils on lipid profile, antioxidant enzymes and glucose tolerance in diabetic rats

PubMed Central

Kochikuzhyil, Benson Mathai; Devi, Kshama; Fattepur, Santosh Raghunandan

2010-01-01

Objective: To study the effect of saturated fatty acid (SFA)-rich dietary vegetable oils on the lipid profile, endogenous antioxidant enzymes and glucose tolerance in type 2 diabetic rats. Materials and Methods: Type 2 diabetes was induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rats. Twenty-eight-day-old normal (N) and diabetic (D) male Wistar rats were fed for 45 days with a fat-enriched special diet (10%) prepared with coconut oil (CO) – lauric acid-rich SFA, palm oil (PO) – palmitic acid-rich SFA and groundnut oil (GNO) – control (N and D). Lipid profile, endogenous antioxidant enzymes and oral glucose tolerance tests were monitored. Results: D rats fed with CO (D + CO) exhibited a significant decrease in the total cholesterol and non-high-density lipoprotein cholesterol. Besides, they also showed a trend toward improving antioxidant enzymes and glucose tolerance as compared to the D + GNO group, whereas D + PO treatment aggravated the dyslipidemic condition while causing a significant decrease in the superoxide dismutase levels when compared to N rats fed with GNO (N + GNO). D + PO treatment also impaired the glucose tolerance when compared to N + GNO and D + GNO. Conclusion: The type of FA in the dietary oil determines its deleterious or beneficial effects. Lauric acid present in CO may protect against diabetes-induced dyslipidemia. PMID:20871763

The evaluation of the local tolerance of vaginal formulations containing dapivirine using the Slug Mucosal Irritation test and the rabbit vaginal irritation test.

PubMed

Dhondt, Marijke M M; Adriaens, Els; Roey, Jens Van; Remon, Jean Paul

2005-08-01

The purpose of this study was to evaluate the local tolerance of vaginal gels (three gels containing dapivirine, the placebo gel, and Conceptrol) with the Slug Mucosal Irritation test and to compare the results with those of the rabbit vaginal irritation test. The irritation potential on the slug mucosa was assessed by the mucus production caused by a repeated treatment for 5 successive days. Additionally, membrane damage was estimated by the protein and enzyme release. By means of a classification prediction model the formulations were classified into four irritation classes. The effect of a 10-day intravaginal application of the gels on the rabbit vaginal and cervical mucosa was evaluated by means of macroscopic and microscopic examination. The placebo and dapivirine gels induced no irritation of the slug mucosa (low mucus production and protein release, no enzyme release) and no vaginal or cervical irritation in rabbits. Conceptrol caused severe irritation of the slug mucosa (increased mucus production, protein release, and enzyme release) and irritation of the rabbit vagina and cervix. The results obtained with the Slug Mucosal Irritation test were comparable to those of the rabbit vaginal irritation test.

The Effect of Various Concentrations of Nitrous Oxide and Oxygen on the Hypersensitive Gag Reflex.

PubMed

De Veaux, Candace K E; Montagnese, Thomas A; Heima, Masahiro; Aminoshariae, Anita; Mickel, Andre

2016-01-01

The purpose of this study was to compare the effectiveness of various concentrations of N 2 O/O 2 on obtunding a hypersensitive gag reflex. We hypothesized that the administration of nitrous oxide and oxygen would obtund a hypersensitive gag reflex enough to allow a patient to tolerate the placement and holding of a digital x-ray sensor long enough to obtain a dental radiograph. Volunteers claiming to have a hypersensitive gag reflex were first screened to validate their claim and then tested by placing a size 2 digital x-ray sensor in the position for a periapical radiograph of the right mandibular molar area and holding it in place for 10 seconds. Subjects were first tested using room air only, then 30%, 50%, or 70% nitrous oxide until they were able to tolerate the sensor without gagging or discomfort. A visual analog scale was used for subjective responses, and other statistical tests were used to analyze the results. We found that for some subjects, 30% nitrous oxide was sufficient; for others, 50% was needed; and for the remainder of the subjects, 70% was sufficient to tolerate the test. Using a combination of 70% nitrous oxide and 30% oxygen allowed all patients claiming to have a hypersensitive gag reflex to tolerate the placement and holding of a digital x-ray sensor long enough to take a periapical radiograph.

Virtual-Reality Distraction and Cold-Pressor Pain Tolerance: Does Avatar Point of View Matter?

PubMed Central

Herbert, Linda J.; Weiss, Karen E.; Jimeno, Monica

2010-01-01

Abstract This study tested the effects of distraction using virtual-reality (VR) technology on acute pain tolerance in young adults. Forty-one undergraduate students, aged 18–23 years, used a VR head-mounted display helmet, steering wheel, and foot pedal to play an auto racing video game while undergoing exposure to very cold water (cold pressor set at 1°C). Two different game views were tested that were hypothesized to affect the degree to which participants felt “present” in the virtual environment: a first-person view, in which the participant saw the virtual environment through the eyes of the game character being manipulated; and a third-person view, in which the participant viewed the game character from a distance. The length of time participants tolerated the cold-water exposure (pain tolerance) under each distraction condition was compared to a baseline (no distraction) trial. Subjects also rated the degree to which they felt “present” in the virtual environment after each distraction trial. Results demonstrated that participants had significantly higher pain tolerance during both VR-distraction conditions relative to baseline (no distraction) trials. Although participants reported a greater sense of presence during the first-person condition than the third-person condition, pain-tolerance scores associated with the two distraction conditions did not differ. The types of VR applications in which presence may be more or less important are discussed. PMID:20950186

Virtual-reality distraction and cold-pressor pain tolerance: does avatar point of view matter?

PubMed

Dahlquist, Lynnda M; Herbert, Linda J; Weiss, Karen E; Jimeno, Monica

2010-10-01

This study tested the effects of distraction using virtual-reality (VR) technology on acute pain tolerance in young adults. Forty-one undergraduate students, aged 18-23 years, used a VR head-mounted display helmet, steering wheel, and foot pedal to play an auto racing video game while undergoing exposure to very cold water (cold pressor set at 1 °C). Two different game views were tested that were hypothesized to affect the degree to which participants felt "present" in the virtual environment: a first-person view, in which the participant saw the virtual environment through the eyes of the game character being manipulated; and a third-person view, in which the participant viewed the game character from a distance. The length of time participants tolerated the cold-water exposure (pain tolerance) under each distraction condition was compared to a baseline (no distraction) trial. Subjects also rated the degree to which they felt "present" in the virtual environment after each distraction trial. Results demonstrated that participants had significantly higher pain tolerance during both VR-distraction conditions relative to baseline (no distraction) trials. Although participants reported a greater sense of presence during the first-person condition than the third-person condition, pain-tolerance scores associated with the two distraction conditions did not differ. The types of VR applications in which presence may be more or less important are discussed.

Pavlovian control of cross-tolerance between pentobarbital and ethanol.

PubMed

Cappell, H; Roach, C; Poulos, C X

1981-01-01

Tolerance to several effects of a number of drugs has been shown to depend on Pavlovian conditioning processes. Experiment I extended the compensatory conditioning model (Siegel 1975) to tolerance to the hypothermic effect of pentobarbital (30 mg/kg). In Experiment I, rats that acquired hypothermic tolerance in one environment did not display tolerance when tested in an environment not previously associated with drug administration. In Experiment II, rats were made tolerant to the hypothermic effect of pentobarbital (30 mg/kg) and tested for cross-tolerance to ethanol (2.5 g/kg). Cross-tolerance was observed, but it was significantly reduced if the test was in an environment different from the one in which tolerance to pentobarbital was originally acquired. Thus, the compensatory conditioning model accounts for at least part of the tolerance and cross-tolerance to the thermic effects of alcohol and pentobarbital. The physiological processes in the CNS underlying tolerance and cross-tolerance for these drugs, therefore, are controlled by associative processes.

Promises and challenges of eco-physiological genomics in the field: Tests of drought responses in switchgrass

USDA-ARS?s Scientific Manuscript database

Knowledge of the physiological and genetic basis of stress tolerance has proven to be critical to understanding adaptation in both agricultural and natural systems. However, many discoveries were initially made in controlled conditions or laboratories, not in the field. To test the comparability o...

Primary hypolactasia diagnosis: Comparison between the gaxilose test, shortened lactose tolerance test, and clinical parameters corresponding to the C/T-13910 polymorphism.

PubMed

Domínguez Jiménez, José Luis; Fernández Suárez, Antonio; Muñoz Colmenero, Aurora Úrsula; Fatela Cantillo, Daniel; López Pelayo, Iratxe

2017-04-01

There is no consensus on the most accurate method to diagnose primary hypolactasia. We aimed to compare the diagnostic accuracy of the new gaxilose test with 2 traditional tests (lactose tolerance test and clinical criteria) for the diagnosis of primary hypolactasia using the C/T-13910 polymorphism as a reference standard. Patients with a clinical suspicion of lactose intolerance were subjected to gaxilose tests, shortened lactose tolerance tests, and symptom questionnaires before and after overload with 50 g lactose and after a lactose-free diet. The diagnostic accuracy and degree of agreement and correlation were assessed using a genetic test (C/T-13910 polymorphism) as a reference standard and their respective 95% confidence intervals. Thirty consecutive patients (70% women) participated in the study. The genetic test confirmed the C/T-13910 polymorphism in 11 patients (36.8%). The presence of diarrhoea and the symptom score after lactose overload, along with the tolerance test, were the variables with the highest degree of agreement (κ > 0.60). Area under the ROC curve was >0.82 (p < 0.05), with sensitivity and specificity values of >0.80. However, the gaxilose test obtained lower values: κ, 0.47; area under curve, 0.75 (0.57-0.94); sensitivity, 0.82 (0.55-1); and specificity, 0.68 (0.45-0.92). The multivariate analysis showed an association between the post-overload symptom questionnaire and the results of the genetic test (odds ratio: 1.17; 1.04-1.31; p < 0.01). The presence of diarrhoea and the symptom score after overload with 50 g lactose showed a higher degree of agreement and diagnostic accuracy for primary hypolactasia than the gaxilose test when the genetic test is used as a reference standard. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Sequence-Based Analysis of Thermal Adaptation and Protein Energy Landscapes in an Invasive Blue Mussel (Mytilus galloprovincialis).

PubMed

Saarman, Norah P; Kober, Kord M; Simison, W Brian; Pogson, Grant H

2017-10-01

Adaptive responses to thermal stress in poikilotherms plays an important role in determining competitive ability and species distributions. Amino acid substitutions that affect protein stability and modify the thermal optima of orthologous proteins may be particularly important in this context. Here, we examine a set of 2,770 protein-coding genes to determine if proteins in a highly invasive heat tolerant blue mussel (Mytilus galloprovincialis) contain signals of adaptive increases in protein stability relative to orthologs in a more cold tolerant M. trossulus. Such thermal adaptations might help to explain, mechanistically, the success with which the invasive marine mussel M. galloprovincialis has displaced native species in contact zones in the eastern (California) and western (Japan) Pacific. We tested for stabilizing amino acid substitutions in warm tolerant M. galloprovincialis relative to cold tolerant M. trossulus with a generalized linear model that compares in silico estimates of recent changes in protein stability among closely related congeners. Fixed substitutions in M. galloprovincialis were 3,180.0 calories per mol per substitution more stabilizing at genes with both elevated dN/dS ratios and transcriptional responses to heat stress, and 705.8 calories per mol per substitution more stabilizing across all 2,770 loci investigated. Amino acid substitutions concentrated in a small number of genes were more stabilizing in M. galloprovincialis compared with cold tolerant M. trossulus. We also tested for, but did not find, enrichment of a priori GO terms in genes with elevated dN/dS ratios in M. galloprovincialis. This might indicate that selection for thermodynamic stability is generic across all lineages, and suggests that the high change in estimated protein stability that we observed in M. galloprovincialis is driven by selection for extra stabilizing substitutions, rather than by higher incidence of selection in a greater number of genes in this lineage. Nonetheless, our finding of more stabilizing amino acid changes in the warm adapted lineage is important because it suggests that adaption for thermal stability has contributed to M. galloprovincialis' superior tolerance to heat stress, and that pairing tests for positive selection and tests for transcriptional response to heat stress can identify candidates of protein stability adaptation. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The comparative evidence for urban species sorting by anthropogenic noise

PubMed Central

Hu, Yang

2018-01-01

Anthropogenic noise is more intense at lower sound frequencies, which could decrease urban tolerance of animals with low-frequency vocalizations. Four large comparative studies tested whether anthropogenic noise filters bird species according to the sound frequencies they use and produced discrepant results. We reanalysed data from these studies to explain their different results. Urban tolerance of bird species (defined here as often occurring and breeding in cities) is very weakly related to urban preference or relative abundance (defined based on changes in population density from urban to nearby rural environments). Data on urban preference/abundance are potentially accurate for individual cities but differ among cities for the same species, whereas existing data on urban tolerance are coarser but provide a more global synthesis. Cross-species comparisons find a positive association between the sound frequency of song and urban tolerance, but not urban preference/abundance. We found that showing an association between song frequency and urban tolerance requires controlling for additional species traits that influence urban living. On the contrary, controlling for other species traits is not required to show a positive association between song frequency and use of noisy relative to quiet areas within the same type of environment. Together, comparative evidence indicates that masking by urban noise is part of a larger set of factors influencing urban living: all else being equal, species with high-frequency sounds are more likely to tolerate cities than species with low-frequency sounds, but they are not more likely to prefer, or to be more abundant in, urban than non-urban habitats. PMID:29515901

The comparative evidence for urban species sorting by anthropogenic noise.

PubMed

Cardoso, Gonçalo C; Hu, Yang; Francis, Clinton D

2018-02-01

Anthropogenic noise is more intense at lower sound frequencies, which could decrease urban tolerance of animals with low-frequency vocalizations. Four large comparative studies tested whether anthropogenic noise filters bird species according to the sound frequencies they use and produced discrepant results. We reanalysed data from these studies to explain their different results. Urban tolerance of bird species (defined here as often occurring and breeding in cities) is very weakly related to urban preference or relative abundance (defined based on changes in population density from urban to nearby rural environments). Data on urban preference/abundance are potentially accurate for individual cities but differ among cities for the same species, whereas existing data on urban tolerance are coarser but provide a more global synthesis. Cross-species comparisons find a positive association between the sound frequency of song and urban tolerance, but not urban preference/abundance. We found that showing an association between song frequency and urban tolerance requires controlling for additional species traits that influence urban living. On the contrary, controlling for other species traits is not required to show a positive association between song frequency and use of noisy relative to quiet areas within the same type of environment. Together, comparative evidence indicates that masking by urban noise is part of a larger set of factors influencing urban living: all else being equal, species with high-frequency sounds are more likely to tolerate cities than species with low-frequency sounds, but they are not more likely to prefer, or to be more abundant in, urban than non-urban habitats.

Mixed-Meal Tolerance Test Versus Glucagon Stimulation Test for the Assessment of β-Cell Function in Therapeutic Trials in Type 1 Diabetes

PubMed Central

Greenbaum, Carla J.; Mandrup-Poulsen, Thomas; McGee, Paula Friedenberg; Battelino, Tadej; Haastert, Burkhard; Ludvigsson, Johnny; Pozzilli, Paolo; Lachin, John M.; Kolb, Hubert

2008-01-01

OBJECTIVE—β-Cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. RESEARCH DESIGN AND METHODS—In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs. RESULTS—Among individuals with up to 4 years’ duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R2 = 0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT, and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age-group. CONCLUSIONS—The MMTT is preferred for the assessment of β-cell function in therapeutic trials in type 1 diabetes. PMID:18628574

Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.

PubMed

Greenbaum, Carla J; Mandrup-Poulsen, Thomas; McGee, Paula Friedenberg; Battelino, Tadej; Haastert, Burkhard; Ludvigsson, Johnny; Pozzilli, Paolo; Lachin, John M; Kolb, Hubert

2008-10-01

Beta-cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs. Among individuals with up to 4 years' duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R(2) = 0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT, and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age-group. The MMTT is preferred for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.

A comparative framework for maneuverability and gust tolerance of aerial microsystems

NASA Astrophysics Data System (ADS)

Campbell, Renee

Aerial microsystems have the potential of navigating low-altitude, cluttered environments such as urban corridors and building interiors. Reliable systems require both agility and tolerance to gusts. While many platform designs are under development, no framework currently exists to quantitatively assess these inherent bare airframe characteristics which are independent of closed loop controllers. This research develops a method to quantify the maneuverability and gust tolerance of vehicles using reachability and disturbance sensitivity sets. The method is applied to a stable flybar helicopter and an unstable flybarless helicopter, whose state space models were formed through system identification. Model-based static H∞ controllers were also implemented on the vehicles and tested in the lab using fan-generated gusts. It is shown that the flybar restricts the bare airframe's ability to maneuver in translational velocity directions. As such, the flybarless helicopter proved more maneuverable and gust tolerant than the flybar helicopter. This approach was specifically applied here to compare stable and unstable helicopter platforms; however, the framework may be used to assess a broad range of aerial microsystems.

Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura

PubMed Central

Yu, Jin; Heck, Susanne; Patel, Vivek; Levan, Jared; Yu, Yu; Bussel, James B.

2008-01-01

Immune thrombocytopenic purpura (ITP) is characterized by the presence of antiplatelet autoantibodies as a result of loss of tolerance. CD4+CD25+ regulatory T cells (Tregs) are important for maintenance of peripheral tolerance. Decreased levels of peripheral Tregs in patients with ITP have been reported. To test whether inefficient production or reduced immunosuppressive activity of Tregs contributes to loss of tolerance in patients with chronic ITP, we investigated the frequency and function of their circulating CD4+CD25hi Tregs. We found a com-parable frequency of circulating CD4+CD25hiFoxp3+ Tregs in patients and controls (n = 16, P > .05). However, sorted CD4+CD25hi cells from patients with chronic ITP (n = 13) had a 2-fold reduction of in vitro immunosuppressive activity compared with controls (n = 10, P < .05). The impaired suppression was specific to Tregs as shown by cross-mixing experiments with T cells from controls. These data suggest that functional defects in Tregs contribute to breakdown of self-tolerance in patients with chronic ITP. PMID:18420827

Effect of mental stress on cold pain in chronic tension-type headache sufferers.

PubMed

Cathcart, Stuart; Winefield, Anthony H; Lushington, Kurt; Rolan, Paul

2009-10-01

Mental stress is a noted contributing factor in chronic tension-type headache (CTH), however the mechanisms underlying this are not clearly understood. One proposition is that stress aggravates already increased pain sensitivity in CTH sufferers. This hypothesis could be partially tested by examining effects of mental stress on threshold and supra-threshold experimental pain processing in CTH sufferers. Such studies have not been reported to date. The present study measured pain detection and tolerance thresholds and ratings of supra-threshold pain stimulation from cold pressor test in CTH sufferers (CTH-S) and healthy Control (CNT) subjects exposed to a 60-min stressful mental task, and in CTH sufferers exposed to a 60-min neutral condition (CTH-N). Headache sufferers had lower pain tolerance thresholds and increased pain intensity ratings compared to controls. Pain detection and tolerance thresholds decreased and pain intensity ratings increased during the stress task, with a greater reduction in pain detection threshold and increase in pain intensity ratings in the CTH-S compared to CNT group. The results support the hypothesis that mental stress contributes to CTH through aggravating already increased pain sensitivity in CTH sufferers.

Gas insufflation of minimal preparation CT of the colon reduces false-positives

PubMed Central

Slater, A; North, M; Hart, M; Ferrett, C

2012-01-01

Objectives Minimal preparation CT of the colon (MPCT colon) is used for investigation of suspected colorectal cancer in frail and/or elderly patients who would be expected to tolerate laxative bowel preparation poorly. Although it has good sensitivity for colorectal cancer it has a poor specificity. We wished to investigate whether distension of the colon with carbon dioxide alone would reduce the number of false-positives, but without making the test arduous or excessively uncomfortable. Methods 134 patients were recruited and underwent MPCT colon with gas insufflation and antispasmodics. Results were compared with a cohort of 134 patients undergoing standard protocol MPCT colon. The numbers of false-positives were compared, as was reader confidence. All trial patients were given a questionnaire documenting their experience. Results The number of false-positives was 15% in the control group and 5% in the trial group; this difference was statistically significant, (p=0.01). Reader confidence was increased in the trial group. Patient tolerance was good, with 95% saying they would have the test again. Conclusion Use of gas insufflation and antispasmodics reduces the false-positives from 15% to 5% without adversely affecting patient tolerance. PMID:21224295

Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats.

PubMed

Wang, Jing-Hua; Bose, Shambhunath; Lim, Soo-Kyoung; Ansari, AbuZar; Chin, Young-Won; Choi, Han Seok; Kim, Hojun

2017-09-22

Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))-the same as metformin alone. Particularly, results of the insulin tolerance test (ITT) showed that combining HCE + metformin dramatically improved insulin sensitivity as compared to metformin treatment alone. Both fecal and serum endotoxin, as well as cytokines (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)) were significantly ameliorated by HCE + metformin compared to metformin alone. Meanwhile, the activation of AMPK (adenosine monophosphate-activated protein kinase) by metformin was distinctly enhanced by HCE. Both of HCE and metformin evidently changed the gut microbiota composition, causing the alteration of bacterial metabolite, like short-chain fatty acids. H. cordata , together with metformin, exerts intensive sensibilization to insulin; the corresponding mechanisms are associated with alleviation of endotoxemia via regulation of gut microbiota, particularly Roseburia , Akkermansia , and Gram-negative bacterium.

Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats

PubMed Central

Bose, Shambhunath; Lim, Soo-Kyoung; Ansari, AbuZar; Chin, Young-Won; Choi, Han Seok; Kim, Hojun

2017-01-01

Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long–Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))—the same as metformin alone. Particularly, results of the insulin tolerance test (ITT) showed that combining HCE + metformin dramatically improved insulin sensitivity as compared to metformin treatment alone. Both fecal and serum endotoxin, as well as cytokines (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)) were significantly ameliorated by HCE + metformin compared to metformin alone. Meanwhile, the activation of AMPK (adenosine monophosphate-activated protein kinase) by metformin was distinctly enhanced by HCE. Both of HCE and metformin evidently changed the gut microbiota composition, causing the alteration of bacterial metabolite, like short-chain fatty acids. H. cordata, together with metformin, exerts intensive sensibilization to insulin; the corresponding mechanisms are associated with alleviation of endotoxemia via regulation of gut microbiota, particularly Roseburia, Akkermansia, and Gram-negative bacterium. PMID:28937612

Comparative study of HbA1c and fasting plasma glucose vs the oral glucose tolerance test for diagnosis of diabetes in people with tuberculosis.

PubMed

Aftab, H; Ambreen, A; Jamil, M; Garred, P; Petersen, J H; Nielsen, S D; Bygbjerg, I C; Christensen, D L

2017-06-01

To compare HbA 1c and fasting plasma glucose assessment, with the 2-h oral glucose tolerance test as reference, in screening for diabetes in people with turberculosis. Individuals (N=268) with newly diagnosed smear-positive tuberculosis were screened for diabetes at a tertiary hospital in Lahore, Pakistan. Diabetes diagnosis was based on WHO criteria: thresholds were ≥48 mmol/mol (≥6.5%) for HbA 1c and ≥7.0mmol/l for fasting plasma glucose. The proportion of participants diagnosed with diabetes was 4.9% (n =13) by oral glucose tolerance test, while 11.9% (n =32) and 14.6% (n =39) were diagnosed with diabetes using HbA 1c and fasting plasma glucose criteria, respectively. The area under the receiver-operating characteristic curve was 0.79 (95% CI 0.64 to 0.94) for HbA 1c and 0.61 (95% CI 0.50 to 0.73) for fasting plasma glucose, with a borderline significant difference between the two tests (P=0.07). HbA 1c and fasting plasma glucose performed equally in terms of diagnosing new diabetes cases in individuals with tuberculosis, but the proportion of participants falsely classified as positive was higher for fasting plasma glucose. This may be explained by acute blood glucose fluctuations when using fasting plasma glucose. HbA 1c may be a more reliable test in individuals with transient hyperglycaemia. © 2017 Diabetes UK.

Mycoprotein reduces glycemia and insulinemia when taken with an oral-glucose-tolerance test.

PubMed

Turnbull, W H; Ward, T

1995-01-01

This study investigated the effects of mycoprotein, a food produced by the continuous fermentation of Fusarium graminearum (Schwabe), on acute glycemia and insulinemia in normal healthy individuals. Subjects participated in two single-meal study periods in a crossover design. After an overnight fast, subjects were given milkshakes containing mycoprotein or a control substance, which were isoenergetic and nutrient balanced. Each milkshake contained 75 g carbohydrate, equivalent to a standard World Health Organization oral-glucose-tolerance test. Blood samples were taken fasting and at 30, 60, 90, and 120 min postprandially for the measurement of serum glucose and insulin. Glycemia was reduced postmeal after mycoprotein compared with the control and was statistically significant at 60 min (13% reduction). Insulinemia was reduced postmeal after mycoprotein compared with the control and was statistically significant at 30 min (19% reduction) and 60 min (36% reduction) postmeal. These results may be significant in the dietary treatment of diabetes.

Can HbA1c be Used to Screen for Glucose Abnormalities Among Adults with Severe Mental Illness?

PubMed

Romain, A J; Letendre, E; Akrass, Z; Avignon, A; Karelis, A D; Sultan, A; Abdel-Baki, A

2017-04-01

Aim: Prediabetes and type 2 diabetes are highly prevalent among individuals with serious mental illness and increased by antipsychotic medication. Although widely recommended, many obstacles prevent these patients from obtaining a proper screening for dysglycemia. Currently, glycated hemoglobin (HbA1c), fasting glucose, and 2-hour glucose levels from the oral glucose tolerance test are used for screening prediabetes and type 2 diabetes. The objective of this study was to investigate if HbA1c could be used as the only screening test among individuals with serious mental illness. Methods: Cross sectional study comparing the sensitivity of HbA1c, fasting glucose, and 2-h oral glucose tolerance test to detect dysglycemias in serious mental illness participants referred for metabolic complications. Results: A total of 84 participants (43 female; aged: 38.5±12.8 years; BMI: 35.0±6.8 kg/m²) was included. Regarding prediabetes, 44, 44 and 76% were identified by HbA1c, fasting glucose, and 2 h- oral glucose tolerance test respectively and for type 2 diabetes, 60, 53 and 66% were identified by HbA1c, fasting glucose and 2 h-oral glucose tolerance test. The overlap between the 3 markers was low (8% of participants for prediabetes and 26% for Type 2 diabetes). Sensitivity of HbA1c were moderate (range 40-62.5%), while its specificity was excellent (92-93%). Conclusion: The present study indicates a low agreement between HbA1c, fasting glucose and 2-h oral glucose tolerance test. It appears that these markers do not identify the same participants. Thus, HbA1c may not be used alone to detect all glucose abnormalities among individuals with serious mental illness. © Georg Thieme Verlag KG Stuttgart · New York.

Acute tolerance to spinally administered morphine compares mechanistically with chronically induced morphine tolerance.

PubMed

Fairbanks, C A; Wilcox, G L

1997-09-01

The mechanistic similarity between acutely and chronically induced morphine tolerance has been previously proposed but remains largely unexplored. Our experiments examined the modulation of acutely induced tolerance to spinally administered morphine by agonists that affect the N-methyl-D-aspartate receptor and nitric oxide synthase systems. Antinociception was detected via the hot water (52.5 degrees C) tail flick test in mice. Intrathecal pretreatment with morphine (40 nmol) produced a 9.6-fold rightward shift in the morphine dose-response curve. This shift confirmed the induction of acute spinal morphine tolerance. Intrathecal copretreatment with the receptor antagonists (competitive and noncompetitive, respectively) dizolcipine (MK801, 3 nmol) or LY235959 (4 pmol) and morphine [40 nmol, intrathecally (i.t.)] attenuated acute tolerance to morphine measured 8 hr later. A 60-min pretreatment of 7-nitroindazole (6 nmol, i.t.), a selective neuronal NOS inhibitor, followed by administration of morphine (40 nmol, i.t.) blocked the induction of morphine tolerance. Intrathecal copretreatment with morphine (40 nmol, i.t.) and agmatine (4 nmol, i.t.), an imidazoline, receptor agonist and putative nitric oxide synthase inhibitor, almost completely abolished acute spinal morphine tolerance. The results of these experiments agree with previous reports using models of chronically induced morphine tolerance. This evidence supports the proposal that the mechanisms responsible for acute morphine tolerance parallel those underlying chronic morphine tolerance. This study attests to the powerful predictive value of acute induction as a model for morphine tolerance.

Immunogenicity testing of therapeutic antibodies in ocular fluids after intravitreal injection.

PubMed

Wessels, Uwe; Zadak, Markus; Reiser, Astrid; Brockhaus, Janis; Ritter, Mirko; Abdolzade-Bavil, Afsaneh; Heinrich, Julia; Stubenrauch, Kay

2018-04-11

High drug concentrations in ocular fluids after intravitreal administration preclude the use of drug-sensitive immunoassays. A drug-tolerant immunoassay is therefore desirable for immunogenicity testing in ophthalmology. Immune complex (IC) antidrug antibody (ADA) assays were established for two species. The assays were compared with the bridging assay in ocular and plasma samples from two preclinical studies. The IC assays showed high drug tolerance, which enabled a reliable ADA detection in ocular fluids after intravitreal administration. The IC assays were superior to the bridging assay in the analysis of ocular fluids with high drug concentrations. The IC assay allows a reliable ADA detection in matrices with high drug concentrations, such as ocular fluids.

Laser and Pressure Resistance Weld of Thin-Wall Cladding for LWR Accident-Tolerant Fuels

NASA Astrophysics Data System (ADS)

Gan, J.; Jerred, N.; Perez, E.; Haggard, D. C.

2017-12-01

FeCrAl alloy with typical composition of approximately Fe-15Cr-5Al is considered a primary candidate cladding material for light water reactor accident-tolerant fuel because of its superior resistance to oxidation in high-temperature steam compared with Zircaloy cladding. Thin-walled FeCrAl cladding at 350 μm wall thickness is required, and techniques for joining endplug to cladding need to be developed. Fusion-based laser weld and solid-state joining with pressure resistance weld were investigated in this study. The results of microstructural characterization, mechanical property evaluation by tensile testing, and hydraulic pressure burst testing of the welds for the cladding-endplug specimen are discussed.

Laser and Pressure Resistance Weld of Thin-Wall Cladding for LWR Accident-Tolerant Fuels

NASA Astrophysics Data System (ADS)

Gan, J.; Jerred, N.; Perez, E.; Haggard, D. C.

2018-02-01

FeCrAl alloy with typical composition of approximately Fe-15Cr-5Al is considered a primary candidate cladding material for light water reactor accident-tolerant fuel because of its superior resistance to oxidation in high-temperature steam compared with Zircaloy cladding. Thin-walled FeCrAl cladding at 350 μm wall thickness is required, and techniques for joining endplug to cladding need to be developed. Fusion-based laser weld and solid-state joining with pressure resistance weld were investigated in this study. The results of microstructural characterization, mechanical property evaluation by tensile testing, and hydraulic pressure burst testing of the welds for the cladding-endplug specimen are discussed.

A role for dynamin in triggering ethanol tolerance.

PubMed

Krishnan, Harish R; Al-Hasan, Yazan M; Pohl, Jascha B; Ghezzi, Alfredo; Atkinson, Nigel S

2012-01-01

A prevailing hypothesis is that the set of genes that underlie the endophenotypes of alcoholism overlap with those responsible for the addicted state. Functional ethanol tolerance, an endophenotype of alcoholism, is defined as a reduced response to ethanol caused by prior ethanol exposure. The neuronal origins of functional rapid tolerance are thought to be a homeostatic response of the nervous system that counters the effects of the drug. Synaptic proteins that regulate neuronal activity are an important evolutionarily conserved target of ethanol. We used mutant analysis in Drosophila to identify synaptic proteins that are important for the acquisition of rapid tolerance to sedation with ethanol. Tolerance was assayed by sedating flies with ethanol vapor and comparing the recovery time of flies after their first sedation and their second sedation. Temperature-sensitive paralytic mutants that alter key facets of synaptic neurotransmission, such as the propagation of action potentials, synaptic vesicle fusion, exocytosis, and endocytosis, were tested for the ability to acquire functional tolerance at both the permissive and restrictive temperatures. The shibire gene encodes Drosophila Dynamin. We tested 2 temperature-sensitive alleles of the gene. The shi(ts1) allele blocked tolerance at both the permissive and restrictive temperatures, while shi(ts2) blocked only at the restrictive temperature. Using the temperature-sensitive property of shi(ts2) , we showed that Dynamin function is required concomitant with exposure to ethanol. A temperature-sensitive allele of the Syntaxin 1A gene, Syx1A(3-69), also blocked the acquisition of ethanol tolerance. We have shown that shibire and Syntaxin 1A are required for the acquisition of rapid functional tolerance to ethanol. Furthermore, the shibire gene product, Dynamin, appears to be required for an immediate early response to ethanol that triggers a cellular response leading to rapid functional tolerance. Copyright © 2011 by the Research Society on Alcoholism.

A Cross-Sectional Study of the Prevalence of Exercise-Induced Hypertension in Childhood Following Repair of Coarctation of the Aorta.

PubMed

Luitingh, Taryn L; Lee, Melissa G Y; Jones, Bryn; Kowalski, Remi; Weskamp Aguero, Sofia; Koleff, Jane; Zannino, Diana; Cheung, Michael M H; d'Udekem, Yves

2018-03-27

Exercise-testing may be a more tolerable method of detecting hypertension in children after coarctation repair compared to gold-standard 24-hour ambulatory blood pressure (BP) monitoring (ABPM). This study aims to determine the prevalence of exercise-induced hypertension and end-organ damage in children after coarctation repair, and the effectiveness of exercise-testing compared to 24-hour ABPM in this population. Exercise-testing (Bruce protocol), transthoracic echocardiogram, 24-hour ABPM, and pulse wave velocity were performed in 41 patients aged 8 to 18 years with previous coarctation repair. Median age at repair was 13 days. Exercise-testing data were compared to healthy paediatric controls. Hypertension was defined as BP >95th percentile on 24-hour ABPM compared to normalised data, and systolic BP (SBP) arbitrarily >200mmHg on exercise-testing. After 13±3years, 39% (14/36) were hypertensive on 24-hour ABPM and 12% (5/41) on exercise-testing. Coarctation patients had a higher peak exercise SBP and reduced endurance compared to controls (164±26mmHg vs. 148±19mmHg, p=0.003; and 13.0±1.7mins vs. 14.2±2.4mins, p=0.007; respectively). All patients with a peak exercise SBP >190mmHg were hypertensive on 24-hour ABPM. Pulse wave velocity was higher in hypertensive patients on exercise-testing and 24-hour ABPM compared to normotensive patients (p=0.004 and p=0.06; respectively). Exercise-testing may be a useful tool to detect hypertension in children and young adults after coarctation repair, particularly in those who do not tolerate 24-hour ABPM. Normative peak exercise BP data for age should be obtained to improve the accuracy of exercise-testing in detecting hypertension. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

The Role of Heat Tolerance Testing in Recovery and Return to Duty

DTIC Science & Technology

2008-10-01

CV diseases Hyperthyroidism Pheochromocytoma Infectious diseases Diabetes mellitus Psychiatric illness Parkinsonism Congenital abnormalities: CF...environments. To assess the heat tolerance status of prior heat stroke patient. Heat tolerance test (HTT) “HTT was effective in evaluating the heat tolerance

The role thermal physiology plays in species invasion

PubMed Central

Kelley, Amanda L.

2014-01-01

The characterization of physiological phenotypes that may play a part in the establishment of non-native species can broaden our understanding about the ecology of species invasion. Here, an assessment was carried out by comparing the responses of invasive and native species to thermal stress. The goal was to identify physiological patterns that facilitate invasion success and to investigate whether these traits are widespread among invasive ectotherms. Four hypotheses were generated and tested using a review of the literature to determine whether they could be supported across taxonomically diverse invasive organisms. The four hypotheses are as follows: (i) broad geographical temperature tolerances (thermal width) confer a higher upper thermal tolerance threshold for invasive rather than native species; (ii) the upper thermal extreme experienced in nature is more highly correlated with upper thermal tolerance threshold for invasive vs. native animals; (iii) protein chaperone expression—a cellular mechanism that underlies an organism's thermal tolerance threshold—is greater in invasive organisms than in native ones; and (iv) acclimation to higher temperatures can promote a greater range of thermal tolerance for invasive compared with native species. Each hypothesis was supported by a meta-analysis of the invasive/thermal physiology literature, providing further evidence that physiology plays a substantial role in the establishment of invasive ectotherms. PMID:27293666

Pathogenic Streptomyces spp. abundance affected by potato cultivars.

PubMed

Nahar, Kamrun; Goyer, Claudia; Zebarth, Bernie J; Burton, David L; Whitney, Sean

2018-04-16

Potato cultivars vary in their tolerance to common scab (CS), however how they affect CS-causing Streptomyces spp. populations over time is poorly understood. This study investigated the effects of potato cultivar on pathogenic Streptomyces spp. abundance, measured using quantitative PCR, in three spatial locations in a CS-infested field: 1) soil close to the plant (SCP); 2) rhizosphere (RS); and 3) geocaulosphere (GS) soils. Two tolerant (Gold Rush, Hindenburg) and two susceptible cultivars (Green Mountain, Agria) were tested. The abundance of pathogenic Streptomyces spp. significantly increased in late August compared with other dates in RS of susceptible cultivars in both years. Abundance of pathogenic Streptomyces spp., when averaged over locations and time, was significantly greater in susceptible cultivars compared with tolerant cultivars in 2014. Principal coordinates analysis showed that SCP and RS soil properties (pH, organic carbon and nitrogen concentrations) explained 68% and 76% of total variation in Streptomyces spp. abundance among cultivars in 2013, respectively, suggesting that cultivars influenced CS pathogen growth conditions. The results suggested that the genetic background of potato cultivars influenced the abundance of pathogenic Streptomyces spp., with 5 to 6 times more abundant Streptomyces spp. in RS of susceptible cultivars compared with tolerant cultivars, which would result in substantially more inoculum left in the field after harvest.  .

The ecological rationality of delay tolerance: insights from capuchin monkeys.

PubMed

Addessi, Elsa; Paglieri, Fabio; Focaroli, Valentina

2011-04-01

Both human and non-human animals often face decisions between options available at different times, and the capacity of delaying gratification has usually been considered one of the features distinguishing humans from other animals. However, this characteristic can widely vary across individuals, species, and types of task and it is still unclear whether it is accounted for by phylogenetic relatedness, feeding ecology, social structure, or metabolic rate. To disentangle these hypotheses, we evaluated temporal preferences in capuchin monkeys, South-American primates that, despite splitting off from human lineage approximately 35 million years ago, show striking behavioural analogies with the great apes. Then, we compared capuchins' performance with that of the other primate species tested so far with the same procedure. Overall, capuchins showed a delay tolerance significantly higher than closely related species, such as marmosets and tamarins, and comparable to that shown by great apes. Capuchins' tool use abilities might explain their comparatively high preference for delayed options in inter-temporal choices. Moreover, as in humans, capuchin females showed a greater delay tolerance than males, possibly because of their less opportunistic foraging style. Thus, our results shed light on the evolutionary origins of self-control supporting explanations of delay tolerance in terms of feeding ecology. Copyright © 2010 Elsevier B.V. All rights reserved.

Network Topologies and Dynamics Leading to Endotoxin Tolerance and Priming in Innate Immune Cells

NASA Astrophysics Data System (ADS)

Fu, Yan; Glaros, Trevor; Zhu, Meng; Wang, Ping; Wu, Zhanghan; Tyson, John; Li, Liwu; Xing, Jianhua

2012-01-01

The innate immune system, acting as the first line of host defense, senses and adapts to foreign challenges through complex intracellular and intercellular signaling networks. Endotoxin tolerance and priming elicited by macrophages are classic examples of the complex adaptation of innate immune cells. Upon repetitive exposures to different doses of bacterial endotoxin (lipopolysaccharide) or other stimulants, macrophages show either suppressed or augmented inflammatory responses compared to a single exposure to the stimulant. Endotoxin tolerance and priming are critically involved in both immune homeostasis and the pathogenesis of diverse inflammatory diseases. However, the underlying molecular mechanisms are not well understood. By means of a computational search through the parameter space of a coarse-grained three-node network with a two-stage Metropolis sampling approach, we enumerated all the network topologies that can generate priming or tolerance. We discovered three major mechanisms for priming (pathway synergy, suppressor deactivation, activator induction) and one for tolerance (inhibitor persistence). These results not only explain existing experimental observations, but also reveal intriguing test scenarios for future experimental studies to clarify mechanisms of endotoxin priming and tolerance.

Tannins from Potentilla officinalis display antiinflammatory effects in the UV erythema test and on atopic skin.

PubMed

Hoffmann, Julia; Wölfle, Ute; Schempp, Christoph M; Casetti, Federica

2016-09-01

Rich in tannins, the rhizome of Potentilla officinalis (PO) has traditionally been used in the topical treatment of inflammatory disorders of the skin and mucous membranes. The objective of the present study was to examine the antiinflammatory effects of PO in the UV erythema test as well as in patients with atopic skin. Using the UV erythema test, the antiinflammatory effects of a PO extract (2 %) - compared to 1 % hydrocortisone acetate - were assessed in a randomized, prospective, placebo-controlled double-blind study of 40 healthy volunteers. In the context of a prospective non-controlled trial, the efficacy and tolerability of 2 % PO cream (applied to defined test areas twice daily for two weeks) was evaluated in twelve adults and twelve children with atopic skin using a partial SCORAD. In addition, the effects on the degree of erythema in the test areas was measured photometrically. In the UV erythema test, PO cream significantly reduced the erythema index compared to the vehicle. The antiinflammatory effects of PO cream were comparable to those of 1 % hydrocortisone acetate cream. The clinical study with atopic patients revealed a significant reduction in the partial SCORAD as well as erythema in the test areas. No adverse events were recorded. PO cream displays antiinflammatory effects in vivo. It is effective in and well tolerated by patients with atopic skin. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Tolerance to the antinociceptive effect of morphine in the absence of short-term presynaptic desensitization in rat periaqueductal gray neurons.

PubMed

Fyfe, Leon W; Cleary, Daniel R; Macey, Tara A; Morgan, Michael M; Ingram, Susan L

2010-12-01

Opioids activate the descending antinociceptive pathway from the ventrolateral periaqueductal gray (vlPAG) by both pre- and postsynaptic inhibition of tonically active GABAergic neurons (i.e., disinhibition). Previous research has shown that short-term desensitization of postsynaptic μ-opioid receptors (MOPrs) in the vlPAG is increased with the development of opioid tolerance. Given that pre- and postsynaptic MOPrs are coupled to different signaling mechanisms, the present study tested the hypothesis that short-term desensitization of presynaptic MOPrs also contributes to opioid tolerance. Twice-daily injections of morphine (5 mg/kg s.c.) for 2 days caused a rightward shift in the morphine dose-response curve on the hot plate test (D(50) = 9.9 mg/kg) compared with saline-pretreated (5.3 mg/kg) male Sprague-Dawley rats. In vitro whole-cell patch-clamp recordings from vlPAG slices revealed that inhibition of evoked inhibitory postsynaptic currents (eIPSCs) by the MOPr-selective agonist [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin was decreased in morphine-tolerant (EC(50) = 708 nM) compared with saline-pretreated rats (EC(50) = 163 nM). However, short-term desensitization of MOPr inhibition of eIPSCs was not observed in either saline- or morphine-pretreated rats. Reducing the number of available MOPrs with the irreversible opioid receptor antagonist, β-chlornaltrexamine decreased maximal MOPr inhibition with no evidence of desensitization, indicating that the lack of observed desensitization is not caused by receptor reserve. These results demonstrate that tolerance to the antinociceptive effect of morphine is associated with a decrease in presynaptic MOPr sensitivity or coupling to effectors, but this change is independent of short-term MOPr desensitization.

Tolerance to the Antinociceptive Effect of Morphine in the Absence of Short-Term Presynaptic Desensitization in Rat Periaqueductal Gray Neurons

PubMed Central

Fyfe, Leon W.; Cleary, Daniel R.; Macey, Tara A.; Morgan, Michael M.

2010-01-01

Opioids activate the descending antinociceptive pathway from the ventrolateral periaqueductal gray (vlPAG) by both pre- and postsynaptic inhibition of tonically active GABAergic neurons (i.e., disinhibition). Previous research has shown that short-term desensitization of postsynaptic μ-opioid receptors (MOPrs) in the vlPAG is increased with the development of opioid tolerance. Given that pre- and postsynaptic MOPrs are coupled to different signaling mechanisms, the present study tested the hypothesis that short-term desensitization of presynaptic MOPrs also contributes to opioid tolerance. Twice-daily injections of morphine (5 mg/kg s.c.) for 2 days caused a rightward shift in the morphine dose-response curve on the hot plate test (D50 = 9.9 mg/kg) compared with saline-pretreated (5.3 mg/kg) male Sprague-Dawley rats. In vitro whole-cell patch-clamp recordings from vlPAG slices revealed that inhibition of evoked inhibitory postsynaptic currents (eIPSCs) by the MOPr-selective agonist [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin was decreased in morphine-tolerant (EC50 = 708 nM) compared with saline-pretreated rats (EC50 = 163 nM). However, short-term desensitization of MOPr inhibition of eIPSCs was not observed in either saline- or morphine-pretreated rats. Reducing the number of available MOPrs with the irreversible opioid receptor antagonist, β-chlornaltrexamine decreased maximal MOPr inhibition with no evidence of desensitization, indicating that the lack of observed desensitization is not caused by receptor reserve. These results demonstrate that tolerance to the antinociceptive effect of morphine is associated with a decrease in presynaptic MOPr sensitivity or coupling to effectors, but this change is independent of short-term MOPr desensitization. PMID:20739455

[Insulin, glucagon and growth hormone responses during glucose, arginine and insulin tolerance tests in children with hyperthyroidism].

PubMed

Kato, T; Matsuura, N; Fujita, H; Fujieda, K; Nohara, Y; Mikami, Y; Abe, K; Fukushima, N

1985-06-20

There are many reports of glucose intolerance in adult patients with hyperthyroidism but few reports of glucose intolerance in hyperthyroid children. In this study, we measured plasma levels of glucose, insulin, glucagon and growth hormone in hyperthyroid children and control subjects by the use of three kinds of tolerance tests: an oral glucose tolerance test, an arginine tolerance test and an insulin tolerance test. In the oral glucose tolerance test, mean fasting glucose levels (79.6 +/- 1.4 mg/dl) rose to maximum levels (157.3 +/- 4.3 mg/dl) at 30 min in hyperthyroid children which were significantly higher than the levels in control subjects (p less than 0.01). The maximum levels of glucose fell slowly and returned to fasting levels at 180 min. In this test, plasma insulin levels increased from basal levels (12.7 +/- 1.9 microU/ml) to maximum levels (120.8 +/- 22.1 microU/ml) at 30 min in the prepubertal age group of hyperthyroidism. On the other hand, in the pubertal age group of hyperthyroidism, maximum levels of insulin were observed at 60 min, but not at 30 min. These maximum levels of insulin of both hyperthyroid age groups were significantly higher than those in the control subjects (p less than 0.05, p less than 0.01 respectively). There was no difference in insulin-glucose ratio at 30 min (delta IRI/delta BG) and insulinogenic index (I.I.) at 0 to 60 min between these two groups of hyperthyroid children and control subjects. However, I.I. at 0 to 120 min and 0 to 180 min decreased significantly in the pubertal age group of hyperthyroidism as compared with those in the control group (p less than 0.05, p less than 0.02 respectively). In the oral glucose tolerance test, plasma glucagon levels decreased from basal levels (74.1 +/- 4.3 pg/ml) to minimum levels (36.4 +/- 4.7 pg/ml) at 90 min in hyperthyroidism, which were significantly lower than those in the controls (p less than 0.05). However, there was no difference in -epsilon delta IRG/epsilon delta BG (cumulative glucagon response/cumulative glucose response) between the subjects with hyperthyroidism and the controls. On the other hand, lower responses of blood glucose, insulin, glucagon and growth hormone to arginine were observed in subjects with hyperthyroidism than in the controls. Moreover in the insulin tolerance test, there was no difference in glucagon and growth hormone response between the subjects with hyperthyroidism and the controls. Thus our conclusions are as follows: A marked increase in blood glucose after oral glucose load was observed in spite of normal insulin-glucose ratio in hyperthyroid children, suggesting the existence of peripheral insulin resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Pharmacokinetics and tolerability of oral dosage forms of huperzine a in healthy Chinese male volunteers: a randomized, single dose, three-period, six-sequence crossover study.

PubMed

Wu, San-Lan; Gan, Jun; Rao, Jing; He, Si-Jie; Zhu, Wen-Wen; Zhao, Ying; Lv, Yong-Ning; Huang, Jian-Geng; Liu, Ya-Ni

2017-10-01

Huperzine A is a potent, reversible, and blood-brain barrier permeable acetylcholinesterase inhibitor. The aim of this study was to compare the pharmacokinetics, tolerability, and bioavailability of two formulations with the established reference formulation of huperzine A in a fasting, healthy Chinese male population. This was a randomized, single-dose, 3-period, 6-sequence crossover study. The plasma concentrations of huperzine A were determined by liquid chromatography tandem mass spectrometry. Tolerability was assessed based on subject interview, vital sign monitoring, physical examination, and routine blood and urine tests. The mean (SD) pharmacokinetic parameters of the reference drug were C max , 1.550 (0.528) ng/mL; t 1/2 , 12.092 (1.898) h; AUC 0-72h , 17.550 (3.794) ng·h/mL. Those of the test formulation A and test formulation B were C max , 1.412 (0.467), 1.521 (0.608) ng/mL; t 1/2 , 12.073 (2.068), 12.271 (1.678) h; AUC 0-72h , 15.286 (3.434) ng·h/mL, 15.673 (3.586) ng·h/mL. The 90% confidence intervals for the AUC 0-72h and C max were between 0.80 and 1.25. No adverse events were reported by the subjects or found with results of clinical laboratory test. The test and reference products met the regulatory criteria for bioequivalence in these fasting, healthy Chinese male volunteers. All three formulations appeared to be well tolerated.

Metabolic screening in patients with polycystic ovary syndrome is largely underutilized among obstetrician-gynecologists.

PubMed

Dhesi, Amy S; Murtough, Katie L; Lim, Jonathan K; Schulkin, Jay; McGovern, Peter G; Power, Michael L; Morelli, Sara S

2016-11-01

Women with polycystic ovary syndrome have substantially higher rates of insulin resistance, impaired glucose tolerance, type 2 diabetes, dyslipidemia, and metabolic syndrome when compared with women without the disease. Given the high prevalence of these comorbidities, guidelines issued by the American College of Obstetricians and Gynecologists and the Endocrine Society recommend that all women with polycystic ovary syndrome undergo screening for impaired glucose tolerance and dyslipidemia with a 2 hour 75 g oral glucose tolerance test and fasting lipid profile upon diagnosis and also undergo repeat screening every 2-5 years and every 2 years, respectively. Although a hemoglobin A1C and/or fasting glucose are widely used screening tests for diabetes, both the American College of Obstetricians and Gynecologists and the Endocrine Society preferentially recommend the 2 hour oral glucose tolerance test in women with polycystic ovary syndrome as a superior indicator of impaired glucose tolerance/diabetes mellitus. However, we found that gynecologists underutilize current recommendations for metabolic screening in women with polycystic ovary syndrome. In an online survey study targeting American College of Obstetricians and Gynecologists fellows and junior fellows, 22.3% of respondents would not order any screening test at the initial visit for at least 50% of their patients with polycystic ovary syndrome. The most common tests used to screen for impaired glucose tolerance in women with polycystic ovary syndrome were hemoglobin A1C (51.0%) and fasting glucose (42.7%). Whereas 54.1% would order a fasting lipid profile in at least 50% of their polycystic ovary syndrome patients, only 7% of respondents order a 2 hour oral glucose tolerance test. We therefore call for increased efforts to encourage obstetrician-gynecologists to address metabolic abnormalities in their patients with polycystic ovary syndrome. Such efforts should include education of physicians early in their careers, at the medical student and resident level. Efforts should also include implementation of continuing medical education activities, both locally and at the national level, to improve understanding of the metabolic implications of polycystic ovary syndrome. Electronic medical record systems should be utilized to generate prompts for appropriate screening tests in patients with a diagnosis of polycystic ovary syndrome. Because obstetrician-gynecologists may be the only physicians seen by many polycystic ovary syndrome patients, particularly those in their young reproductive years, such interventions could effectively promote optimal preventative health care and early diagnosis of metabolic comorbidities in these at-risk women. Copyright © 2016 Elsevier Inc. All rights reserved.

Candidate genes and molecular markers associated with heat tolerance in colonial Bentgrass.

PubMed

Jespersen, David; Belanger, Faith C; Huang, Bingru

2017-01-01

Elevated temperature is a major abiotic stress limiting the growth of cool-season grasses during the summer months. The objectives of this study were to determine the genetic variation in the expression patterns of selected genes involved in several major metabolic pathways regulating heat tolerance for two genotypes contrasting in heat tolerance to confirm their status as potential candidate genes, and to identify PCR-based markers associated with candidate genes related to heat tolerance in a colonial (Agrostis capillaris L.) x creeping bentgrass (Agrostis stolonifera L.) hybrid backcross population. Plants were subjected to heat stress in controlled-environmental growth chambers for phenotypic evaluation and determination of genetic variation in candidate gene expression. Molecular markers were developed for genes involved in protein degradation (cysteine protease), antioxidant defense (catalase and glutathione-S-transferase), energy metabolism (glyceraldehyde-3-phosphate dehydrogenase), cell expansion (expansin), and stress protection (heat shock proteins HSP26, HSP70, and HSP101). Kruskal-Wallis analysis, a commonly used non-parametric test used to compare population individuals with or without the gene marker, found the physiological traits of chlorophyll content, electrolyte leakage, normalized difference vegetative index, and turf quality were associated with all candidate gene markers with the exception of HSP101. Differential gene expression was frequently found for the tested candidate genes. The development of candidate gene markers for important heat tolerance genes may allow for the development of new cultivars with increased abiotic stress tolerance using marker-assisted selection.

Candidate genes and molecular markers associated with heat tolerance in colonial Bentgrass

PubMed Central

Jespersen, David; Belanger, Faith C.; Huang, Bingru

2017-01-01

Elevated temperature is a major abiotic stress limiting the growth of cool-season grasses during the summer months. The objectives of this study were to determine the genetic variation in the expression patterns of selected genes involved in several major metabolic pathways regulating heat tolerance for two genotypes contrasting in heat tolerance to confirm their status as potential candidate genes, and to identify PCR-based markers associated with candidate genes related to heat tolerance in a colonial (Agrostis capillaris L.) x creeping bentgrass (Agrostis stolonifera L.) hybrid backcross population. Plants were subjected to heat stress in controlled-environmental growth chambers for phenotypic evaluation and determination of genetic variation in candidate gene expression. Molecular markers were developed for genes involved in protein degradation (cysteine protease), antioxidant defense (catalase and glutathione-S-transferase), energy metabolism (glyceraldehyde-3-phosphate dehydrogenase), cell expansion (expansin), and stress protection (heat shock proteins HSP26, HSP70, and HSP101). Kruskal-Wallis analysis, a commonly used non-parametric test used to compare population individuals with or without the gene marker, found the physiological traits of chlorophyll content, electrolyte leakage, normalized difference vegetative index, and turf quality were associated with all candidate gene markers with the exception of HSP101. Differential gene expression was frequently found for the tested candidate genes. The development of candidate gene markers for important heat tolerance genes may allow for the development of new cultivars with increased abiotic stress tolerance using marker-assisted selection. PMID:28187136

Fuel containment and damage tolerance for large composite primary aircraft structures. Phase 1: Testing

NASA Technical Reports Server (NTRS)

Sandifer, J. P.

1983-01-01

Technical problems associated with fuel containment and damage tolerance of composite material wings for transport aircraft were identified. The major tasks are the following: (1) the preliminary design of damage tolerant wing surface using composite materials; (2) the evaluation of fuel sealing and lightning protection methods for a composite material wing; and (3) an experimental investigation of the damage tolerant characteristics of toughened resin graphite/epoxy materials. The test results, the test techniques, and the test data are presented.

Barley yellow dwarf virus Infection Leads to Higher Chemical Defense Signals and Lower Electrophysiological Reactions in Susceptible Compared to Tolerant Barley Genotypes.

PubMed

Paulmann, Maria K; Kunert, Grit; Zimmermann, Matthias R; Theis, Nina; Ludwig, Anatoli; Meichsner, Doreen; Oelmüller, Ralf; Gershenzon, Jonathan; Habekuss, Antje; Ordon, Frank; Furch, Alexandra C U; Will, Torsten

2018-01-01

Barley yellow dwarf virus (BYDV) is a phloem limited virus that is persistently transmitted by aphids. Due to huge yield losses in agriculture, the virus is of high economic relevance. Since the control of the virus itself is not possible, tolerant barley genotypes are considered as the most effective approach to avoid yield losses. Although several genes and quantitative trait loci are known and used in barley breeding for virus tolerance, little is known about molecular and physiological backgrounds of this trait. Therefore, we compared the anatomy and early defense responses of a virus susceptible to those of a virus-tolerant cultivar. One of the very early defense responses is the transmission of electrophysiological reactions. Electrophysiological reactions to BYDV infection might differ between susceptible and tolerant cultivars, since BYDV causes disintegration of sieve elements in susceptible cultivars. The structure of vascular bundles, xylem vessels and sieve elements was examined using microscopy. All three were significantly decreased in size in infected susceptible plants where the virus causes disintegration of sieve elements. This could be associated with an uncontrolled ion exchange between the sieve-element lumen and apoplast. Further, a reduced electrophysiological isolation would negatively affect the propagation of electrophysiological reactions. To test the influence of BYDV infection on electrophysiological reactions, electropotential waves (EPWs) induced by leaf-tip burning were recorded using aphids as bioelectrodes. EPWs in infected susceptible plants disappeared already after 10 cm in contrast to those in healthy susceptible or infected tolerant or healthy tolerant plants. Another early plant defense reaction is an increase in reactive oxygen species (ROS). Using a fluorescent dye, we found a significant increase in ROS content in infected susceptible plants but not in infected tolerant plants. Similar results were found for the phytohormones abscisic acid and three jasmonates. Salicylic acid levels were generally higher after BYDV infection compared to uninfected plants. Heat stimulation caused an increase in jasmonates. By shedding light on the plant defense mechanisms against BYDV, this study, provides further knowledge for breeding virus tolerant plants.

Barley yellow dwarf virus Infection Leads to Higher Chemical Defense Signals and Lower Electrophysiological Reactions in Susceptible Compared to Tolerant Barley Genotypes

PubMed Central

Paulmann, Maria K.; Kunert, Grit; Zimmermann, Matthias R.; Theis, Nina; Ludwig, Anatoli; Meichsner, Doreen; Oelmüller, Ralf; Gershenzon, Jonathan; Habekuss, Antje; Ordon, Frank; Furch, Alexandra C. U.; Will, Torsten

2018-01-01

Barley yellow dwarf virus (BYDV) is a phloem limited virus that is persistently transmitted by aphids. Due to huge yield losses in agriculture, the virus is of high economic relevance. Since the control of the virus itself is not possible, tolerant barley genotypes are considered as the most effective approach to avoid yield losses. Although several genes and quantitative trait loci are known and used in barley breeding for virus tolerance, little is known about molecular and physiological backgrounds of this trait. Therefore, we compared the anatomy and early defense responses of a virus susceptible to those of a virus-tolerant cultivar. One of the very early defense responses is the transmission of electrophysiological reactions. Electrophysiological reactions to BYDV infection might differ between susceptible and tolerant cultivars, since BYDV causes disintegration of sieve elements in susceptible cultivars. The structure of vascular bundles, xylem vessels and sieve elements was examined using microscopy. All three were significantly decreased in size in infected susceptible plants where the virus causes disintegration of sieve elements. This could be associated with an uncontrolled ion exchange between the sieve-element lumen and apoplast. Further, a reduced electrophysiological isolation would negatively affect the propagation of electrophysiological reactions. To test the influence of BYDV infection on electrophysiological reactions, electropotential waves (EPWs) induced by leaf-tip burning were recorded using aphids as bioelectrodes. EPWs in infected susceptible plants disappeared already after 10 cm in contrast to those in healthy susceptible or infected tolerant or healthy tolerant plants. Another early plant defense reaction is an increase in reactive oxygen species (ROS). Using a fluorescent dye, we found a significant increase in ROS content in infected susceptible plants but not in infected tolerant plants. Similar results were found for the phytohormones abscisic acid and three jasmonates. Salicylic acid levels were generally higher after BYDV infection compared to uninfected plants. Heat stimulation caused an increase in jasmonates. By shedding light on the plant defense mechanisms against BYDV, this study, provides further knowledge for breeding virus tolerant plants. PMID:29563918

Acceptance- versus Change-Based Pain Management: The Role of Psychological Acceptance

ERIC Educational Resources Information Center

Blacker, Kara J.; Herbert, James D.; Forman, Evan M.; Kounios, John

2012-01-01

This study compared two theoretically opposed strategies for acute pain management: an acceptance-based and a change-based approach. These two strategies were compared in a within-subjects design using the cold pressor test as an acute pain induction method. Participants completed a baseline pain tolerance assessment followed by one of the two…

Impact of CPAP on physical exercise tolerance and sympathetic-vagal balance in patients with chronic heart failure.

PubMed

Reis, Hugo V; Borghi-Silva, Audrey; Catai, Aparecida M; Reis, Michel S

2014-01-01

Chronic heart failure (CHF) leads to exercise intolerance. However, non-invasive ventilation is able to improve functional capacity of patients with CHF. The aim of this study was to evaluate the effectiveness of continuous positive airway pressure (CPAP) on physical exercise tolerance and heart rate variability (HRV) in patients with CHF. Method : Seven men with CHF (62 ± 8 years) and left ventricle ejection fraction of 41 ± 8% were submitted to an incremental symptom-limited exercise test (IT) on the cicloergometer. On separate days, patients were randomized to perform four constant work rate exercise tests to maximal tolerance with and without CPAP (5 cmH2O) in the following conditions: i) at 50% of peak work rate of IT; and ii) at 75% of peak work rate of IT. At rest and during these conditions, instantaneous heart rate (HR) was recorded using a cardiofrequencimeter and HRV was analyzed in time domain (SDNN and RMSSD indexes). For statistical procedures, Wilcoxon test or Kruskall-Wallis test with Dunn's post-hoc were used accordingly. In addition, categorical variables were analysed through Fischer's test (p<0.05). There were significant improvements in exercise tolerance at 75% of peak work rate of IT with CPAP (405 ± 52 vs. 438 ± 58 s). RMSSD indexes were lower during exercise tests compared to CPAP at rest and with 50% of peak work rate of IT. These data suggest that CPAP appears to be a useful strategy to improve functional capacity in patients with CHF. However, the positive impact of CPAP did not generate significant changes in the HRV during physical exercises.

Sex differences in antinociceptive tolerance to delta-9-tetrahydrocannabinol in the rat

PubMed Central

Wakley, Alexa A.; Wiley, Jenny L.; Craft, Rebecca M.

2014-01-01

Background Sex differences in cannabinoid effects have been reported in rodents, with adult females typically being more sensitive than adult males. The present study compared the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC) in adult, gonadally intact female vs. male rats. Methods Cumulative dose-effect curves were obtained for THC (1.0–18 mg/kg i.p.) on warm water tail withdrawal and paw pressure tests. Vehicle or the sex-specific ED80 dose for THC was administered twice daily for 9 days; THC dose-effect curves were then re-determined. Results On the pre-chronic test day, THC was significantly more potent in females than males in producing antinociception on the tail withdrawal and paw pressure tests. After 9 days of twice-daily THC treatment (5.4 mg/kg/injection in females, 7.6 mg/kg/injection in males), THC potency on both tests decreased more in females than males. On the tail withdrawal test, chronic THC produced 4.2- vs. 2.8-fold increases in ED50 values in females vs. males, respectively. On the paw pressure test, chronic THC produced 4.4- vs. 2.9-fold increases in ED50 values in females vs. males, respectively. Chronic THC treatment did not significantly disrupt estrous cycling in females. Conclusions These results demonstrate that – even when sex differences in acute THC potency are controlled for – females develop more antinociceptive tolerance to THC than males. Given the importance of drug tolerance in the development of drug dependence, these results suggest that females may be more vulnerable than males to developing dependence after chronic cannabinoid exposure. PMID:25131716

Fasting Serum Taurine-Conjugated Bile Acids Are Elevated in Type 2 Diabetes and Do Not Change With Intensification of Insulin

PubMed Central

Wewalka, Marlene; Patti, Mary-Elizabeth; Barbato, Corinne; Houten, Sander M.

2014-01-01

Context: Bile acids (BAs) are newly recognized signaling molecules in glucose and energy homeostasis. Differences in BA profiles with type 2 diabetes mellitus (T2D) remain incompletely understood. Objective: The objective of the study was to assess serum BA composition in impaired glucose-tolerant, T2D, and normal glucose-tolerant persons and to monitor the effects of improving glycemia on serum BA composition in T2D patients. Design and Setting: This was a cross-sectional cohort study in a general population (cohort 1) and nonrandomized intervention (cohort 2). Patients and Interventions: Ninety-nine volunteers underwent oral glucose tolerance testing, and 12 persons with T2D and hyperglycemia underwent 8 weeks of intensification of treatment. Main Outcome Measures: Serum free BA and respective taurine and glycine conjugates were measured by HPLC tandem mass spectrometry. Results: Oral glucose tolerance testing identified 62 normal-, 25 impaired glucose-tolerant, and 12 T2D persons. Concentrations of total taurine-conjugated BA were higher in T2D and intermediate in impaired- compared with normal glucose-tolerant persons (P = .009). Univariate regression revealed a positive association between total taurine-BA and fasting glucose (R = 0.37, P < .001), postload glucose (R = 0.31, P < .002), hemoglobin A1c (R = 0.26, P < .001), fasting insulin (R = 0.21, P = .03), and homeostatic model assessment-estimated insulin resistance (R = 0.26, P = .01) and an inverse association with oral disposition index (R = −0.36, P < .001). Insulin-mediated glycemic improvement in T2D patients did not change fasting serum total BA or BA composition. Conclusion: Fasting taurine-conjugated BA concentrations are higher in T2D and intermediate in impaired compared with normal glucose-tolerant persons and are associated with fasting and postload glucose. Serum BAs are not altered in T2D in response to improved glycemia. Further study may elucidate whether this pattern of taurine-BA conjugation can be targeted to provide novel therapeutic approaches to treat T2D. PMID:24432996

Exercise increases pressure pain tolerance but not pressure and heat pain thresholds in healthy young men.

PubMed

Vaegter, H B; Hoeger Bement, M; Madsen, A B; Fridriksson, J; Dasa, M; Graven-Nielsen, T

2017-01-01

Exercise causes an acute decrease in the pain sensitivity known as exercise-induced hypoalgesia (EIH), but the specificity to certain pain modalities remains unknown. This study aimed to compare the effect of isometric exercise on the heat and pressure pain sensitivity. On three different days, 20 healthy young men performed two submaximal isometric knee extensions (30% maximal voluntary contraction in 3 min) and a control condition (quiet rest). Before and immediately after exercise and rest, the sensitivity to heat pain and pressure pain was assessed in randomized and counterbalanced order. Cuff pressure pain threshold (cPPT) and pain tolerance (cPTT) were assessed on the ipsilateral lower leg by computer-controlled cuff algometry. Heat pain threshold (HPT) was recorded on the ipsilateral foot by a computer-controlled thermal stimulator. Cuff pressure pain tolerance was significantly increased after exercise compared with baseline and rest (p < 0.05). Compared with rest, cPPT and HPT were not significantly increased by exercise. No significant correlation between exercise-induced changes in HPT and cPPT was found. Test-retest reliability before and after the rest condition was better for cPPT and CPTT (intraclass correlation > 0.77) compared with HPT (intraclass correlation = 0.54). The results indicate that hypoalgesia after submaximal isometric exercise is primarily affecting tolerance of pressure pain compared with the pain threshold. These data contribute to the understanding of how isometric exercise influences pain perception, which is necessary to optimize the clinical utility of exercise in management of chronic pain. The effect of isometric exercise on pain tolerance may be relevant for patients in chronic musculoskeletal pain as a pain-coping strategy. WHAT DOES THIS STUDY ADD?: The results indicate that hypoalgesia after submaximal isometric exercise is primarily affecting tolerance of pressure pain compared with the heat and pressure pain threshold. These data contribute to the understanding of how isometric exercise influences pain perception, which is necessary to optimize the clinical utility of exercise in management of chronic pain. © 2016 European Pain Federation - EFIC®.

The Design and Semi-Physical Simulation Test of Fault-Tolerant Controller for Aero Engine

NASA Astrophysics Data System (ADS)

Liu, Yuan; Zhang, Xin; Zhang, Tianhong

2017-11-01

A new fault-tolerant control method for aero engine is proposed, which can accurately diagnose the sensor fault by Kalman filter banks and reconstruct the signal by real-time on-board adaptive model combing with a simplified real-time model and an improved Kalman filter. In order to verify the feasibility of the method proposed, a semi-physical simulation experiment has been carried out. Besides the real I/O interfaces, controller hardware and the virtual plant model, semi-physical simulation system also contains real fuel system. Compared with the hardware-in-the-loop (HIL) simulation, semi-physical simulation system has a higher degree of confidence. In order to meet the needs of semi-physical simulation, a rapid prototyping controller with fault-tolerant control ability based on NI CompactRIO platform is designed and verified on the semi-physical simulation test platform. The result shows that the controller can realize the aero engine control safely and reliably with little influence on controller performance in the event of fault on sensor.

Low temperature tolerance, cold hardening and acclimation in tadpoles of the neotropical túngara frog (Engystomops pustulosus).

PubMed

Vo, Pacific; Gridi-Papp, Marcos

2017-05-01

Many frogs from temperate climates can tolerate low temperatures and increase their thermal tolerance through hardening and acclimation. Most tropical frogs, on the other hand, fail to acclimate to low temperatures. This lack of acclimation ability is potentially due to lack of selection pressure for acclimation because cold weather is less common in the tropics. We tested the generality of this pattern by characterizing the critical temperature minimum (CTMin), hardening, and acclimation responses of túngara frogs (Engystomops pustulosus). These frogs belong to a family with unknown thermal ecology. They are found in a tropical habitat with a highly constant temperature regime. The CTMin of the tadpoles was on average 12.5°C. Pre-metamorphic tadpoles hardened by 1.18°C, while metamorphic tadpoles hardened by 0.36°C. When raised at 21°C, tadpoles acclimated expanding their cold tolerance by 1.3°C in relation to larvae raised at 28°C. These results indicate that the túngara frog has a greatly reduced cold tolerance when compared to species from temperate climates, but it responds to cold temperatures with hardening and acclimation comparable to those of temperate-zone species. Cold tolerance increased with body length but cold hardening was more extensive in pre-metamorphic tadpoles than in metamorphic ones. This study shows that lack of acclimation ability is not general to the physiology of tropical anurans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transcriptome profiling of Kentucky bluegrass (Poa pratensis L.) accessions in response to salt stress.

PubMed

Bushman, B Shaun; Amundsen, Keenan L; Warnke, Scott E; Robins, Joseph G; Johnson, Paul G

2016-01-13

Kentucky bluegrass (Poa pratensis L.) is a prominent turfgrass in the cool-season regions, but it is sensitive to salt stress. Previously, a relatively salt tolerant Kentucky bluegrass accession was identified that maintained green colour under consistent salt applications. In this study, a transcriptome study between the tolerant (PI 372742) accession and a salt susceptible (PI 368233) accession was conducted, under control and salt treatments, and in shoot and root tissues. Sample replicates grouped tightly by tissue and treatment, and fewer differentially expressed transcripts were detected in the tolerant PI 372742 samples compared to the susceptible PI 368233 samples, and in root tissues compared to shoot tissues. A de novo assembly resulted in 388,764 transcripts, with 36,587 detected as differentially expressed. Approximately 75 % of transcripts had homology based annotations, with several differences in GO terms enriched between the PI 368233 and PI 372742 samples. Gene expression profiling identified salt-responsive gene families that were consistently down-regulated in PI 372742 and unlikely to contribute to salt tolerance in Kentucky bluegrass. Gene expression profiling also identified sets of transcripts relating to transcription factors, ion and water transport genes, and oxidation-reduction process genes with likely roles in salt tolerance. The transcript assembly represents the first such assembly in the highly polyploidy, facultative apomictic Kentucky bluegrass. The transcripts identified provide genetic information on how this plant responds to and tolerates salt stress in both shoot and root tissues, and can be used for further genetic testing and introgression.

An innovative and highly drug-tolerant approach for detecting neutralizing antibodies directed to therapeutic antibodies.

PubMed

Sloan, John H; Conway, Richard G; Pottanat, Thomas G; Troutt, Jason S; Higgs, Richard E; Konrad, Robert J; Qian, Yue-Wei

2016-10-01

Immunogenicity testing of biotherapeutic drugs is a regulatory requirement. Herein, we describe a drug-tolerant assay for detecting neutralizing antibodies against a therapeutic antibody. Excess target of the therapeutic antibody was incorporated into the detection step of an affinity capture elution assay. Signal generated from binding of antidrug antibody (ADA) to the therapeutic antibody was compared with signal from binding of ADA to the therapeutic antibody preincubated with its target. The results demonstrated that the target blocked binding of the therapeutic antibody to neutralizing monkey ADA and to two anti-idiotypic antibodies. This highly drug-tolerant novel approach enables the detection of neutralizing antibodies and allows for one basic assay format to achieve complete characterization of ADA responses.

Physiological and molecular characterization of drought responses and identification of candidate tolerance genes in cassava

PubMed Central

Turyagyenda, Laban F.; Kizito, Elizabeth B.; Ferguson, Morag; Baguma, Yona; Agaba, Morris; Harvey, Jagger J. W.; Osiru, David S. O.

2013-01-01

Cassava is an important root crop to resource-poor farmers in marginal areas, where its production faces drought stress constraints. Given the difficulties associated with cassava breeding, a molecular understanding of drought tolerance in cassava will help in the identification of markers for use in marker-assisted selection and genes for transgenic improvement of drought tolerance. This study was carried out to identify candidate drought-tolerance genes and expression-based markers of drought stress in cassava. One drought-tolerant (improved variety) and one drought-susceptible (farmer-preferred) cassava landrace were grown in the glasshouse under well-watered and water-stressed conditions. Their morphological, physiological and molecular responses to drought were characterized. Morphological and physiological measurements indicate that the tolerance of the improved variety is based on drought avoidance, through reduction of water loss via partial stomatal closure. Ten genes that have previously been biologically validated as conferring or being associated with drought tolerance in other plant species were confirmed as being drought responsive in cassava. Four genes (MeALDH, MeZFP, MeMSD and MeRD28) were identified as candidate cassava drought-tolerance genes, as they were exclusively up-regulated in the drought-tolerant genotype to comparable levels known to confer drought tolerance in other species. Based on these genes, we hypothesize that the basis of the tolerance at the cellular level is probably through mitigation of the oxidative burst and osmotic adjustment. This study provides an initial characterization of the molecular response of cassava to drought stress resembling field conditions. The drought-responsive genes can now be used as expression-based markers of drought stress tolerance in cassava, and the candidate tolerance genes tested in the context of breeding (as possible quantitative trait loci) and engineering drought tolerance in transgenics. PMID:23519782

Insulin Effects on Glucose Tolerance, Hypermetabolic Response, and Circadian-metabolic Protein Expression in a Rat Burn and Disuse Model

DTIC Science & Technology

2014-04-23

laboratory, body mass, GTT, and protein expression values for fasted healthy rats subjected to housing in metabolic cages, the stress of sham and GTT...in IBH rats compared with VBH and CC. Insulin was withheld for 24 h, and rats were fasted 10 h in preparation for the procedure. Glucose tolerance...timeline. Animals were fasted for 10 h prior to testing, which was performed on day 7 or 8 for cage control rats and day 14 for insulin and vehicle

Loop-mediated isothermal amplification test for detection of Neisseria gonorrhoeae in urine samples and tolerance of the assay to the presence of urea.

PubMed

Edwards, Thomas; Burke, Patricia A; Smalley, Helen B; Gillies, Liz; Hobbs, Glyn

2014-06-01

A loop-mediated isothermal amplification (LAMP) assay for open reading frame 1 (ORF1) of the glutamine synthetase gene of Neisseria gonorrhoeae was able to tolerate urea concentrations of ≤ 1.8 M, compared with a PCR assay that was functional at concentrations of <100 mM. The LAMP assay was as sensitive as the PCR assay while being faster and simpler to perform. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Tolerability to prolonged lifting tasks. A validation of the recommended limits.

PubMed

Capodaglio, P; Bazzini, G

1997-01-01

Prolonged physical exertion is subjectively regulated by the perception of effort. This preliminary study was conducted to validate the use of subjective perceptions of effort in assessing objectively tolerable workloads for prolonged lifting tasks. Ten healthy male subjects tested their maximal lifting capacity (MLC) on a lift dynamometer (LidoLift, Loredan Biomed., West Sacramento, CA) and underwent incremental and 30-minute endurance lifting tests. Cardiorespiratory parameters were monitored with an oxygen uptake analyzer, mechanical parameters were calculated using a computerized dynamometer. Ratings of perceived exertion were given on Borg's 10-point scale. Physiological responses to repetitive lifting were matched with subjective perceptions. A single-variable statistical regression for power functions was performed to obtain the individual "iso-perception" curves as functions of the mechanical work exerted. We found that the "iso-perception" curve corresponding to a "moderate" perception of effort may represent the individual "tolerance threshold" for prolonged lifting tasks, since physiological responses at this level of intensity did not change significantly and the respiratory exchange ratio was less than one. The individually tolerable weight for lifting tasks lasting 30 min has been expressed as a percentage of the isoinertial MLC value and compared with the currently recommended limits for prolonged lifting tasks (Italian legislation D.L. 626/94). On the basis of our preliminary results a "tolerance threshold" of 20% MLC has been proposed for prolonged lifting tasks.

Intestinal absorption of an arginine-containing peptide in cystinuria

PubMed Central

Asatoor, A. M.; Harrison, B. D. W.; Milne, M. D.; Prosser, D. I.

1972-01-01

Separate tolerance tests involving oral intake of the dipeptide, L-arginyl-L-aspartate, and of a corresponding free amino acid mixture, were carried out in a single type 2 cystinuric patient. Absorption of aspartate was within normal limits, whilst that of arginine was normal after the peptide but considerably reduced after the amino acid mixture. The results are compared with the increments of serum arginine found in eight normal subjects after the oral intake of the free amino acid mixture. Analyses of urinary pyrrolidine and of tetramethylenediamine in urine samples obtained after the two tolerance tests in the patient support the view that arginine absorption was subnormal after the amino acid mixture but within normal limits after the dipeptide. PMID:5045711

A Residual Mass Ballistic Testing Method to Compare Armor Materials or Components (Residual Mass Ballistic Testing Method)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benjamin Langhorst; Thomas M Lillo; Henry S Chu

2014-05-01

A statistics based ballistic test method is presented for use when comparing multiple groups of test articles of unknown relative ballistic perforation resistance. The method is intended to be more efficient than many traditional methods for research and development testing. To establish the validity of the method, it is employed in this study to compare test groups of known relative ballistic performance. Multiple groups of test articles were perforated using consistent projectiles and impact conditions. Test groups were made of rolled homogeneous armor (RHA) plates and differed in thickness. After perforation, each residual projectile was captured behind the target andmore » its mass was measured. The residual masses measured for each test group were analyzed to provide ballistic performance rankings with associated confidence levels. When compared to traditional V50 methods, the residual mass (RM) method was found to require fewer test events and be more tolerant of variations in impact conditions.« less

Reciprocity explains food sharing in humans and other primates independent of kin selection and tolerated scrounging: a phylogenetic meta-analysis.

PubMed

Jaeggi, Adrian V; Gurven, Michael

2013-10-07

Helping, i.e. behaviour increasing the fitness of others, can evolve when directed towards kin or reciprocating partners. These predictions have been tested in the context of food sharing both in human foragers and non-human primates. Here, we performed quantitative meta-analyses on 32 independent study populations to (i) test for overall effects of reciprocity on food sharing while controlling for alternative explanations, methodological biases, publication bias and phylogeny and (ii) compare the relative effects of reciprocity, kinship and tolerated scrounging, i.e. sharing owing to costs imposed by others. We found a significant overall weighted effect size for reciprocity of r = 0.20-0.48 for the most and least conservative measure, respectively. Effect sizes did not differ between humans and other primates, although there were species differences in in-kind reciprocity and trade. The relative effect of reciprocity in sharing was similar to those of kinship and tolerated scrounging. These results indicate a significant independent contribution of reciprocity to human and primate helping behaviour. Furthermore, similar effect sizes in humans and primates speak against cognitive constraints on reciprocity. This study is the first to use meta-analyses to quantify these effects on human helping and to directly compare humans and other primates.

Reciprocity explains food sharing in humans and other primates independent of kin selection and tolerated scrounging: a phylogenetic meta-analysis

PubMed Central

Jaeggi, Adrian V.; Gurven, Michael

2013-01-01

Helping, i.e. behaviour increasing the fitness of others, can evolve when directed towards kin or reciprocating partners. These predictions have been tested in the context of food sharing both in human foragers and non-human primates. Here, we performed quantitative meta-analyses on 32 independent study populations to (i) test for overall effects of reciprocity on food sharing while controlling for alternative explanations, methodological biases, publication bias and phylogeny and (ii) compare the relative effects of reciprocity, kinship and tolerated scrounging, i.e. sharing owing to costs imposed by others. We found a significant overall weighted effect size for reciprocity of r = 0.20–0.48 for the most and least conservative measure, respectively. Effect sizes did not differ between humans and other primates, although there were species differences in in-kind reciprocity and trade. The relative effect of reciprocity in sharing was similar to those of kinship and tolerated scrounging. These results indicate a significant independent contribution of reciprocity to human and primate helping behaviour. Furthermore, similar effect sizes in humans and primates speak against cognitive constraints on reciprocity. This study is the first to use meta-analyses to quantify these effects on human helping and to directly compare humans and other primates. PMID:23945693

Effect of Ezetimibe on Insulin Secretion in db/db Diabetic Mice

PubMed Central

Zhong, Yong; Wang, Jun; Gu, Ping; Shao, Jiaqing; Lu, Bin; Jiang, Shisen

2012-01-01

Objective. To investigate the effect of ezetimibe on the insulin secretion in db/db mice. Methods. The db/db diabetic mice aged 8 weeks were randomly assigned into 2 groups and intragastrically treated with ezetimibe or placebo for 6 weeks. The age matched db/m mice served as controls. At the end of experiment, glucose tolerance test was performed and then the pancreas was collected for immunohistochemistry. In addition, in vitro perfusion of pancreatic islets was employed for the detection of insulin secretion in the first phase. Results. In the ezetimibe group, the fasting blood glucose was markedly reduced, and the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly lowered when compared with those in the control group (P < 0.05). At 120 min after glucose tolerance test, the area under curve in the ezetimibe group was significantly smaller than that in the control group (P < 0.05), but the AUCINS0−30 was markedly higher. In vitro perfusion of pancreatic islets revealed the first phase insulin secretion was improved. In addition, the insulin expression in the pancreas in the ezetimibe group was significantly increased as compared to the control group. Conclusion. Ezetimibe can improve glucose tolerance, recover the first phase insulin secretion, and protect the function of β cells in mice. PMID:23118741

Pre-gravid physical activity and reduced risk of glucose intolerance in pregnancy: the role of insulin sensitivity.

PubMed

Retnakaran, Ravi; Qi, Ying; Sermer, Mathew; Connelly, Philip W; Zinman, Bernard; Hanley, Anthony J G

2009-04-01

Pre-gravid physical activity has been associated with a reduced risk of gestational diabetes mellitus (GDM), although neither the types of exercise nor the physiologic mechanisms underlying this protective effect have been well-studied. Thus, we sought to study the relationships between types of pre-gravid physical activity and metabolic parameters in pregnancy, including glucose tolerance, insulin sensitivity and beta-cell function. A total of 851 women underwent a glucose challenge test (GCT) and a 3-h oral glucose tolerance test (OGTT) in late pregnancy, yielding four glucose tolerance groups: (i) GDM; (ii) gestational impaired glucose tolerance (GIGT); (iii) abnormal GCT with normal glucose tolerance on OGTT (abnormal GCT NGT); and (iv) normal GCT with NGT on OGTT (normal GCT NGT). Pre-gravid physical activity was assessed using the Baecke questionnaire, which measures (i) total physical activity and (ii) its three component domains: work, nonsport leisure-time, and vigorous/sports activity. Glucose tolerance status improved across increasing quartiles of pre-gravid total physical activity (P = 0.0244). Whereas neither work nor nonsport leisure-time activity differed between glucose tolerance groups, pre-gravid vigorous/sports activity was significantly higher in women with normal GCT NGT compared to women with (i) abnormal GCT NGT (P = 0.0018) (ii) GIGT (P = 0.0025), and (iii) GDM (P = 0.0044). In particular, vigorous/sports activity correlated with insulin sensitivity (measured by IS(OGTT)) (r = 0.21, P < 0.0001). Furthermore, on multiple linear regression analysis, pre-gravid vigorous/sports activity emerged as a significant independent predictor of IS(OGTT) in pregnancy (t = 4.97, P < 0.0001). Pre-gravid vigorous/sports activity is associated with a reduced risk of glucose intolerance in pregnancy, an effect likely mediated by enhanced insulin sensitivity.

Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance.

PubMed

Sheikh, Saba; Gudipaty, Lalitha; De Leon, Diva D; Hadjiliadis, Denis; Kubrak, Christina; Rosenfeld, Nora K; Nyirjesy, Sarah C; Peleckis, Amy J; Malik, Saloni; Stefanovski, Darko; Cuchel, Marina; Rubenstein, Ronald C; Kelly, Andrea; Rickels, Michael R

2017-01-01

Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined β-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon responses compared with PS-CF and normal control subjects, indicating reduced β-cell secretory capacity and α-cell function. Fasting proinsulin-to-C-peptide and proinsulin secretory ratios during glucose potentiation were higher in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF compared with normal control subjects. These findings indicate that despite "normal" glucose tolerance, adolescents and adults with PI-CF have impairments in functional islet mass and associated early-phase insulin secretion, which with decreased incretin responses likely leads to the early development of postprandial hyperglycemia in CF. © 2017 by the American Diabetes Association.

Different cultivation methods to acclimatise ammonia-tolerant methanogenic consortia.

PubMed

Tian, Hailin; Fotidis, Ioannis A; Mancini, Enrico; Angelidaki, Irini

2017-05-01

Bioaugmentation with ammonia tolerant-methanogenic consortia was proposed as a solution to overcome ammonia inhibition during anaerobic digestion process recently. However, appropriate technology to generate ammonia tolerant methanogenic consortia is still lacking. In this study, three basic reactors (i.e. batch, fed-batch and continuous stirred-tank reactors (CSTR)) operated at mesophilic (37°C) and thermophilic (55°C) conditions were assessed, based on methane production efficiency, incubation time, TAN/FAN (total ammonium nitrogen/free ammonia nitrogen) levels and maximum methanogenic activity. Overall, fed-batch cultivation was clearly the most efficient method compared to batch and CSTR. Specifically, by saving incubation time up to 150%, fed-batch reactors were acclimatised to nearly 2-fold higher FAN levels with a 37%-153% methanogenic activity improvement, compared to batch method. Meanwhile, CSTR reactors were inhibited at lower ammonia levels. Finally, specific methanogenic activity test showed that hydrogenotrophic methanogens were more active than aceticlastic methanogens in all FAN levels above 540mgNH 3 -NL -1 . Copyright © 2017 Elsevier Ltd. All rights reserved.

Topical treatment of tinea pedis using 6% coriander oil in unguentum leniens: a randomized, controlled, comparative pilot study.

PubMed

Beikert, F C; Anastasiadou, Z; Fritzen, B; Frank, U; Augustin, M

2013-01-01

The antifungal activity of coriander oil has already been demonstrated in vitro. Evaluation of the efficacy and tolerability of 6% coriander oil in unguentum leniens in the treatment of interdigital tinea pedis. Half-side comparative pilot study on subjects with symmetric, bilateral interdigital tinea pedis. Active drug and placebo control were applied twice daily on the affected areas, and follow-up visits were performed on days 14 and 28. 40 participants (mean age 52.5 years, 60% male) were included in the study. For 6% coriander oil in unguentum leniens, a highly significant improvement of the clinical signs (p < 0.0001) was observed during the entire observation period; the number of positive fungal cultures also tended to decrease (p = 0.0654). The tolerability of the tested substances was good. Coriander oil is effective and well tolerated in the treatment of interdigital tinea pedis. Copyright © 2013 S. Karger AG, Basel.

Protective Role of Parenting Attitude on the Behavioral and Neurocognitive Development of the Children from Economically Disadvantaged Families.

PubMed

Jung, Da-Eun; Bhang, Soo-Young; Lee, Won-Hye; Yoon, Hae-Joo; Jung, Hee-Yeon; Kim, Yeni

2018-06-01

Association between home environment and the behavioral and neurocognitive development of children from a community childcare center for low-income families was examined (aged 6 to 12 years, n=155). The parents performed a questionnaire on home environment (K-HOME-Q) to assess home environment including parenting attitude and the Child Behavior Checklist (K-CBCL). The children performed the Wechsler Intelligence (IQ) Scale, Stroop interference test (Stroop), word fluency test (WF), and design fluency test (DF) to assess their neurocognitive development. 'Nurturing of Development' and 'Variety of Language Interaction' scores from the K-HOME-Q, were inversely associated with total behavior problems, externalization, rule-breaking, and aggressive behavior subscales of K-CBCL, and 'Emotional atmosphere' and 'Tolerance toward the child' scores showed inverse associations with the total behavior problems, rule-breaking, aggressive behavior, and withdrawn/depressed subscales. Despite economic hardship, the mean scores of the neurocognitive tests were comparable to the average level of Korean children's normative sample. However, 'Nurturing of Development' and 'Tolerance toward the Child' score of K-HOME-Q were associated with better executive function (IQ, WF, DF). These results suggest that parental stimulation of development and tolerant parenting attitude may offer protection against the negative effects of suboptimal economic environment on children's behavior and neurocognitive development.

Stress co-tolerance and trehalose content in baking strains of Saccharomyces cerevisiae.

PubMed

Lewis, J G; Learmonth, R P; Attfield, P V; Watson, K

1997-01-01

Fourteen wild-type baking strains of Saccharomyces cerevisiae were grown in batch culture to true stationary phase (exogenous carbon source exhausted) and tested for their trehalose content and their tolerance to heat (52 degrees C for 4.5 min), ethanol (20% v/v for 30 min), H2O2 (0.3 M for 60 min), rapid freezing (-196 degrees C for 20 min, cooling rate 200 degrees C min-1), slow freezing (-20 degrees C for 24 h, cooling rate 3 degrees C min(-1)), salt (growth in 1.5 M NaCl agar) or acetic acid (growth in 0.4% w/v acetic acid agar) stresses. Stress tolerance among the strains was highly variable and up to 1000-fold differences existed between strains for some types of stress. Compared with previously published reports, all strains were tolerant to H2O2 stress. Correlation analysis of stress tolerance results demonstrated relationships between tolerance to H2O2 and tolerance to all stresses except ethanol. This may imply that oxidative processes are associated with a wide variety of cellular stresses and also indicate that the general robustness associated with industrial yeast may be a result of their oxidative stress tolerance. In addition, H2O2 tolerance might be a suitable marker for the general assessment of stress tolerance in yeast strains. Trehalose content failed to correlate with tolerance to any stress except acetic acid. This may indicate that the contribution of trehalose to tolerance to other stresses is either small or inconsistent and that trehalose may not be used as a general predictor of stress tolerance in true stationary phase yeast.

Tolerance and Cross-Tolerance to Head Twitch Behavior Elicited by Phenethylamine- and Tryptamine-Derived Hallucinogens in Mice

PubMed Central

Smith, Douglas A.; Bailey, Jessica M.; Williams, Diarria

2014-01-01

The serotonin 5-hydroxytryptamine 2A (5-HT2A) receptor is a potential therapeutic target to a host of neuropsychiatric conditions, but agonist actions at this site are linked to abuse-related hallucinogenic effects that may limit therapeutic efficacy of chronic drug administration. Tolerance to some effects of hallucinogens has been observed in humans and laboratory animals, but the understanding of tolerance and cross-tolerance between distinct structural classes of hallucinogens is limited. Here, we used the drug-elicited head twitch response (HTR) in mice to assess the development of tolerance and cross-tolerance with two phenethylamine-derived [DOI (2,5-dimethoxy-4-iodoamphetamine) and 2C-T-7 (2,5-dimethoxy-4-propylthiophenethylamine)] and two tryptamine-derived [DPT (N,N-dipropyltryptamine) and DIPT (N,N-diisopropyltryptamine)] drugs with agonist affinity for 5-HT2A receptors. Tolerance developed to HTR elicited by daily DOI or 2C-T-7, but not to HTR elicited by DPT or DIPT. DOI-elicited tolerance was not surmountable with dose, and a similar insurmountable cross-tolerance was evident when DOI-tolerant mice were tested with various doses of 2C-T-7 or DPT. These studies suggest that the use of phenethylamine-derived hallucinogens as therapeutic agents may be limited not only by their abuse potential, but also by the rapid development of tolerance that would likely be maintained even if a patient were switched to a different 5-HT2A agonist medication from a distinct structural class. However, these experiments also imply that tryptamine-derived hallucinogens might have a reduced potential for tolerance development, compared with phenethylamine-derived 5-HT2A agonists, and might therefore be more suitable for chronic administration in a therapeutic context. PMID:25271256

Diagnostic Accuracies of Glycated Hemoglobin, Fructosamine, and Homeostasis Model Assessment of Insulin Resistance in Predicting Impaired Fasting Glucose, Impaired Glucose Tolerance, or New Onset Diabetes After Transplantation.

PubMed

Rosettenstein, Kerri; Viecelli, Andrea; Yong, Kenneth; Nguyen, Hung Do; Chakera, Aron; Chan, Doris; Dogra, Gursharan; Lim, Ee Mun; Wong, Germaine; Lim, Wai H

2016-07-01

New onset diabetes after transplantation (NODAT) is associated with a 3-fold greater risk of cardiovascular disease events, with early identification and treatment potentially attenuating this risk. The optimal screening test to identify those with NODAT remains unclear, and the aim of this study was to examine the diagnostic accuracies of 4 screening tests in identifying impaired fasting glucose, impaired glucose tolerance (IGT), and NODAT. This is a single-center prospective cohort study of 83 nondiabetic kidney transplant recipients between 2008 and 2011. Oral glucose tolerance test was considered the gold standard in identifying IFG/IGT or NODAT. Diagnostic accuracies of random blood glucose, glycated hemoglobin (HBA1c), fructosamine, and Homeostasis Model Assessment-Insulin Resistance in predicting IFG/IGT or NODAT were assessed using the area under the receiver operating characteristic curve. Forty (48%) recipients had IFG/IGT or NODAT. Compared with HBA1c with adjusted area under the curve (AUC) of 0.88 (95% confidence interval [95% CI], 0.77-0.93), fructosamine was the most accurate test with adjusted AUC of 0.92 (95% CI, 0.83-0.96). The adjusted AUCs of random blood glucose and Homeostasis Model Assessment-Insulin Resistance in identifying IFG/IGT were between 0.81 and 0.85. Restricting to identifying IGT/NODAT using 2-hour oral glucose tolerance test (n = 66), fructosamine was the most accurate diagnostic test with adjusted AUC of 0.93 (95% CI, 0.84-0.99), but not statistically different to HBA1c with adjusted AUC of 0.88 (95% CI, 0.76-0.96). Although HBA1c is an acceptable and widely used screening test in detecting IFG/IGT or NODAT, fructosamine may be a more accurate diagnostic test but this needs to be further examined in larger cohorts.

[Tolerance, safety and efficacy of the one-day preparation of PEG3350 + bisacodyl compared to 2 days of PEG3350 + bisacodyl in pediatric patients].

PubMed

Portillo Canizalez, Ligia Marcela; Blanco Rodriguez, Gerardo; Teyssier Morales, Gustavo; Penchyna Grub, Jaime; Trauernicht Mendieta, Sean; Zurita-Cruz, Jessie Nallely

Multiple intestinal preparations have been used in children undergoing colonoscopy, with variable limitation due to acceptance, tolerance, and proper cleaning. The objective of this study was to compare the tolerability, safety and efficacy of the colonoscopy preparation with 1 day with PEG 3350 (poliethylenglycol) (4g/kg/day) + bisacodyl compared to 2 days of preparation with PEG 3350 (2g/kg/day) + bisacodyl in pediatric patients. A clinical, randomized, and blind trial was performed. Patients aged 2 to 18 years scheduled for colonoscopy were included. Patients were randomized into two groups: 1 day of preparation with PEG 3350 4g/kg/day + bisacodyl and 2 days of preparation with PEG 3350 2g/kg/day + bisacodyl. Through a questionnaire, physical examination and endoscopic evaluation (Boston scale), the tolerance, safety and efficacy of the 2 preparations to be evaluated were determined. Student's t test was performed for quantitative variables and χ 2 for qualitative variables. There were no significant differences in compliance rates, adverse effects, and extent of colonoscopic evaluation. Tolerance and safety between the intestinal preparation for 1-day colonoscopy with PEG 3350 (4g/kg/day) + bisacodyl and the 2-day preparation with PEG 3350 (2g/kg/day) + bisacodyl were similar. The quality of cleanliness was good in both groups, being partially more effective in the 1-day group with PEG 3350 (4g/kg/day). Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Ethanol Reversal of Tolerance to the Antinociceptive Effects of Oxycodone and Hydrocodone.

PubMed

Jacob, Joanna C; Poklis, Justin L; Akbarali, Hamid I; Henderson, Graeme; Dewey, William L

2017-07-01

This study compared the development of tolerance to two orally bioavailable prescription opioids, oxycodone and hydrocodone, to that of morphine, and the reversal of this tolerance by ethanol. Oxycodone (s.c.) was significantly more potent in the mouse tail-withdrawal assay than either morphine or hydrocodone. Oxycodone was also significantly more potent in this assay than hydrocodone when administered orally. Tolerance was seen following chronic subcutaneous administration of each of the three drugs and by the chronic administration of oral oxycodone, but not following the chronic oral administration of hydrocodone. Ethanol (1 g/kg i.p.) significantly reversed the tolerance to the subcutaneous administration of each of the three opioids that developed when given 30 minutes prior to challenge doses. It took twice as much ethanol, when given orally, to reverse the tolerance to oxycodone. We investigated whether the observed tolerance to oxycodone and its reversal by ethanol were due to biodispositional changes or reflected a true neuronal tolerance. As expected, a relationship between brain oxycodone concentrations and activity in the tail-immersion test existed following administration of acute oral oxycodone. Following chronic treatment, brain oxycodone concentrations were significantly lower than acute concentrations. Oral ethanol (2 g/kg) reversed the tolerance to chronic oxycodone, but did not alter brain concentrations of either acute or chronic oxycodone. These studies show that there is a metabolic component of tolerance to oxycodone; however, the reversal of that tolerance by ethanol is not due to an alteration of the biodisposition of oxycodone, but rather is neuronal in nature. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Sensitivity and specificity of modified 100-g oral glucose tolerance tests for diagnosis of gestational diabetes mellitus.

PubMed

Hansarikit, Jarunee; Manotaya, Saknan

2011-05-01

To study the sensitivity and specificity of the modified 100-g oral glucose tolerance test for diagnosis of gestational diabetes mellitus (GDM). Medical records of pregnant women attending the antenatal clinic of King Chulalongkorn Memorial Hospital, Thailand, who underwent a 100-g oral glucose tolerance test (OGTT) during March 2004 to September 2009, were retrospectively reviewed. Three modified criteria were proposed for diagnosis of GDM. The screening efficacy of the modified criteria were assessed, using the National Diabetes Data Group (NDDG) criterion as gold standard. A total of 729 records were reviewed, 511 were included for analysis. Using the NDDG criterion as the gold standard, the modified II criterion has the highest sensitivity of 96.8%, and the highest accuracy of 90.8%. The modified II criterion can detect the same proportion of maternal and neonatal complications, compared to the NDDG criterion. The modified II criterion, using the fasting plasma glucose and 2-hour plasma glucose measurements, showed high sensitivity and accuracy, with moderate specificity for diagnosis of GDM. Its potential use as an alternative to standard 100-g OGTT should be evaluated in the prospective study.

Musical Agency during Physical Exercise Decreases Pain.

PubMed

Fritz, Thomas H; Bowling, Daniel L; Contier, Oliver; Grant, Joshua; Schneider, Lydia; Lederer, Annette; Höer, Felicia; Busch, Eric; Villringer, Arno

2017-01-01

Objectives: When physical exercise is systematically coupled to music production, exercisers experience improvements in mood, reductions in perceived effort, and enhanced muscular efficiency. The physiology underlying these positive effects remains unknown. Here we approached the investigation of how such musical agency may stimulate the release of endogenous opioids indirectly with a pain threshold paradigm. Design: In a cross-over design we tested the opioid-hypothesis with an indirect measure, comparing the pain tolerance of 22 participants following exercise with or without musical agency. Method: Physical exercise was coupled to music by integrating weight-training machines with sensors that control music-synthesis in real time. Pain tolerance was measured as withdrawal time in a cold pressor test. Results: On average, participants tolerated cold pain for ~5 s longer following exercise sessions with musical agency. Musical agency explained 25% of the variance in cold pressor test withdrawal times after factoring out individual differences in general pain sensitivity. Conclusions: This result demonstrates a substantial pain reducing effect of musical agency in combination with physical exercise, probably due to stimulation of endogenous opioid mechanisms. This has implications for exercise endurance, both in sports and a multitude of rehabilitative therapies in which physical exercise is effective but painful.

Musical Agency during Physical Exercise Decreases Pain

PubMed Central

Fritz, Thomas H.; Bowling, Daniel L.; Contier, Oliver; Grant, Joshua; Schneider, Lydia; Lederer, Annette; Höer, Felicia; Busch, Eric; Villringer, Arno

2018-01-01

Objectives: When physical exercise is systematically coupled to music production, exercisers experience improvements in mood, reductions in perceived effort, and enhanced muscular efficiency. The physiology underlying these positive effects remains unknown. Here we approached the investigation of how such musical agency may stimulate the release of endogenous opioids indirectly with a pain threshold paradigm. Design: In a cross-over design we tested the opioid-hypothesis with an indirect measure, comparing the pain tolerance of 22 participants following exercise with or without musical agency. Method: Physical exercise was coupled to music by integrating weight-training machines with sensors that control music-synthesis in real time. Pain tolerance was measured as withdrawal time in a cold pressor test. Results: On average, participants tolerated cold pain for ~5 s longer following exercise sessions with musical agency. Musical agency explained 25% of the variance in cold pressor test withdrawal times after factoring out individual differences in general pain sensitivity. Conclusions: This result demonstrates a substantial pain reducing effect of musical agency in combination with physical exercise, probably due to stimulation of endogenous opioid mechanisms. This has implications for exercise endurance, both in sports and a multitude of rehabilitative therapies in which physical exercise is effective but painful. PMID:29387030

[Repeated body position change training can improve human head-down tilt tolerance].

PubMed

Wu, Bin; Wu, Ping; Xue, Yue-Ying; Liu, Xing-Hua; Wang, Yan-Lei; Jiang, Shi-Zhong

2008-02-01

To verify the hypothesis that repeated body position change training can improve human head-down tilt (HDT) tolerance. Six young healthy subjects were trained with repeated position change for 9 times and 11 days according to protocol of alternative head-down and head-up tilts, each time of training lasted for about 35 min. Their HDT tolerance (- 30 degrees/30 min) were determined before and after training. (1) Compared with the data before training, subjects' symptom scores during HDT test after training decreased significantly (6.00 +/- 3.79 vs 1.00 +/- 0.63, P < 0.05), magnitude of the decreased heart rate increased significantly (-0.6 +/- 2.5 vs -4.4 +/- 3.6, P < 0.01). (2) Before training, blood flow volume of internal jugular vein (IJV) during HDT decreased significantly and that of internal carotid artery (ICA) increased significantly at the beginning period of HDT compared with pre-HDT (P < 0.01), while blood flow volume of the common carotid artery (CCA) presented increasing trend. After training, there was no significant difference in blood flow volume of IJV between during HDT and pre-HDT, that of ICA and CCA presented decreasing trend in the final period of HDT compared with Pre-HDT. Repeated body position change training can improve human head-down tilt tolerance. And its main causation is that headward shift of blood volume is restrained to some extend during HDT after training.

Testing the air pollution tolerances of shade tree cultivars

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karnosky, D.J.

1978-01-01

A program in progress to test the relative air pollution tolerances of some commonly planted shade tree cultivars is described. The relative sulfur dioxide and ozone tolerances of several cultivars of acer, fagus, fraxinus, ginkgo, gleditsia, platanus, and quercus species are being determined by examination of foliar response to short-term, high-concentration fumigations. In a follow-up study, the extent of foliar injury, growth reduction, and mortality caused by air pollution will be examined for the same cultivars grown in test plantings in and around New York City. The correlation of the relative sulfur dioxide and ozone tolerances, as determined by themore » controlled-fumigation tests, with urban survival and growth will be useful in determining the adequacy of acute exposure fumigations in testing the air pollution tolerances of the tree species under study.« less

Comparison of safety, efficacy and tolerability of dexibuprofen and ibuprofen in the treatment of osteoarthritis of the hip or knee.

PubMed

Zamani, Omid; Böttcher, Elke; Rieger, Jörg D; Mitterhuber, Johann; Hawel, Reinhold; Stallinger, Sylvia; Eller, Norbert

2014-06-01

In this observer-blinded, multicenter, non-inferiority study, 489 patients suffering from painful osteoarthritis of the hip or knee were included to investigate safety and tolerability of Dexibuprofen vs. Ibuprofen powder for oral suspension. Only patients who had everyday joint pain for the past 3 months and "moderate" to "severe" global pain intensity in the involved hip/knee of within the last 48 h were enrolled. The treatment period was up to 14 days with a control visit after 3 days. The test product was Dexibuprofen 400 mg powder for oral suspension (daily dose 800 mg) compared to Ibuprofen 400 mg powder for oral suspension (daily dose 1,600 mg). Gastrointestinal adverse drug reactions were reported in 8 patients (3.3 %) in the Dexibuprofen group and in 19 patients (7.8 %) in the Ibuprofen group. Statistically significant non-inferiority was shown for Dexibuprofen. Comparing both groups by a Chi square test showed a statistical significant lower proportion of related gastrointestinal events in the Dexibuprofen group. All analyses of secondary tolerability parameters showed the same result of a significantly better safety profile in this therapy setting for Dexibuprofen compared to Ibuprofen. The sum of pain intensity, pain relief and global assessments showed no significant difference between treatment groups. In summary, analyses revealed at least non-inferiority in terms of efficacy and a statistically significant better safety profile for the Dexibuprofen treatment.

Oxygen-limited thermal tolerance is seen in a plastron-breathing insect and can be induced in a bimodal gas exchanger.

PubMed

Verberk, Wilco C E P; Bilton, David T

2015-07-01

Thermal tolerance has been hypothesized to result from a mismatch between oxygen supply and demand. However, the generality of this hypothesis has been challenged by studies on various animal groups, including air-breathing adult insects. Recently, comparisons across taxa have suggested that differences in gas exchange mechanisms could reconcile the discrepancies found in previous studies. Here, we test this suggestion by comparing the behaviour of related insect taxa with different gas exchange mechanisms, with and without access to air. We demonstrate oxygen-limited thermal tolerance in air-breathing adults of the plastron-exchanging water bug Aphelocheirus aestivalis. Ilyocoris cimicoides, a related, bimodal gas exchanger, did not exhibit such oxygen-limited thermal tolerance and relied increasingly on aerial gas exchange with warming. Intriguingly, however, when denied access to air, oxygen-limited thermal tolerance could also be induced in this species. Patterns in oxygen-limited thermal tolerance were found to be consistent across life-history stages in these insects, with nymphs employing the same gas exchange mechanisms as adults. These results advance our understanding of oxygen limitation at high temperatures; differences in the degree of respiratory control appear to modulate the importance of oxygen in setting tolerance limits. © 2015. Published by The Company of Biologists Ltd.

Oxygen-limited thermal tolerance is seen in a plastron-breathing insect and can be induced in a bimodal gas exchanger

PubMed Central

Verberk, Wilco C. E. P.; Bilton, David T.

2015-01-01

ABSTRACT Thermal tolerance has been hypothesized to result from a mismatch between oxygen supply and demand. However, the generality of this hypothesis has been challenged by studies on various animal groups, including air-breathing adult insects. Recently, comparisons across taxa have suggested that differences in gas exchange mechanisms could reconcile the discrepancies found in previous studies. Here, we test this suggestion by comparing the behaviour of related insect taxa with different gas exchange mechanisms, with and without access to air. We demonstrate oxygen-limited thermal tolerance in air-breathing adults of the plastron-exchanging water bug Aphelocheirus aestivalis. Ilyocoris cimicoides, a related, bimodal gas exchanger, did not exhibit such oxygen-limited thermal tolerance and relied increasingly on aerial gas exchange with warming. Intriguingly, however, when denied access to air, oxygen-limited thermal tolerance could also be induced in this species. Patterns in oxygen-limited thermal tolerance were found to be consistent across life-history stages in these insects, with nymphs employing the same gas exchange mechanisms as adults. These results advance our understanding of oxygen limitation at high temperatures; differences in the degree of respiratory control appear to modulate the importance of oxygen in setting tolerance limits. PMID:25964420

[Body composition in women with gestational diabetes mellitus].

PubMed

Moreno Martinez, Socorro; Tufiño Olivares, Edith; Chávez Loya, Vicente; Rodríguez Morán, Martha; Guerrero Romero, Fernando; Levario Carrillo, Margarita

2009-06-01

Several techniques have been used to determine body composition during pregnancy. To determine the characteristics of body composition in women with gestational diabetes mellitus in comparison with women with normal glucose tolerance and pre-gestacional diabetes. Pregnant women with gestational diabetes mellitus, pre-gestacional diabetes, and normal glucose tolerance, between 24 to 32 weeks of single gestation, were enrolled in a cross-sectional study. Screening of DMG was carried out using 50 g of glucose load; diagnosis was confirmed by oral glucose tolerance test. Evaluation of body composition was carried out by bioelectrical impedance. The Kruskal Wallis test was used for statistical analysis. A total of 79 women were included; of these, diagnosis of gestational diabetes mellitus, pre-gestacional diabetes, and normal glucose tolerance was established in 14, 9, and 56 women, respectively. Pre-gestational body mass index was greater in women with diabetes (p < 0.01). Fat free mass and total body water were similar in the studied groups. Fat mass was greater in women with gestational diabetes mellitus (range 21.0-29.4 kg) and patients with pre-gestacional diabetes (range 26.4-32.7 kg) than in the women with normal glucose tolerance (range 150.8-25.9 kg), p < 0.01. The body composition of women, between 24 to 32 weeks of single gestation, is different in the women with gestational diabetes mellitus compared with women with normal glucose tolerance. Women with gestational diabetes mellitus show a significant increase in fat mass without significant changes in the fat free mass and total body water.

Changes in glucose-elicited blood metabolite responses following weight loss and long term weight maintenance in obese individuals with impaired glucose tolerance.

PubMed

Geidenstam, Nina; Danielsson, Anders P H; Spégel, Peter; Ridderstråle, Martin

2016-03-01

Weight loss improves insulin sensitivity and glucose tolerance in obese subjects with impaired glucose tolerance (IGT), but the long term dynamic effects on blood metabolites other than glucose during an oral glucose tolerance test (OGTT), are largely unknown. Here, we studied changes in OGTT-elicited metabolite patterns in obese subjects during a diet-induced weight loss study. Blood samples from 14 obese individuals with IGT were collected at 0, 30 and 120 min during a standard 75 g OGTT at baseline (BMI 44 ± 2 kg/m(2)), after weight loss (BMI 36 ± 2 kg/m(2)) and after weight maintenance (BMI 35 ± 2 kg/m(2)). Serum metabolite levels were analyzed by gas chromatography/mass spectrometry and compared to a lean glucose tolerant group. Changes in the OGTT-elicited metabolite patterns occurred differentially during weight loss and weight maintenance. Enhanced suppression of aromatic amino acids were associated with decreased insulinogenic index observed after weight loss (tyrosine: r=0.72, p=0.013; phenylalanine: r=0.63, p=0.039). The OGTT-elicited suppression and/or lack of increase in levels of glutamate, glutamine, isoleucine, leucine, and the fatty acids laurate, oleate and palmitate, improved towards the lean profile after weight maintenance, paralleling an improvement in glucose tolerance. The greater heterogeneity in the response before and after weight loss in the obese, compared to lean subjects, was markedly reduced after weight maintenance. Diet-induced weight loss followed by weight maintenance results in changes in metabolite profiles associated with either hepatic insulin sensitivity or peripheral glucose tolerance. Our results highlight the importance of evaluating the effects of weight loss and weight maintenance separately. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparing the Robustness of High-Frequency Traveling-Wave Tube Slow-Wave Circuits

NASA Technical Reports Server (NTRS)

Chevalier, Christine T.; Wilson, Jeffrey D.; Kory, Carol L.

2007-01-01

A three-dimensional electromagnetic field simulation software package was used to compute the cold-test parameters, phase velocity, on-axis interaction impedance, and attenuation, for several high-frequency traveling-wave tube slow-wave circuit geometries. This research effort determined the effects of variations in circuit dimensions on cold-test performance. The parameter variations were based on the tolerances of conventional micromachining techniques.

Pain perception and cardiovascular system response among athletes playing contact sports.

PubMed

Leźnicka, Katarzyna; Pawlak, Matthias; Białecka, Monika; Safranow, Krzysztof; Cięszczyk, Paweł

2017-01-01

The aim of this study was to determine whether the contact sports change the perception of pain as assessed by the cold pressor test (CPT), and if the test induces the same reaction of the cardiovascular system in contact athletes and non-athletes. The study involved 321 healthy men; 140 contact athletes and 181 students of the University of Szczecin (control). Pain threshold and pain tolerance were evaluated using CPT. Cardiovascular measurements were made during CPT. The contact athletes showed a much higher tolerance to pain than the control group (median time 120 vs. 94 s, respectively, p = 0.0002). The thresholds of pain in both groups did not differ significantly between the groups. Systolic blood pressure measured before and during the test in all three measurements was statistically significantly higher in athletes compared with the control group. Heart rate and diastolic blood pressure did not differ significantly between the studied groups.

Role of self-reported individual differences in preference for and tolerance of exercise intensity in fitness testing performance.

PubMed

Hall, Eric E; Petruzzello, Steven J; Ekkekakis, Panteleimon; Miller, Paul C; Bixby, Walter R

2014-09-01

Performance in fitness tests could depend on factors beyond the bioenergetic and skeletomuscular systems, such as individual differences in preference for and tolerance of different levels of exercise-induced somatosensory stimulation. Although such individual-difference variables could play a role in exercise testing and prescription, they have been understudied. The purpose of these studies was to examine the relationships of self-reported preference for and tolerance of exercise intensity with performance in fitness tests. Participants in study I were 516 men and women volunteers from a campus community, and participants in study II were 42 men recruit firefighters undergoing a 6-week training program. Both the Preference and Tolerance scores exhibited significant relationships with performance in several fitness tests and with body composition and physical activity participation. Preference and Tolerance did not change after the training program in study II, despite improvements in objective and perceived fitness, supporting their conceptualization as dispositional traits. Preference and Tolerance scores could be useful not only in ameliorating the current understanding of the determinants of physical performance, but also in personalizing exercise prescriptions and, thus, delivering exercise experiences that are more pleasant, tolerable, and sustainable.

The Yeast HAL1 Gene Improves Salt Tolerance of Transgenic Tomato1

PubMed Central

Gisbert, Carmina; Rus, Ana M.; Bolarín, M. Carmen; López-Coronado, J. Miguel; Arrillaga, Isabel; Montesinos, Consuelo; Caro, Manuel; Serrano, Ramon; Moreno, Vicente

2000-01-01

Overexpression of the HAL1 gene in yeast has a positive effect on salt tolerance by maintaining a high internal K+ concentration and decreasing intracellular Na+ during salt stress. In the present work, the yeast gene HAL1 was introduced into tomato (Lycopersicon esculentum Mill.) by Agrobacterium tumefaciens-mediated transformation. A sample of primary transformants was self-pollinated, and progeny from both transformed and non-transformed plants (controls) were evaluated for salt tolerance in vitro and in vivo. Results from different tests indicated a higher level of salt tolerance in the progeny of two different transgenic plants bearing four copies or one copy of the HAL1 gene. In addition, measurement of the intracellular K+ to Na+ ratios showed that transgenic lines were able to retain more K+ than the control under salt stress. Although plants and yeast cannot be compared in an absolute sense, these results indicate that the mechanism controlling the positive effect of the HAL1 gene on salt tolerance may be similar in transgenic plants and yeast. PMID:10806256

Study of fault tolerant software technology for dynamic systems

NASA Technical Reports Server (NTRS)

Caglayan, A. K.; Zacharias, G. L.

1985-01-01

The major aim of this study is to investigate the feasibility of using systems-based failure detection isolation and compensation (FDIC) techniques in building fault-tolerant software and extending them, whenever possible, to the domain of software fault tolerance. First, it is shown that systems-based FDIC methods can be extended to develop software error detection techniques by using system models for software modules. In particular, it is demonstrated that systems-based FDIC techniques can yield consistency checks that are easier to implement than acceptance tests based on software specifications. Next, it is shown that systems-based failure compensation techniques can be generalized to the domain of software fault tolerance in developing software error recovery procedures. Finally, the feasibility of using fault-tolerant software in flight software is investigated. In particular, possible system and version instabilities, and functional performance degradation that may occur in N-Version programming applications to flight software are illustrated. Finally, a comparative analysis of N-Version and recovery block techniques in the context of generic blocks in flight software is presented.

The initial tolerance to sub-lethal Cd exposure is the same among ten naïve pond populations of Daphnia magna, but their micro-evolutionary potential to develop resistance is very different.

PubMed

Messiaen, Marlies; Janssen, Colin Roger; De Meester, Luc; De Schamphelaere, Karel André Clara

2013-11-15

Genetic variation complicates predictions of both the initial tolerance and the long-term (micro-evolutionary) response of natural Daphnia populations to chemical stressors from results of standard single-clone laboratory ecotoxicity tests. In order to investigate possible solutions to this problem, we aimed to compare the initial sub-lethal tolerance to Cd of 10 naïve natural pond populations of Daphnia magna as well as their evolutionary potential to develop increased resistance. We did so by measuring reproductive performance of 120 clones, i.e. 12 clones hatched from the recent dormant egg bank of each of 10 populations, both in absence (Cd-free control) and presence of 4.4 μg Cd/L. We show that the initial tolerance, defined as the reproductive performance of individuals of the first generation exposed to Cd relative to that in a Cd-free control was not significantly different among the 10 studied pond populations and averaged 0.82 ± 0.04 over these populations. Moreover, these populations' initial tolerances were also not significantly different from the mean initial tolerance of 0.87 ± 0.08 at 4.0 μg Cd/L measured for a group of 7 often-used laboratory clones, collected from a range of European ecotoxicity testing laboratories. This indicates that the initial response of naïve natural pond populations to sub-lethal Cd can be relatively accurately predicted from ecotoxicity test data from only a handful of laboratory clones. We then used estimates of broad-sense heritability of Cd tolerance (H(2)) - based on the same dataset - as a proxy of these populations' capacities to evolutionarily respond to Cd in terms of the development of increased resistance, which is here defined as the increase with time of the frequency of clones with a higher Cd tolerance in the population (accompanied with an increase of mean Cd-tolerance of the population above the initial tolerance). We show that the populations' estimated H(2) values of Cd-tolerance cover almost the entire theoretically possible range, ranging from not significantly different from zero (for five populations) to between 0.48 and 0.81 (for the five other populations). This indicates that, unlike the initial tolerance to Cd, the (long-term) micro-evolutionary response to Cd may be very different among natural pond populations. Therefore, we conclude that it may be very difficult to predict the long-term response of an unstudied population to chemical stress from tolerance data on a sample of other populations. It is therefore suggested that new methods for forecasting long-term responses should be explored, such as the development of predictive models based on the combination of population-genomic and tolerance time-series data. Copyright © 2013 Elsevier B.V. All rights reserved.

Peptide Glutamine Supplementation for Tolerance of Intermittent Exercise in Soccer Players

PubMed Central

Favano, Alessandra; Santos-Silva, Paulo Roberto; Nakano, Eduardo Yoshio; Pedrinelli, André; Hernandez, Arnaldo José; Greve, Julia Maria D’Andrea

2008-01-01

OBJECTIVE To investigate whether supplementation of carbohydrate together with peptide glutamine would increase exercise tolerance in soccer players. METHODS Nine male soccer players (mean age: 18.4 ± 1.1 years; body mass: 69.2 ± 4.6 kg; height: 175.5 ± 7.3 cm; and maximum oxygen consumption of 57.7 ± 4.8 ml·kg−1·min−1) were evaluated. All of them underwent a cardiopulmonary exercise test and followed a protocol that simulated the movements of a soccer game in order to evaluate their tolerance to intermittent exercise. By means of a draw, either carbohydrate with peptide glutamine (CARBOGLUT: 50g of maltodextrin + 3.5g of peptide glutamine in 250 ml of water) or carbohydrate alone (CARBO: 50g of maltodextrin in 250 ml of water) was administered in order to investigate the enhancement of the soccer players’ performances. The solution was given thirty minutes before beginning the test, which was performed twice with a one-week interval between tests. RESULTS A great improvement in the time and distance covered was observed when the athletes consumed the CARBOGLUT mixture. Total distance covered was 12750 ± 4037m when using CARBO, and 15571 ± 4184m when using CARBOGLUT (p<0.01); total duration of tolerance was 73 ± 23 min when using CARBO and 88 ± 24 min when using CARBOGLUT (p<0.01). CONCLUSION The CARBOGLUT mixture was more efficient in increasing the distance covered and the length of time for which intermittent exercise was tolerated. CARBOGLUT also reduced feelings of fatigue in the players compared with the use of the CARBO mixture alone. PMID:18297203

Tolerance of Erythrocytes in Poultry: Induction and Specificity

PubMed Central

Mitchison, N. A.

1962-01-01

Measurement of the rate of elimination of 51Cr-labelled erythrocytes provides a reliable test of immunity in fowls. Chickens can be rendered tolerant of homologous and turkey erythrocytes, as judged by this test, by receiving a series of transfusions of irradiated blood. The series were arranged so that foreign cells remained present in the circulation from the time of hatching. Tolerance induced by this treatment is generally incomplete, but can last indefinitely. In some chickens the manifestation of tolerance of turkey erythrocytes is delayed, probably because of passive transmission of antibody from the dam. Chickens old enough to react against small transfusions of homologous blood can still be rendered tolerant by massive transfusions. Tolerance of the erythrocytes from an individual donor extends only slightly to those from other donors. Tolerance acquired in this way, through transfusion of irradiated blood, stands in contrast to the more stable and complete tolerance that can be acquired through administration of viable cells. Viable cells, on the other hand, provide a less sensitive test, for birds which tolerate skin homografts often eliminate rapidly erythrocytes from the same donor. PMID:14474652

Emergency department treatment of viral gastritis using intravenous ondansetron or dexamethasone in children.

PubMed

Stork, Christine M; Brown, Kathleen M; Reilly, Tracey H; Secreti, LaLaina; Brown, Lawrence H

2006-10-01

To compare the efficacy of intravenous ondansetron or dexamethasone compared with intravenous fluid therapy alone in children presenting to the emergency department with refractory vomiting from viral gastritis who had failed attempts at oral hydration. This double-blind, randomized, controlled trial was performed in a tertiary care pediatric emergency department. Children aged 6 months to 12 years presenting with more than three episodes of vomiting in the past 24 hours, mild/moderate dehydration, and failed oral hydration were included. Patients with other medical causes were excluded. Subjects were randomized to dexamethasone 1 mg/kg (15 mg maximum), ondansetron 0.15 mg/kg, or placebo (normal saline [NS], 10 mL). All subjects also received intravenous NS at 10-20 mL/kg/hr. Oral fluid tolerance was evaluated at two and four hours. Those not tolerating oral fluids at four hours were admitted. Discharged patients were evaluated at 24 and 72 hours for vomiting and repeat health care visits. The primary study outcome was hospitalization rates between the groups. Data were analyzed using chi-square test, Kruskal-Wallis test, Mantel-Haenszel test, and analysis of variance, with p < 0.05 considered significant. A total of 166 subjects were enrolled; data for analysis were available for 44 NS-treated patients, 46 ondansetron-treated patients, and 47 dexamethasone-treated patients. Hospital admission occurred in nine patients (20.5%) receiving placebo (NS alone), two patients (4.4%) receiving ondansetron, and seven patients (14.9%) receiving dexamethasone, with ondansetron significantly different from placebo (p = 0.02). Similarly, at two hours, more ondansetron-treated patients (39 [86.6%]) tolerated oral hydration than NS-treated patients (29 [67.4%]; relative risk, 1.28; 95% confidence interval = 1.02 to 1.68). There were no differences in number of mean episodes of vomiting or repeat visits to health care at 24 and 72 hours in the ondansetron, dexamethasone, or NS groups. In children with dehydration secondary to vomiting from acute viral gastritis, ondansetron with intravenous rehydration improves tolerance of oral fluids after two hours and reduces the hospital admission rate when compared with intravenous rehydration with or without dexamethasone.

Spinal antinociception of synthetic omega-conotoxin SO-3, a selective N-type neuronal voltage-sensitive calcium channel blocker, and its effects on morphine analgesia in chemical stimulus tests in rodent.

PubMed

Yan, Ling-Di; Liu, Yan-Li; Zhang, Lei; Dong, Hua-Jin; Zhou, Pei-Lan; Su, Rui-Bin; Gong, Ze-Hui; Huang, Pei-Tang

2010-06-25

SO-3, a novel Omega-superfamily conotoxin derived from Conus striatus, selectively inhibits N-type neuronal voltage-sensitive calcium channels. In current study, antinociception of SO-3 compared with MVIIA or morphine and its effects on morphine analgesia were investigated in rodent chemical stimulus tests after acute or repeated intrathecal administration. In mice acetic acid writhing test, similar to MVIIA, SO-3 caused dose- and time-dependent spinal antinociception with ED(50) of 0.25 microg/kg and t(1/2) of 4h, which was more potent and longer-acting than morphine. In rat formalin test after intrathecal bolus injection, SO-3 produced dose- and time-dependent antinociception by suppressing acute (ED(50), 1.79 microg/kg) and tonic phases (ED(50), 0.41 microg/kg), which was similar to MVIIA and approximately 10-fold potency and twice longer-acting of morphine in blocking tonic phase responses. After repeated intrathecal injections twice daily for 5 consecutive days, SO-3 produced analgesia without loss of potency whereas morphine produced analgesia tolerance in rat formalin test; further, SO-3 still produced potent analgesia in morphine-tolerant rats. SO-3 co-administered with morphine left-shift the dose-response curve of morphine in mice acetic acid writhing test and significantly potentiated morphine analgesia in rat formalin test. No changes in motor function were seen in mice or rats receiving antinociceptive doses of SO-3 whereas MVIIA caused motor dysfunction at doses of 1.0-2.0 microg/kg in rats. This study showed that (1) novel SO-3 produced potent and long-acting spinal antinociception without observable motor dysfunction, (2) SO-3 significantly potentiated morphine analgesia, (3) After repeated intrathecal administration, SO-3 produced neither tolerance nor cross-tolerance to morphine analgesia. (c) 2010 Elsevier B.V. All rights reserved.

Simultaneous Transplantation of Hematopoietic Stem Cells and a Vascularized Composite Allograft Leads to Tolerance

PubMed Central

Mathes, David W.; Chang, Jeff; Hwang, Billanna; Graves, Scott S.; Storer, Barry E.; Butts-Miwongtum, Tiffany; Sale, George E.; Storb, Rainer

2014-01-01

Background We have previously demonstrated that tolerance to a vascularized composite allograft (VCA) can be achieved after the establishment of mixed chimerism. Here, we test the hypothesis that tolerance to a VCA in our dog leukocyte antigen (DLA)-matched canine model is not dependent on the previous establishment of mixed chimerism and can be induced coincident with hematopoietic cell transplantation (HCT). Methods Eight DLA-matched, minor antigen mismatched dogs received 200 cGy of radiation and a VCA transplant. Four dogs received donor bone marrow at the time of VCA transplantation (group 1) while a second group of 4 dogs did not (group 2). All recipients received a limited course of post-grafting immunosuppression. All dogs that received HCT and VCA were given donor, third party and autologous skin grafts. Results All group 1 recipients were tolerant to their VCA (> 62 weeks). Three of the four dogs in group 2 rejected their VCA transplants after the cessation of immunosuppression. Biopsies obtained from muscle and skin of VCA from group 1 showed few infiltrating cells compared to extensive infiltrates in biopsies of VCA from group 2. Compared to autologous skin and muscle, elevated levels of CD3+ FoxP3+ T-regulatory cells were found in skin and muscle obtained from VCA of HCT recipients. All group 1 animals were tolerant to their donor skin graft and promptly rejected the third-part skin grafts. Conclusion These data demonstrated donor specific tolerance to all components of the VCA can be established through simultaneous nonmyeloablative allogeneic HCT and VCA transplant protocol. PMID:24918616

Rare Sugar Syrup Containing d-Allulose but Not High-Fructose Corn Syrup Maintains Glucose Tolerance and Insulin Sensitivity Partly via Hepatic Glucokinase Translocation in Wistar Rats.

PubMed

Shintani, Tomoya; Yamada, Takako; Hayashi, Noriko; Iida, Tetsuo; Nagata, Yasuo; Ozaki, Nobuaki; Toyoda, Yukiyasu

2017-04-05

Ingestion of high-fructose corn syrup (HFCS) is associated with the risk of both diabetes and obesity. Rare sugar syrup (RSS) has been developed by alkaline isomerization of HFCS and has anti-obesity and anti-diabetic effects. However, the influence of RSS on glucose metabolism has not been explored. We investigated whether long-term administration of RSS maintains glucose tolerance and whether the underlying mechanism involves hepatic glucokinase translocation. Wistar rats were administered water, RSS, or HFCS in drinking water for 10 weeks and then evaluated for glucose tolerance, insulin tolerance, liver glycogen content, and subcellular distribution of liver glucokinase. RSS significantly suppressed body weight gain and abdominal fat mass (p < 0.05). The glucose tolerance test revealed significantly higher blood glucose levels in the HFCS group compared to the water group, whereas the RSS group had significantly lower blood glucose levels from 90 to 180 min (p < 0.05). At 30, 60, and 90 min, the levels of insulin in the RSS group were significantly lower than those in the water group (p < 0.05). The amount of hepatic glycogen was more than 3 times higher in the RSS group than that in the other groups. After glucose loading, the nuclear export of glucokinase was significantly increased in the RSS group compared to the water group. These results imply that RSS maintains glucose tolerance and insulin sensitivity, at least partly, by enhancing nuclear export of hepatic glucokinase.

Down-Regulating α-Galactosidase Enhances Freezing Tolerance in Transgenic Petunia1

PubMed Central

Pennycooke, Joyce C.; Jones, Michelle L.; Stushnoff, Cecil

2003-01-01

α-Galactosidase (α-Gal; EC 3.2.1.22) is involved in many aspects of plant metabolism, including hydrolysis of the α-1,6 linkage of raffinose oligosaccharides during deacclimation. To examine the relationship between endogenous sugars and freezing stress, the expression of α-Gal was modified in transgenic petunia (Petunia × hybrida cv Mitchell). The tomato (Lycopersicon esculentum) Lea-Gal gene under the control of the Figwort Mosaic Virus promoter was introduced into petunia in the sense and antisense orientations using Agrobacterium tumefaciens-mediated transformation. RNA gel blots confirmed that α-Gal transcripts were reduced in antisense lines compared with wild type, whereas sense plants had increased accumulation of α-Gal mRNAs. α-Gal activity followed a similar trend, with reduced activity in antisense lines and increased activity in all sense lines evaluated. Raffinose content of nonacclimated antisense plants increased 12- to 22-fold compared with wild type, and 22- to 53-fold after cold acclimation. Based upon electrolyte leakage tests, freezing tolerance of the antisense lines increased from –4°C for cold-acclimated wild-type plants to –8°C for the most tolerant antisense line. Down-regulating α-Gal in petunia results in an increase in freezing tolerance at the whole-plant level in nonacclimated and cold-acclimated plants, whereas overexpression of the α-Gal gene caused a decrease in endogenous raffinose and impaired freezing tolerance. These results suggest that engineering raffinose metabolism by transformation with α-Gal provides an additional method for improving the freezing tolerance of plants. PMID:14500789

Metabolic responses in a model of insulin resistance: comparison between oral glucose and meal tolerance tests.

PubMed

Berthiaume, Nathalie; Zinker, Bradley A

2002-05-01

The purpose of this investigation was to compare the benefits of a meal tolerance test (MTT) against those of an oral glucose tolerance test (OGTT) in one of the most commonly used models of insulin resistance, the Zucker fatty rat. Comparison of these two oral challenges will facilitate determination of the most effective means of inducing both glucose and insulin responses in this particular model and allow for possible therapeutic benefits to be examined more effectively. Eight-week-old Zucker fatty rats (n = 7 or 8) were used to perform either an OGTT or a MTT following an overnight fast. The OGTT contained a final amount of carbohydrate (CHO) of 1.2 g/kg body weight (BW). The MTT (commercially available liquid meal), in addition to having fat and protein, included a final amount of available CHO and volume to match the OGTT. A saline-treated group served as control. A greater glucose excursion was observed following the OGTT compared to the MTT. The maximal change in glucose from baseline was 140 +/- 10 mg/dL (a 2.1-fold rise) for the OGTT compared to 86.3 +/- 6.1 mg/dL (a 1.7-fold rise) for the MTT (P <.05). The MTT induced a greater change from baseline in insulin response compared to the OGTT (7.5 +/- 1.1 v 3.9 +/- 0.5 ng/mL, MTT v OGTT, respectively; P <.05). The saline challenge induced only minimal glucose and insulin responses in comparison to the other treatments. These results suggest that, in a model of insulin resistance, the MTT is a more potent insulin stimulator than glucose alone. A mixed meal, such as a MTT, provides a complete nutrient challenge (CHO, fat, and protein) that will induce both glucose and insulin responses, enabling a better capacity to detect differences in one of the most often used models of insulin resistance, the Zucker fatty rat. Copyright 2002, Elsevier Science (USA). All rights reserved.

Effects of celiac superior mesenteric ganglionectomy on glucose homeostasis and hormonal changes during oral glucose tolerance testing in rats.

PubMed

Kumakura, Atsushi; Shikuma, Junpei; Ogihara, Norikazu; Eiki, Jun-ichi; Kanazawa, Masao; Notoya, Yōko; Kikuchi, Masatoshi; Odawara, Masato

2013-01-01

The liver plays an important role in maintaining glucose homeostasis in the body. In the prandial state, some of the glucose which is absorbed by the gastrointestinal tract is converted into glycogen and stored in the liver. In contrast, the liver produces glucose by glycogenolysis and gluconeogenesis while fasting. Thus, the liver contributes to maintaining blood glucose level within normoglycemic range. Glycogenesis and glycogenolysis are regulated by various mechanisms including hormones, the sympathetic and parasympathetic nervous systems and the hepatic glucose content. In this study, we examined a rat model in which the celiac superior mesenteric ganglion (CSMG) was resected. We attempted to elucidate how the celiac sympathetic nervous system is involved in regulating glucose homeostasis by assessing the effects of CSMG resection on glucose excursion during an oral glucose tolerance test, and by examining hepatic glycogen content and hepatic glycogen phosphorylase (GP) activity. On the oral glucose tolerance test, CSMG-resected rats demonstrated improved glucose tolerance and significantly increased GP activity compared with sham-operated rats, whereas there were no significant differences in insulin, glucagon or catecholamine levels between the 2 groups. These results suggest that the celiac sympathetic nervous system is involved in regulating the rate of glycogen consumption through GP activity. In conclusion, the examined rat model showed that the celiac sympathetic nervous system regulates hepatic glucose metabolism in conjunction with vagal nerve innervations and is a critical component in the maintenance of blood glucose homeostasis.

Unpredictable Feeding Impairs Glucose Tolerance in Growing Lambs

PubMed Central

Jaquiery, Anne L.; Oliver, Mark H.; Landon-Lane, Nina; Matthews, Samuel J.; Harding, Jane E.; Bloomfield, Frank H.

2013-01-01

Irregular eating is associated with insulin resistance and metabolic disease in adults but may affect young, growing children differently. We investigated the metabolic effects of unpredictable feeding in female juvenile lambs randomly assigned to receive, for six weeks, maintenance feed given twice daily in equal portions (Control Group, C; n = 24) or the same weekly feed amount in aliquots of variable size at unpredictable times (Unpredictable Group, U; n = 21). Intravenous glucose tolerance tests (IVGTT), insulin tolerance tests (ITT), and measurement of diurnal plasma cortisol concentrations were performed pre and post the dietary intervention. Groups were compared using t test and RM ANOVA. Weight gain was similar in both groups (C 18±2%; U 16±2% of initial body weight). Glucose area under the curve (AUC) was unchanged in C (AUC pre 818±34, post 801±33 mmol.min.l−1), but increased by 20% in U (pre 830±25, post 1010±19 mmol.min.l−1; p<0.0001), with an inadequate insulin response to glucose load (log(AUC insulin first 40 minutes) post intervention C 1.49±0.04 vs U 1.36±0.04 ng.min.ml−1; p = 0.03). Insulin tolerance and diurnal variation of plasma cortisol concentrations were not different between groups. Unpredictable feeding impairs insulin response to glucose in growing lambs despite high quality food and normal weight gain. Irregular eating warrants investigation as a potentially remediable risk factor for disordered glucose metabolism. PMID:23613779

Sub-lethal heat treatment affects the tolerance of Cronobacter sakazakii BCRC 13988 to various organic acids, simulated gastric juice and bile solution.

PubMed

Hsiao, Wan-Ling; Ho, Wei-Li; Chou, Cheng-Chun

2010-12-15

Cronobacter spp., formerly Enterobacter sakazakii, are considered emerging opportunistic pathogens and the etiological agent of life-threatening bacterial infections in infants. In the present study, C. sakazakii BCRC 13988 was first subjected to sub-lethal heat treatment at 47°C for 15min. Survival rates of the heat-shocked and non-shocked C. sakazakii cells in phosphate buffer solution (PBS, pH 4.0) containing organic acids (e.g. acetic, propionic, citric, lactic or tartaric acid), simulated gastric juice (pH 2.0-4.0), and bile solution (0.5 and 2.0%) were examined. Results revealed that sub-lethal heat treatment enhanced the test organism's tolerance to organic acids, although the extent of increased acid tolerance varied with the organic acid examined. Compared with the control cells, heat-shocked C. sakazakii cells after 120-min of exposure, exhibited the largest increase in tolerance in the lactic acid-containing PBS. Furthermore, although heat shock did not affect the behavior of C. sakazakii in bile solution, it increased the test organism's survival when exposed to simulated gastric juice with a pH of 3.0-4.0. Copyright © 2010. Published by Elsevier B.V.

Automatic, nondestructive test monitors in-process weld quality

NASA Technical Reports Server (NTRS)

Deal, F. C.

1968-01-01

Instrument automatically and nondestructively monitors the quality of welds produced in microresistance welding. It measures the infrared energy generated in the weld as the weld is made and compares this energy with maximum and minimum limits of infrared energy values previously correlated with acceptable weld-strength tolerances.

Analgesic tolerance to morphine is regulated by PPARγ

PubMed Central

de Guglielmo, Giordano; Kallupi, Marsida; Scuppa, Giulia; Stopponi, Serena; Demopulos, Gregory; Gaitanaris, George; Ciccocioppo, Roberto

2014-01-01

Background and Purpose Opioid drugs are potent analgesics. However, their chronic use leads to the rapid development of tolerance to their analgesic effects and subsequent increase of significant side effects, including drug dependence and addiction. Here, we investigated the role of PPARγ in the development of analgesic tolerance to morphine in mice. Experimental Approach We monitored analgesia on alternate days using the tail immersion test. Key Results Daily administration of morphine (30 mg·kg−1, bid) resulted in the rapid development of tolerance to thermal analgesia. Co-administration of pioglitazone (10 and 30 mg·kg−1, bid) significantly attenuated the development and expression of tolerance. However, pretreatment with GW-9662 (5 mg·kg−1, bid), a selective PPARγ antagonist, completely abolished this effect. Injection of GW-9662 and a lower dose of morphine (15 mg·kg−1, bid) accelerated the development of tolerance to its antinociceptive effect. Subsequently, we found that conditional neuronal PPARγ knockout (KO) mice develop a more rapid and pronounced tolerance to morphine antinociception compared with wild-type (WT) controls. Moreover, in PPARγ KO mice, pioglitazone was no longer able to prevent the development of morphine tolerance. Conclusions and Implications Overall, our results demonstrate that PPARγ plays a tonic role in the modulation of morphine tolerance, and its pharmacological activation may help to reduce its development. These findings provide new information about the role of neuronal PPARγ and suggest that combining PPARγ agonists with opioid analgesics may reduce the development of tolerance and possibly attenuate the potential for opioid abuse. PMID:25048682

Atlantic DIP: high prevalence of abnormal glucose tolerance post partum is reduced by breast-feeding in women with prior gestational diabetes mellitus.

PubMed

O'Reilly, Michael W; Avalos, Gloria; Dennedy, Michael C; O'Sullivan, Eoin P; Dunne, Fidelma

2011-12-01

Gestational diabetes (GDM) is associated with adverse fetal and maternal outcomes, and identifies women at risk of future type 2 diabetes mellitus (T2DM). Breast-feeding may improve post partum maternal glucose tolerance. Our objective was to identify the prevalence of post partum dysglycemia after GDM, to delineate associated factors and to examine the effect of lactation on post partum glucose tolerance. We compared post partum 75 g oral glucose tolerance test (OGTT) results from 300 women with GDM and 220 controls with normal gestational glucose tolerance (NGT) in five regional centers. Breast-feeding data was collected at time of OGTT. Methods Post partum OGTT results were classified as normal (fasting plasma glucose (FPG) <5.6 mmol/l, 2 h <7.8 mmol/l) and abnormal (impaired fasting glucose (IFG), FPG 5.6-6.9 mmol/l; impaired glucose tolerance (IGT), 2 h glucose 7.8-11 mmol/l; IFG+IGT; T2DM, FPG ≥7 mmol/l±2 h glucose ≥11.1 mmol/l). Binary logistic regression was used to identify factors predictive of persistent hyperglycemia. Five hundred and twenty women were tested; six (2.7%) with NGT in pregnancy had post partum dysglycemia compared with 57 (19%) with GDM in index pregnancy (P<0.001). Non-European ethnicity (odds ratio (OR) 3.40; 95% confidence interval (CI) 1.45-8.02, P=0.005), family history of T2DM (OR 2.14; 95% CI 1.06-4.32, P=0.034), and gestational insulin use (OR 2.62; 95% CI 1.17-5.87, P=0.019) were associated with persistent dysglycemia. The prevalence of persistent hyperglycemia was significantly lower in women who breast-fed vs bottle-fed post partum (8.2 vs 18.4%, P<0.001). Non-European ethnicity, gestational insulin use, family history of T2DM, and elevated body mass index were associated with persistent dysglycemia after GDM. Breast-feeding may confer beneficial metabolic effects after GDM and should be encouraged.

Negative Density Dependence Regulates Two Tree Species at Later Life Stage in a Temperate Forest

PubMed Central

Piao, Tiefeng; Chun, Jung Hwa; Yang, Hee Moon; Cheon, Kwangil

2014-01-01

Numerous studies have demonstrated that tree survival is influenced by negative density dependence (NDD) and differences among species in shade tolerance could enhance coexistence via resource partitioning, but it is still unclear how NDD affects tree species with different shade-tolerance guilds at later life stages. In this study, we analyzed the spatial patterns for trees with dbh (diameter at breast height) ≥2 cm using the pair-correlation g(r) function to test for NDD in a temperate forest in South Korea after removing the effects of habitat heterogeneity. The analyses were implemented for the most abundant shade-tolerant (Chamaecyparis obtusa) and shade-intolerant (Quercus serrata) species. We found NDD existed for both species at later life stages. We also found Quercus serrata experienced greater NDD compared with Chamaecyparis obtusa. This study indicates that NDD regulates the two abundant tree species at later life stages and it is important to consider variation in species' shade tolerance in NDD study. PMID:25058660

Habitat degradation correlates with tolerance to climate-change related stressors in the green mussel Perna viridis from West Java, Indonesia.

PubMed

Wendling, Carolin Charlotte; Huhn, Mareike; Ayu, Nurina; Bachtiar, Ramadian; von Juterzenka, Karen; Lenz, Mark

2013-06-15

It is unclear whether habitat degradation correlates with tolerance of marine invertebrates to abiotic stress. We therefore tested whether resistance to climate change-related stressors differs between populations of the green mussel Perna viridis from a heavily impacted and a mostly pristine site in West Java, Indonesia. In laboratory experiments, we compared their oxygen consumption and mortality under lowered salinity (-13 and -18 units, both responses), hypoxia (0.5 mg/l, mortality only) and thermal stress (+7 °C, mortality only). Mussels from the eutrophied and polluted Jakarta Bay showed a significantly smaller deviation from their normal oxygen consumption and higher survival rates when stressed than their conspecifics from the unaffected Lada Bay. This shows that human induced habitat degradation correlates with mussel tolerance to environmental stress. We discuss possible mechanisms - e.g. the selection of tolerant genotypes or habitat-specific differences in the nutritional status of the mussels - that could explain our observation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Variation in copper and zinc tolerance and accumulation in 12 willow clones: implications for phytoextraction*

PubMed Central

Yang, Wei-dong; Wang, Yu-yan; Zhao, Feng-liang; Ding, Zhe-li; Zhang, Xin-cheng; Zhu, Zhi-qiang; Yang, Xiao-e

2014-01-01

Willows (Salix spp.) have shown high potential for the phytoextraction of heavy metals. This study compares variations in copper (Cu) and zinc (Zn) tolerance and accumulation potential among 12 willow clones grown in a nutrient solution treated with 50 μmol/L of Cu or Zn, respectively. The results showed differences in the tolerance and accumulation of Cu and Zn with respect to different species/clones. The biomass variation among clones in response to Cu or Zn exposure ranged from the stimulation of growth to inhibition, and all of the clones tested showed higher tolerance to Cu than to Zn. The clones exhibited less variation in Cu accumulation but larger variation in Zn accumulation. Based on translocation factors, it was found that most of the Cu was retained in the roots and that Zn was more mobile than Cu for all clones. It is concluded that most willow clones are good accumulators of Zn and Cu. PMID:25183033

Intraspecific variation in the response of Taxodium distichum seedlings to salinity

USGS Publications Warehouse

Allen, J.A.; Chambers, J.L.; McKinney, D.

1994-01-01

Seedlings of 15 open-pollinated families of baldcypress (Taxodium distichum) were tested for their tolerance to combined salinty and flooding stress. Ten of the families were from coastal locations in Louisiana or Alabama, USA, that were slightly brackish. The other families were from locations not affected by saltwater intrusion. Five salinity levels were investigated--0,2,4,6, and 8 g -1 artificial seawater -- all with flooding to approximately 5 cm above the soil surface. Survival, height growth, leaf area and total biomass all declined with increasing salinity. Significant variation was found among salinity levels, families, and salinity x family interactions for leaf area and total biomass. Two tolerance indices were also developed to compare family response with salinity. In general, families from brackish sources had greater total biomass, leaf area, and tolerance index values than families from freshwater sources at the higher slainity levels. A selection and breeding program designed to develop moderately salt-tolerant baldcypress seedlings for use in wetland restoration projects and other applications appears to be well-justified.

A Novel Rice Cytochrome P450 Gene, CYP72A31, Confers Tolerance to Acetolactate Synthase-Inhibiting Herbicides in Rice and Arabidopsis1[C][W][OPEN

PubMed Central

Saika, Hiroaki; Horita, Junko; Taguchi-Shiobara, Fumio; Nonaka, Satoko; Nishizawa-Yokoi, Ayako; Iwakami, Satoshi; Hori, Kiyosumi; Matsumoto, Takashi; Tanaka, Tsuyoshi; Itoh, Takeshi; Yano, Masahiro; Kaku, Koichiro; Shimizu, Tsutomu; Toki, Seiichi

2014-01-01

Target-site and non-target-site herbicide tolerance are caused by the prevention of herbicide binding to the target enzyme and the reduction to a nonlethal dose of herbicide reaching the target enzyme, respectively. There is little information on the molecular mechanisms involved in non-target-site herbicide tolerance, although it poses the greater threat in the evolution of herbicide-resistant weeds and could potentially be useful for the production of herbicide-tolerant crops because it is often involved in tolerance to multiherbicides. Bispyribac sodium (BS) is an herbicide that inhibits the activity of acetolactate synthase. Rice (Oryza sativa) of the indica variety show BS tolerance, while japonica rice varieties are BS sensitive. Map-based cloning and complementation tests revealed that a novel cytochrome P450 monooxygenase, CYP72A31, is involved in BS tolerance. Interestingly, BS tolerance was correlated with CYP72A31 messenger RNA levels in transgenic plants of rice and Arabidopsis (Arabidopsis thaliana). Moreover, Arabidopsis overexpressing CYP72A31 showed tolerance to bensulfuron-methyl (BSM), which belongs to a different class of acetolactate synthase-inhibiting herbicides, suggesting that CYP72A31 can metabolize BS and BSM to a compound with reduced phytotoxicity. On the other hand, we showed that the cytochrome P450 monooxygenase CYP81A6, which has been reported to confer BSM tolerance, is barely involved, if at all, in BS tolerance, suggesting that the CYP72A31 enzyme has different herbicide specificities compared with CYP81A6. Thus, the CYP72A31 gene is a potentially useful genetic resource in the fields of weed control, herbicide development, and molecular breeding in a broad range of crop species. PMID:24406793

Impaired glucose tolerance in first-episode drug-naïve patients with schizophrenia: relationships with clinical phenotypes and cognitive deficits.

PubMed

Chen, D C; Du, X D; Yin, G Z; Yang, K B; Nie, Y; Wang, N; Li, Y L; Xiu, M H; He, S C; Yang, F D; Cho, R Y; Kosten, T R; Soares, J C; Zhao, J P; Zhang, X Y

2016-11-01

Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus with impaired glucose tolerance (IGT) than normals. We examined the relationship between IGT and clinical phenotypes or cognitive deficits in first-episode, drug-naïve (FEDN) Han Chinese patients with schizophrenia. A total of 175 in-patients were compared with 31 healthy controls on anthropometric measures and fasting plasma levels of glucose, insulin and lipids. They were also compared using a 75 g oral glucose tolerance test and the homeostasis model assessment of insulin resistance (HOMA-IR). Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Of the patients, 24.5% had IGT compared with none of the controls, and they also had significantly higher levels of fasting blood glucose and 2-h glucose after an oral glucose load, and were more insulin resistant. Compared with those patients with normal glucose tolerance, the IGT patients were older, had a later age of onset, higher waist or hip circumference and body mass index, higher levels of low-density lipoprotein and triglycerides and higher insulin resistance. Furthermore, IGT patients had higher PANSS total and negative symptom subscale scores, but no greater cognitive impairment except on the emotional intelligence index of the MCCB. IGT occurs with greater frequency in FEDN schizophrenia, and shows association with demographic and anthropometric parameters, as well as with clinical symptoms but minimally with cognitive impairment during the early course of the disorder.

MicroRNA156 improves drought stress tolerance in alfalfa (Medicago sativa) by silencing SPL13.

PubMed

Arshad, Muhammad; Feyissa, Biruk A; Amyot, Lisa; Aung, Banyar; Hannoufa, Abdelali

2017-05-01

Alfalfa (Medicago sativa) is an important forage crop that is often grown in areas that frequently experience drought and water shortage. MicroRNA156 (miR156) is an emerging tool for improving various traits in plants. We tested the role of miR156d in drought response of alfalfa, and observed a significant improvement in drought tolerance of miR156 overexpression (miR156OE) alfalfa genotypes compared to the wild type control (WT). In addition to higher survival and reduced water loss, miR156OE genotypes also maintained higher stomatal conductance compared to WT during drought stress. Furthermore, we observed an enhanced accumulation of compatible solute (proline) and increased levels of abscisic acid (ABA) and antioxidants in miR156OE genotypes. Similarly, alfalfa plants with reduced expression of miR156-targeted SPL13 showed reduced water loss and enhanced stomatal conductance, chlorophyll content and photosynthetic assimilation. Several genes known to be involved in drought tolerance were differentially expressed in leaf and root of miR156 overexpression plants. Taken together, our findings reveal that miR156 improves drought tolerance in alfalfa at least partially by silencing SPL13. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Insulin and C-peptide secretion in non-obese patients with polycystic ovarian disease.

PubMed

Mahabeer, S; Jialal, I; Norman, R J; Naidoo, C; Reddi, K; Joubert, S M

1989-09-01

Plasma glucose, immunoreactive insulin (IRI) and C-peptide responses during an oral glucose tolerance test (oGTT) were assessed in 11 non-obese patients with polycystic ovarian disease (PCOD) and 11 reference subjects matched for age, height and weight. Also, 6 patients with PCOD and 6 normal women were subjected to intravenous glucose tolerance testing (ivGTT) On oGTT, all subjects exhibited normal glucose tolerance; however, PCOD patients had significantly higher mean plasma glucose levels at 30, 60, 90 and 120 min and higher mean incremental glucose areas. In addition the patients with polycystic ovaries showed higher mean basal IRI and C-peptide levels, higher mean glucose stimulated IRI and C-peptide levels and higher mean incremental IRI and C-peptide values. The molar ratios of C-peptide/IRI were significantly lower in the PCOD group at all time intervals after glucose stimulation when compared to the normal women. During ivGTT, there were significantly higher mean glucose levels at 5, 40, 50 and 60 min in the PCOD group when compared to the reference group. The IRI response to intravenous glucose in the PCOD women was similar to the reference group. The findings on oGTT suggest that non-obese patients with PCOD have increased pancreatic IRI secretion as well as impaired hepatic extraction of the hormone.

SU-F-T-271: Comparing IMRT QA Pass Rates Before and After MLC Calibration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mazza, A; Perrin, D; Fontenot, J

Purpose: To compare IMRT QA pass rates before and after an in-house MLC leaf calibration procedure. Methods: The MLC leaves and backup jaws on four Elekta linear accelerators with MLCi2 heads were calibrated using the EPID-based RIT Hancock Test as the means for evaluation. The MLCs were considered to be successfully calibrated when they could pass the Hancock Test with criteria of 1 mm jaw position tolerance, and 1 mm leaf position tolerance. IMRT QA results were collected pre- and postcalibration and analyzed using gamma analysis with 3%/3mm DTA criteria. AAPM TG-119 test plans were also compared pre- and post-calibration,more » at both 2%/2mm DTA and 3%/3mm DTA. Results: A weighted average was performed on the results for all four linear accelerators. The pre-calibration IMRT QA pass rate was 98.3 ± 0.1%, compared with the post-calibration pass rate of 98.5 ± 0.1%. The TG-119 test plan results showed more of an improvement, particularly at the 2%/2mm criteria. The averaged results were 89.1% pre and 96.1% post for the C-shape plan, 94.8% pre and 97.1% post for the multi-target plan, 98.6% pre and 99.7% post for the prostate plan, 94.7% pre and 94.8% post for the head/neck plan. Conclusion: The patient QA results did not show statistically significant improvement at the 3%/3mm DTA criteria after the MLC calibration procedure. However, the TG-119 test cases did show significant improvement at the 2%/2mm level.« less

Effects of rumen-protected Capsicum oleoresin on productivity and responses to a glucose tolerance test in lactating dairy cows.

PubMed

Oh, J; Harper, M; Giallongo, F; Bravo, D M; Wall, E H; Hristov, A N

2017-03-01

The objective of this experiment was to investigate the effects of rumen-protected Capsicum oleoresin (RPC) supplementation on feed intake, milk yield and composition, nutrient utilization, fecal microbial ecology, and responses to a glucose tolerance test in lactating dairy cows. Nine multiparous Holstein cows were used in a replicated 3 × 3 Latin square design balanced for residual effects with three 28-d periods. Each period consisted of 14 d for adaptation and 14 d for data collection and sampling. Treatments were 0 (control), 100, and 200 mg of RPC/cow per day. They were mixed with a small portion of the total mixed ration and top-dressed. Glucose tolerance test was conducted once during each experimental period by intravenous administration of glucose at a rate of 0.3 g/kg of body weight. Dry matter intake was not affected by RPC. Milk yield tended to increase for RPC treatments compared to the control. Feed efficiency was linearly increased by RPC supplementation. Concentrations of fat, true protein, and lactose in milk were not affected by RPC. Apparent total-tract digestibility of dry matter, organic matter, and crude protein was linearly increased, and fecal nitrogen excretion was linearly decreased by RPC supplementation. Rumen-protected Capsicum oleoresin did not affect the composition of fecal bacteria. Glucose concentration in serum was not affected by RPC supplementation post glucose challenge. However, compared to the control, RPC decreased serum insulin concentration at 5, 10, and 40 min post glucose challenge. The area under the insulin concentration curve was also decreased 25% by RPC. Concentration of nonesterified fatty acids and β-hydroxybutyrate in serum were not affected by RPC following glucose administration. In this study, RPC tended to increase milk production and increased feed efficiency in dairy cows. In addition, RPC decreased serum insulin concentration during the glucose tolerance test, but glucose concentration was not affected by treatment. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Comparative effects of cyclo-oxygenase and nitric oxide synthase inhibition on the development and reversal of spinal opioid tolerance

PubMed Central

Powell, Kelly J; Hosokawa, Akiko; Bell, Andrew; Sutak, Maaja; Milne, Brian; Quirion, Remi; Jhamandas, Khem

1999-01-01

This study examined the effects of the COX inhibitors, ketorolac and ibuprofen, and the NOS inhibitor L-NAME for their potential to both inhibit the development and reverse tolerance to the antinociceptive action of morphine. Repeated administration of intrathecal morphine (15 μg), once daily, resulted in a progressive decline of antinociceptive effect and an increase in the ED50 value in the tailflick and paw pressure tests. Co-administration of ketorolac (30 and 45 μg) or S(+) ibuprofen (10 μg) with morphine (15 μg) prevented the decline of antinociceptive effect and increase in ED50 value. Similar treatment with L-NAME (100 μg) exerted weaker effects. Administration of S(+) but not R(−) ibuprofen (10 mg kg−1) had similar effects on systemic administration of morphine (15 mg kg−1). Intrathecal or systemic administration of the COX or NOS inhibitors did not alter the baseline responses in either tests. Acute keterolac or S(+) ibuprofen also did not potentiate the acute actions of spinal or systemic morphine, but chronic intrathecal administration of these agents increased the potency of acute morphine. In animals already tolerant to intrathecal morphine, subsequent administration of ketorolac (30 μg) with morphine (15 μg) partially restored the antinociceptive effect and ED50 value of acute morphine, reflecting the reversal of tolerance. Intrathecal L-NAME (100 μg) exerted a weaker effect. These data suggest that spinal COX activity, and to a lesser extent NOS activity, contributes to the development and expression of opioid tolerance. Inhibition of COX may represent a useful approach for the prevention as well as reversal of opioid tolerance. PMID:10401553

Immediate reactions to iodinated contrast media.

PubMed

Morales-Cabeza, Cristina; Roa-Medellín, Dasha; Torrado, Inés; De Barrio, Manuel; Fernández-Álvarez, Carmen; Montes-Aceñero, Juan Francisco; De La Riva, Inmaculada; Prieto-García, Alicia

2017-12-01

Immediate hypersensitivity reactions (IHRs) to iodinated contrast media (ICMs) remain a common clinical concern. Positive skin test and basophil activation test results suggest a specific IgE-mediated mechanism in some cases. Skin test and controlled challenge test (CCT) are useful to manage these patients. To study clinical and allergologic features of IHRs to ICMs in a Spanish tertiary hospital during a 7-year period. Demographic and clinical data concerning the reaction were recorded. Patients treated at the Allergy Department of Hospital General Universitario Gregorio Marañón, Madrid, Spain, underwent skin tests. In those with positive results, CCTs with an alternative skin-test-negative ICM was performed. Global reaction rate was calculated and compared for each ICM. A total of 342 reactions occurred in 329 patients. Cutaneous symptoms were the most common (87.7%). A total of 196 patients underwent an allergy workup, 15 (7.6%) of whom had positive skin test results. Reactions were more severe in patients with positive vs negative skin test results (grade 1, 46.7% vs 73.6%; grade 2, 33.3% vs 20.9%; grade 3, 20% vs 5.46%; P < .05). Three patients had cross-reactivity to 3 ICMs, all including ioversol and iomeprol. Six patients allergic to iopamidol tolerated ioversol and 1 tolerated iomeprol. Four patients allergic to ioversol and 1 allergic to iomeprol tolerated iopamidol. The global reaction rate was 0.2%, differing for each ICM (iopamidol, 0.14%; ioversol, 0.2%; and iomeprol, 0.4%; P < .001). Positive skin test results were found in a low percentage of patients in whom skin test-based CCT identified an alternative non-cross-reactive ICM. Low-grade cross-reactivity was found, especially between iopamidol and ioversol. Reactions were more severe in patients with positive skin test results. The reaction rate was greater for iomeprol compared with iopamidol (reaction rate, 2.8%) and ioversol (reaction rate, 2%). This study identified a possible underlying specific IgE-mediated mechanism by positive skin test result in a low percentage of patients with IHRs to ICMs. In these patients, the CCT based on skin test results was useful for identifying an alternative non-cross-reactive ICM. More studies are needed to investigate the underlying mechanism in patients with IHRs and negative skin test results. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A single bout of high-intensity interval exercise and work-matched moderate-intensity exercise has minimal effect on glucose tolerance and insulin sensitivity in 7- to 10-year-old boys.

PubMed

Cockcroft, Emma J; Williams, Craig A; Jackman, Sarah R; Bassi, Shikhar; Armstrong, Neil; Barker, Alan R

2018-01-01

The purpose of this study was to assess the acute effect of high-intensity interval exercise (HIIE) and moderate-intensity exercise (MIE) on glucose tolerance, insulin sensitivity and fat oxidation in young boys. Eleven boys (8.8 ± 0.8 y) completed three conditions: 1) HIIE; 2) work-matched MIE; and 3) rest (CON) followed by an oral glucose tolerance test (OGTT) to determine glucose tolerance and insulin sensitivity (Cederholm index). Fat oxidation was measured following the OGTT using indirect calorimetry. There was no effect for condition on plasma [glucose] and [insulin] area under the curve (AUC) responses following the OGTT (P > 0.09). However, there was a "trend" for a condition effect for insulin sensitivity with a small increase after HIIE (P = 0.04, ES = 0.28, 9.7%) and MIE (P = 0.07, ES = 0.21, 6.5%) compared to CON. There was an increase in fat oxidation AUC following HIIE (P = 0.008, ES = 0.79, 38.9%) compared to CON, but with no differences between MIE and CON and HIIE and MIE (P > 0.13). In conclusion, 7- to 10-year-old boys may have limited scope to improve insulin sensitivity and glucose tolerance after a single bout of HIIE and MIE. However, fat oxidation is augmented after HIIE but not MIE.

Local tolerance and stability up to 24 months of a new 20% proline-stabilized polyclonal immunoglobulin for subcutaneous administration.

PubMed

Maeder, Werner; Lieby, Patricia; Sebald, Andrea; Spycher, Martin; Pedrussio, Renzo; Bolli, Reinhard

2011-01-01

Subcutaneous administration of human IgG is an alternative to intravenous replacement therapy that is associated with more stable serum IgG levels and fewer systemic adverse events. Highly concentrated IgG solutions are most convenient to minimize infusion volume, but their preparation and stability presents substantial technical difficulties. We report on the stability and local tolerance of IgPro20, an l-proline-stabilized, 20% polyvalent human IgG developed for subcutaneous administration. Stability was tested according to ICH guidelines. Local tolerance and vasoactivity were examined in rabbit and rat models, respectively. The presence of l-proline in IgPro20 reduced viscosity and addition of Polysorbate 80 and inert gassing improved the appearance of the solution. After storage at 25 °C for 24 months, monomer + dimer content, aggregates, and fragments were within specification (≥ 90.0%, ≤ 4.0%, and ≤ 10.0%, respectively), and Fc function and antibody activities were maintained. In rats, intravenous injection of IgPro20 produced mild and transient hypotension comparable to that seen with intravenous IgG products. Local tolerance of IgPro20 in rabbits was comparable to that of a marketed subcutaneous IgG, Beriglobin P. Functionality and quality of IgPro20 are maintained during storage at 25 °C for at least 24 months. The product is well tolerated as assessed in animal models. Copyright © 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

Influence of sediment presence on freshwater mussel thermal tolerance

USGS Publications Warehouse

Archambault, Jennifer M.; Cope, W. Gregory; Kwak, Thomas J.

2014-01-01

Median lethal temperature (LT50) data from water-only exposures with the early life stages of freshwater mussels suggest that some species may be living near their upper thermal tolerances. However, evaluation of thermal sensitivity has never been conducted in sediment. Mussels live most of their lives burrowed in sediment, so understanding the effect of sediment on thermal sensitivity is a necessary step in evaluating the effectiveness of the water-only standard method, on which the regulatory framework for potential thermal criteria currently is based, as a test of thermal sensitivity. We developed a method for testing thermal sensitivity of juvenile mussels in sediment and used the method to assess thermal tolerance of 4 species across a range of temperatures common during summer. Stream beds may provide a thermal refuge in the wild, but we hypothesized that the presence of sediment alone does not alter thermal sensitivity. We also evaluated the effects of 2 temperature acclimation levels (22 and 27°C) and 2 water levels (watered and dewatered treatments). We then compared results from the sediment tests to those conducted using the water-only standard methods. We also conducted water-only LT tests with mussel larvae (glochidia) for comparison with the juvenile life stage. We found few consistent differences in thermal tolerance between sediment and water-only treatments, between acclimation temperatures, between waterlevel treatments, among species, or between juvenile and glochidial life stages (LT50 range = 33.3-37.2°C; mean = 35.6°C), supporting our hypothesis that the presence of sediment alone does not alter thermal sensitivity. The method we developed has potential for evaluating the role of other stressors (e.g., contaminants) in a more natural and complex environment.

Real-life feasibility and effectiveness of home-based pulmonary rehabilitation in chronic obstructive pulmonary disease requiring medical equipment.

PubMed

Coquart, Jérémy B; Le Rouzic, Olivier; Racil, Ghazi; Wallaert, Benoit; Grosbois, Jean-Marie

2017-01-01

Pulmonary rehabilitation (PR) is a key treatment of chronic obstructive pulmonary disease (COPD) but studies are still needed to identify the most pertinent criteria to personalize this intervention and improve its efficacy. This real-life retrospective study compared the effects of home-based PR on exercise tolerance, anxiety, depression, and health-related quality of life (HRQoL) in COPD patients, according to their medical equipment. Exercise tolerance, anxiety, depression, and HRQoL were evaluated in 109 patients equipped with long-term oxygen therapy (LTOT), 84 patients with noninvasive ventilation (NIV), 25 patients with continuous positive airway pressure (CPAP), and 80 patients with no equipment (NE), before, just after, and 6 and 12 months after PR. At baseline, the body mass index in the CPAP and NIV groups was higher ( p <0.05) than in the other two groups, and the forced expiratory volume in 1 second was lower in the LTOT and NIV groups ( p <0.001). All parameters improved after PR in the four groups ( p <0.05), but for exercise tolerance, only the 6-minute stepper test showed maintained improvement after 6 and 12 months, whereas the 10 times sit-to-stand and timed up-and-go tests were only improved just after PR. At every time point, exercise tolerance was lower in the LTOT group ( p <0.05), with a similar trend in the NIV group. Despite differences in the medical equipment to treat COPD, home-based PR showed comparable feasibility, safety, and efficacy in all equipment-based groups. Medical equipment should therefore not be a barrier to home-based PR.

Effect of hypovolemia, infusion, and oral rehydration on plasma electrolytes, ADH, renin activity, and +G/z/ tolerance

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Brock, P. J.; Haines, R. F.; Rositano, S. A.; Montgomery, L. D.; Keil, L. C.

1977-01-01

Effects on plasma volume, electrolyte shifts, and +G(z) tolerance induced by: (1) blood withdrawal; (2) blood infusion; and (3) oral fluid intake, were determined at 0.5 G/min in centrifugation tests of six ambulatory male patients, aged 21 to 27 yrs. Hypovolemia induced by withdrawal of 400 ml blood, blood infusion followed by repeated centrifugation, effects of consuming an isotonic drink (0.9% NaCl) to achieve oral rehydration, and donning of red adaptation goggles were studied for effects on acceleration tolerance, pre-acceleration and post-acceleration plasma renin activity (PRA) and plasma vasopressin levels. No significant changes in post-acceleration PRA compared to pre-acceleration PRA were found, and administration of oral rehydration is found as effective as blood replacement in counteracting hypovolemic effects.

Intraspecific variability of Steinernema feltiae strains from Cemoro Lawang, eastern Java, Indonesia.

PubMed

Addis, T; Mulawarman, M; Waeyenberge, L; Moens, M; Viaene, N; Ehlers, R U

2010-01-01

Four strains of Steinernema feltiae from Eastern Java, Indonesia were characterized based on morphometric, morphological and molecular data. In addition, their virulence against last instar Tenebrio molitor and heat tolerance was tested. Infective juvenile have a mean body length ranging from 749 to 792 microm. The maximum sequence difference among the four strains was 7 bp (8.8%) in the ITS and 2 bp (0.3%) in D2D3 regions of the rDNA. All the strains are not reproductively isolated and can reproduce with European strain S. feltiae Owiplant. The lowest LC50 was observed for strain SCM (373) and the highest for S. feltiae strain Owiplant (458) IJs/40 T. molitor. All four strains showed relatively better mean heat tolerance when compared with S. feltiae Owiplant, both in adapted and non-adapted heat tolerance experiments.

Proteomic analysis of the flooding tolerance mechanism in mutant soybean.

PubMed

Komatsu, Setsuko; Nanjo, Yohei; Nishimura, Minoru

2013-02-21

Flooding stress of soybean is a serious problem because it reduces growth; however, flooding-tolerant cultivars have not been identified. To analyze the flooding tolerance mechanism of soybean, the flooding-tolerant mutant was isolated and analyzed using a proteomic technique. Flooding-tolerance tests were repeated five times using gamma-ray irradiated soybeans, whose root growth (M6 stage) was not suppressed even under flooding stress. Two-day-old wild-type and mutant plants were subjected to flooding stress for 2days, and proteins were identified using a gel-based proteomic technique. In wild-type under flooding stress, levels of proteins related to development, protein synthesis/degradation, secondary metabolism, and the cell wall changed; however, these proteins did not markedly differ in the mutant. In contrast, an increased number of fermentation-related proteins were identified in the mutant under flooding stress. The root tips of mutant plants were not affected by flooding stress, even though the wild-type plants had damaged root. Alcohol dehydrogenase activity in the mutant increased at an early stage of flooding stress compared with that of the wild-type. Taken together, these results suggest that activation of the fermentation system in the early stages of flooding may be an important factor for the acquisition of flooding tolerance in soybean. Copyright © 2012 Elsevier B.V. All rights reserved.

An experimental test of host’s life history traits modulation in response to cuckoo parasitism risk

PubMed Central

Parejo, Deseada; Martínez, Juan Gabriel; Sánchez-Tójar, Alfredo; Precioso, Marta; Molina-Morales, Mercedes; Avilés, Jesús M.

2017-01-01

Hosts can counteract parasites through defences based on resistance and/or tolerance. The mechanistic basis of tolerance, which involve defensive mechanisms minimizing parasite damage after a successful parasitic attack, remains poorly explored in the study of cuckoo-host interactions. Here, we experimentally explore the possibility that the risk of great spotted cuckoo Clamator glandarius parasitism may induce tolerance defences in magpie Pica pica hosts through plasticity in life-history traits. We predict that magpies exposed to auditory cues indicating high parasitism risk will more likely exhibit resistance and/or modify their life-history traits to minimize parasitism costs (i.e. tolerance) compared to magpies under low parasitism risk. We found that manipulating the perceived parasitism risk did not affect host resistance (i.e. rejection of parasitic eggs) nor host life-history traits. Unexpectedly, host’s egg volume increased over the season in nests exposed to auditory cues of control non-harmful hoopoes Upupa epops. Our results do not provide support for inducible defences (either based on resistance or tolerance) in response to risk of parasitism in magpie hosts. Even so, we encourage studying plastic expression of breeding strategies in response to risk of cuckoo parasitism to achieve a better understanding of the mechanistic basis of tolerance defences. PMID:28658287

Polyamine Transporters and Polyamines Increase Furfural Tolerance during Xylose Fermentation with Ethanologenic Escherichia coli Strain LY180

PubMed Central

Geddes, Ryan D.; Wang, Xuan; Yomano, Lorraine P.; Miller, Elliot N.; Zheng, Huabao; Shanmugam, Keelnatham T.

2014-01-01

Expression of genes encoding polyamine transporters from plasmids and polyamine supplements increased furfural tolerance (growth and ethanol production) in ethanologenic Escherichia coli LY180 (in AM1 mineral salts medium containing xylose). This represents a new approach to increase furfural tolerance and may be useful for other organisms. Microarray comparisons of two furfural-resistant mutants (EMFR9 and EMFR35) provided initial evidence for the importance of polyamine transporters. Each mutant contained a single polyamine transporter gene that was upregulated over 100-fold (microarrays) compared to that in the parent LY180, as well as a mutation that silenced the expression of yqhD. Based on these genetic changes, furfural tolerance was substantially reconstructed in the parent, LY180. Deletion of potE in EMFR9 lowered furfural tolerance to that of the parent. Deletion of potE and puuP in LY180 also decreased furfural tolerance, indicating functional importance of the native genes. Of the 8 polyamine transporters (18 genes) cloned and tested, half were beneficial for furfural tolerance (PotE, PuuP, PlaP, and PotABCD). Supplementing AM1 mineral salts medium with individual polyamines (agmatine, putrescine, and cadaverine) also increased furfural tolerance but to a smaller extent. In pH-controlled fermentations, polyamine transporter plasmids were shown to promote the metabolism of furfural and substantially reduce the time required to complete xylose fermentation. This increase in furfural tolerance is proposed to result from polyamine binding to negatively charged cellular constituents such as nucleic acids and phospholipids, providing protection from damage by furfural. PMID:25063650

Association between glucose intolerance and bacterial colonisation in an adult population with cystic fibrosis, emergence of Stenotrophomonas maltophilia.

PubMed

Lehoux Dubois, C; Boudreau, V; Tremblay, F; Lavoie, A; Berthiaume, Y; Rabasa-Lhoret, R; Coriati, A

2017-05-01

Diabetes is common in cystic fibrosis (CF). Glucose can be detected in the airway when the blood glucose is elevated, which favours bacterial growth. We investigated the relationship between dysglycemia and lung pathogens in CF. Cross-sectional and prospective analysis of CF patients (N=260) who underwent a 2h-oral glucose tolerance test. Clinical data was collected. Stenotrophomonas maltophilia (S. maltophilia) was the sole bacteria increased in dysglycemic (AGT: 20.2%, CFRD: 21.6%) patients compared to normotolerants (NGT: 8.7%). S. maltophilia positive patients with dysglycemia had more pulmonary exacerbation events compared to NGTs (1.22 vs 0.63, P=0.003). The interaction between S. maltophilia colonisation and glucose tolerance status significantly increases the risk of lower lung function (P=0.003). Its growth was not affected by the evolution of the glucose tolerance after three years follow-up. Prevalence of S. maltophilia was higher in dysglycemic patients, supporting the idea that S. maltophilia is a marker of disease severity in CF. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

A comparative pharmacokinetic and tolerability analysis of the novel orotic acid salt form of tenofovir disoproxil and the fumaric acid salt form in healthy subjects

PubMed Central

Kim, Yu Kyong; Choi, Mun Ju; Oh, Tae Young; Yu, Kyung-Sang; Lee, SeungHwan

2017-01-01

A novel orotic acid salt form of tenofovir disoproxil (DA-2802) was developed and is expected to replace the fumaric acid salt form. The pharmacokinetic (PK) characteristics and tolerability profiles of DA-2802 were compared to those of tenofovir disoproxil fumarate (TDF, Viread®) in healthy subjects. A randomized, open-label, single-dose study was conducted in 36 healthy subjects using a two-treatment, two-period, and two-sequence crossover design. Subjects received a single oral dose of 319 mg DA-2802 or 300 mg TDF, during each period, with a 7-day washout. Serial blood samples were collected pre-dosing and up to 72 hours post-dosing in each period, for determination of serum tenofovir concentration, which was measured by ultra-performance liquid chromatography-tandem mass spectrometry. A non-compartmental method was used to obtain PK parameters of tenofovir. For comparison between the two tenofovir disoproxil salts, the 90% confidence intervals (90% CIs) of geometric mean ratios of DA-2802 to TDF for the maximum concentration (Cmax) and the area under the concentration–time curve to the last quantifiable concentration (AUC0–t) were determined. The tolerability profiles of tenofovir were assessed by evaluation of adverse events and vital signs, physical examination, ECG, and clinical laboratory tests. The serum tenofovir concentration–time profiles of DA-2802 or TDF were comparable in 32 subjects who completed the study. In both profiles, a two-compartmental elimination with first-order elimination kinetics in the terminal phase was reported in a few subjects, showing a secondary peak in the initial phase of elimination. The geometric mean ratio (90% CI) of DA-2802 to TDF was 0.898 (0.815–0.990) for Cmax and 0.904 (0.836–0.978) for AUC0–t. There were no clinically significant findings in the tolerability assessments. DA-2802 showed comparable PK characteristics and tolerability profiles to TDF. PMID:29158663

Tolerance and cross-tolerance to head twitch behavior elicited by phenethylamine- and tryptamine-derived hallucinogens in mice.

PubMed

Smith, Douglas A; Bailey, Jessica M; Williams, Diarria; Fantegrossi, William E

2014-12-01

The serotonin 5-hydroxytryptamine 2A (5-HT2A) receptor is a potential therapeutic target to a host of neuropsychiatric conditions, but agonist actions at this site are linked to abuse-related hallucinogenic effects that may limit therapeutic efficacy of chronic drug administration. Tolerance to some effects of hallucinogens has been observed in humans and laboratory animals, but the understanding of tolerance and cross-tolerance between distinct structural classes of hallucinogens is limited. Here, we used the drug-elicited head twitch response (HTR) in mice to assess the development of tolerance and cross-tolerance with two phenethylamine-derived [DOI (2,5-dimethoxy-4-iodoamphetamine) and 2C-T-7 (2,5-dimethoxy-4-propylthiophenethylamine)] and two tryptamine-derived [DPT (N,N-dipropyltryptamine) and DIPT (N,N-diisopropyltryptamine)] drugs with agonist affinity for 5-HT2A receptors. Tolerance developed to HTR elicited by daily DOI or 2C-T-7, but not to HTR elicited by DPT or DIPT. DOI-elicited tolerance was not surmountable with dose, and a similar insurmountable cross-tolerance was evident when DOI-tolerant mice were tested with various doses of 2C-T-7 or DPT. These studies suggest that the use of phenethylamine-derived hallucinogens as therapeutic agents may be limited not only by their abuse potential, but also by the rapid development of tolerance that would likely be maintained even if a patient were switched to a different 5-HT2A agonist medication from a distinct structural class. However, these experiments also imply that tryptamine-derived hallucinogens might have a reduced potential for tolerance development, compared with phenethylamine-derived 5-HT2A agonists, and might therefore be more suitable for chronic administration in a therapeutic context. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Effects of cholinergic and beta-adrenergic blockade on orthostatic tolerance in healthy subjects

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Sather, T. M.

2000-01-01

Cardiovascular responses during a graded lower body negative pressure (LBNP) protocol were compared before and after atropine and propranolol administration to test the hypothesis that both sympathetic and parasympathetic control of cardio-acceleration are associated with syncopal predisposition to orthostatic stress in healthy subjects. Eleven men were categorized into two groups having high (HT, N = 6) or low (LT, N = 5) tolerance based on their total time before the onset of presyncopal symptoms. HT and LT groups were similar in physical characteristics, fitness, and baseline cardiovascular measurements. Atropine treatment had no effect on LBNP tolerance or mean arterial pressure at presyncope, despite an atropine-induced increase in heart rate. Propranolol treatment reduced (p<0.05) LBNP tolerance in both groups. Diminished LBNP tolerance after propranolol administration was associated with reductions in cardiac output, whereas increase in systemic peripheral resistance from baseline to presyncope was unaffected by propranolol. Reduction in cardiac output and LBNP tolerance after beta blockade reflected a chronotropic effect because lower LBNP tolerance for the HT (-50%) and LT (-39%) groups was associated with dramatic reductions (p <0.05) in the magnitude of LBNP-induced tachycardia without significant effects on stroke volume at presyncope. Absence of an atropine-induced difference in cardiac output and systemic peripheral resistance between HT and LT groups failed to support the notion that cardiac vagal withdrawal represents a predominant mechanism that could account for differences in orthostatic tolerance. Because a reduction in LBNP tolerance in both HT and LT groups after propranolol treatment was most closely associated with reduced tachycardia, the data suggest that a primary autonomically mediated mechanism for maintenance of mean arterial pressure and orthostatic tolerance in healthy subjects is beta adrenergic-induced tachycardia.

Developing sporophytes transition from an inducible to a constitutive ecological strategy of desiccation tolerance in the moss Aloina ambigua: effects of desiccation on fitness

PubMed Central

Stark, Lloyd R.; Brinda, John C.

2015-01-01

Background and Aims Two ecological strategies of desiccation tolerance exist in plants, constitutive and inducible. Because of difficulties in culturing sporophytes, very little is known about desiccation tolerance in this generation and how desiccation affects sexual fitness. Methods Cultured sporophytes and vegetative shoots from a single genotype of the moss Aloina ambigua raised in the laboratory were tested for their strategy of desiccation tolerance by desiccating the shoot–sporophyte complex and vegetative shoots at different intensities, and comparing outcomes with those of undried shoot–sporophyte complexes and vegetative shoots. By using a dehardened clonal line, the effects of field, age and genetic variance among plants were removed. Key Results The gametophyte and embryonic sporophyte were found to employ a predominantly inducible strategy of desiccation tolerance, while the post-embryonic sporophyte was found to employ a moderately constitutive strategy of desiccation tolerance. Further, desiccation reduced sporophyte fitness, as measured by sporophyte mass, seta length and capsule size. However, the effects of desiccation on sporophyte fitness were reduced if the stress occurred during embryonic development as opposed to postembryonic desiccation. Conclusions The effects of desiccation on dehardened sporophytes of a bryophyte are shown for the first time. The transition from one desiccation tolerance strategy to the other in a single structure or generation is shown for only the second time in plants and for the first time in bryophytes. Finding degrees of inducible strategies of desiccation tolerance in different life phases prompts the formulation of a continuum hypothesis of ecological desiccation tolerance in mosses, where desiccation tolerance is not an either/or phenomenon, but varies in degree along a gradient of ecological inducibility. PMID:25578378

Physiological response of glandular-haired alfalfa to potato leafhopper (Hemiptera: Cicadellidae) injury.

PubMed

Lamp, W O; Alexander, L C; Nguyen, M

2007-02-01

Plant tolerance to herbivory is a key approach for managing pests. In alfalfa, Medicago sativa, the potato leafhopper, Empoasca fabae, is a major pest as a result of the cascade of plant responses to piercing-sucking injury. To identify tolerance to its injury based on alfalfa physiology, experiments were conducted in the field and greenhouse. In our comparison of the response of field-grown alfalfa cultivars to standardized leafhopper densities, net photosynthesis and transpiration rates of 'Geneva' leaves were reduced by 18 and 21%, respectively, by leafhopper presence compared with a rate change of <1% of resistant 'EverGreen' leaves. Under greenhouse conditions, alfalfa clones varied in their level of gas exchange (net photosynthesis and transpiration) and stem elongation responses to leafhopper injury. For example, in the comparison of seven clones, net photosynthesis declined an average of 40.7% with leafhopper injury, although individual clones varied from 26.6 to 74.3% reduction. Internode elongation after 2 d was 60.3% less on injured stems compared with healthy stems, but again, the individual clones varied from 17.3 to 91.9%. In a time-course study of selected clones, clones varied in their level of injury just after and 3 d after insect removal. Gas exchange responses of all clones recovered by 7 d after cessation of injury. In a choice test, leafhoppers spent similar amounts of time on the susceptible clone and the most tolerant clone; however, their precise feeding behaviors were not measured. Thus, the variable response of clones to injury may be either true physiological tolerance or antixenosis from a change in feeding behavior. This study showed putative tolerance to leafhopper injury among alfalfa genotypes, suggesting that tolerance could be the basis for crop protection in alfalfa from potato leafhopper injury.

Religion and the Unmaking of Prejudice toward Muslims: Evidence from a Large National Sample

PubMed Central

Shaver, John H.; Troughton, Geoffrey; Sibley, Chris G.; Bulbulia, Joseph A.

2016-01-01

In the West, anti-Muslim sentiments are widespread. It has been theorized that inter-religious tensions fuel anti-Muslim prejudice, yet previous attempts to isolate sectarian motives have been inconclusive. Factors contributing to ambiguous results are: (1) failures to assess and adjust for multi-level denomination effects; (2) inattention to demographic covariates; (3) inadequate methods for comparing anti-Muslim prejudice relative to other minority group prejudices; and (4) ad hoc theories for the mechanisms that underpin prejudice and tolerance. Here we investigate anti-Muslim prejudice using a large national sample of non-Muslim New Zealanders (N = 13,955) who responded to the 2013 New Zealand Attitudes and Values Study. We address previous shortcomings by: (1) building Bayesian multivariate, multi-level regression models with denominations modeled as random effects; (2) including high-resolution demographic information that adjusts for factors known to influence prejudice; (3) simultaneously evaluating the relative strength of anti-Muslim prejudice by comparing it to anti-Arab prejudice and anti-immigrant prejudice within the same statistical model; and (4) testing predictions derived from the Evolutionary Lag Theory of religious prejudice and tolerance. This theory predicts that in countries such as New Zealand, with historically low levels of conflict, religion will tend to increase tolerance generally, and extend to minority religious groups. Results show that anti-Muslim and anti-Arab sentiments are confounded, widespread, and substantially higher than anti-immigrant sentiments. In support of the theory, the intensity of religious commitments was associated with a general increase in tolerance toward minority groups, including a poorly tolerated religious minority group: Muslims. Results clarify religion’s power to enhance tolerance in peaceful societies that are nevertheless afflicted by prejudice. PMID:26959976

Strong Costs and Benefits of Winter Acclimatization in Drosophila melanogaster

PubMed Central

Schou, Mads Fristrup; Loeschcke, Volker; Kristensen, Torsten Nygaard

2015-01-01

Studies on thermal acclimation in insects are often performed on animals acclimated in the laboratory under conditions that are not ecologically relevant. Costs and benefits of acclimation responses under such conditions may not reflect costs and benefits in natural populations subjected to daily and seasonal temperature fluctuations. Here we estimated costs and benefits in thermal tolerance limits in relation to winter acclimatization of Drosophila melanogaster. We sampled flies from a natural habitat during winter in Denmark (field flies) and compared heat and cold tolerance of these to that of flies collected from the same natural population, but acclimated to 25 °C or 13 °C in the laboratory (laboratory flies). We further obtained thermal performance curves for egg-to-adult viability of field and laboratory (25 °C) flies, to estimate possible cross-generational effects of acclimation. We found much higher cold tolerance and a lowered heat tolerance in field flies compared to laboratory flies reared at 25 °C. Flies reared in the laboratory at 13 °C exhibited the same thermal cost-benefit relations as the winter acclimatized flies. We also found a cost of winter acclimatization in terms of decreased egg-to-adult viability at high temperatures of eggs laid by winter acclimatized flies. Based on our findings we suggest that winter acclimatization in nature can induce strong benefits in terms of increased cold tolerance. These benefits can be reproduced in the laboratory under ecologically relevant rearing and testing conditions, and should be incorporated in species distribution modelling. Winter acclimatization also leads to decreased heat tolerance. This may create a mismatch between acclimation responses and the thermal environment, e.g. if temperatures suddenly increase during spring, under current and expected more variable future climatic conditions. PMID:26075607

Strong Costs and Benefits of Winter Acclimatization in Drosophila melanogaster.

PubMed

Schou, Mads Fristrup; Loeschcke, Volker; Kristensen, Torsten Nygaard

2015-01-01

Studies on thermal acclimation in insects are often performed on animals acclimated in the laboratory under conditions that are not ecologically relevant. Costs and benefits of acclimation responses under such conditions may not reflect costs and benefits in natural populations subjected to daily and seasonal temperature fluctuations. Here we estimated costs and benefits in thermal tolerance limits in relation to winter acclimatization of Drosophila melanogaster. We sampled flies from a natural habitat during winter in Denmark (field flies) and compared heat and cold tolerance of these to that of flies collected from the same natural population, but acclimated to 25 °C or 13 °C in the laboratory (laboratory flies). We further obtained thermal performance curves for egg-to-adult viability of field and laboratory (25 °C) flies, to estimate possible cross-generational effects of acclimation. We found much higher cold tolerance and a lowered heat tolerance in field flies compared to laboratory flies reared at 25 °C. Flies reared in the laboratory at 13 °C exhibited the same thermal cost-benefit relations as the winter acclimatized flies. We also found a cost of winter acclimatization in terms of decreased egg-to-adult viability at high temperatures of eggs laid by winter acclimatized flies. Based on our findings we suggest that winter acclimatization in nature can induce strong benefits in terms of increased cold tolerance. These benefits can be reproduced in the laboratory under ecologically relevant rearing and testing conditions, and should be incorporated in species distribution modelling. Winter acclimatization also leads to decreased heat tolerance. This may create a mismatch between acclimation responses and the thermal environment, e.g. if temperatures suddenly increase during spring, under current and expected more variable future climatic conditions.

Hypoxia tolerance and responses to hypoxic stress during heart and skeletal muscle inflammation in Atlantic salmon (Salmo salar).

PubMed

Lund, Morten; Krudtaa Dahle, Maria; Timmerhaus, Gerrit; Alarcon, Marta; Powell, Mark; Aspehaug, Vidar; Rimstad, Espen; Jørgensen, Sven Martin

2017-01-01

Heart and skeletal muscle inflammation (HSMI) is associated with Piscine orthoreovirus (PRV) infection and is an important disease in Atlantic salmon (Salmo salar) aquaculture. Since PRV infects erythrocytes and farmed salmon frequently experience environmental hypoxia, the current study examined mutual effects of PRV infection and hypoxia on pathogenesis and fish performance. Furthermore, effects of HSMI on hypoxia tolerance, cardiorespiratory performance and blood oxygen transport were studied. A cohabitation trial including PRV-infected post-smolts exposed to periodic hypoxic stress (4 h of 40% O2; PRV-H) at 4, 7 and 10 weeks post-infection (WPI) and infected fish reared under normoxic conditions (PRV) was conducted. Periodic hypoxic stress did not influence infection levels or histopathological changes in the heart. Individual incipient lethal oxygen saturation (ILOS) was examined using a standardized hypoxia challenge test (HCT). At 7 WPI, i.e. peak level of infection, both PRV and PRV-H groups exhibited reduced hypoxia tolerance compared to non-infected fish. Three weeks later (10 WPI), during peak levels of pathological changes, reduced hypoxia tolerance was still observed for the PRV group while PRV-H performed equal to non-infected fish, implying a positive effect of the repeated exposure to hypoxic stress. This was in line with maximum heart rate (fHmax) measurements, showing equal performance of PRV-H and non-infected groups, but lower fHmax above 19°C as well as lower temperature optimum (Topt) for aerobic scope for PRV, suggesting reduced cardiac performance and thermal tolerance. In contrast, the PRV-H group had reduced hemoglobin-oxygen affinity compared to non-infected fish. In conclusion, Atlantic salmon suffering from HSMI have reduced hypoxia tolerance and cardiac performance, which can be improved by preconditioning fish to transient hypoxic stress episodes.

Hypoxia tolerance and responses to hypoxic stress during heart and skeletal muscle inflammation in Atlantic salmon (Salmo salar)

PubMed Central

Krudtaa Dahle, Maria; Timmerhaus, Gerrit; Alarcon, Marta; Powell, Mark; Aspehaug, Vidar; Rimstad, Espen; Jørgensen, Sven Martin

2017-01-01

Heart and skeletal muscle inflammation (HSMI) is associated with Piscine orthoreovirus (PRV) infection and is an important disease in Atlantic salmon (Salmo salar) aquaculture. Since PRV infects erythrocytes and farmed salmon frequently experience environmental hypoxia, the current study examined mutual effects of PRV infection and hypoxia on pathogenesis and fish performance. Furthermore, effects of HSMI on hypoxia tolerance, cardiorespiratory performance and blood oxygen transport were studied. A cohabitation trial including PRV-infected post-smolts exposed to periodic hypoxic stress (4 h of 40% O2; PRV-H) at 4, 7 and 10 weeks post-infection (WPI) and infected fish reared under normoxic conditions (PRV) was conducted. Periodic hypoxic stress did not influence infection levels or histopathological changes in the heart. Individual incipient lethal oxygen saturation (ILOS) was examined using a standardized hypoxia challenge test (HCT). At 7 WPI, i.e. peak level of infection, both PRV and PRV-H groups exhibited reduced hypoxia tolerance compared to non-infected fish. Three weeks later (10 WPI), during peak levels of pathological changes, reduced hypoxia tolerance was still observed for the PRV group while PRV-H performed equal to non-infected fish, implying a positive effect of the repeated exposure to hypoxic stress. This was in line with maximum heart rate (fHmax) measurements, showing equal performance of PRV-H and non-infected groups, but lower fHmax above 19°C as well as lower temperature optimum (Topt) for aerobic scope for PRV, suggesting reduced cardiac performance and thermal tolerance. In contrast, the PRV-H group had reduced hemoglobin-oxygen affinity compared to non-infected fish. In conclusion, Atlantic salmon suffering from HSMI have reduced hypoxia tolerance and cardiac performance, which can be improved by preconditioning fish to transient hypoxic stress episodes. PMID:28700748

Impact response of graphite/epoxy fabric structures

NASA Technical Reports Server (NTRS)

Lagace, Paul A.; Kraft, Michael J.

1990-01-01

The impact damage resistance and damage tolerance of graphite/epoxy fabric plate (coupon) and cylinder structures were investigated and compared in an analytical and experimental study. Hercules A370-5H/3501-6 five-harness satin weave cloth in a quasi-isotropic (0,45)(sub s) laminate configuration was utilized. Specimens were impacted with 12.7 mm diameter steel spheres at velocities ranging from 10 m/s to 100 m/s. Damage resistance of the specimens was determined through the use of dye penetrant enhanced x-radiography, sectioning, epoxy burnoff, and visual methods. Damage tolerance of the flat plate structures was assessed in a residual tensile test while damage tolerance of the cylinder structures was assessed via pressurization tests. Impacted fabric laminates exhibited matrix crushing, fiber breakage, delamination, and fiber bundle disbonds; the latter being a unique damage mode for fabric laminates. Plate delamination and bundle disbonding was found to be more extensive around the central core area of fiber damage in the coupon specimens than in the cylinder specimens which showed a cleaner damage area due to impact. Damage resistance and damage tolerance were predicted by utilizing a five-step analysis approach previously utilized for coupon configurations. Two of the five steps were adapted to account for the effects of the structural configuration of the pressurized cylinder. The damage resistance analysis provided good correlation to the fiber damage region of both the coupon and cylinder specimens. There was little difference in the size of this region in the two specimen types. However, the analysis was not able to predict the distribution of damage through-the-thickness. This was important in assessing the damage tolerance of the cylinders. The damage tolerance analysis was able to predict the residual tensile strength of the coupons. A general methodology to predict the impact damage resistance and damage tolerance of composite structures utilizing coupon data is presented.

Characterization of multi-drug tolerant persister cells in Streptococcus suis.

PubMed

Willenborg, Jörg; Willms, Daniela; Bertram, Ralph; Goethe, Ralph; Valentin-Weigand, Peter

2014-05-12

Persister cells constitute a subpopulation of dormant cells within a microbial population which are genetically identical but phenotypically different to regular cells. Notably, persister cells show an elevated tolerance to antimicrobial agents. Thus, they are considered to represent a microbial 'bet-hedging' strategy and are of particular importance in pathogenic bacteria. We studied the ability of the zoonotic pathogen Streptococcus (S.) suis to form multi-drug tolerant variants and identified persister cells dependent on the initial bacterial growth phase. We observed lower numbers of persisters in exponential phase cultures than in stationary growth phase populations. S. suis persister cells showed a high tolerance to a variety of antibiotics, and the phenotype was not inherited as tested with four passages of S. suis populations. Furthermore, we provide evidence that the persister phenotype is related to expression of genes involved in general metabolic pathways since we found higher numbers of persister cells in a mutant strain defective in the catabolic arginine deiminase system as compared to its parental wild type strain. Finally, we observed persister cell formation also in other S. suis strains and pathogenic streptococcal species. Taken together, this is the first study that reports multi-drug tolerant persister cells in the zoonotic pathogen S. suis.

Improving salinity tolerance of plants through conventional breeding and genetic engineering: An analytical comparison.

PubMed

Ashraf, Muhammad; Akram, Nudrat Aisha

2009-01-01

The last century has witnessed a substantial improvement in yield potential, quality and disease resistance in crops. This was indeed the outcome of conventional breeding, which was achieved with little or no knowledge of underlying physiological and biochemical phenomena related to a trait. Also the resources utilized on programs involving conventional breeding were not of great magnitude. Plant breeders have also been successful during the last century in producing a few salt-tolerant cultivars/lines of some potential crops through conventional breeding, but this again has utilized modest resources. However, this approach seems now inefficient due to a number of reasons, and alternatively, genetic engineering for improving crop salt tolerance is being actively followed these days by the plant scientists, world-over. A large number of transgenic lines with enhanced salt tolerance of different crops can be deciphered from the literature but up to now only a very few field-tested cultivars/lines are known despite the fact that considerable resources have been expended on the sophisticated protocols employed for generating such transgenics. This review analytically compares the achievements made so far in terms of producing salt-tolerant lines/cultivars through conventional breeding or genetic engineering.

Expression of Finger Millet EcDehydrin7 in Transgenic Tobacco Confers Tolerance to Drought Stress.

PubMed

Singh, Rajiv Kumar; Singh, Vivek Kumar; Raghavendrarao, Sanagala; Phanindra, Mullapudi Lakshmi Venkata; Venkat Raman, K; Solanke, Amolkumar U; Kumar, Polumetla Ananda; Sharma, Tilak Raj

2015-09-01

One of the critical alarming constraints for agriculture is water scarcity. In the current scenario, global warming due to climate change and unpredictable rainfall, drought is going to be a master player and possess a big threat to stagnating gene pool of staple food crops. So it is necessary to understand the mechanisms that enable the plants to cope with drought stress. In this study, effort was made to prospect the role of EcDehydrin7 protein from normalized cDNA library of drought tolerance finger millet in transgenic tobacco. Biochemical and molecular analyses of T0 transgenic plants were done for stress tolerance. Leaf disc assay, seed germination test, dehydration assay, and chlorophyll estimation showed EcDehydrin7 protein directly link to drought tolerance. Northern and qRT PCR analyses shows relatively high expression of EcDehydrin7 protein compare to wild type. T0 transgenic lines EcDehydrin7(11) and EcDehydrin7(15) shows superior expression among all lines under study. In summary, all results suggest that EcDehydrin7 protein has a remarkable role in drought tolerance and may be used for sustainable crop breeding program in other food crops.

An optimized implementation of a fault-tolerant clock synchronization circuit

NASA Technical Reports Server (NTRS)

Torres-Pomales, Wilfredo

1995-01-01

A fault-tolerant clock synchronization circuit was designed and tested. A comparison to a previous design and the procedure followed to achieve the current optimization are included. The report also includes a description of the system and the results of tests performed to study the synchronization and fault-tolerant characteristics of the implementation.

Experiments in fault tolerant software reliability

NASA Technical Reports Server (NTRS)

Mcallister, David F.; Tai, K. C.; Vouk, Mladen A.

1987-01-01

The reliability of voting was evaluated in a fault-tolerant software system for small output spaces. The effectiveness of the back-to-back testing process was investigated. Version 3.0 of the RSDIMU-ATS, a semi-automated test bed for certification testing of RSDIMU software, was prepared and distributed. Software reliability estimation methods based on non-random sampling are being studied. The investigation of existing fault-tolerance models was continued and formulation of new models was initiated.

Pilot Study: Foam Wedge Chin Support Static Tolerance Testing

DTIC Science & Technology

2017-10-24

AFRL-SA-WP-SR-2017-0026 Pilot Study : Foam Wedge Chin Support Static Tolerance Testing Austin M. Fischer, BS1; William W...COVERED (From – To) April – October 2017 4. TITLE AND SUBTITLE Pilot Study : Foam Wedge Chin Support Static Tolerance Testing 5a. CONTRACT NUMBER...prototype to mitigate the increase in helmet weight and forward center of gravity. The purpose of this pilot study was to determine the feasibility and

Female Pubertal Timing and Problem Behaviour: The Role of Culture

ERIC Educational Resources Information Center

Skoog, Therese; Stattin, Hakan; Ruiselova, Zdena; Ozdemir, Metin

2013-01-01

We tested the peer-socialization/contextual-amplification explanation for the link between early female puberty and problem behaviour. We propose that in cultures with high tolerance for adolescent heterosexual involvement, early puberty should be linked with problem behaviour--not in other cultures. We compared girls in two cultures (Slovakia and…

Pharmacological activity and toxicity of some neurotropic agents under conditions of experimental hypodynamia

NASA Technical Reports Server (NTRS)

Kirichek, L. T.

1980-01-01

The indices of pharmacological range, risk coefficients, ED50, LD50, the size of the area of toxic activity, and maximal tolerated and absolute lethal doses were compared in hypodynamic mice. The pharmacological activity of the test neurotropic agents exhibiting a central action underwent change, but their toxicity remained unchanged.

Orthostatic Intolerance and Motion Sickness After Parabolic Flight

NASA Technical Reports Server (NTRS)

Schlegel, Todd T.; Brown, Troy E.; Wood, Scott J.; Benavides, Edgar W.; Bondar, Roberta L.; Stein, Flo; Moradshahi, Peyman; Harm, Deborah L.; Low, Phillip A.

1999-01-01

Orthostatic intolerance is common in astronauts after prolonged space flight. However, the "push-pull effect" in military aviators suggests that brief exposures to transitions between hypo- and hypergravity are sufficient to induce untoward autonomic cardiovascular physiology in susceptible individuals. We therefore investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy test subjects before and after a seated 2-hr parabolic flight. At the same time, we also investigated relationships between parabolic flight-induced vomiting and changes in orthostatic and autonomic cardiovascular function. After parabolic flight, 8 of 16 subjects could not tolerate a 30-min upright tilt test, compared to 2 of 16 before flight. Whereas new intolerance in non-Vomiters resembled the clinical postural tachycardia syndrome (POTS), new intolerance in Vomiters was characterized by comparatively isolated upright hypocapnia and cerebral vasoconstriction. As a group, Vomiters also had evidence for increased postflight fluctuations in efferent vagal-cardiac nerve traffic occurring independently of any superimposed change in respiration. Results suggest that syndromes of orthostatic intolerance resembling those occurring after space flight can occur after a brief (i.e., 2-hr) parabolic flight.

Lower-body negative-pressure exercise and bed-rest-mediated orthostatic intolerance

NASA Technical Reports Server (NTRS)

Schneider, Suzanne M.; Watenpaugh, Donald E.; Lee, Stuart M C.; Ertl, Andrew C.; Williams, W. Jon; Ballard, Richard E.; Hargens, Alan R.

2002-01-01

PURPOSE: Supine, moderate exercise is ineffective in maintaining orthostatic tolerance after bed rest (BR). Our purpose was to test the hypothesis that adding an orthostatic stress during exercise would maintain orthostatic function after BR. METHODS: Seven healthy men completed duplicate 15-d 6 degrees head-down tilt BR using a crossover design. During one BR, subjects did not exercise (CON). During another BR, subjects exercised for 40 min.d(-1) on a supine treadmill against 50-60 mm Hg LBNP (EX). Exercise training consisted of an interval exercise protocol of 2- to 3-min intervals alternating between 41 and 65% (.)VO(2max). Before and after BR, an LBNP tolerance test was performed in which the LBNP chamber was decompressed in 10-mm Hg stages every 3 min until presyncope. RESULTS: LBNP tolerance, as assessed by the cumulative stress index (CSI) decreased after BR in both the CON (830 +/- 144, pre-BR vs 524 +/- 56 mm Hg.min, post-BR) and the EX (949 +/- 118 pre-BR vs 560 +/- 44 mm Hg.min, post-BR) conditions. However, subtolerance (0 to -50 mm Hg LBNP) heart rates were lower and systolic blood pressures were better maintained after BR in the EX condition compared with CON. CONCLUSION: Moderate exercise performed against LBNP simulating an upright 1-g environment failed to protect orthostatic tolerance after 15 d of BR.

Dietary baked egg accelerates resolution of egg allergy in children.

PubMed

Leonard, Stephanie A; Sampson, Hugh A; Sicherer, Scott H; Noone, Sally; Moshier, Erin L; Godbold, James; Nowak-Węgrzyn, Anna

2012-08-01

Baked egg is tolerated by a majority of egg-allergic children. To characterize immunologic changes associated with ingestion of baked egg and evaluate the role that baked egg diets play in the development of tolerance to regular egg. Egg-allergic subjects who tolerated baked egg challenge incorporated baked egg into their diet. Immunologic parameters were measured at follow-up visits. A comparison group strictly avoiding egg was used to evaluate the natural history of the development of tolerance. Of the 79 subjects in the intent-to-treat group followed for a median of 37.8 months, 89% now tolerate baked egg and 53% now tolerate regular egg. Of 23 initially baked egg-reactive subjects, 14 (61%) subsequently tolerated baked egg and 6 (26%) now tolerate regular egg. Within the initially baked egg-reactive group, subjects with persistent reactivity to baked egg had higher median baseline egg white (EW)-specific IgE levels (13.5 kU(A)/L) than those who subsequently tolerated baked egg (4.4 kU(A)/L; P= .04) and regular egg (3.1 kU(A)/L; P= .05). In subjects ingesting baked egg, EW-induced skin prick test wheal diameter and EW-, ovalbumin-, and ovomucoid-specific IgE levels decreased significantly, while ovalbumin- and ovomucoid-specific IgG(4) levels increased significantly. Subjects in the per-protocol group were 14.6 times more likely than subjects in the comparison group (P< .0001) to develop regular egg tolerance, and they developed tolerance earlier (median 50.0 vs 78.7 months; P< .0001). Initiation of a baked egg diet accelerates the development of regular egg tolerance compared with strict avoidance. Higher serum EW-specific IgE level is associated with persistent baked and regular egg reactivity, while initial baked egg reactivity is not. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Hydromorphone efficacy and treatment protocol impact on tolerance and mu-opioid receptor regulation.

PubMed

Kumar, Priyank; Sunkaraneni, Soujanya; Sirohi, Sunil; Dighe, Shveta V; Walker, Ellen A; Yoburn, Byron C

2008-11-12

This study examined the antinociceptive (analgesic) efficacy of hydromorphone and hydromorphone-induced tolerance and regulation of mu-opioid receptor density. Initially s.c. hydromorphone's time of peak analgesic (tail-flick) effect (45 min) and ED50 using standard and cumulative dosing protocols (0.22 mg/kg, 0.37 mg/kg, respectively) were determined. The apparent analgesic efficacy (tau) of hydromorphone was then estimated using the operational model of agonism and the irreversible mu-opioid receptor antagonist clocinnamox. Mice were injected with clocinnamox (0.32-25.6 mg/kg, i.p.) and 24 h later, the analgesic potency of hydromorphone was determined. The tau value for hydromorphone was 35, which suggested that hydromorphone is a lower analgesic efficacy opioid agonist. To examine hydromorphone-induced tolerance, mice were continuously infused s.c. with hydromorphone (2.1-31.5 mg/kg/day) for 7 days and then morphine cumulative dose response studies were performed. Other groups of mice were injected with hydromorphone (2.2-22 mg/kg/day) once, or intermittently every 24 h for 7 days. Twenty-four hours after the last injection, mice were tested using morphine cumulative dosing studies. There was more tolerance with infusion treatments compared to intermittent treatment. When compared to higher analgesic efficacy opioids, hydromorphone infusions induced substantially more tolerance. Finally, the effect of chronic infusion (31.5 mg/kg/day) and 7 day intermittent (22 mg/kg/day) hydromorphone treatment on spinal cord mu-opioid receptor density was determined. Hydromorphone did not produce any change in mu-opioid receptor density following either treatment. These results support suggestions that analgesic efficacy is correlated with tolerance magnitude and regulation of mu-opioid receptors when opioid agonists are continuously administered. Taken together, these studies indicate that analgesic efficacy and treatment protocol are important in determining tolerance and regulation of mu-opioid receptors.

The effects of horizontal body casting on blood volume, drug responsiveness, and +Gz tolerance in the rhesus monkey

NASA Technical Reports Server (NTRS)

Dickey, D. T.; Billman, G. E.; Teoh, K.; Sandler, H.; Stone, H. L.

1982-01-01

To simulate the weightless condition, eight rhesus monkeys, instrumented with solid-state pressure transducers, were horizontally restrained in body casts for 28 days. Blood volume decreased an average of 13% after 14 days of restraint, due mainly to a drop in plasma volume. Aortic pressure and heart rate responses to norepinephrine and phenylephrine decreased after 14 days of restraint. The monkeys did not show a statistically significant decreased tolerance to a 90 deg sudden upright tilt after horizontal restraint. During the fifth week of casting, four animals were subjected to +Gz acceleration tests on a centrifuge. The acceleration tolerance of the casted monkeys was significantly reduced compared to four similarly instrumented control animals. These findings indicate that the cardiovascular deconditioning associated with simulated weightlessness results from an inability to maintain central blood volume during orthostatic stress.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katti, Amogh; Di Fatta, Giuseppe; Naughton III, Thomas J

Future extreme-scale high-performance computing systems will be required to work under frequent component failures. The MPI Forum's User Level Failure Mitigation proposal has introduced an operation, MPI_Comm_shrink, to synchronize the alive processes on the list of failed processes, so that applications can continue to execute even in the presence of failures by adopting algorithm-based fault tolerance techniques. This MPI_Comm_shrink operation requires a fault tolerant failure detection and consensus algorithm. This paper presents and compares two novel failure detection and consensus algorithms. The proposed algorithms are based on Gossip protocols and are inherently fault-tolerant and scalable. The proposed algorithms were implementedmore » and tested using the Extreme-scale Simulator. The results show that in both algorithms the number of Gossip cycles to achieve global consensus scales logarithmically with system size. The second algorithm also shows better scalability in terms of memory and network bandwidth usage and a perfect synchronization in achieving global consensus.« less

Oral challenges with four apple cultivars result in significant differences in oral allergy symptoms.

PubMed

Nybom, Hilde; Cervin-Hoberg, Charlotte; Andersson, Morgan

2013-01-01

We analyzed the hypoallergenic potential of a recently bred apple selection with unusually low content of Mal d 1, using an oral challenge model with three additional apple cultivars for comparison. Sixty-six birch pollen-allergic individuals with a history of oral allergy syndrome after apple intake were subjected to a double-blind oral provocation with two apple cultivars (B:0654 and 'Discovery'). Thirteen also tested two other apple cultivars ('Ingrid Marie' and 'Gloster'). Three doses were given consecutively, 30 min apart: 10 g without peel, and 10 and 50 g with peel. A final assessment was conducted 30 min after the last intake. Oral symptoms were graded from 0 to 5. Total oral symptom score (TOS) included all scores for each cultivar at all time points. B:0654 induced significantly higher TOS than 'Discovery' when tested by 66 individuals, in spite of its lower Mal d 1 content. TOS values were higher in females and increased with increasing age of the individuals when challenged with 'Discovery'. Among the 13 individuals who tested all four cultivars, B:0654 produced a higher score after the second dose compared to 'Ingrid Marie'. This was also the case after the third dose compared to 'Ingrid Marie' and 'Gloster', and again 30 min after the last intake compared to each of the other three cultivars, as well as a higher TOS compared to each of the other three cultivars (all p < 0.01). Our test was safe and well tolerated, and produced significant differences among the apple cultivars. Contrary to expectations, B:0654 was less well tolerated than the other three cultivars. Copyright © 2013 S. Karger AG, Basel.

Effect of Salsalate on Insulin Action, Secretion, and Clearance in Nondiabetic, Insulin-Resistant Individuals: A Randomized, Placebo-Controlled Study

PubMed Central

Liu, Alice; Ariel, Danit; Abbasi, Fahim; Lamendola, Cindy; Grove, Kaylene; Tomasso, Vanessa; Ochoa, Hector; Reaven, Gerald

2014-01-01

OBJECTIVE Salsalate treatment has been shown to improve glucose homeostasis, but the mechanism remains unclear. The aim of this study was to evaluate the effect of salsalate treatment on insulin action, secretion, and clearance rate in nondiabetic individuals with insulin resistance. RESEARCH DESIGN AND METHODS This was a randomized (2:1), single-blind, placebo-controlled study of salsalate (3.5 g daily for 4 weeks) in nondiabetic individuals with insulin resistance. All individuals had measurement of glucose tolerance (75-g oral glucose tolerance test), steady-state plasma glucose (SSPG; insulin suppression test), and insulin secretion and clearance rate (graded-glucose infusion test) before and after treatment. RESULTS Forty-one individuals were randomized to salsalate (n = 27) and placebo (n = 14). One individual from each group discontinued the study. Salsalate improved fasting (% mean change −7% [95% CI −10 to −14] vs. 1% [−3 to 5], P = 0.005) but not postprandial glucose concentration compared with placebo. Salsalate also lowered fasting triglyceride concentration (−25% [−34 to −15] vs. −6% [−26 to 14], P = 0.04). Salsalate had no effect on SSPG concentration or insulin secretion rate but significantly decreased insulin clearance rate compared with placebo (−23% [−30 to −16] vs. 3% [−10 to 15], P < 0.001). Salsalate was well tolerated, but four individuals needed a dose reduction due to symptoms. CONCLUSIONS Salsalate treatment in nondiabetic, insulin-resistant individuals improved fasting, but not postprandial, glucose and triglyceride concentration. These improvements were associated with a decrease in insulin clearance rate without change in insulin action or insulin secretion. PMID:24963111

Tolerance of cultivated and wild plants of different taxonomy to soil contamination by kerosene.

PubMed

Sharonova, Natalia; Breus, Irina

2012-05-01

In laboratory experiments on leached chernozem contaminated by kerosene (1-15 wt.%), germination of 50 plants from 21 families (cultivated and wild, annual and perennial, mono- and dicotyledonous) as affected by kerosene type and concentration and plant features was determined. Tested plants formed three groups: more tolerant, less tolerant, and intolerant, in which relative germination was more than 70%, 30-70% and less than 30%, respectively. As parameters of soil phytotoxicity, effective kerosene concentrations (EC) causing germination depression of 10%, 25% and 50% were determined. EC values depended on the plant species and varied in a wide range of kerosene concentrations: 0.02-7.3% (EC(10)), 0.05-8.1% (EC(25)), and 0.2-12.7% (EC(50)). The reported data on germination in soils contaminated by oil and petrochemicals were generalized. The comparison showed that at very high contamination levels (10 and 15%) kerosene was 1.3-1.6 times more phytotoxic than diesel fuel and 1.3-1.4 times more toxic than crude oil, and at low (1 and 2%) and medium (3 and 5%) levels the toxicity of these contaminants was close differing by a factor of 1.1-1.2. Tolerance of plants to soil contamination had a species-specific nature and, on the average, decreased in the following range of families: Fabaceae (germination decrease of 10-60% as compared to an uncontaminated control)>Brassicaceae (5-70%)>Asteraceae (25-95%)>Poaceae (10-100%). The monocotyledonous species tested were characterized as medium- and low-stable to contamination, whereas representatives of dicotyledonous plants were met in all groups of tolerance. Tested wild plants, contrary to reference data on oil toxicity, were more sensitive to kerosene than cultivated. No correlation was observed between degree of plant tolerance to kerosene and mass of seeds. The evidence indicates factors as structure and properties of testa, structure of germ, type of storage compounds, and type of seed germination (underground or aboveground) are more important. Copyright © 2012 Elsevier B.V. All rights reserved.

Pregabalin role in inhibition of morphine analgesic tolerance and physical dependency in rats.

PubMed

Hasanein, Parisa; Shakeri, Saeed

2014-11-05

Pregabalin is recently proposed as analgesic or adjuvant in pain management. While previous preclinical investigations have evaluated pregabalin-opioid interactions, the effect of pregabalin on opioid tolerance and dependency has not yet been studied. Here we evaluated the effects of different doses of pregabalin (50, 100 and 200mg/kg, s.c.) on morphine-induced tolerance and dependency in rats. Adult male Wistar rats were rendered tolerant to analgesic effect of morphine by injection of morphine (10mg/kg, s.c.) twice daily for 7 days. To develop morphine dependence, rats were given escalating doses of morphine. To determine the effect of pregabalin on the development of morphine tolerance and dependence, different doses of pregabalin were administrated before morphine. The tail-flick and naloxone precipitation withdrawal tests were used to evaluate the degree of tolerance and dependence, respectively. Chronic morphine-injected rats showed significant decrements in the percentage maximum possible effect (%MPE) of morphine on the days 5 and 7 (32.5%±3.5, 21.5%±4, respectively) compared to the first day (100%) which showed morphine tolerance. Pregabalin 200mg/kg completely prevented the development of morphine tolerance. In addition, concomitant treatment of morphine with pregabalin attenuated almost all of the naloxone-induced withdrawal signs which include weight loss, jumping, penis licking, teeth chattering, wet dog shakes, rearing, standing, sniffing, face grooming and paw tremor. These data show that pregabaline has a potential anti-tolerant/anti-dependence property against chronic usage of morphine. Therefore, pregabalin appears to be a promising candidate for the treatment of opioid addiction after confirming by future clinical studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Polyamine transporters and polyamines increase furfural tolerance during xylose fermentation with ethanologenic Escherichia coli strain LY180.

PubMed

Geddes, Ryan D; Wang, Xuan; Yomano, Lorraine P; Miller, Elliot N; Zheng, Huabao; Shanmugam, Keelnatham T; Ingram, Lonnie O

2014-10-01

Expression of genes encoding polyamine transporters from plasmids and polyamine supplements increased furfural tolerance (growth and ethanol production) in ethanologenic Escherichia coli LY180 (in AM1 mineral salts medium containing xylose). This represents a new approach to increase furfural tolerance and may be useful for other organisms. Microarray comparisons of two furfural-resistant mutants (EMFR9 and EMFR35) provided initial evidence for the importance of polyamine transporters. Each mutant contained a single polyamine transporter gene that was upregulated over 100-fold (microarrays) compared to that in the parent LY180, as well as a mutation that silenced the expression of yqhD. Based on these genetic changes, furfural tolerance was substantially reconstructed in the parent, LY180. Deletion of potE in EMFR9 lowered furfural tolerance to that of the parent. Deletion of potE and puuP in LY180 also decreased furfural tolerance, indicating functional importance of the native genes. Of the 8 polyamine transporters (18 genes) cloned and tested, half were beneficial for furfural tolerance (PotE, PuuP, PlaP, and PotABCD). Supplementing AM1 mineral salts medium with individual polyamines (agmatine, putrescine, and cadaverine) also increased furfural tolerance but to a smaller extent. In pH-controlled fermentations, polyamine transporter plasmids were shown to promote the metabolism of furfural and substantially reduce the time required to complete xylose fermentation. This increase in furfural tolerance is proposed to result from polyamine binding to negatively charged cellular constituents such as nucleic acids and phospholipids, providing protection from damage by furfural. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Alcohol-induced tolerance and physical dependence in mice with ethanol insensitive α1 GABAA receptors

PubMed Central

Werner, David F.; Swihart, Andrew R.; Ferguson, Carolyn; Lariviere, William R.; Harrison, Neil L.; Homanics, Gregg E.

2009-01-01

Background Although many people consume alcohol (ethanol), it remains unknown why some become addicted. Elucidating the molecular mechanisms of tolerance and physical dependence (withdrawal) may provide insight into alcohol addiction. While the exact molecular mechanisms of ethanol action are unclear, γ-aminobutyric acid type A receptors (GABAA-Rs) have been extensively implicated in ethanol action. The α1 GABAA-R subunit is associated with tolerance and physical dependence, but its exact role remains unknown. In this report, we tested the hypothesis that α1-GABAA-Rs mediate in part these effects of ethanol. Methods Ethanol-induced behavioral responses related to tolerance and physical dependence were investigated in knockin mice that have ethanol-insensitive α1 GABAA-Rs and wildtype controls. Acute functional tolerance (AFT) was assessed using the stationary dowel and loss of righting reflex assays. Chronic tolerance was assessed on the loss of righting reflex, fixed speed rotarod, hypothermia, and radiant tail flick assays following ten consecutive days of ethanol exposure. Withdrawal-related hyperexcitability was assessed by handling-induced convulsions following 3 cycles of ethanol vapor exposure/withdrawal. Immunoblots were used to assess α1 protein levels. Results Compared to controls, knockin mice displayed decreased AFT and chronic tolerance to ethanol-induced motor ataxia, and also displayed heightened ethanol-withdrawal hyperexcitability. No differences between wildtype and knockin mice were seen in other ethanol-induced behavioral measures. Following chronic exposure to ethanol, control mice displayed reductions in α1 protein levels, but knockins did not. Conclusions We conclude that α1-GABAA-Rs play a role in tolerance to ethanol-induced motor ataxia and withdrawal-related hyperexcitability. However, other aspects of behavioral tolerance and physical dependence do not rely on α1-containing GABAA-Rs. PMID:19032579

Improving isopropanol tolerance and production of Clostridium beijerinckii DSM 6423 by random mutagenesis and genome shuffling.

PubMed

Gérando, H Máté de; Fayolle-Guichard, F; Rudant, L; Millah, S K; Monot, F; Ferreira, Nicolas Lopes; López-Contreras, A M

2016-06-01

Random mutagenesis and genome shuffling was applied to improve solvent tolerance and isopropanol/butanol/ethanol (IBE) production in the strictly anaerobic bacteria Clostridium beijerinckii DSM 6423. Following chemical mutagenesis with N-methyl-N-nitro-N-nitrosoguanidine (NTG), screening of putatively improved strains was done by submitting the mutants to toxic levels of inhibitory chemicals or by screening for their tolerance to isopropanol (>35 g/L). Suicide substrates, such as ethyl or methyl bromobutyrate or alcohol dehydrogenase inhibitors like allyl alcohol, were tested and, finally, 36 mutants were isolated. The fermentation profiles of these NTG mutant strains were characterized, and the best performing mutants were used for consecutive rounds of genome shuffling. Screening of strains with further enhancement in isopropanol tolerance at each recursive shuffling step was then used to spot additionally improved strains. Three highly tolerant strains were finally isolated and able to withstand up to 50 g/L isopropanol on plates. Even if increased tolerance to the desired end product was not always accompanied by higher production capabilities, some shuffled strains showed increased solvent titers compared to the parental strains and the original C. beijerinckii DSM 6423. This study confirms the efficiency of genome shuffling to generate improved strains toward a desired phenotype such as alcohol tolerance. This tool also offers the possibility of obtaining improved strains of Clostridium species for which targeted genetic engineering approaches have not been described yet.

Evidence for increased cardiac compliance during exposure to simulated microgravity

NASA Technical Reports Server (NTRS)

Koenig, S. C.; Convertino, V. A.; Fanton, J. W.; Reister, C. A.; Gaffney, F. A.; Ludwig, D. A.; Krotov, V. P.; Trambovetsky, E. V.; Latham, R. D.

1998-01-01

We measured hemodynamic responses during 4 days of head-down tilt (HDT) and during graded lower body negative pressure (LBNP) in invasively instrumented rhesus monkeys to test the hypotheses that exposure to simulated microgravity increases cardiac compliance and that decreased stroke volume, cardiac output, and orthostatic tolerance are associated with reduced left ventricular peak dP/dt. Six monkeys underwent two 4-day (96 h) experimental conditions separated by 9 days of ambulatory activities in a crossover counterbalance design: 1) continuous exposure to 10 degrees HDT and 2) approximately 12-14 h per day of 80 degrees head-up tilt and 10-12 h supine (control condition). Each animal underwent measurements of central venous pressure (CVP), left ventricular and aortic pressures, stroke volume, esophageal pressure (EsP), plasma volume, alpha1- and beta1-adrenergic responsiveness, and tolerance to LBNP. HDT induced a hypovolemic and hypoadrenergic state with reduced LBNP tolerance compared with the control condition. Decreased LBNP tolerance with HDT was associated with reduced stroke volume, cardiac output, and peak dP/dt. Compared with the control condition, a 34% reduction in CVP (P = 0.010) and no change in left ventricular end-diastolic area during HDT was associated with increased ventricular compliance (P = 0.0053). Increased cardiac compliance could not be explained by reduced intrathoracic pressure since EsP was unaltered by HDT. Our data provide the first direct evidence that increased cardiac compliance was associated with headward fluid shifts similar to those induced by exposure to spaceflight and that reduced orthostatic tolerance was associated with lower cardiac contractility.

Breast-feeding is associated with reduced postpartum maternal glucose intolerance after gestational diabetes.

PubMed

O'Reilly, M; Avalos, G; Dennedy, M C; O'Sullivan, E P; Dunne, F P

2012-05-01

Gestational diabetes mellitus (GDM) is associated with adverse foetal and maternal outcomes, and identifies women at risk of future Type 2 Diabetes Mellitus (T2DM). Breast-feeding may improve postpartum maternal glucose tolerance. We prospectively examined the prevalence of postpartum dysglycaemia after GDM and examined the effect of lactation on postpartum glucose tolerance. We compared postpartum 75g oral glucose tolerance test (OGTT) results from 300 women with GDM and 220 controls with normal gestational glucose tolerance (NGT). Breast-feeding data was collected at time of OGTT. Postpartum OGTT results were classified as normal [fasting plasma glucose (FPG) < 5.6mmol/l, 2-h < 7.8 mmol/l] and abnormal [impaired fasting glucose (IFG), FPG 5.6-6.9 mmol/l; impaired glucose tolerance (IGT), 2-h glucose 7.8-11 mmol/l; IFG+IGT; T2DM, FPG > or = 7 mmol/l +/- 2h glucose > or = 11.1 mmol/l]. 6 (2.7%) with NGT in pregnancy had postpartum dysglycaemia compared to 57 (19%) with GDM in index pregnancy (p < 0.001). Non-European ethnicity (OR 3.40, 95% CI 1.45-8.02, p = 0.005), family history of T2DM (OR 2.14, 95% CI 1.06-4.32, p = 0.034) and gestational insulin use (OR 2.62, 95% CI 1.17-5.87 p = 0.019) were associated with persistent dysglycaemia. The prevalence of persistent hyperglycaemia was significantly lower in women who breast-fed versus bottle-fed postpartum (8.2% v 18.4%, p < 0.001). Breast-feeding may confer beneficial metabolic effects after GDM and should be encouraged.

Chromium effects on glucose tolerance and insulin sensitivity in persons at risk for diabetes mellitus.

PubMed

Ali, Ather; Ma, Yingying; Reynolds, Jesse; Wise, John Pierce; Inzucchi, Silvio E; Katz, David L

2011-01-01

To investigate the effects of daily chromium picolinate supplementation on serum measures of glucose tolerance and insulin sensitivity in patients at high risk for type 2 diabetes mellitus. We conducted a randomized, double-blind, placebo-controlled, modified cross-over clinical trial with 6-month sequences of intervention and placebo followed by a 6-month postintervention assessment. Adult patients with impaired fasting glucose, impaired glucose tolerance, or metabolic syndrome were enrolled. Participants received 6-month sequences of chromium picolinate or placebo at 1 of 2 dosages (500 or 1000 mcg daily). Primary outcome measures were change in fasting plasma glucose, 2-hour plasma glucose during oral glucose tolerance testing, fasting and 2-hour insulin, and homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes included anthropometric measures, blood pressure, endothelial function, hemoglobin A1c, lipids, and urinary microalbumin. Fifty-nine participants were enrolled. No changes were seen in glucose level, insulin level, or HOMA-IR (all P>.05) after 6 months of chromium at either dosage level (500 mcg or 1000 mcg daily) when compared with placebo. None of the secondary outcomes improved with either chromium dosage compared with placebo (P>.05). Chromium supplementation does not appear to ameliorate insulin resistance or impaired glucose metabolism in patients at risk for type 2 diabetes and thus is unlikely to attenuate diabetes risk.

Comparison of saline tolerance among genetically similar species of Fusarium and Meloidogyne recovered from marine and terrestrial habitats

NASA Astrophysics Data System (ADS)

Elmer, W. H.; LaMondia, J. A.

2014-08-01

Successful plant pathogens co-evolve and adapt to the environmental constraints placed on host plants. We compared the salt tolerance of two salt marsh pathogens, Fusarium palustre and Meloidogyne spartinae, to genetically related terrestrial species, F. sporotrichioides and Meloidogyne hapla, to assess whether the salt marsh species had acquired selective traits for persisting in saline environments or if salt tolerance was comparable among Fusarium and Meloidogyne species. Comparisons of both species were made in vitro in vessels containing increasing concentration of NaCl. We observed that F. palustre was more tolerant to NaCl than F. sporotrichioides. The radial expansion of F. palustre on NaCl-amended agar plates was unaffected by increasing concentrations up to 0.3 M. F. sporotrichioides showed large reductions in growth at the same concentrations. Survival of M. hapla was greatest at 0 M, and reduced by half in a 0.3 M solution for 4 days. No juveniles survived exposure to 0.3 M NaCl for 12 days. M. spartinae survived at all NaCl concentrations tested, including 1.0 M for at least 12 days. These findings are consistent with the hypothesis that marine organisms in the upper tidal zone must osmoregulate to withstand a wide range of salinity and provide evidence that these pathogens evolved in saline conditions and are not recent introductions from terrestrial niches.

Comparing Tolerance of Ambiguity in Veterinary and Medical Students.

PubMed

Hancock, Jason; Hammond, Jennifer A; Roberts, Martin; Mattick, Karen

Current guidelines suggest that educators in both medical and veterinary professions should do more to ensure that students can tolerate ambiguity. Designing curricula to achieve this requires the ability to measure and understand differences in ambiguity tolerance among and within professional groups. Although scales have been developed to measure tolerance of ambiguity in both medical and veterinary professions, no comparative studies have been reported. We compared the tolerance of ambiguity of medical and veterinary students, hypothesizing that veterinary students would have higher tolerance of ambiguity, given the greater patient diversity and less well-established evidence base underpinning practice. We conducted a secondary analysis of questionnaire data from first- to fourth-year medical and veterinary students. Tolerance of ambiguity scores were calculated and compared using the TAMSAD scale (29 items validated for the medical student population), the TAVS scale (27 items validated for the veterinary student population), and a scale comprising the 22 items common to both scales. Using the TAMSAD and TAVS scales, medical students had a significantly higher mean tolerance of ambiguity score than veterinary students (56.1 vs. 54.1, p<.001 and 60.4 vs. 58.5, p=.002, respectively) but no difference was seen when only the 22 shared items were compared (56.1 vs. 57.2, p=.513). The results do not support our hypothesis and highlight that different findings can result when different tools are used. Medical students may have slightly higher tolerance of ambiguity than veterinary students, although this depends on the scale used.

Neurotoxicity profile of supermethrin, a new pyrethroid insecticide.

PubMed

Hornychova, M; Frantik, E; Kubat, J; Formanek, J

1995-11-01

The use of a standard two-tier neurotoxicity screening procedure in the context of risk assessment is exemplified. Testing of a new pyrethroid in rats addressed the following sequence of questions: Does the substance evoke neurotoxic symptoms in sublethal doses? Do these symptoms reflect a primary neurotropic action? What are the dynamic characteristics of injury, the clinical profile of effect, and the relative potency of the tested substance compared to similar compounds? - The testing protocol is an animal analogue of a systematic neurological and psychological examination in man. First tier tests (structured observation, motor activity measurement, simple neurological examination) were applied after the first dose, during repeated dosing phase and in the restitution phase. Facultative tests for the second-tier examination (motor activity pattern, learning/retention test, evoked potentials, dynamic motor performance) were selected on the basis of effects revealed by the first-tier testing. Supermethrin evoked acute neurotoxicity in sublethal doses, ranging from 1/30 to 1/15 of LD50. The clinical pattern was similar to other cyano-substituted pyrethroids. Behavioural inhibition was transient and complete tolerance to it developed after 4-week repeated dosing. No indications of long-lasting changes in neuronal excitability or in learning and memory processes were found. Ataxia and excitomotoric phenomena dominated both the acute and the subchronic picture. Marked and persistent motor disturbances, including symptoms of lower motoneuron injury, were limited to individual animals of the highest, near-lethal dose group (27 mg-kg-1). Compared to lambda-cyhalothrin, the effects of supermethrin were 2 to 3 times weaker, disappeared more rapidly, cumulated less, and had higher tendency to tolerance.

Functional toxicity and tolerance patterns of bioavailable Pd(II), Pt(II), and Rh(III) on suspended Saccharomyces cerevisiae cells assayed in tandem by a respirometric biosensor.

PubMed

Frazzoli, Chiara; Dragone, Roberto; Mantovani, Alberto; Massimi, Cristiana; Campanella, Luigi

2007-12-01

Toxicological implications of exposure to bioavailable platinum group metals, here Pd, Pt, and Rh, are still to be clarified. This study obtained by a biosensor-based method preliminary information on potential effects on cellular metabolism as well as on possible tolerance mechanisms. Aerobic respiration was taken as the toxicological end point to perform tandem tests, namely functional toxicity test and tolerance test. Cells were suspended in the absence of essential constituents for growth. The dose-response curves obtained by exposure (2 h) to the metals (nanogram per gram range) suggested the same mechanisms of action, with Rh showing the greatest curve steepness and the lowest EC50 value. Conservative (95% lower confidence interval) EC10 values were 187, 85 and 51 ng g(-1) for Pt, Pd, and Rh respectively. Tolerance patterns were tested during the same runs. The full tolerance obtained after 12 h of exposure to each metal suggested mitochondrial inhibition of aerobic respiration as a target effect. The hazard rating of the metals in the tolerance test changed in the Rh EC50 range, where Rh showed the lowest toxicity. The observed tolerance might suggest a protective mechanism such as metallothionein induction at concentrations around the EC50 values. The performance of the bioassay was satisfactory, in terms of the limit of detection, repeatability, reproducibility, roboustness, sensibility, and stability; the method's critical uncertainty sources were identified for improvements.

Comparative assessment of local tolerance of alcohols commonly used in alcohol-based hand rubs for hand hygiene.

PubMed

Manche, Monique; Foligné, Benoît; Sauty, Mathieu; Platel, Anne; Vercauteren, Eric; Rauwel, Gaétan; Catoire, Sophie; Ficheux, Hervé; Criquelion, Jacques; Nesslany, Fabrice

2017-10-01

Hand hygiene plays a key role in nosocomial infection prevention. To achieve users' adherence, products' dermal tolerance is essential. We aimed at making a comparative assessment of skin irritation and phototoxicity of the 3 alcohols commonly used in alcohol-based hand rubs (Ethanol, Propan-2-ol, Propan-1-ol) at 60, 70, 80 or 85% w/w in water or with co-formulates (hydrating, emollient and skin protective agents). In vitro validated OECD methods 439 and 432 were used. For irritation, EpiSkin™ Small Model was the chosen Reconstructed Human Epidermis (RhE). For phototoxicity, co-formulates alone or in mixture with and without alcohol were tested using BALB/c 3T3 cell cultures. Whilst Ethanol and Propan-2-ol could not be differentiated and displayed good skin tolerance profiles, Propan-1-ol based products lead to significant viability impairments of RhE at 60, 70 or 80% and at 60% in the presence of co-formulates. However, these results could not be reproduced in another RhE model. Taking also into account bibliographic data on Propan-1-ol, this suggests that our results are probably related to a lack of specificity of the used RhE. Therefore, it can be relevant in case of significant results to use two different RhE models before performing any classification and/or performing any complementary tests. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nadolol reduces insulin sensitivity in liver cirrhosis: a randomized double-blind crossover trial.

PubMed

Lee, Wai Gin; Murphy, Rinki; McCall, John L; Gane, Edward J; Soop, Mattias; Tura, Andrea; Plank, Lindsay D

2017-03-01

Liver cirrhosis is frequently complicated by portal hypertension leading to increased mortality from variceal bleeding and hepatic decompensation. Noncardioselective β-blockers not only reduce portal hypertension and prevent variceal bleeding in cirrhosis but also impair glucose tolerance and insulin sensitivity in other settings. This study aimed to determine whether nonselective β-blockade with nadolol impairs glucose metabolism in liver cirrhosis. A randomized, double-blind, placebo-controlled crossover trial of nadolol in cirrhotic patients examined insulin sensitivity, disposition index, and glucose tolerance. Stable cirrhotic patients of mixed etiology underwent an intravenous glucose tolerance test and hyperinsulinemic-euglycemic clamp for the measurement of insulin secretion and insulin sensitivity (n = 16) and a 75-g oral glucose tolerance test (n = 17). These measurements were conducted twice (after 3 months of treatment with nadolol or placebo and, after a 1-month washout period, after 3 months on the alternative treatment). Total body fat and plasma catecholamines were measured at the end of each 3-month treatment. Compared with placebo, nadolol treatment reduced insulin sensitivity (79.7 ± 10.1 vs 99.6 ± 10.3 μL/kg fat-free mass·min -1 ·(mU/L) -1 , P = .005). Insulin secretion was unchanged (P = .24), yielding a lower disposition index with nadolol (6083 ± 2007 vs 8692 ± 2036, P = .050). There was no change in total body fat or plasma catecholamines. A 2-hour plasma glucose concentration from the oral glucose tolerance test was higher on nadolol than placebo (10.8 ± 0.9 vs 9.9 ± 0.9 mmol/L, P = .035). Nadolol significantly worsened insulin sensitivity, glycemia, and disposition index in patients with liver cirrhosis. These findings may have significant clinical implications because cirrhosis is already associated with an increased prevalence of diabetes. Copyright © 2016 John Wiley & Sons, Ltd.

An Assessment of Cold Hardiness and Biochemical Adaptations for Cold Tolerance Among Different Geographic Populations of the Bactrocera dorsalis (Diptera: Tephritidae) in China

PubMed Central

Wang, Junhua; Zeng, Ling; Han, Zhaojun

2014-01-01

Abstract The cold hardiness of larvae, pupae, and adults of the oriental fruit fly, Bactrocera Dorsalis (Hendel) (Diptera: Tephritidae) was characterized first, and then body water, total sugar and glycerol contents, and activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and alcohol dehydrogenase (ADH) of different geographical populations subjected to suitable rearing conditions and under sublethal low-temperature stress were compared. The cold hardiness of different populations was well correlated with the latitudes of distributions. The northern marginal population (31.6° N) had higher cold tolerance than southern populations (23.1° N and 24.3° N). Among different life stages, larvae had the least cold tolerance, whereas pupae had the most tolerance. Under suitable rearing conditions, the marginal population had lower activities of all four tested enzymes than that of the southern populations and also had lower body water and higher total sugar and glycerol contents. The low-temperature stress induced higher SOD, CAT, POD, and ADH activities of all tested life stages and of all tested populations with higher increase intensity in adults and pupae than in larvae. The increase intensity was higher in the marginal population than in the southern populations. Pupae in the marginal population and adults in the southern populations showed the largest activity enhancement, which agreed with the insect’s overwinter stages in their respective locations. Lower temperature stress lowered body water and total sugar contents and increased glycerol contents. The results revealed a strong correlation between the cold hardiness of a population and the concentration or activity of various biochemicals and enzymes known to be involved in cold tolerance. The marginal population of B. dorsalis might have evolved a new biotype with better adaption to low temperature. PMID:25527597

Cold adaptation, aging, and Korean women divers haenyeo.

PubMed

Lee, Joo-Young; Park, Joonhee; Kim, Siyeon

2017-08-08

We have been studying the thermoregulatory responses of Korean breath-hold women divers, called haenyeo, in terms of aging and cold adaptation. During the 1960s to the 1980s, haenyeos received attention from environmental physiologists due to their unique ability to endure cold water while wearing only a thin cotton bathing suit. However, their overall cold-adaptive traits have disappeared since they began to wear wetsuits and research has waned since the 1980s. For social and economic reasons, the number of haenyeos rapidly decreased to 4005 in 2015 from 14,143 in 1970 and the average age of haenyeos is about 75 years old at present. For the past several years, we revisited and explored older haenyeos in terms of environmental physiology, beginning with questionnaire and field studies and later advancing to thermal tolerance tests in conjunction with cutaneous thermal threshold tests in a climate chamber. As control group counterparts, older non-diving females and young non-diving females were compared with older haenyeos in the controlled experiments. Our findings were that older haenyeos still retain local cold tolerance on the extremities despite their aging. Finger cold tests supported more superior local cold tolerance for older haenyeos than for older non-diving females. However, thermal perception in cold reflected aging effects rather than local cold acclimatization. An interesting finding was the possibility of positive cross-adaptation which might be supported by greater heat tolerance and cutaneous warm perception thresholds of older haenyeos who adapted to cold water. It was known that cold-adaptive traits of haenyeos disappeared, but we confirmed that cold-adaptive traits are still retained on the face and hands which could be interpreted by a mode switch to local adaptation from the overall adaptation to cold. Further studies on cross-adaptation between chronic cold stress and heat tolerance are needed.

Use of the Bovine Udder Skin model to evaluate the tolerability of Mesem cosmetic cream.

PubMed

Raak, Christa; Molsberger, Friedrich; Pittermann, Wolfgang; Bertram, Mathias; Robens, Sibylle; Ostermann, Thomas

2017-09-01

Observational studies of Mesem cream (based on Mesembryanthemum crystallinum L. plant extract) found that it had positive effects on skin hydration and smoothing of the skin. However, some patients reported skin irritation effects. The current study evaluated the skin tolerability of Mesem cream, as compared to the carrier cream (without the active ingredient), by using the isolated perfused bovine udder skin model. The primary outcomes investigated were cytotoxicity (i.e. cell viability), assessed with the MTT assay, and irritancy and inflammation, assessed by measuring PGE₂ tissue levels. A total reaction score was calculated by combining the results for each parameter. In the case of a single topical application, significant differences were found between the carrier cream and the Mesem cream. While the application of carrier cream resulted in low cytotoxicity (-8.4% change in viability, as compared to the untreated control), the Mesem cream was more cytotoxic (-18.7% change). In addition, one hour after application, PGE₂ levels were higher in Mesem cream-treated skin, as compared to carrier cream-treated skin (16.6% versus 11.3%). Further experiments (tape-stripped skin and repeated application) also found significant differences between the two creams in the results obtained. Evaluation of the effectiveness, safety and tolerability of phyto-cosmetic products is important. Our results confirmed the findings of two previous human observational studies (the human patch test and open application study). Future experiments to understand the underlying principles of its effectiveness, safety and tolerability should include extracts of M. crystallinum L. juice, as well as the Mesem cream itself. 2017 FRAME.

Impaired fasting glucose and impaired glucose tolerance in children and adolescents with overweight/obesity.

PubMed

Di Bonito, P; Pacifico, L; Chiesa, C; Valerio, G; Miraglia Del Giudice, E; Maffeis, C; Morandi, A; Invitti, C; Licenziati, M R; Loche, S; Tornese, G; Franco, F; Manco, M; Baroni, M G

2017-04-01

To investigate in a large sample of overweight/obese (OW/OB) children and adolescents the prevalence of prediabetic phenotypes such as impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and to assess their association with cardiometabolic risk (CMR) factors including hepatic steatosis (HS). Population data were obtained from the CARdiometabolic risk factors in children and adolescents in ITALY study. Between 2003 and 2013, 3088 youths (972 children and 2116 adolescents) received oral glucose tolerance test (OGTT) and were included in the study. In 798 individuals, abdominal ultrasound for identification of HS was available. The prevalence of IFG (3.2 vs. 3.3%) and IGT (4.6 vs. 5.0%) was similar between children and adolescents. Children with isolated IGT had a 2-11 fold increased risk of high LDL-C, non-HDL-C, Tg/HDL-C ratio, and low insulin sensitivity, when compared to those with normal glucose tolerance (NGT). No significant association of IFG with any CMR factor was found in children. Among adolescents, IGT subjects, and to a lesser extent those with IFG, showed a worse CMR profile compared to NGT subgroup. In the overall sample, IGT phenotype showed a twofold increased risk of HS compared to NGT subgroup. Our study shows an unexpected similar prevalence of IFG and IGT between children and adolescents with overweight/obesity. The IGT phenotype was associated with a worse CMR profile in both children and adolescents. Phenotyping prediabetes conditions by OGTT should be done as part of prediction and prevention of cardiometabolic diseases in OW/OB youth since early childhood.

Ascorbic acid enhances oxidative stress tolerance and biological control efficacy of Pichia caribbica against postharvest blue mold decay of apples.

PubMed

Li, Chaolan; Zhang, Hongyin; Yang, Qiya; Komla, Mahunu Gustav; Zhang, Xiaoyun; Zhu, Shuyun

2014-07-30

The effect of ascorbic acid (VC) on improving oxidative stress tolerance of Pichia caribbica and biocontrol efficacy against blue mold caused by Penicillium expansum on apples was investigated. P. caribbica showed susceptibility to the oxidative stress in vitro test, and 250 μg/mL VC treatment improved its oxidative stress tolerance. The higher viability exhibited by VC-treated yeast was associated with a lower intracellular ROS level. The activities of antioxidant enzymes of P. caribbica were improved by VC treatment, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX). Additionally, VC-treated yeast exhibited greater biocontrol activity against P. expansum and faster growth when stored at 25 and 4 °C, respectively, compared to the performance of the non-VC-treated yeast. In response to the VC treatment under oxidative stress, several differentially expressed proteins were identified in P. caribbica, and most of the poteins were confirmed to be related to basic metabolism. Therefore, the application of ascorbic acid is a useful approach to improve oxidative stress tolerance of P. caribbica and its biocontrol efficacy on apples.

Pore-water and epibenthic exposures in contaminated sediments using embryos of two estuarine fish species

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jelinski, J.A.; Anderson, S.L.

1995-12-31

The authors` objectives were to determine the feasibility of using embryos of two fish species, Menidia beryllina and Atherinops affinis, in estuarine sediment toxicity tests at ambient temperatures and salinities, and to compare pore-water and sediment water interface corer (SWIC) exposure techniques using these same species. The ultimate goal is to determine whether these pore-water and SWIC methods can be used in in situ exposure studies. Sediment samples were collected at both a reference and contaminated site at the Mare Island Naval Shipyard in San Francisco Bay. Pore-water testes were conducted using methods developed in the laboratory, and SWIC testsmore » were conducted using a modification of B. Anderson et al. Salinity and temperature tolerance experiments revealed that M. beryllina embryos can tolerate temperatures between 160 C and 240 C and salinities of 10 ppt to 25 ppt, whereas A. affinis has a temperature range between 160 C and 200 C. Comparisons between pore-water and SWIC exposures at a reference site within MINSY showed no significant difference in hatching success. However, hatching success in SWIC exposures was significantly lower than pore-water exposures at a previously characterized contaminated site. In conclusion, both M. beryllina and A. affinis embryos may be useful for sediment and in situ toxicity testing in estuarine environments. Their wide temperature and salinity tolerances allow for minimal test manipulations, and M. beryllina showed excellent hatching success in reference sediments for both types of exposures.« less

Presyncopal/Non-Presyncopal Outcomes of Post Spaceflight Stand Tests are Consistent from Flight to Flight

NASA Technical Reports Server (NTRS)

Martin, D. S.; Meck, J. V.

2004-01-01

The overall prevalence of orthostatic hypotension after short duration (6-18 d) spaceflight is 20% with existing countermeasures. However, it is not known if the outcomes of stand tests for orthostatic tolerance are consistent within individuals on subsequent flights, or if first time fliers are more (or less) likely to experience orthostatic hypotension and presyncope than are veteran astronauts. Fifty astronauts were studied retrospectively. Stand test data, which had been collected before and after spaceflight, were compared from at least two flights for each astronaut. For twenty-five of these astronauts, their first flight in this database was also their first time to fly into space. For the remaining 25, their first flight in this database was their second, third or fourth flight, as data were available. No subject became presyncopal during preflight testing. Of the 50 subjects, 45 (90%) had the same outcome on their first and second fligh ts of this study. Of 14 subjects on whom we had data from a third mission, 12 had the same stand test outcome on all three flights (86% same outcome across three flights). There was no correlation between flight duration and orthostatic tolerance (r = 0.39). These data support the idea that astronauts are predisposed to orthostatic tolerance/intolerance after spaceflight and that this predisposition is not altered by subsequent flights. Flight durations within this data set did not alter the likelihood of orthostatic intolerance and rookie fliers were no more likely to experience orthostatic intolerance than were veteran astronauts.

Testing For EM Upsets In Aircraft Control Computers

NASA Technical Reports Server (NTRS)

Belcastro, Celeste M.

1994-01-01

Effects of transient electrical signals evaluated in laboratory tests. Method of evaluating nominally fault-tolerant, aircraft-type digital-computer-based control system devised. Provides for evaluation of susceptibility of system to upset and evaluation of integrity of control when system subjected to transient electrical signals like those induced by electromagnetic (EM) source, in this case lightning. Beyond aerospace applications, fault-tolerant control systems becoming more wide-spread in industry; such as in automobiles. Method supports practical, systematic tests for evaluation of designs of fault-tolerant control systems.

Enhancement of geraniol resistance of Escherichia coli by MarA overexpression.

PubMed

Shah, Asad Ali; Wang, Chonglong; Chung, Young-Ryun; Kim, Jae-Yean; Choi, Eui-Sung; Kim, Seon-Won

2013-03-01

Improvement of a microorganism's tolerance against organic solvents is required for a microbial factory producing terpenoid based biofuels. The bacterial genes, marA, imp, cls and cti have been found to increase organic solvent tolerance. Thus, the tolerance against the following terpenoids (isopentenol, geraniol, myrcene, and farnesol) was studied with overexpression of marA, imp, cls and cti genes in Escherichia coli. The marA overexpression significantly enhanced the tolerance of E. coli against geraniol, whereas there was no tolerance improvement against the terpenoids by overexpression of cls and cti genes. The imp overexpression even yielded sensitive phenotype to the tested solvents. The colony forming efficiency of the marA overexpressing E. coli was increased by 10(4)-fold in plate overlay of geraniol compared to that of wild type E. coli and a two-fold decrease of intracellular geraniol accumulation was also observed in liquid culture of geraniol. Single knock-out mutations of marA, or one of the following genes (acrA, acrB and tolC) encoding AcrAB-TolC efflux pump made E. coli hypersensitive to geraniol. The geraniol tolerance conferred by marA overexpression was attributed to the AcrAB-TolC efflux pump that is activated by MarA. Copyright © 2012 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Test and analysis results for composite transport fuselage and wing structures

NASA Technical Reports Server (NTRS)

Deaton, Jerry W.; Kullerd, Susan M.; Madan, Ram C.; Chen, Victor L.

1992-01-01

Automated tow placement (ATP) and stitching of dry textile composite preforms followed by resin transfer molding (RTM) are being studied as cost effective manufacturing processes for obtaining damage tolerant fuselage and wing structures for transport aircraft. Data are presented to assess the damage tolerance of ATP and RTM fuselage elements with stitched-on stiffeners from compression tests of impacted three J-stiffened panels and from stiffener pull-off tests. Data are also presented to assess the damage tolerance of RTM wing elements which had stitched skin and stiffeners from impacted single stiffener and three blade stiffened compression tests and stiffener pull-off tests.

Metabolic and hormonal changes induced by pioglitazone in polycystic ovary syndrome: a randomized, placebo-controlled clinical trial.

PubMed

Aroda, Vanita R; Ciaraldi, Theodore P; Burke, Paivi; Mudaliar, Sunder; Clopton, Paul; Phillips, Susan; Chang, R Jeffrey; Henry, Robert R

2009-02-01

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, compensatory hyperinsulinemia, increased prevalence of impaired glucose tolerance, and increased ovarian androgen biosynthesis. The aim of the study was to evaluate effects of pioglitazone on whole body insulin action and ovarian androgen biosynthesis in PCOS. We performed a randomized placebo-controlled trial. The study was conducted at the Special Diagnostic and Treatment Unit of the Veterans Affairs Medical Center, San Diego, and the University of California, San Diego, General Clinical Research Center. A total of 23 subjects with PCOS were evaluated at baseline and end of treatment. Six age- and body mass index-matched women without PCOS were normal controls for baseline evaluation. Subjects with PCOS were randomized to oral placebo or pioglitazone 45 mg daily for 6 months. The primary outcome measures were whole body insulin action as measured by hyperinsulinemic euglycemic clamp and ovarian androgen biosynthesis as measured by leuprolide-stimulated production of 17-hydroxyprogesterone (17-OHP). Compared with placebo, pioglitazone treatment significantly improved multiple measures of insulin action, including glucose disposal rate (P < 0.01), 2-h glucose during 75-g oral glucose tolerance test (P < 0.01), area under the curve glucose during oral glucose tolerance test (P < 0.01), serum adiponectin (P < 0.01), and fasting hyperinsulinemia (P < 0.01). Compared to placebo, pioglitazone treatment reduced the increment of leuprolide-stimulated 17-OHP (P < 0.02). Improvements in glucose disposal rate correlated with reductions in 17-OHP stimulation (P < 0.02). Compared to placebo, pioglitazone treatment in PCOS was associated with improvements in insulin action and glucose homeostasis and ameliorated the hyperandrogenic ovarian response.

Comparison of Flow and Volume Incentive Spirometry on Pulmonary Function and Exercise Tolerance in Open Abdominal Surgery: A Randomized Clinical Trial.

PubMed

Kumar, Amaravadi Sampath; Alaparthi, Gopala Krishna; Augustine, Alfred Joseph; Pazhyaottayil, Zulfeequer Chundaanveetil; Ramakrishna, Anand; Krishnakumar, Shyam Krishnan

2016-01-01

Surgical procedures in abdominal area lead to changes in pulmonary function, respiratory mechanics and impaired physical capacity leading to postoperative pulmonary complications, which can affect up to 80% of upper abdominal surgery. To evaluate the effects of flow and volume incentive spirometry on pulmonary function and exercise tolerance in patients undergoing open abdominal surgery. A randomized clinical trial was conducted in a hospital of Mangalore city in Southern India. Thirty-seven males and thirteen females who were undergoing abdominal surgeries were included and allocated into flow and volume incentive spirometry groups by block randomization. All subjects underwent evaluations of pulmonary function with measurement of Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), Peak Expiratory Flow (PEF). Preoperative and postoperative measurements were taken up to day 5 for both groups. Exercise tolerance measured by Six- Minute Walk Test during preoperative period and measured again at the time of discharge for both groups. Pulmonary function was analysed by post-hoc analysis and carried out using Bonferroni's 't'-test. Exercise tolerance was analysed by Paired 'T'-test. Pulmonary function (FVC, FEV1, and PEFR) was found to be significantly decreased in 1(st), 2(nd) and 3(rd) postoperative day when compared with preoperative day. On 4(th) and 5(th) postoperative day the pulmonary function (FVC, FEV1, and PEFR) was found to be better preserved in both flow and volume incentive spirometry groups. The Six-Minute Walk Test showed a statistically significant improvement in pulmonary function on the day of discharge than in the preoperative period. In terms of distance covered, the volume- incentive spirometry group showed a greater statistically significant improvement from the preoperative period to the time of discharge than was exhibited by the flow incentive spirometry group. Flow and volume incentive spirometry can be safely recommended to patients undergoing open abdominal surgery as there have been no adverse events recorded. Also, these led to a demonstrable improvement in pulmonary function and exercise tolerance.

Comparison of Flow and Volume Incentive Spirometry on Pulmonary Function and Exercise Tolerance in Open Abdominal Surgery: A Randomized Clinical Trial

PubMed Central

Kumar, Amaravadi Sampath; Augustine, Alfred Joseph; Pazhyaottayil, Zulfeequer Chundaanveetil; Ramakrishna, Anand; Krishnakumar, Shyam Krishnan

2016-01-01

Introduction Surgical procedures in abdominal area lead to changes in pulmonary function, respiratory mechanics and impaired physical capacity leading to postoperative pulmonary complications, which can affect up to 80% of upper abdominal surgery. Aim To evaluate the effects of flow and volume incentive spirometry on pulmonary function and exercise tolerance in patients undergoing open abdominal surgery. Materials and Methods A randomized clinical trial was conducted in a hospital of Mangalore city in Southern India. Thirty-seven males and thirteen females who were undergoing abdominal surgeries were included and allocated into flow and volume incentive spirometry groups by block randomization. All subjects underwent evaluations of pulmonary function with measurement of Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), Peak Expiratory Flow (PEF). Preoperative and postoperative measurements were taken up to day 5 for both groups. Exercise tolerance measured by Six- Minute Walk Test during preoperative period and measured again at the time of discharge for both groups. Pulmonary function was analysed by post-hoc analysis and carried out using Bonferroni’s ‘t’-test. Exercise tolerance was analysed by Paired ‘T’-test. Results Pulmonary function (FVC, FEV1, and PEFR) was found to be significantly decreased in 1st, 2nd and 3rd postoperative day when compared with preoperative day. On 4th and 5th postoperative day the pulmonary function (FVC, FEV1, and PEFR) was found to be better preserved in both flow and volume incentive spirometry groups. The Six-Minute Walk Test showed a statistically significant improvement in pulmonary function on the day of discharge than in the preoperative period. In terms of distance covered, the volume- incentive spirometry group showed a greater statistically significant improvement from the preoperative period to the time of discharge than was exhibited by the flow incentive spirometry group. Conclusion Flow and volume incentive spirometry can be safely recommended to patients undergoing open abdominal surgery as there have been no adverse events recorded. Also, these led to a demonstrable improvement in pulmonary function and exercise tolerance. PMID:26894090

β-Cell secretory defects are present in pancreatic insufficient cystic fibrosis with 1-hour oral glucose tolerance test glucose ≥155 mg/dL.

PubMed

Nyirjesy, Sarah C; Sheikh, Saba; Hadjiliadis, Denis; De Leon, Diva D; Peleckis, Amy J; Eiel, Jack N; Kubrak, Christina; Stefanovski, Darko; Rubenstein, Ronald C; Rickels, Michael R; Kelly, Andrea

2018-06-08

Patients with pancreatic insufficient cystic fibrosis (PI-CF) meeting standard criteria for normal glucose tolerance display impaired β-cell secretory capacity and early-phase insulin secretion defects. We sought evidence of impaired β-cell secretory capacity, a measure of functional β-cell mass, among those with early glucose intolerance (EGI), defined as 1-hour oral glucose tolerance test (OGTT) glucose ≥155 mg/dL (8.6 mmol/L). A cross-sectional study was conducted in the Penn and CHOP Clinical & Translational Research Centers. PI-CF categorized by OGTT as normal (PI-NGT: 1-hour glucose <155 mg/dL and 2-hour <140 mg/dL [7.8 mmol/L]; n = 13), PI-EGI (1-hour ≥155 mg/dL and 2-hour <140 mg/dL; n = 13), impaired (PI-IGT: 2-hour ≥140 and <200 mg/dL [11.1 mmol/L]; n = 8), and diabetic (cystic fibrosis-related diabetes, CFRD: 2-hour ≥200 mg/dL; n = 8) participated. Post-prandial glucose tolerance and insulin secretion, and β-cell secretory capacity and demand were derived from mixed-meal tolerance tests (MMTTs), and glucose-potentiated arginine (GPA) tests, respectively. PI-EGI had elevated post-prandial glucose with reduced early-phase insulin secretion during MMTT compared to PI-NGT (P < .05). PI-EGI also exhibited impaired acute insulin and C-peptide responses to GPA (P < .01 vs PI-NGT), measures of β-cell secretory capacity. Proinsulin secretory ratios were higher under hyperglycemic clamp conditions in PI-IGT and CFRD (P < .05 vs PI-NGT), and correlated with 1-hour glucose in PI-CF (P < .01). PI-CF patients with 1-hour OGTT glucose ≥155 mg/dL already manifest impaired β-cell secretory capacity with associated early-phase insulin secretion defects. Avoiding hyperglycemia in patients with EGI may be important for preventing excessive insulin demand indicated by disproportionately increased proinsulin secretion. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A novel rice cytochrome P450 gene, CYP72A31, confers tolerance to acetolactate synthase-inhibiting herbicides in rice and Arabidopsis.

PubMed

Saika, Hiroaki; Horita, Junko; Taguchi-Shiobara, Fumio; Nonaka, Satoko; Nishizawa-Yokoi, Ayako; Iwakami, Satoshi; Hori, Kiyosumi; Matsumoto, Takashi; Tanaka, Tsuyoshi; Itoh, Takeshi; Yano, Masahiro; Kaku, Koichiro; Shimizu, Tsutomu; Toki, Seiichi

2014-11-01

Target-site and non-target-site herbicide tolerance are caused by the prevention of herbicide binding to the target enzyme and the reduction to a nonlethal dose of herbicide reaching the target enzyme, respectively. There is little information on the molecular mechanisms involved in non-target-site herbicide tolerance, although it poses the greater threat in the evolution of herbicide-resistant weeds and could potentially be useful for the production of herbicide-tolerant crops because it is often involved in tolerance to multiherbicides. Bispyribac sodium (BS) is an herbicide that inhibits the activity of acetolactate synthase. Rice (Oryza sativa) of the indica variety show BS tolerance, while japonica rice varieties are BS sensitive. Map-based cloning and complementation tests revealed that a novel cytochrome P450 monooxygenase, CYP72A31, is involved in BS tolerance. Interestingly, BS tolerance was correlated with CYP72A31 messenger RNA levels in transgenic plants of rice and Arabidopsis (Arabidopsis thaliana). Moreover, Arabidopsis overexpressing CYP72A31 showed tolerance to bensulfuron-methyl (BSM), which belongs to a different class of acetolactate synthase-inhibiting herbicides, suggesting that CYP72A31 can metabolize BS and BSM to a compound with reduced phytotoxicity. On the other hand, we showed that the cytochrome P450 monooxygenase CYP81A6, which has been reported to confer BSM tolerance, is barely involved, if at all, in BS tolerance, suggesting that the CYP72A31 enzyme has different herbicide specificities compared with CYP81A6. Thus, the CYP72A31 gene is a potentially useful genetic resource in the fields of weed control, herbicide development, and molecular breeding in a broad range of crop species. © 2014 American Society of Plant Biologists. All Rights Reserved.

Aniracetam and DNQX affect the acquisition of rapid tolerance to ethanol in mice.

PubMed

Rial, Daniel; Takahashi, Reinaldo Naoto; Morato, Gina Struffaldi

2009-03-01

Several studies have emphasized the role of learning in the development of rapid tolerance and have shown that glutamate-mediated neurotransmission plays an important role in this phenomenon. Since the AMPA/kainate receptor system is directly involved in plasticity mechanisms, the influence of this receptor system on rapid tolerance induced by ethanol was studied using the rotarod. In the first experiment, mice were pretreated with aniracetam, an agonist of AMPA/kainate receptors, 30 min before ethanol (2.75 g/kg; IP) treatment, and tested on the rotarod. After 24 h, the groups were tested on the rotarod under ethanol treatment. Aniracetam facilitated the acquisition of rapid tolerance to ethanol. In the second experiment, mice received DNQX, a competitive antagonist of the AMPA receptor, 30 min before ethanol treatment (3 g/kg) and submitted to the rotarod. This dose of ethanol produced tolerance per se. Groups were tested under ethanol treatment (1.75 g/kg) after 24 h. DNQX blocked rapid tolerance to ethanol. Using a similar protocol, the third experiment showed that DNQX blocked the aniracetam-induced facilitation of rapid tolerance to ethanol. Our results show that aniracetam facilitates whereas DNQX blocks ethanol tolerance, suggesting that the non-NMDA receptors are involved in this phenomenon.

Evaluation of Drought Tolerance of the Vietnamese Soybean Cultivars Provides Potential Resources for Soybean Production and Genetic Engineering

PubMed Central

Nguyen, Quang Thien; Hoang, Xuan Lan Thi; Thao, Nguyen Phuong; Tran, Lam-Son Phan

2014-01-01

Drought is one of the greatest constraints to soybean production in many countries, including Vietnam. Although a wide variety of the newly produced cultivars have been produced recently in Vietnam through classical breeding to cope with water shortage, little knowledge of their molecular and physiological responses to drought has been discovered. This study was conducted to quickly evaluate drought tolerance of thirteen local soybean cultivars for selection of the best drought-tolerant cultivars for further field test. Differences in drought tolerance of cultivars were assessed by root and shoot lengths, relative water content, and drought-tolerant index under both normal and drought conditions. Our data demonstrated that DT51 is the strongest drought-tolerant genotype among all the tested cultivars, while the highest drought-sensitive phenotype was observed with MTD720. Thus, DT51 could be subjected to further yield tests in the field prior to suggesting it for use in production. Due to their contrasting drought-tolerant phenotypes, DT51 and MTD720 provide excellent genetic resources for further studies underlying mechanisms regulating drought responses and gene discovery. Our results provide vital information to support the effort of molecular breeding and genetic engineering to improve drought tolerance of soybean. PMID:24804248

The benefits of the 3T3 NRU test in the safety assessment of cosmetics: long-term experience from pre-marketing testing in the Czech Republic.

PubMed

Jírová, D; Kejlová, K; Brabec, M; Bendová, H; Kolárová, H

2003-01-01

We have introduced the 3T3 NRU cytotoxicity test for methodological, economical and ethical reasons as a regular part of tier pre-marketing testing to assess local tolerance of raw materials for cosmetics, household chemicals and final cosmetic products. Using the 3T3 cell line according to the standard INVITTOX protocol No.64 (NRU Assay) the borderline concentration, relevant to the highest tolerated dose, is determined for each material. The toxic effect is reached at different concentration levels specific for individual cosmetics categories, depending on their chemical characteristics. Typical ranges of cytotoxicity for specific categories of cosmetics were established after testing of hundreds of materials. The range lies between 1 microg/ml (anti-dandruff shampoos), up to 2000 microg/ml (toothpastes and mouthwashes). The 3T3 NRU cytotoxicity test is a sensitive tool able to identify more aggressive products, that are also more likely to evoke irritation in human skin. It was even possible to detect protective effects of one natural herbal ingredient. The comparative study of cytotoxicity test results and human patch test results from a group of essential oils is presented. Cytotoxicity tests represent a highly ethical approach for estimation of irritancy. On the basis of in vitro test results suggesting low risk we can proceed to confirmatory tests in human volunteers.

Natto and viscous vegetables in a Japanese-style breakfast improved insulin sensitivity, lipid metabolism and oxidative stress in overweight subjects with impaired glucose tolerance.

PubMed

Taniguchi-Fukatsu, Akiko; Yamanaka-Okumura, Hisami; Naniwa-Kuroki, Yuko; Nishida, Yuka; Yamamoto, Hironori; Taketani, Yutaka; Takeda, Eiji

2012-04-01

We previously suggested that the consumption of natto and viscous vegetables as part of a Japanese-style meal based on white rice (WR) reduced postprandial glucose and insulin levels in healthy subjects. The aim of the present study was to assess whether a single breakfast of natto and viscous vegetables or the same breakfast consumed for 2 weeks could improve glucose control, insulin sensitivity, lipid metabolism and oxidative stress in overweight subjects with impaired glucose tolerance (IGT). A total of eleven free-living subjects with IGT followed a randomised, crossover breakfast intervention for 2 weeks. The test meal included boiled WR with natto (viscous fermented soyabeans), Japanese yam and okra. The control meal included WR with non-viscous boiled soyabeans, potatoes and broccoli. Both meals contained comparable amounts of carbohydrate, fat, protein and fibre. The test meal reduced acute glucose and insulin responses compared to the control meal in the study participants. Insulin sensitivity was assessed using the composite insulin sensitivity index (CISI) after both the test and control meal periods. The test meal resulted in improvements in CISI compared to the baseline, whereas no significant changes were observed after the control meal period. Serum levels of both total and LDL-cholesterol were assessed before and after the test meal period and found to decrease significantly. There was also a tendency towards reduced serum malondialdehyde-modified LDL and N(ɛ)-carboxymethyllysine. No differences were observed in the measures of chronic glycaemic control. Thus, we conclude that a breakfast of natto and viscous vegetables consumed for 2 weeks improves insulin sensitivity, serum lipid and oxidative stress.

78 FR 79579 - Energy Conservation Program: Alternative Efficiency Determination Methods, Basic Model Definition...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-31

... Working Group agreed on a one- sided 5 percent tolerance when comparing the validation test results to the... one DOE representative. 78 FR 22431. The members of the Working Group were selected to ensure a broad... Issues 1. Pre-Approval The Working Group unanimously recommended that DOE not require pre- approval for...

ACUTE AND REPEATED INHALATION OF TOLUENE BY RATS PERFORMING A SIGNAL DETECTION TASK LEADS TO BEHAVIORAL TOLERANCE ON SOME PERFORMANCE MEASURES.

EPA Science Inventory

Previous work showed that trichloroethylene (TCE) impairs accuracy and latency in a signal detection task (SDT) in rats, and that these effects abate during repeated exposures if rats inhale TCE during SDT testing. The present experiment compared the effects of acute and repeated...

Validation of insulin sensitivity and secretion indices derived from the liquid meal tolerance test.

PubMed

Maki, Kevin C; Kelley, Kathleen M; Lawless, Andrea L; Hubacher, Rachel L; Schild, Arianne L; Dicklin, Mary R; Rains, Tia M

2011-06-01

A liquid meal tolerance test (LMTT) has been proposed as a useful alternative to more labor-intensive methods of assessing insulin sensitivity and secretion. This substudy, conducted at the conclusion of a randomized, double-blind crossover trial, compared insulin sensitivity indices from a LMTT (Matsuda insulin sensitivity index [MISI] and LMTT disposition index [LMTT-DI]) with indices derived from minimal model analysis of results from the insulin-modified intravenous glucose tolerance test (IVGTT) (insulin sensitivity index [S(I)] and disposition index [DI]). Participants included men (n = 16) and women (n = 8) without diabetes but with increased abdominal adiposity (waist circumference ≥102 cm and ≥89 cm, respectively) and mean age of 48.9 years. The correlation between S(I) and the MISI was 0.776 (P < 0.0001). The respective associations between S(I) and MISI with waist circumference (r = -0.445 and -0.554, both P < 0.05) and body mass index were similar (r = -0.500 and -0.539, P < 0.05). The correlation between DI and LMTT-DI was 0.604 (P = 0.002). These results indicate that indices of insulin sensitivity and secretion derived from the LMTT correlate well with those from the insulin-modified IVGTT with minimal model analysis, suggesting that they may be useful for application in clinical and population studies of glucose homeostasis.

The induction of menadione stress tolerance in the marine microalga, Dunaliella viridis, through cold pretreatment and modulation of the ascorbate and glutathione pools.

PubMed

Madadkar Haghjou, Maryam; Colville, Louise; Smirnoff, Nicholas

2014-11-01

The effect of cold pretreatment on menadione tolerance was investigated in the cells of the marine microalga, Dunaliella viridis. In addition, the involvement of ascorbate and glutathione in the response to menadione stress was tested by treating cell suspensions with l-galactono-1,4-lactone, an ascorbate precursor, and buthionine sulfoximine, an inhibitor of glutathione synthesis. Menadione was highly toxic to non cold-pretreated cells, and caused a large decrease in cell number. Cold pretreatment alleviated menadione toxicity and cold pretreated cells accumulated lower levels of reactive oxygen species, and had enhanced antioxidant capacity due to increased levels of β-carotene, reduced ascorbate and total glutathione compared to non cold-pretreated cells. Cold pretreatment also altered the response to l-galactono-1,4-lactone and buthionine sulfoximine treatments. Combined l-galactono-1,4-lactone and menadione treatment was lethal in non-cold pretreated cells, but in cold-pretreated cells it had a positive effect on cell numbers compared to menadione alone. Overall, exposure of Dunaliella cells to cold stress enhanced tolerance to subsequent oxidative stress induced by menadione. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Insulin sensitivity and beta-cell function in healthy cats: assessment with the use of the hyperglycemic glucose clamp.

PubMed

Slingerland, L I; Robben, J H; van Haeften, T W; Kooistra, H S; Rijnberk, A

2007-05-01

A hyperglycemic clamp (HGC) was developed for use in conscious cats. In 21 healthy, normal glucose tolerant cats glucose disposal rate (M), insulin sensitivity (ISI (HGC)), and beta-cell response (I) at arterial plasma glucose of 9 mmol.l (-1) were measured. The HGC was tolerated well and steady state glucose infusion was achieved. Compared to values reported for humans, M values for the cats were low, which appeared to relate to both a low ISI (HGC) and a low I. HGC measures correlated with fasting plasma glucose and insulin concentrations as well as with their HOMA (homeostasis model assessment) and QUICKI (quantitative insulin sensitivity check index) counterparts. Also, I and ISI (HGC) correlated with their counterparts derived from intravenous glucose tolerance tests. In conclusion, this is the first report of hyperglycemic glucose clamping in cats. The procedure (HGC) allows for measurements of glucose disposal, beta-cell response and insulin sensitivity. Compared to human data, both insulin sensitivity and insulin secretion appeared to be low in cats. This is compatible with the carnivorous nature of this species, for which insulin resistance would be advantageous during periods of restricted food availability.

High Performance and Cost-Effective Direct Methanol Fuel Cells: Fe-N-C Methanol-Tolerant Oxygen Reduction Reaction Catalysts.

PubMed

Sebastián, David; Serov, Alexey; Artyushkova, Kateryna; Gordon, Jonathan; Atanassov, Plamen; Aricò, Antonino S; Baglio, Vincenzo

2016-08-09

Direct methanol fuel cells (DMFCs) offer great advantages for the supply of power with high efficiency and large energy density. The search for a cost-effective, active, stable and methanol-tolerant catalyst for the oxygen reduction reaction (ORR) is still a great challenge. In this work, platinum group metal-free (PGM-free) catalysts based on Fe-N-C are investigated in acidic medium. Post-treatment of the catalyst improves the ORR activity compared with previously published PGM-free formulations and shows an excellent tolerance to the presence of methanol. The feasibility for application in DMFC under a wide range of operating conditions is demonstrated, with a maximum power density of approximately 50 mW cm(-2) and a negligible methanol crossover effect on the performance. A review of the most recent PGM-free cathode formulations for DMFC indicates that this formulation leads to the highest performance at a low membrane-electrode assembly (MEA) cost. Moreover, a 100 h durability test in DMFC shows suitable applicability, with a similar performance-time behavior compared to common MEAs based on Pt cathodes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Insulin Resistance Atherosclerosis Study.

PubMed

Saad, M F; Anderson, R L; Laws, A; Watanabe, R M; Kades, W W; Chen, Y D; Sands, R E; Pei, D; Savage, P J; Bergman, R N

1994-09-01

An insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis was compared with the glucose clamp in 11 subjects with normal glucose tolerance (NGT), 20 with impaired glucose tolerance (IGT), and 24 with non-insulin-dependent diabetes mellitus (NIDDM). The insulin sensitivity index (SI) was calculated from FSIGTT using 22- and 12-sample protocols (SI(22) and SI(12), respectively). Insulin sensitivity from the clamp was expressed as SI(clamp) and SIP(clamp). Minimal model parameters were similar when calculated with SI(22) and SI(12). SI could not be distinguished from 0 in approximately 50% of diabetic patients with either protocol. SI(22) correlated significantly with SI(clamp) in the whole group (r = 0.62), and in the NGT (r = 0.53), IGT (r = 0.48), and NIDDM (r = 0.41) groups (P < 0.05 for each). SI(12) correlated significantly with SI(clamp) in the whole group (r = 0.55, P < 0.001) and in the NGT (r = 0.53, P = 0.046) and IGT (r = 0.58, P = 0.008) but not NIDDM (r = 0.30, P = 0.085) groups. When SI(22), SI(clamp), and SIP(clamp) were expressed in the same units, SI(22) was 66 +/- 5% (mean +/- SE) and 50 +/- 8% lower than SI(clamp) and SIP(clamp), respectively. Thus, minimal model analysis of the insulin-modified FSIGTT provides estimates of insulin sensitivity that correlate significantly with those from the glucose clamp. The correlation was weaker, however, in NIDDM. The insulin-modified FSIGTT can be used as a simple test for assessment of insulin sensitivity in population studies involving nondiabetic subjects. Additional studies are needed before using this test routinely in patients with NIDDM.

Ovomucoid (Gal d 1) specific IgE detected by microarray system predict tolerability to boiled hen's egg and an increased risk to progress to multiple environmental allergen sensitisation.

PubMed

Alessandri, C; Zennaro, D; Scala, E; Ferrara, R; Bernardi, M Livia; Santoro, M; Palazzo, P; Mari, A

2012-03-01

Egg allergy is a very common finding in early childhood. Detecting hen's egg (HE) allergy outgrowing and reintroduction of food containing egg is a task for the allergist. We sought to evaluate the suitability of boiled egg food challenge compared with IgE to allergenic molecules from HE white using a microarray system. Sixty-eight children referring to our centre by the family paediatricians for a suspected egg allergy were enrolled. Patients underwent double-blind, placebo-controlled food challenge with boiled and raw eggs. Challenge outcomes were compared with skin tests performed using egg white and yolk commercial extracts, to prick-prick test with boiled and raw egg white and yolk, total IgE, egg white specific IgE detected using ImmunoCAP and IgE to egg allergens available on the immunosolid phase allergen chip (ISAC) 103 microarray. Nineteen subjects (28%) were reactive to both raw and boiled egg, 14 (20.5%) to raw egg only and 35 (51.4%) tolerated both boiled and raw egg. Efficiency analysis was carried out using both raw and boiled egg challenges as gold standard. Forty four of 47 Gal d 1 negative patients tolerated boiled egg (94%). Conversely, 20 of 21 Gal d 1 positive patients reacted to raw egg (95%). None of the other tests was able to discriminate patients' response to HE challenge. Furthermore, Gal d 1 positivity seems to lead to broader environmental allergen IgE sensitization. The Gal d 1 IgE reactivity appears to be a very good predictor of HE clinical allergy. Gal d 1 positive children have a high frequency of HE allergy, whereas Gal d 1 negative children have a high frequency of tolerance to boiled egg. Multiple specific IgE detection by means of ISAC improves the diagnostic approach in HE allergic children, disclosing other food and inhalant allergic sensitizations, anyhow requiring a comprehensive clinical evaluation. © 2011 Blackwell Publishing Ltd.

Parental Effect of Long Acclimatization on Thermal Tolerance of Juvenile Sea Cucumber Apostichopus japonicus

PubMed Central

Dong, Yun-wei

2015-01-01

To evaluate the thermal resistance of marine invertebrates to elevated temperatures under scenarios of future climate change, it is crucial to understand parental effect of long acclimatization on thermal tolerance of offspring. To test whether there is parental effect of long acclimatization, adult sea cucumbers (Apostichopus japonicus) from the same broodstock were transplanted southward and acclimatized at high temperature in field mesocosms. Four groups of juvenile sea cucumbers whose parents experienced different durations of high temperature acclimatization were established. Upper thermal limits, oxygen consumption and levels of heat shock protein mRNA of juveniles was determined to compare thermal tolerance of individuals from different groups. Juvenile sea cucumbers whose parents experienced high temperature could acquire high thermal resistance. With the increase of parental exposure duration to high temperature, offspring became less sensitive to high temperature, as indicated by higher upper thermal limits (LT50), less seasonal variations of oxygen consumption, and stable oxygen consumption rates between chronic and acute thermal stress. The relatively high levels of constitutive expression of heat-shock proteins should contribute to the high thermal tolerance. Together, these results indicated that the existence of a parental effect of long acclimatization would increase thermal tolerance of juveniles and change the thermal sensitivity of sea cucumber to future climate change. PMID:26580550

Overexpression of a Chimeric Gene, OsDST-SRDX, Improved Salt Tolerance of Perennial Ryegrass

PubMed Central

Cen, Huifang; Ye, Wenxing; Liu, Yanrong; Li, Dayong; Wang, Kexin; Zhang, Wanjun

2016-01-01

The Drought and Salt Tolerance gene (DST) encodes a C2H2 zinc finger transcription factor, which negatively regulates salt tolerance in rice (Oryza sativa). Phylogenetic analysis of six homologues of DST genes in different plant species revealed that DST genes were conserved evolutionarily. Here, the rice DST gene was linked to an SRDX domain for gene expression repression based on the Chimeric REpressor gene-Silencing Technology (CRES-T) to make a chimeric gene (OsDST-SRDX) construct and introduced into perennial ryegrass by Agrobacterium-mediated transformation. Integration and expression of the OsDST-SRDX in transgenic plants were tested by PCR and RT-PCR, respectively. Transgenic lines overexpressing the OsDST-SRDX fusion gene showed obvious phenotypic differences and clear resistance to salt-shock and to continuous salt stresses compared to non-transgenic plants. Physiological analyses including relative leaf water content, electrolyte leakage, proline content, malondialdehyde (MDA) content, H2O2 content and sodium and potassium accumulation indicated that the OsDST-SRDX fusion gene enhanced salt tolerance in transgenic perennial ryegrass by altering a wide range of physiological responses. To our best knowledge this study is the first report of utilizing Chimeric Repressor gene-Silencing Technology (CRES-T) in turfgrass and forage species for salt-tolerance improvement. PMID:27251327

Tolerance measurements on internal- and external-hexagon implants.

PubMed

Braian, Michael; De Bruyn, Hugo; Fransson, Håkan; Christersson, Cecilia; Wennerberg, Ann

2014-01-01

To measure the horizontal machining tolerances of the interface between internal- and external-hexagon implants and analogs with corresponding components after delivery from the manufacturer. These values may be a valuable tool for evaluating increasing misfit caused by fabrication, processing, and wear. Seven implants and seven analogs with external- and internal-hexagon connections (Biomet 3i) with corresponding prefabricated gold cylinders and gold screws, prefabricated cylindric plastic cylinders, and laboratory screws were studied. One set of components from the external and internal groups was measured manually and digitally. Measurements from the test subjects were compared with identical measurements from the virtual model to obtain threshold values. The virtual model was then used to obtain optimally oriented cuts. The horizontal machining tolerances for castable plastic abutments on external implants were 12 ± 89 μm, and for internal implants they were 86 ± 47 μm. Tolerance measurements on prefabricated gold abutments for external implants were 44 ± 9 μm, and for internal implants they were 58 ± 28 μm. The groups with metallic components showed the smallest tolerance at < 50 μm for the external group and < 90 μm for the internal group. The prefabricated plastic cylinder groups ranged from < 100 μm for external and < 130 μm for internal connection.

Transgenic rice expressing a codon-modified synthetic CP4-EPSPS confers tolerance to broad-spectrum herbicide, glyphosate.

PubMed

Chhapekar, Sushil; Raghavendrarao, Sanagala; Pavan, Gadamchetty; Ramakrishna, Chopperla; Singh, Vivek Kumar; Phanindra, Mullapudi Lakshmi Venkata; Dhandapani, Gurusamy; Sreevathsa, Rohini; Ananda Kumar, Polumetla

2015-05-01

Highly tolerant herbicide-resistant transgenic rice was developed by expressing codon-modified synthetic CP4--EPSPS. The transformants could tolerate up to 1% commercial glyphosate and has the potential to be used for DSR (direct-seeded rice). Weed infestation is one of the major biotic stress factors that is responsible for yield loss in direct-seeded rice (DSR). Herbicide-resistant rice has potential to improve the efficiency of weed management under DSR. Hence, the popular indica rice cultivar IR64, was genetically modified using Agrobacterium-mediated transformation with a codon-optimized CP4-EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) gene, with N-terminal chloroplast targeting peptide from Petunia hybrida. Integration of the transgenes in the selected rice plants was confirmed by Southern hybridization and expression by Northern and herbicide tolerance assays. Transgenic plants showed EPSPS enzyme activity even at high concentrations of glyphosate, compared to untransformed control plants. T0, T1 and T2 lines were tested by herbicide bioassay and it was confirmed that the transgenic rice could tolerate up to 1% of commercial Roundup, which is five times more in dose used to kill weeds under field condition. All together, the transgenic rice plants developed in the present study could be used efficiently to overcome weed menace.

Characterization of multi-drug tolerant persister cells in Streptococcus suis

PubMed Central

2014-01-01

Background Persister cells constitute a subpopulation of dormant cells within a microbial population which are genetically identical but phenotypically different to regular cells. Notably, persister cells show an elevated tolerance to antimicrobial agents. Thus, they are considered to represent a microbial ‘bet-hedging’ strategy and are of particular importance in pathogenic bacteria. Results We studied the ability of the zoonotic pathogen Streptococcus (S.) suis to form multi-drug tolerant variants and identified persister cells dependent on the initial bacterial growth phase. We observed lower numbers of persisters in exponential phase cultures than in stationary growth phase populations. S. suis persister cells showed a high tolerance to a variety of antibiotics, and the phenotype was not inherited as tested with four passages of S. suis populations. Furthermore, we provide evidence that the persister phenotype is related to expression of genes involved in general metabolic pathways since we found higher numbers of persister cells in a mutant strain defective in the catabolic arginine deiminase system as compared to its parental wild type strain. Finally, we observed persister cell formation also in other S. suis strains and pathogenic streptococcal species. Conclusions Taken together, this is the first study that reports multi-drug tolerant persister cells in the zoonotic pathogen S. suis. PMID:24885389

Effects of elevated temperature on coral reef fishes: loss of hypoxia tolerance and inability to acclimate.

PubMed

Nilsson, Göran E; Ostlund-Nilsson, Sara; Munday, Philip L

2010-08-01

Water temperature is expected to rise on coral reefs due to global warming. Here, we have examined if increased temperature reduces the hypoxia tolerance of coral reef fish (measured as critical [O(2)]), and if temperature acclimation in adults can change the resting rate of O(2) consumption and critical [O(2)]. Two common species from Lizard Island (Great Barrier Reef, Australia) were tested, Doederlein's cardinalfish (Ostorhinchus doederleini) and lemon damselfish (Pomacentrus moluccensis). In both species, a 3 degrees C rise in water temperature caused increased oxygen consumption and reduced hypoxia tolerance, changes that were not reduced by acclimation to the higher temperature for 7 to 22 days. Critical [O(2)] increased by 71% in the cardinalfish and by 23% in the damselfish at 32 degrees C compared to 29 degrees C. The higher oxygen needs are likely to reduce the aerobic scope, which could negatively affect the capacity for feeding, growth and reproduction. The reduced hypoxia tolerance may force the fishes out of their nocturnal shelters in the coral matrix, exposing them to predation. The consequences for population and species survival could be severe unless developmental phenotypic plasticity within generations or genetic adaptation between generations could produce individuals that are more tolerant to a warmer future. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Parental Effect of Long Acclimatization on Thermal Tolerance of Juvenile Sea Cucumber Apostichopus japonicus.

PubMed

Wang, Qing-Lin; Yu, Shan-Shan; Dong, Yun-Wei

2015-01-01

To evaluate the thermal resistance of marine invertebrates to elevated temperatures under scenarios of future climate change, it is crucial to understand parental effect of long acclimatization on thermal tolerance of offspring. To test whether there is parental effect of long acclimatization, adult sea cucumbers (Apostichopus japonicus) from the same broodstock were transplanted southward and acclimatized at high temperature in field mesocosms. Four groups of juvenile sea cucumbers whose parents experienced different durations of high temperature acclimatization were established. Upper thermal limits, oxygen consumption and levels of heat shock protein mRNA of juveniles was determined to compare thermal tolerance of individuals from different groups. Juvenile sea cucumbers whose parents experienced high temperature could acquire high thermal resistance. With the increase of parental exposure duration to high temperature, offspring became less sensitive to high temperature, as indicated by higher upper thermal limits (LT50), less seasonal variations of oxygen consumption, and stable oxygen consumption rates between chronic and acute thermal stress. The relatively high levels of constitutive expression of heat-shock proteins should contribute to the high thermal tolerance. Together, these results indicated that the existence of a parental effect of long acclimatization would increase thermal tolerance of juveniles and change the thermal sensitivity of sea cucumber to future climate change.

Glucose concentration in the blood of intact and alloxan-treated mice after pretreatment with commercial preparations of Stevia rebaudiana (Bertoni).

PubMed

Raskovic, Aleksandar; Gavrilovic, Maja; Jakovljevic, Vida; Sabo, Jan

2004-01-01

The study was concerned with the effect of mice pretreatment with two commercial products of Stevia rebaudiana Bertoni on the blood glucose concentration. One group of mice was pretreated four days with 200 mg/kg of Stevita (Stevita Co, INC, Arlington Texas) (stevia) and the other with 20 mg/kg of Clear Steviosides liquid (Stevita Co, INC, Herbal supplement, Brazil) (stevioside), whereas the animals of control group received at the same time physiological solution. Blood glucose concentration was measured before pretreatment and four days after that. The changes in glucose level were provoked by glucose-tolerance test (500 mg/kg, p.o.) and subcutaneous injection of adrenaline (0.2 mg/kg). The same procedure of measuring blood glucose was applied on the mice with alloxan-induced diabetes mellitus (two doses of 100 mg/kg with a 24-hour interval). Blood glucose levels in mice pretreated with stevia and stevioside were lower compared with control (7.82:6.82:8.01). Also, a smaller increase in this parameter compared to control was registered with pretreated mice in the glucose-tolerance test, pretreatment with stevioside being again more effective (8.68:6.36:5.82). Pretreatment with stevioside caused no significant increase in blood glucose concentration after administering adrenaline, which was not the case with the animals pretreated with stevia and control. Pretreatment with stevia, and to a greater extent with stevioside, protected test animals from the toxic action of alloxan compared with controls.

Immediate hypersensitivity to moxifloxacin with tolerance to ciprofloxacin: report of three cases and review of the literature.

PubMed

Chang, Brenda; Knowles, Sandra R; Weber, Elizabeth

2010-04-01

To report 3 cases of immediate hypersensitivity reactions to moxifloxacin in patients who tolerated ciprofloxacin. A 71-year-old man, a 44-year-old woman, and a 70-year-old woman with a history of a moxifloxacin reaction developed an immediate hypersensitivity reaction upon oral challenge with moxifloxacin in our Drug Safety Clinic. The reaction was mainly characterized by pruritus and urticaria, although dyspnea and hypotension were noted in the first and second patient, respectively. Two of the patients had negative oral challenge tests with ciprofloxacin and all 3 patients tolerated full treatment courses of oral ciprofloxacin. In all 3 cases, use of the Naranjo probability scale indicated a highly probable adverse drug reaction. Moxifloxacin, similar to other fluoroquinolones, can cause immediate hypersensitivity reactions. Previous publications have reported both cross-reactivity and a lack of cross-reactivity among various fluoroquinolones. The 3 patients discussed demonstrated a lack of cross-reactivity between moxifloxacin and ciprofloxacin since they tolerated oral challenge tests and full treatment courses of ciprofloxacin. Moxifloxacin has unique side chains at positions 7 and 8 on its bicyclic ring structure. Antigenic specificity to particular side chains at positions 7 and 8 on the bicyclic ring structure of moxifloxacin may explain this lack of cross-reactivity. Higher reporting rates of anaphylaxis to moxifloxacin compared to other fluoroquinolones may also be related to side chain specificity, although definitive evidence for this is lacking. Based on our experience, patients who develop immediate hypersensitivity reactions to moxifloxacin may receive ciprofloxacin therapy in an appropriately monitored setting if they have previously tolerated full treatment courses of ciprofloxacin. Research into whether there is a specific side chain reaction unique to moxifloxacin is warranted.

Desiccation tolerance, longevity and seed-siring ability of entomophilous pollen from UK native orchid species

PubMed Central

Marks, Timothy R.; Seaton, Philip T.; Pritchard, Hugh W.

2014-01-01

Background and Aims Pollinator-limited seed-set in some terrestrial orchids is compensated for by the presence of long-lived flowers. This study tests the hypothesis that pollen from these insect-pollinated orchids should be desiccation tolerant and relatively long lived using four closely related UK terrestrial species; Anacamptis morio, Dactylorhiza fuchsii, D. maculata and Orchis mascula. Methods Pollen from the four species was harvested from inflorescences and germinated in vitro, both immediately and also after drying to simulate interflower transit. Their tolerance to desiccation and short-term survival was additionally assessed after 3 d equilibration at a range of relative humidities (RHs), and related to constructed sorption isotherms (RH vs. moisture content, MC). Ageing of D. fuchsii pollen was further tested over 2 months against temperature and RH, and the resultant survival curves were subjected to probit analysis, and the distribution of pollen death in time (σ) was determined. The viability and siring ability, following artificial pollinations, were determined in D. fuchsii pollen following storage for 6 years at –20 °C. Key Results The pollen from all four species exhibited systematic increases in germinability and desiccation tolerance as anthesis approached, and pollen from open flowers generally retained high germinability. Short-term storage revealed sensitivity to low RH, whilst optimum survival occurred at comparable RHs in all species. Similarly, estimated pollen life spans (σ) at differing temperatures were longest under the dry conditions. Despite a reduction in germination and seeds per capsule, long-term storage of D. fuchsii pollen did not impact on subsequent seed germination in vitro. Conclusions Substantial pollen desiccation tolerance and life span of the four entomophilous orchids reflects a resilient survival strategy in response to unpredictable pollinator visitation, and presents an alternative approach to germplasm conservation. PMID:25006180

Antigen-specific tolerance inhibits autoimmune uveitis in pre-sensitized animals by deletion and CD4+CD25+ T-regulatory cells.

PubMed

Matta, Bharati; Jha, Purushottam; Bora, Puran S; Bora, Nalini S

2010-02-01

The objective of this study was to inhibit experimental autoimmune anterior uveitis (EAAU) by establishing antigen-specific immune tolerance in animals pre-sensitized with melanin-associated antigen (MAA). Intravenous administration of MAA on days 6, 7, 8 and 9 post-immunization induced tolerance and inhibited EAAU in all Lewis rats. The number of cells (total T cells, CD4(+) T cells and CD8(+) T cells) undergoing apoptosis dramatically increased in the popliteal lymph nodes (LNs) of the tolerized animals compared with non-tolerized animals. In addition, Fas ligand (FasL), TNF receptor 1 (TNFR1) and caspase-8 were upregulated in tolerized rats. Proliferation of total lymphocytes, CD4(+)T cells and CD8(+) T cells (harvested from the popliteal LNs) in response to antigenic stimulation was drastically reduced in the state of tolerance compared with the cells from non-tolerized animals. The level of interferon (IFN)-gamma and IL-2 decreased, whereas TGF-beta2 was elevated in the state of tolerance. Furthermore, the number of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) increased in the popliteal LNs of tolerized animals compared with non-tolerized animals. In conclusion, our results suggest that deletion of antigen-specific T cells by apoptosis and active suppression mediated by Tregs has an important role in the induction of antigen specific immune tolerance in animals with an established immune response against MAA.

[Psychotherapy impact on effectiveness of in-hospital physical rehabilitation in patients with acute coronary syndrome].

PubMed

Sumin, A N; Khaĭredinova, O P; Sumina, L Iu; Variushkina, E V; Doronin, D V; Galimzianov, D M; Masin, A N; Gol'dberg, G A

2000-01-01

Of 103 patients with acute coronary syndrome (mean age 51.6 +/- 0.9 years) 47 patients participated in 5 group psychotherapeutic sessions added to conversional rehabilitation program. Psychotherapy included progressive muscular relaxation, neurolinguistic programming, eriksonian hypnosis, therapeutic metaphora. Psychotherapy decreased the hear rate, number of ventricular extrasystoles, stimulated tonicity of the parasympathetic nervous system. Compared to the controls, the test patients developed higher exercise tolerance and lower reactivity of the central hemodynamics in all the exercise tests.

Generating Phenotypic Diversity in a Fungal Biocatalyst to Investigate Alcohol Stress Tolerance Encountered during Microbial Cellulosic Biofuel Production

PubMed Central

Hennessy, Rosanna C.; Doohan, Fiona; Mullins, Ewen

2013-01-01

Consolidated bioprocessing (CBP) of lignocellulosic biomass offers an alternative route to renewable energy. The crop pathogen Fusarium oxysporum is a promising fungal biocatalyst because of its broad host range and innate ability to co-saccharify and ferment lignocellulose to bioethanol. A major challenge for cellulolytic CBP-enabling microbes is alcohol inhibition. This research tested the hypothesis that Agrobacterium tumefaciens - mediated transformation (ATMT) could be exploited as a tool to generate phenotypic diversity in F. oxysporum to investigate alcohol stress tolerance encountered during CBP. A random mutagenesis library of gene disruption transformants (n=1,563) was constructed and screened for alcohol tolerance in order to isolate alcohol sensitive or tolerant phenotypes. Following three rounds of screening, exposure of select transformants to 6% ethanol and 0.75% n-butanol resulted respectively in increased (≥11.74%) and decreased (≤43.01%) growth compared to the wild –type (WT). Principal component analysis (PCA) quantified the level of phenotypic diversity across the population of genetically transformed individuals and isolated candidate strains for analysis. Characterisation of one strain, Tr. 259, ascertained a reduced growth phenotype under alcohol stress relative to WT and indicated the disruption of a coding region homologous to a putative sugar transporter (FOXG_09625). Quantitative PCR (RT-PCR) showed FOXG_09625 was differentially expressed in Tr. 259 compared to WT during alcohol-induced stress (P<0.05). Phylogenetic analysis of putative sugar transporters suggests diverse functional roles in F. oxysporum and other filamentous fungi compared to yeast for which sugar transporters form part of a relatively conserved family. This study has confirmed the potential of ATMT coupled with a phenotypic screening program to select for genetic variation induced in response to alcohol stress. This research represents a first step in the investigation of alcohol tolerance in F. oxysporum and has resulted in the identification of several novel strains, which will be of benefit to future biofuel research. PMID:24147009

Fault-tolerant onboard digital information switching and routing for communications satellites

NASA Technical Reports Server (NTRS)

Shalkhauser, Mary JO; Quintana, Jorge A.; Soni, Nitin J.; Kim, Heechul

1993-01-01

The NASA Lewis Research Center is developing an information-switching processor for future meshed very-small-aperture terminal (VSAT) communications satellites. The information-switching processor will switch and route baseband user data onboard the VSAT satellite to connect thousands of Earth terminals. Fault tolerance is a critical issue in developing information-switching processor circuitry that will provide and maintain reliable communications services. In parallel with the conceptual development of the meshed VSAT satellite network architecture, NASA designed and built a simple test bed for developing and demonstrating baseband switch architectures and fault-tolerance techniques. The meshed VSAT architecture and the switching demonstration test bed are described, and the initial switching architecture and the fault-tolerance techniques that were developed and tested are discussed.

[New visual field testing possibilities (a preliminary report)].

PubMed

Erichev, V P; Ermolaev, A P; Antonov, A A; Grigoryan, G L; Kosova, D V

2018-01-01

There are currently no portable mobile perimeters that allow visual field testing outside ophthalmologist's examination rooms. To develop a mobile perimetry technique based on use of a virtual reality headset (VR). The study involved 26 patients (30 eyes) with II-III stage primary open-angle glaucoma (POAG) with compensated IOP. Perimetry was performed for each patient twice - on Humphrey analyzer (test 30-2, 76 points) and employing similar strategy on a perimeter integrated into VR headset (Total Vision, Russia). Visual field testing was performed with an interval from 1 hour to 3 days. The results were comparatively analyzed. Patients tolerated the examination well. Comparative analysis of preliminary perimetry results obtained with both methods showed high degree of identity, so the results were concluded to be comparable. By visually isolating the wearer, VR headset achieves elimination of distractions and stable light conditions for visual field testing. The headset-perimeter is compact, mobile, easily transportable, can be used in the work of visiting medical teams and for examination at home.

Measuring the ambiguity tolerance of medical students: a cross-sectional study from the first to sixth academic years

PubMed Central

2014-01-01

Background Tolerance of ambiguity, or the extent to which ambiguous situations are perceived as desirable, is an important component of the attitudes and behaviors of medical students. However, few studies have compared this trait across the years of medical school. General practitioners are considered to have a higher ambiguity tolerance than specialists. We compared ambiguity tolerance between general practitioners and medical students. Methods We designed a cross-sectional study to evaluate the ambiguity tolerance of 622 medical students in the first to sixth academic years. We compared this with the ambiguity tolerance of 30 general practitioners. We used the inventory for measuring ambiguity tolerance (IMA) developed by Reis (1997), which includes three measures of ambiguity tolerance: openness to new experiences, social conflicts, and perception of insoluble problems. Results We obtained a total of 564 complete data sets (return rate 90.1%) from medical students and 29 questionnaires (return rate 96.7%) from general practitioners. In relation to the reference groups defined by Reis (1997), medical students had poor ambiguity tolerance on all three scales. No differences were found between those in the first and the sixth academic years, although we did observe gender-specific differences in ambiguity tolerance. We found no differences in ambiguity tolerance between general practitioners and medical students. Conclusions The ambiguity tolerance of the students that we assessed was below average, and appeared to be stable throughout the course of their studies. In contrast to our expectations, the general practitioners did not have a higher level of ambiguity tolerance than the students did. PMID:24405525

Measuring the ambiguity tolerance of medical students: a cross-sectional study from the first to sixth academic years.

PubMed

Weissenstein, Anne; Ligges, Sandra; Brouwer, Britta; Marschall, Bernhard; Friederichs, Hendrik

2014-01-09

Tolerance of ambiguity, or the extent to which ambiguous situations are perceived as desirable, is an important component of the attitudes and behaviors of medical students. However, few studies have compared this trait across the years of medical school. General practitioners are considered to have a higher ambiguity tolerance than specialists. We compared ambiguity tolerance between general practitioners and medical students. We designed a cross-sectional study to evaluate the ambiguity tolerance of 622 medical students in the first to sixth academic years. We compared this with the ambiguity tolerance of 30 general practitioners. We used the inventory for measuring ambiguity tolerance (IMA) developed by Reis (1997), which includes three measures of ambiguity tolerance: openness to new experiences, social conflicts, and perception of insoluble problems. We obtained a total of 564 complete data sets (return rate 90.1%) from medical students and 29 questionnaires (return rate 96.7%) from general practitioners. In relation to the reference groups defined by Reis (1997), medical students had poor ambiguity tolerance on all three scales. No differences were found between those in the first and the sixth academic years, although we did observe gender-specific differences in ambiguity tolerance. We found no differences in ambiguity tolerance between general practitioners and medical students. The ambiguity tolerance of the students that we assessed was below average, and appeared to be stable throughout the course of their studies. In contrast to our expectations, the general practitioners did not have a higher level of ambiguity tolerance than the students did.

Obese mice on a high-fat alternate-day fasting regimen lose weight and improve glucose tolerance.

PubMed

Joslin, P M N; Bell, R K; Swoap, S J

2017-10-01

Alternate-day fasting (ADF) causes body weight (BW) loss in humans and rodents. However, it is not clear that ADF while maintaining a high-fat (HF) diet results in weight loss and the accompanying improvement in control of circulating glucose. We tested the hypotheses that a high-fat ADF protocol in obese mice would result in (i) BW loss, (ii) improved glucose control, (iii) fluctuating phenotypes on 'fasted' days when compared to 'fed' days and (iv) induction of torpor on 'fasted days'. We evaluated the physiological effects of ADF in diet-induced obese mice for BW, heart rate (HR), body temperature (T b ), glucose tolerance, insulin responsiveness, blood parameters (leptin, insulin, free fatty acids) and hepatic gene expression. Diet-induced obese male C57BL/6J mice lost one-third of their pre-diet BW while on an ADF diet for 10 weeks consisting of HF food. The ADF protocol improved glucose tolerance and insulin sensitivity, although mice on a fast day were less glucose tolerant than the same mice on a fed day. ADF mice on a fast day had low circulating insulin, but had an enhanced response to an insulin-assisted glucose tolerance test, suggesting the impaired glucose tolerance may be a result of insufficient insulin production. On fed days, ADF mice were the warmest, had a high HR and displayed hepatic gene expression and circulating leptin that closely mimicked that of mice fed an ad lib HF diet. ADF mice never entered torpor as assessed by HR and T b . However, on fast days, they were the coolest, had the slowest HR, and displayed hepatic gene expression and circulating leptin that closely mimicked that of Chow-Fed mice. Collectively, the ADF regimen with a HF diet in obese mice results in weight loss, improved blood glucose control, and daily fluctuations in selected physiological and biochemical parameters in the mouse. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Variation and Defect Tolerance for Nano Crossbars

NASA Astrophysics Data System (ADS)

Tunc, Cihan

With the extreme shrinking in CMOS technology, quantum effects and manufacturing issues are getting more crucial. Hence, additional shrinking in CMOS feature size seems becoming more challenging, difficult, and costly. On the other hand, emerging nanotechnology has attracted many researchers since additional scaling down has been demonstrated by manufacturing nanowires, Carbon nanotubes as well as molecular switches using bottom-up manufacturing techniques. In addition to the progress in manufacturing, developments in architecture show that emerging nanoelectronic devices will be promising for the future system designs. Using nano crossbars, which are composed of two sets of perpendicular nanowires with programmable intersections, it is possible to implement logic functions. In addition, nano crossbars present some important features as regularity, reprogrammability, and interchangeability. Combining these features, researchers have presented different effective architectures. Although bottom-up nanofabrication can greatly reduce manufacturing costs, due to low controllability in the manufacturing process, some critical issues occur. Bottom- up nanofabrication process results in high variation compared to conventional top- down lithography used in CMOS technology. In addition, an increased failure rate is expected. Variation and defect tolerance methods used for conventional CMOS technology seem inadequate for adapting to emerging nano technology because the variation and the defect rate for emerging nano technology is much more than current CMOS technology. Therefore, variations and defect tolerance methods for emerging nano technology are necessary for a successful transition. In this work, in order to tolerate variations for crossbars, we introduce a framework that is established based on reprogrammability and interchangeability features of nano crossbars. This framework is shown to be applicable for both FET-based and diode-based nano crossbars. We present a characterization testing method which requires minimal number of test vectors. We formulate the variation optimization problem using Simulated Annealing with different optimization goals. Furthermore, we extend the framework for defect tolerance. Experimental results and comparison of proposed framework with exhaustive methods confirm its effectiveness for both variation and defect tolerance.

Effect of Different Insulin Response Patterns During Oral Glucose Tolerance Test on Glycemia in Individuals with Normal Glucose Tolerance.

PubMed

Praveen, Edavan Pulikkanath; Chouhan, Sunil; Sahoo, Jayaprakash; Goel, Sudhir K; Dwivedi, Sada Nand; Khurana, Madan Lal; Kulshreshtha, Bindu; Ammini, Ariachery C

2016-05-01

Research is still going on for detecting the earliest glucose homeostasis derangements in individuals, which is crucial for the prevention of glucose intolerance. This cross-sectional study analyzes different insulin response patterns during the oral glucose tolerance test (OGTT) and their implications on glycemia in normoglycemic individuals. The sample frame was the "Offspring of Individuals with Diabetes Study" database. All participants underwent OGTT. Blood samples were collected at 0, 30, 60, and 120 min for measurement of insulin, C-peptide, and proinsulin levels. Normal glucose tolerant individuals were selected for analysis. Four hundred fifty subjects (mean age, 25 years) were included and divided into two groups according to timing of plasma insulin peaking during OGTT: Group 1, peaking at 30 min; and Group 2, peaking at 60 or 120 min. Body mass index (BMI) and insulin resistance were comparable between the groups; however, Group 2 showed a significantly higher 60- and 120-min glucose level and lower disposition index. Based on the magnitude of the insulin levels, Group 1 was subdivided into Group N (normal pattern) and Group E (exaggerated pattern) with a 30-min insulin cutoff of 74 μU/mL (Group E, ≥74 μU/mL). Group 2 was subdivided into Group DL (delayed and limited pattern; 60-min insulin <73.0 μU/mL and 120-min insulin <80.0 μU/mL) and Group DE (delayed and exaggerated pattern; 60-min insulin ≥73.0 μU/mL or 120-min insulin ≥80.0 μU/mL). Group DE showed a significantly higher area under the curve (AUC) of glucose compared with the other groups and had a lower disposition index and high-density lipoprotein levels. Group DL had significantly lower insulin resistance and BMI compared with Group E but showed a similar AUC of glucose. A delayed insulin pattern was associated with higher postprandial glucose levels. Individuals with delayed and exaggerated insulin secretion may have a higher risk for glucose intolerance.

Tolerance of freshwater test organisms to formulated sediments for use as control materials in whole-sediment toxicity tests

USGS Publications Warehouse

Kemble, N.E.; Dwyer, F.J.; Ingersoll, C.G.; Dawson, T.D.; Norberg-King, T. J.

1999-01-01

A method is described for preparing formulated sediments for use intoxicity testing. Ingredients used to prepare formulated sediments included commercially available silt, clay, sand, humic acid, dolomite, and α-cellulose (as a source of organic carbon). α-Cellulose was selected as the source of organic carbon because it is commercially available, consistent from batch to batch, and low in contaminant concentrations. The tolerance of freshwater test organisms to formulated sediments for use as control materials in whole-sediment toxicity testing was evaluated. Sediment exposures were conducted for 10 d with the amphipod Hyalella azteca, the midges Chironomus riparius and C. tentans, and the oligochaete Lumbriculus variegatus and for 28 d with H. azteca. Responses of organisms in formulated sediments was compared with a field-collected control sediment that has routinely been used to determine test acceptability. Tolerance of organisms to formulated sediments was evaluated by determining responses to varying levels of α-cellulose, to varying levels of grain size, to evaluation of different food types, or to evaluation of different sources of overlying water. In the 10-d exposures, survival of organisms exposed to the formulated sediments routinely met or exceeded the responses of test organisms exposed to the control sediment and routinely met test acceptability criteria required in standard methods. Growth of amphipods and oligochaetes in 10-d exposures with formulated sediment was often less than growth of organisms in the field-collected control sediment. Additional research is needed, using the method employed to prepare formulated sediment, to determine if conditioning formulated sediments before starting 10-d tests would improve the growth of amphipods. In the 28-d exposures, survival of H. azteca was low when reconstituted water was used as the source of overlying water. However, when well water was used as the source of overlying water in 28-d exposures, consistent responses of amphipods were observed in both formulated and control sediments.

Yeasts associated with an abandoned mining area in Pernek and their tolerance to different chemical elements.

PubMed

Vadkertiová, Renáta; Molnárová, Jana; Lux, Alexander; Vaculík, Marek; Lišková, Desana

2016-05-01

Four plants, Cirsium arvense (creeping thistle), Equisetum arvense (field horsetail), Oxalis acetosella (wood sorrel) and Phragmites australis (common reed), which grew in an abandoned Sb-mining area in Pernek (Malé Karpaty Mts., Slovakia), were investigated for the yeast species. Yeasts were isolated from both the leaves of the plants and the soil adjacent to the plants. In total, 65 yeast cultures, belonging to 11 ascomycetous and 5 basidiomycetous yeast species, were isolated. The species most frequently isolated from both the soil and leaf samples were Trichosporon porosum, Galactomyces candidus and Candida solani, whereas Aureobasidium pullulans, Candida tsuchiyae and Sporidiobolus metaroseus were isolated exclusively from the plant leaves. All the yeast species isolated were tested for their tolerance to two heavy metals (Cd, Zn) and three metalloids (As, Sb and Si). The yeasts isolated from both the leaves and soils exhibited a high tolerance level to both As and Sb, present in elevated concentrations at the locality. Among the yeast species tested, Cryptococcus musci, a close relative to Cryptococcus humicola, was the species most tolerant to all the chemical elements tested, with the exception of Si. It grew in the presence of 200 mmol/L Zn, 200 mmol/L Cd, 60 mmol/L As and 50 mmol/L Sb, and therefore, it can be considered as a multi-tolerant species. Some of the yeast species were tolerant to the individual chemical elements. The yeast-like species Trichosporon laibachii exhibited the highest tolerance to Si of all yeasts tested, and Cryptococcus flavescens and Lindnera saturnus showed the same tolerance as Cryptococcus musci to Zn and As, respectively. The majority of the yeasts showed a notably low tolerance to Cd (not exceeded 0.5 mmol/L), which was present in small amounts in the soil. However, Candida solani, isolated from the soil, exhibited a higher tolerance to Cd (20 mmol/L) than to As (2 mmol/L).

Comparative analysis of transcriptome in two wheat genotypes with contrasting levels of drought tolerance

USDA-ARS?s Scientific Manuscript database

Drought tolerance is a complex trait that is governed by multiple genes. To identify the potential candidate genes, comparative analysis of drought stress-responsive transcriptome between drought-tolerant (Triticum aestivum Cv. C306) and drought-sensitive (Triticum aestivum Cv. WL711) genotypes was ...

Is sexual reproduction of high-mountain plants endangered by heat?

PubMed

Ladinig, Ursula; Pramsohler, Manuel; Bauer, Ines; Zimmermann, Sonja; Neuner, Gilbert; Wagner, Johanna

2015-04-01

Strong solar irradiation in combination with still air and dry soil can cause prostrate high-mountain plants to heat up considerably and ultimately suffer heat damage. Such heat damage has been repeatedly shown for vegetative structures, but not for reproductive structures, which we expected to be particularly vulnerable to heat. Heat effects on cold-adapted plants may increase with rising global temperatures and the predicted increase in heat waves. We have tested the heat tolerance of reproductive versus vegetative shoots at different reproductive stages, comparing ten common plant species from different elevation belts in the European Alps. Plant samples were exposed to temperatures in 2-K steps of 30 min each between 42 and 56 °C. Heat damage was assessed by visual rating and vital staining. Reproductive shoots were on average 2.5 K less heat tolerant (LT50, i.e. the mean temperature causing 50 % heat damage, 47.2 °C) than vegetative shoots (mean LT50 49.7 °C). Initial heat injuries (mean LT10) were observed at 43-45 °C in heat-susceptible species and at 45-47 °C in more heat-tolerant species, in at least one reproductive stage. Generally, heat tolerance was significantly higher during fruiting than during the bud stages and anthesis. Prostrate species with acaulescent buds and flowers tolerated heat better than those with caulescent buds and flowers. Petals were the most heat-susceptible plant structure and mature pollen the most heat tolerant. Based on these data, heat tolerance of reproductive structures appears to be adapted to the prevailing maximum temperatures which the plants experience during different reproductive stages in their environment. During hot spells, however, heat tolerance thresholds may be exceeded. More frequent heat waves would decrease the reproductive output and, consequently, the competitiveness of heat-susceptible species.

Developing sporophytes transition from an inducible to a constitutive ecological strategy of desiccation tolerance in the moss Aloina ambigua: effects of desiccation on fitness.

PubMed

Stark, Lloyd R; Brinda, John C

2015-03-01

Two ecological strategies of desiccation tolerance exist in plants, constitutive and inducible. Because of difficulties in culturing sporophytes, very little is known about desiccation tolerance in this generation and how desiccation affects sexual fitness. Cultured sporophytes and vegetative shoots from a single genotype of the moss Aloina ambigua raised in the laboratory were tested for their strategy of desiccation tolerance by desiccating the shoot-sporophyte complex and vegetative shoots at different intensities, and comparing outcomes with those of undried shoot-sporophyte complexes and vegetative shoots. By using a dehardened clonal line, the effects of field, age and genetic variance among plants were removed. The gametophyte and embryonic sporophyte were found to employ a predominantly inducible strategy of desiccation tolerance, while the post-embryonic sporophyte was found to employ a moderately constitutive strategy of desiccation tolerance. Further, desiccation reduced sporophyte fitness, as measured by sporophyte mass, seta length and capsule size. However, the effects of desiccation on sporophyte fitness were reduced if the stress occurred during embryonic development as opposed to postembryonic desiccation. The effects of desiccation on dehardened sporophytes of a bryophyte are shown for the first time. The transition from one desiccation tolerance strategy to the other in a single structure or generation is shown for only the second time in plants and for the first time in bryophytes. Finding degrees of inducible strategies of desiccation tolerance in different life phases prompts the formulation of a continuum hypothesis of ecological desiccation tolerance in mosses, where desiccation tolerance is not an either/or phenomenon, but varies in degree along a gradient of ecological inducibility. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Postnatal Pancreatic Islet β Cell Function and Insulin Sensitivity at Different Stages of Lifetime in Rats Born with Intrauterine Growth Retardation

PubMed Central

Liu, Cuiping; Xu, Kuanfeng; Mao, Xiaodong; Liu, Chao

2011-01-01

Epidemiological studies have linked intrauterine growth retardation (IUGR) to the metabolic diseases, consisting of insulin resistance, type 2 diabetes, obesity and coronary artery disease, during adult life. To determine the internal relationship between IUGR and islet β cell function and insulin sensitivity, we established the IUGR model by maternal nutrition restriction during mid- to late-gestation. Glucose tolerance test and insulin tolerance test(ITT) in vivo and glucose stimulated insulin secretion(GSIS) test in vitro were performed at different stages in IUGR and normal groups. Body weight, pancreas weight and pancreas/body weight of IUGR rats were much lower than those in normal group before 3 weeks of age. While the growth of IUGR rats accelerated after 3 weeks, pancreas weight and pancreas/body weight remained lower till 15 weeks of age. In the newborns, the fasting glucose and insulin levels of IUGR rats were both lower than those of controls, whereas glucose levels at 120 and 180 min after glucose load were significantly higher in IUGR group. Between 3 and 15 weeks of age, both the fasting glucose and insulin levels were elevated and the glucose tolerance was impaired with time in IUGR rats. At age 15 weeks, the area under curve of insulin(AUCi) after glucose load in IUGR rats elevated markedly. Meanwhile, the stimulating index of islets in IUGR group during GSIS test at age 15 weeks was significantly lower than that of controls. ITT showed no significant difference in two groups before 7 weeks of age. However, in 15-week-old IUGR rats, there was a markedly blunted glycemic response to insulin load compared with normal group. These findings demonstrate that IUGR rats had both impaired pancreatic development and deteriorated glucose tolerance and insulin sensitivity, which would be the internal causes why they were prone to develop type 2 diabetes. PMID:22022381

Effect of prucalopride on intestinal gas tolerance in patients with functional bowel disorders and constipation.

PubMed

Malagelada, Carolina; Nieto, Adoración; Mendez, Sara; Accarino, Anna; Santos, Javier; Malagelada, Juan-R; Azpiroz, Fernando

2017-08-01

Patients with functional bowel disorders develop gas retention and symptoms in response to intestinal gas loads that are well tolerated by healthy subjects. Stimulation of 5HT-4 receptors in the gut has both prokinetic and antinociceptive effects. The aim of this study is to determine the effect of prucalopride, a highly selective 5HT-4 agonist, on gas transit and tolerance in women with functional bowel disorders complaining of constipation. Twenty-four women with functional bowel disorders complaining of constipation were included in the study. Patients were studied twice on separate days in a cross-over design. On each study day, an intestinal gas challenge test was performed. During the five previous days, prucalopride (2 mg/day) or placebo was administered. Abdominal symptoms, stool frequency, and stool consistency were recorded during the treatment period on daily questionnaires. During the gas challenge test, prucalopride did not decrease the volume of gas retained in the subset of patients who had significant gas retention (≥ 200 mL) while on placebo. However, in those patients who had increased symptoms during the gas test (≥ 3 on a 0 to 6 scale) when on placebo, prucalopride did significantly reduce the perception of symptoms (2.3 ± 0.5 mean score vs 3.5 ± 0.3 on placebo; P = 0.045). During the treatment period with prucalopride, patients exhibited an increase in the total number of bowel movements and decreased stool consistency compared with placebo. Prucalopride reduces abdominal symptoms without modifying gas retention when patients with functional bowel disorders are challenged with the gas transit and tolerance test. European Clinical Trials Database (EudraCT2011-006354-86). © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Efficacy and tolerability of fimasartan, a new angiotensin receptor blocker, compared with losartan (50/100 mg): a 12-week, phase III, multicenter, prospective, randomized, double-blind, parallel-group, dose escalation clinical trial with an optional 12-week extension phase in adult Korean patients with mild-to-moderate hypertension.

PubMed

Lee, Sang Eun; Kim, Yong-Jin; Lee, Hae-Young; Yang, Han-Mo; Park, Chang-Gyu; Kim, Jae-Joong; Kim, Soon-Kil; Rhee, Moo-Yong; Oh, Byung-Hee

2012-03-01

Angiotensin receptor blockers (ARBs) is an effective and well tolerated first-line antihypertensive drug. Fimasartan is a newly developed ARB that has not been compared with other ARBs with regard to its efficacy and tolerability. The goal of this study was to determine the noninferiority of fimasartan to losartan with regard to its efficacy and tolerability in adult Korean patients with mild-to-moderate hypertension. This was a randomized, multicenter, double-blind, parallel group, dose escalation, Phase III, noninferiority clinical trial. Patients aged 18 to 70 years with mild-to-moderate hypertension were randomized to receive either fimasartan 60/120 mg daily or losartan 50/100 mg daily with optional titration. Antihypertensive efficacy and tolerability were evaluated for 12 weeks. The primary end point was noninferiority of improvement in mean siDBP from baseline to week 12 for fimasartan compared with losartan. The incidence and severity of adverse events (AEs) and adverse drug reactions (ADRs) were evaluated to assess their tolerability. In addition, some patients whose blood pressure reached goal levels participated in a 24-week extension study for additional assessment of tolerability and efficacy. Five hundred six patients were randomly allocated to receive fimasartan (n = 256) or losartan (n = 250). There was no significant difference in baseline demographic characteristics between the 2 treatment groups (fimasartan-treated group-mean age, 53.96 [8.79] years; mean weight, 70.58 [11.73] kg; male, 68.02%; losartan-treated group-mean age, 53.58 [9.61] years; mean weight, 69.80 [11.08] kg; male, 70.17%). At week 12, siDBP was significantly decreased from baseline in both groups (-11.26 [7.53] mm Hg in the fimasartan group and -8.56 [7.72] mm Hg in the losartan group [P < 0.0001]). The between-group difference was 2.70 mm Hg (P = 0.0002), and the lower limit of the 2-sided 95% CI (1.27 mm Hg) was higher than the prespecified noninferiority margin (-2.5 mm Hg). The incidence of ADRs were 7.84% and 10.40% in the fimasartan and losartan groups, respectively (χ(2) test, P = 0.3181). The efficacy of fimasartan was maintained over 24 weeks, and its tolerability was comparable with losartan in the extension study. In this study with eligible adult Korean patients who had mild-to-moderate hypertension, the reduction of siDBP after 12 weeks of treatment with fimasartan 60/120 mg was noninferior to that of losartan 50/100 mg. By post hoc comparison, between-group differences in siDBP were significant in favor of fimasartan, suggesting superiority to losartan. There was no statistically significant difference in tolerability between the groups. This efficacy and tolerability were maintained throughout the additional 12-week extension study. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Gastrointestinal tolerance and plasma status of carotenoids, EPA and DHA with a fiber-enriched tube feed in hospitalized patients initiated on tube nutrition: Randomized controlled trial.

PubMed

Jakobsen, L H; Wirth, R; Smoliner, C; Klebach, M; Hofman, Z; Kondrup, J

2017-04-01

During the first days of tube feeding (TF) gastrointestinal (GI) complications are common and administration of sufficient nutrition is a challenge. Not all standard nutritionally complete formulas contain dietary fiber, fish oil or carotenoids, key dietary nutrients for health and wellbeing. The aim of this study was to investigate the effects of a fiber, fish oil and carotenoid enriched TF formula on diarrhea, constipation and nutrient bioavailability. A multi-center randomized, double-blind, controlled, parallel trial compared the effects of a dietary fiber, fish oil and carotenoid-enriched TF formula (test) with an isocaloric non-enriched formula (control) in 51 patients requiring initiation of TF. Incidence of diarrhea and constipation (based on stool frequency and consistency) was recorded daily. Plasma status of EPA, DHA and carotenoids was measured after 7 days. The incidence of diarrhea was lower in patients receiving the test formula compared with the control group (19% vs. 48%, p = 0.034). EPA and DHA status (% of total plasma phospholipids) was higher after 7 days in test compared with control group (EPA: p = 0.002, DHA: p = 0.082). Plasma carotenoid levels were higher after 7 days in the test group compared with control group (lutein: p = 0.024, α-carotene: p = 0.005, lycopene: p = 0.020, β-carotene: p = 0.054). This study suggests that the nutrient-enriched TF formula tested might have a positive effect on GI tolerance with less diarrhea incidence and significantly improved EPA, DHA and carotenoid plasma levels during the initiation of TF in hospitalized patients who are at risk of diarrhea and low nutrient status. This trial was registered at trialregister.nl; registration number 2924. Copyright © 2016. Published by Elsevier Ltd.

Early and progressive insulin resistance in young, non-obese cancer survivors treated with hematopoietic stem cell transplantation.

PubMed

Bizzarri, Carla; Pinto, Rita M; Ciccone, Sara; Brescia, Letizia P; Locatelli, Franco; Cappa, Marco

2015-09-01

It is unclear whether there is a causative relationship between the development of metabolic syndrome (MS) and increased risk of early cardiovascular morbidity in patients receiving hematopoietic stem cell transplantation (HSCT) during childhood. Early identification of risk factors associated with insulin resistance, MS, and abnormal glucose tolerance during childhood or adolescence in these patients could represent a useful tool for preventing cardiovascular disorders. In a single-center, prospective, descriptive, cross-sectional study, we studied 45 survivors of hematological malignancies (age: 13.9 ± 4.8 years) treated with HSCT before the age of 18 years and 90 matched healthy controls. We collected clinical, imaging, and laboratory data including oral glucose tolerance test (OGTT). 7/45 patients (15.6%) showed abnormal glucose tolerance at OGTT, 1/45 (2.2%) was obese, and none fulfilled the criteria for MS. A waist/height ratio >0.5 was associated with patients with abnormal glucose tolerance (85.7% of cases), compared to patients with normal glucose tolerance (42.1%) and controls (23.3%). In patients with abnormal glucose tolerance, use of total body irradiation (TBI) as conditioning regimen was more common, and time elapsed from HSCT was longer. Patients treated with HSCT may develop insulin resistance early after transplantation. They do not show overt obesity, but have redistribution of fat tissue with central fat accumulation. The main factors associated with increased metabolic risk are TBI and time from HSCT. Evaluation of MS and glucose tolerance should be part of hormonal follow-up, which should be routinely proposed to these patients. © 2015 Wiley Periodicals, Inc.

Handling Ibuprofen Increases Pain Tolerance and Decreases Perceived Pain Intensity in a Cold Pressor Test

PubMed Central

Rutchick, Abraham M.; Slepian, Michael L.

2013-01-01

Pain contributes to health care costs, missed work and school, and lower quality of life. Extant research on psychological interventions for pain has focused primarily on developing skills that individuals can apply to manage their pain. Rather than examining internal factors that influence pain tolerance (e.g., pain management skills), the current work examines factors external to an individual that can increase pain tolerance. Specifically, the current study examined the nonconscious influence of exposure to meaningful objects on the perception of pain. Participants (N = 54) completed a cold pressor test, examined either ibuprofen or a control object, then completed another cold pressor test. In the second test, participants who previously examined ibuprofen reported experiencing less intense pain and tolerated immersion longer (relative to baseline) than those who examined the control object. Theoretical and applied implications of these findings are discussed. PMID:23469170

Specialized physiological studies in support of manned space flight

NASA Technical Reports Server (NTRS)

Luft, U. C.

1976-01-01

Subjects were tested for tolerance to lower body negative pressure (LBNP) before and after acute dehydration by working intermittenly for two hours without fluid replacement. On the second day there-after the LBNP tests were repeated before and after acute dehydration. The LBNP test consisted of 5 min long consective stages at -20, -30, -40, -50 and -60 Torr. Tests were terminated when syncope was imminent or the full sequence was completed. Tolerance was expressed in terms of cumulative stress in Torr x min. Measurements of body mass, density, fat fraction and total body water (TBW) were made before and after acclimation. Blood volume and its constituents were determined before and after each of the four LBNP tests. During LBNP, heart rate, blood pressure, and changes in calf and forearm volume were recorded every minute. Results showed: acute dehydration caused a significant loss in average LBNP tolerance on all subjects. Acclimation to heat did not significantly affect LBNP tolerance in hydrated subjects but significantly improved it on dehydrated subjects.

Discerning morpho-anatomical, physiological and molecular multiformity in cultivated and wild genotypes of lentil with reconciliation to salinity stress

PubMed Central

Singh, Chandan Kumar; Kumari, Shanti; Singh Tomar, Ram Sewak; Karwa, Sourabh; Singh, Rajendra; Singh, Raja Bahadur; Sarkar, Susheel Kumar; Pal, Madan

2017-01-01

One hundred and sixty two genotypes of different Lens species were screened for salinity tolerance in hydroponics at 40, 80 and 120 mM sodium chloride (NaCl) for 30 d. The germination, seedling growth, biomass accumulation, seedling survivability, salinity scores, root and shoot anatomy, sodium ion (Na+), chloride ion (Cl-) and potassium ion (K+) concentrations, proline and antioxidant activities were measured to evaluate the performance of all the genotypes. The results were compared in respect of physiological (Na+, K+ and Cl-) and seed yield components obtained from field trials for salinity stress conducted during two years. Expression of salt tolerance in hydroponics was found to be reliable indicator for similarity in salt tolerance between genotypes and was evident in saline soil based comparisons. Impressive genotypic variation for salinity tolerance was observed among the genotypes screened under hydroponic and saline field conditions. Plant concentrations of Na+ and Cl- at 120 mM NaCl were found significantly correlated with germination, root and shoot length, fresh and dry weight of roots and shoots, seedling survivability, salinity scores and K+ under controlled conditions and ranked the genotypes along with their seed yield in the field. Root and shoot anatomy of tolerant line (PDL-1) and wild accession (ILWL-137) showed restricted uptake of Na+ and Cl- due to thick layer of their epidermis and endodermis as compared to sensitive cultigen (L-4076). All the genotypes were scanned using SSR markers for genetic diversity, which generated high polymorphism. On the basis of cluster analysis and population structure the contrasting genotypes were grouped into different classes. These markers may further be tested to explore their potential in marker-assisted selection. PMID:28542267

Biotransformation of glyceryl trinitrate occurs concurrently with relaxation of rabbit aorta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brien, J.F.; McLaughlin, B.E.; Breedon, T.H.

1986-05-01

This study was conducted to test the hypothesis that biotransformation of glyceryl trinitrate (GTN) is involved in GTN-induced relaxation of vascular smooth muscle. Isolated rabbit aortic strips (RAS) were contracted submaximally with phenylephrine (PE) and then were incubated with 0.5 microM (/sup 14/C)GTN in a time course study. GTN-induced relaxation (inhibition of PE-induced tone) of RAS was monitored and tissue GTN and glyceryl-1,2- and 1,3-dinitrate (GDN) concentrations were measured by thin-layer chromatography and liquid scintillation spectrometry at 0.5, 1, 2 and 20 min after incubation. Biotransformation of GTN to GDN occurred during GTN-induced relaxation of RAS. The tissue GDN concentrationmore » was dependent on the time duration of incubation with GTN and was related to the magnitude of GTN-induced tissue relaxation. At the 20-min interval, the GDN concentration in the incubation medium indicated appreciable efflux of GDN metabolites from the RAS. In the biotransformation of GTN by RAS, there was about 4-fold preferential formation of 1,2-GDN compared with 1,3-GDN. RAS were made tolerant to GTN in vitro by incubation with 500 microM GTN for 1 hr. After washing, GTN-tolerant and nontolerant (incubation with vehicle for 1 hr) RAS were contracted submaximally with PE, and then were incubated with 0.5 microM (/sup 14/C)GTN for 2 min. GTN-induced relaxation of RAS and tissue GDN concentration were significantly less for GTN-tolerant tissue compared with nontolerant tissue. Tissue GTN concentration was similar for both GTN-tolerant and nontolerant RAS, which indicated that the tissue uptake of GTN was similar and that GTN biotransformation was diminished in tolerant tissue.(ABST« less

Discerning morpho-anatomical, physiological and molecular multiformity in cultivated and wild genotypes of lentil with reconciliation to salinity stress.

PubMed

Singh, Dharmendra; Singh, Chandan Kumar; Kumari, Shanti; Singh Tomar, Ram Sewak; Karwa, Sourabh; Singh, Rajendra; Singh, Raja Bahadur; Sarkar, Susheel Kumar; Pal, Madan

2017-01-01

One hundred and sixty two genotypes of different Lens species were screened for salinity tolerance in hydroponics at 40, 80 and 120 mM sodium chloride (NaCl) for 30 d. The germination, seedling growth, biomass accumulation, seedling survivability, salinity scores, root and shoot anatomy, sodium ion (Na+), chloride ion (Cl-) and potassium ion (K+) concentrations, proline and antioxidant activities were measured to evaluate the performance of all the genotypes. The results were compared in respect of physiological (Na+, K+ and Cl-) and seed yield components obtained from field trials for salinity stress conducted during two years. Expression of salt tolerance in hydroponics was found to be reliable indicator for similarity in salt tolerance between genotypes and was evident in saline soil based comparisons. Impressive genotypic variation for salinity tolerance was observed among the genotypes screened under hydroponic and saline field conditions. Plant concentrations of Na+ and Cl- at 120 mM NaCl were found significantly correlated with germination, root and shoot length, fresh and dry weight of roots and shoots, seedling survivability, salinity scores and K+ under controlled conditions and ranked the genotypes along with their seed yield in the field. Root and shoot anatomy of tolerant line (PDL-1) and wild accession (ILWL-137) showed restricted uptake of Na+ and Cl- due to thick layer of their epidermis and endodermis as compared to sensitive cultigen (L-4076). All the genotypes were scanned using SSR markers for genetic diversity, which generated high polymorphism. On the basis of cluster analysis and population structure the contrasting genotypes were grouped into different classes. These markers may further be tested to explore their potential in marker-assisted selection.

Evaluation of water binding, seed coat permeability and germination characteristics of wheat seeds equilibrated at different relative humidities.

PubMed

Chatterjee, Nabamita; Nagarajan, Shantha

2006-08-01

The relative binding of seed water and seed coat membrane stability were measured in two contrasting wheat (Triticum aestivum L) varieties, HDR 77 (drought-tolerant) and HD 2009 (susceptible) using seed water sorption isotherms, electrical conductivity (EC) of leachates and desorption-absorption isotherms. Analysis of sorption isotherm at 25 degrees C showed that the seeds of HDR 77 had significantly higher number of strong binding sites, with correspondingly greater amount of seed water as strongly bound water, as compared to HD 2009. Total number of binding sites was also higher in HDR 77 than HD 2009, which explained the better desiccation tolerance and higher capacity to bind water in seeds of HDR 77. EC of seed leachate in both varieties did not change with respect to change in equilibrium relative humidity (RII), indicating the general seed coat membrane stability of wheat seeds. However, absolute conductivity values were higher for HD 2009. showing its relatively porous seed coat membrane. Significantly lower area enclosed by the desorption-absorption isotherm loop in HDR 77, as compared to HD 2009 also indicated the greater membrane integrity of HDR 77. Germination and seedling vigour of HD 2009 were reduced when equilibrated over very low and very high RH. In contrast, germination and vigour in HDR 77 were maintained high, except at very high RH, indicating again its desiccation tolerance. Thus, the study demonstrated the relative drought tolerance of HDR 77, on the basis of seed water-binding characteristics and seed membrane stability. Seed membrane stability as measured by seed leachate conductivity or as area under dehydration-rehydration loop may be used as a preliminary screening test for drought tolerance in wheat.

Tolerance and resistance of invasive and native Eupatorium species to generalist herbivore insects

NASA Astrophysics Data System (ADS)

Wang, Rui-Fang; Feng, Yu-Long

2016-11-01

Invasive plants are exotic species that escape control by native specialist enemies. However, exotic plants may still be attacked by locally occurring generalist enemies, which can influence the dynamics of biological invasions. If invasive plants have greater defensive (resistance and tolerance) capabilities than indigenous plants, they may experience less damage from native herbivores. In the present study, we tested this prediction using the invasive plant Eupatorium adenophorum and two native congeners under simulated defoliation and generalist herbivore insect (Helicoverpa armigera and Spodoptera litura) treatments. E. adenophorum was less susceptible and compensated more quickly to damages in biomass production from both treatments compared to its two congeners, exhibiting greater herbivore tolerance. This strong tolerance to damage was associated with greater resource allocation to aboveground structures, leading to a higher leaf area ratio and a lower root: crown mass ratio than those of its native congeners. E. adenophorum also displayed a higher resistance index (which integrates acid detergent fiber, nitrogen content, carbon/nitrogen ratio, leaf mass per area, toughness, and trichome density) than its two congeners. Thus, H. armigera and S. litura performed poorly on E. adenophorum, with less leaf damage, a lengthened insect developmental duration, and decreased pupating: molting ratios compared to those of the native congeners. Strong tolerance and resistance traits may facilitate the successful invasion of E. adenophorum in China and may decrease the efficacy of leaf-feeding biocontrol agents. Our results highlight both the need for further research on defensive traits and their role in the invasiveness and biological control of exotic plants, and suggest that biocontrol of E. adenophorum in China would require damage to the plant far in excess of current levels.

The benzomorphan-based LP1 ligand is a suitable MOR/DOR agonist for chronic pain treatment.

PubMed

Pasquinucci, Lorella; Parenti, Carmela; Turnaturi, Rita; Aricò, Giuseppina; Marrazzo, Agostino; Prezzavento, Orazio; Ronsisvalle, Simone; Georgoussi, Zafiroula; Fourla, Danai-Dionysia; Scoto, Giovanna M; Ronsisvalle, Giuseppe

2012-01-02

Powerful analgesics relieve pain primarily through activating mu opioid receptor (MOR), but the long-term use of MOR agonists, such as morphine, is limited by the rapid development of tolerance. Recently, it has been observed that simultaneous stimulation of the delta opioid receptor (DOR) and MOR limits the incidence of tolerance induced by MOR agonists. 3-[(2R,6R,11R)-8-hydroxy-6,11-dimethyl-1,4,5,6-tetrahydro-2,6-methano-3-benzazocin-3(2H)-yl]-N-phenylpropanamide (LP1) is a centrally acting agent with antinociceptive activity comparable to morphine and is able to bind and activate MOR and DOR. The aim of this work was to evaluate and compare the induction of tolerance to antinociceptive effects from treatment with LP1 and morphine. Here, we evaluated the pharmacological effects of LP1 administered at a dose of 4 mg/kg subcutaneously (s.c.) twice per day for 9 days to male Sprague-Dawley rats. In addition, the LP1 mechanism of action was assessed by measurement of LP1-induced [(35)S]GTPγS binding to the MOR and DOR. Data obtained from the radiant heat tail flick test showed that LP1 maintained its antinociceptive profile until the ninth day, while tolerance to morphine (10mg/kg s.c. twice per day) was observed on day 3. Moreover, LP1 significantly enhanced [(35)S]GTPγS binding in the membranes of HEK293 cells expressing either the MOR or the DOR. LP1 is a novel analgesic agent for chronic pain treatment, and its low tolerance-inducing capability may be correlated with its ability to bind both the MOR and DOR. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparison of desiccation tolerance among Listeria monocytogenes, Escherichia coli O157:H7, Salmonella enterica, and Cronobacter sakazakii in powdered infant formula.

PubMed

Koseki, Shigenobu; Nakamura, Nobutaka; Shiina, Takeo

2015-01-01

Bacterial pathogens such as Listeria monocytogenes, Escherichia coli O157:H7, Salmonella enterica, and Cronobacter sakazakii have demonstrated long-term survival in/on dry or low-water activity (aw) foods. However, there have been few comparative studies on the desiccation tolerance among these bacterial pathogens separately in a same food matrix. In the present study, the survival kinetics of the four bacterial pathogens separately inoculated onto powdered infant formula as a model low-aw food was compared during storage at 5, 22, and 35°C. No significant differences in the survival kinetics between E. coli O157:H7 and L. monocytogenes were observed. Salmonella showed significantly higher desiccation tolerance than these pathogens, and C. sakazakii demonstrated significantly higher desiccation tolerance than all other three bacteria studied. Thus, the desiccation tolerance was represented as C. sakazakii > Salmonella > E. coli O157:H7 = L. monocytogenes. The survival kinetics of each bacterium was mathematically analyzed, and the observed kinetics was successfully described using the Weibull model. To evaluate the variability of the inactivation kinetics of the tested bacterial pathogens, the Monte Carlo simulation was performed using assumed probability distribution of the estimated fitted parameters. The simulation results showed that the storage temperature significantly influenced survival of each bacterium under the dry environment, where the bacterial inactivation became faster with increasing storage temperature. Furthermore, the fitted rate and shape parameters of the Weibull model were successfully modelled as a function of temperature. The numerical simulation of the bacterial inactivation was realized using the functions of the parameters under arbitrary fluctuating temperature conditions.

Low Velocity Impact Damage to Carbon/Epoxy Laminates

NASA Technical Reports Server (NTRS)

Nettles, Alan T.

2011-01-01

Impact damage tends to be more detrimental to a laminate's compression strength as compared to tensile strength. Proper use of Non Destructive Evaluation (NDE) Techniques can remove conservatism (weight) from many structures. Test largest components economically feasible as coupons. If damage tolerance is a driver, then consider different resin systems. Do not use a single knockdown factor to account for damage.

Multi-parameter comparison of a standardized mixed meal tolerance test in healthy and type 2 diabetic subjects: the PhenFlex challenge.

PubMed

Wopereis, Suzan; Stroeve, Johanna H M; Stafleu, Annette; Bakker, Gertruud C M; Burggraaf, Jacobus; van Erk, Marjan J; Pellis, Linette; Boessen, Ruud; Kardinaal, Alwine A F; van Ommen, Ben

2017-01-01

A key feature of metabolic health is the ability to adapt upon dietary perturbations. Recently, it was shown that metabolic challenge tests in combination with the new generation biomarkers allow the simultaneous quantification of major metabolic health processes. Currently, applied challenge tests are largely non-standardized. A systematic review defined an optimal nutritional challenge test, the "PhenFlex test" (PFT). This study aimed to prove that PFT modulates all relevant processes governing metabolic health thereby allowing to distinguish subjects with different metabolic health status. Therefore, 20 healthy and 20 type 2 diabetic (T2D) male subjects were challenged both by PFT and oral glucose tolerance test (OGTT). During the 8-h response time course, 132 parameters were quantified that report on 26 metabolic processes distributed over 7 organs (gut, liver, adipose, pancreas, vasculature, muscle, kidney) and systemic stress. In healthy subjects, 110 of the 132 parameters showed a time course response. Patients with T2D showed 18 parameters to be significantly different after overnight fasting compared to healthy subjects, while 58 parameters were different in the post-challenge time course after the PFT. This demonstrates the added value of PFT in distinguishing subjects with different health status. The OGTT and PFT response was highly comparable for glucose metabolism as identical amounts of glucose were present in both challenge tests. Yet the PFT reports on additional processes, including vasculature, systemic stress, and metabolic flexibility. The PFT enables the quantification of all relevant metabolic processes involved in maintaining or regaining homeostasis of metabolic health. Studying both healthy subjects and subjects with impaired metabolic health showed that the PFT revealed new processes laying underneath health. This study provides the first evidence towards adopting the PFT as gold standard in nutrition research.

Comparative Analysis of Disruption Tolerant Network Routing Simulations in the One and NS-3

DTIC Science & Technology

2017-12-01

real systems with less work compared to ns-2. In order to meet the design goals of ns-3, the entire code structure changed to a modular design . As a...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS COMPARATIVE ANALYSIS OF DISRUPTION TOLERANT NETWORK ROUTING SIMULATIONS IN THE ONE AND NS-3...Thesis 03-23-2016 to 12-15-2017 4. TITLE AND SUBTITLE COMPARATIVE ANALYSIS OF DISRUPTION TOLERANT NETWORK ROUTING SIMULATIONS IN THE ONE AND NS-3 5

Input Correlations for Irradiation Creep of FeCrAl and SiC Based on In-Pile Halden Test Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Terrani, K. A.; Karlsen, T. M.; Yamamoto, Yukinori

2016-05-01

Swelling and creep behavior of wrought FeCrAl alloys and CVD-SiC, two candidate accident tolerant fuel cladding materials, are being examined using in-pile tests at the Halden reactor. The outcome of these tests are material property correlations that are inputs into fuel performance analysis tools. The results are discussed and compared with what is available in literature from irradiation experiments in other reactors or out-of-pile tests. Specific recommendation on what correlations should be used for swelling, thermal, and irradiation creep for each material are provided in this document.

Impact of Pesticide Resistance on Toxicity and Tolerance of Hostplant Phytochemicals in Amyelois Transitella (Lepidoptera: Pyralidae)

PubMed Central

Bagchi, Vikram A.; Siegel, Joel P.; Demkovich, Mark R.; Zehr, Luke N.; Berenbaum, May R.

2016-01-01

For some polyphagous insects, adaptation to phytochemically novel plants can enhance resistance to certain pesticides, but whether pesticide resistance expands tolerance to phytochemicals has not been examined. Amyelois transitella Walker (navel orangeworm) is an important polyphagous pest of nut and fruit tree crops in California. Bifenthrin resistance, partially attributable to enhanced cytochrome P450 (P450)-mediated detoxification, has been reported in an almond-infesting population exposed to intense pesticide selection. We compared the toxicity of bifenthrin and three phytochemicals–chlorogenic acid, and the furanocoumarins xanthotoxin and bergapten–to three strains of A. transitella: pyrethroid-resistant R347 (maintained in the laboratory for ∼10 generations), fig-derived FIG (in the laboratory for ∼25 generations), and CPQ–a laboratory strain derived from almonds ∼40 years ago). Whereas both Ficus carica (fig) and Prunus dulcis (almond) contain chlorogenic acid, furanocoumarins occur only in figs. Both R347 and FIG exhibited 2-fold greater resistance to the three phytochemicals compared with CPQ; surprisingly, bifenthrin resistance was highest in FIG. Piperonyl butoxide, a P450 synergist, increased toxicity of all three phytochemicals only in CPQ, implicating alternate tolerance mechanisms in R347 and FIG. To test the ability of the strains to utilize novel hostplants directly, we compared survival on diets containing seeds of Wisteria sinensis and Prosopis pallida, two non-host Fabaceae species; survival of FIG was highest and survival of R347 was lowest. Our results suggest that, while P450-mediated pesticide resistance enhances tolerance of certain phytochemicals in this species, it is only one of multiple biochemical adaptations associated with acquiring novel hostplants. PMID:27620560

Impact of Pesticide Resistance on Toxicity and Tolerance of Hostplant Phytochemicals in Amyelois Transitella (Lepidoptera: Pyralidae).

PubMed

Bagchi, Vikram A; Siegel, Joel P; Demkovich, Mark R; Zehr, Luke N; Berenbaum, May R

2016-01-01

For some polyphagous insects, adaptation to phytochemically novel plants can enhance resistance to certain pesticides, but whether pesticide resistance expands tolerance to phytochemicals has not been examined. Amyelois transitella Walker (navel orangeworm) is an important polyphagous pest of nut and fruit tree crops in California. Bifenthrin resistance, partially attributable to enhanced cytochrome P450 (P450)-mediated detoxification, has been reported in an almond-infesting population exposed to intense pesticide selection. We compared the toxicity of bifenthrin and three phytochemicals-chlorogenic acid, and the furanocoumarins xanthotoxin and bergapten-to three strains of A. transitella: pyrethroid-resistant R347 (maintained in the laboratory for ∼10 generations), fig-derived FIG (in the laboratory for ∼25 generations), and CPQ-a laboratory strain derived from almonds ∼40 years ago). Whereas both Ficus carica (fig) and Prunus dulcis (almond) contain chlorogenic acid, furanocoumarins occur only in figs. Both R347 and FIG exhibited 2-fold greater resistance to the three phytochemicals compared with CPQ; surprisingly, bifenthrin resistance was highest in FIG. Piperonyl butoxide, a P450 synergist, increased toxicity of all three phytochemicals only in CPQ, implicating alternate tolerance mechanisms in R347 and FIG. To test the ability of the strains to utilize novel hostplants directly, we compared survival on diets containing seeds of Wisteria sinensis and Prosopis pallida, two non-host Fabaceae species; survival of FIG was highest and survival of R347 was lowest. Our results suggest that, while P450-mediated pesticide resistance enhances tolerance of certain phytochemicals in this species, it is only one of multiple biochemical adaptations associated with acquiring novel hostplants. © The Author 2016. Published by Oxford University Press on behalf of the Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparing passive angle-torque curves recorded simultaneously with a load cell versus an isokinetic dynamometer during dorsiflexion stretch tolerance assessments.

PubMed

Buckner, Samuel L; Jenkins, Nathaniel D M; Costa, Pablo B; Ryan, Eric D; Herda, Trent J; Cramer, Joel T

2015-05-01

The purpose of the present study was to compare the passive angle-torque curves and the passive stiffness (PS, N m °(-)(1)) values recorded simultaneously from a load cell versus an isokinetic dynamometer during dorsiflexion stretch tolerance assessments in vivo. Nine healthy men (mean ± SD age = 21.4 ± 1.6 years) completed stretch tolerance assessments on a custom-built apparatus where passive torque was measured simultaneously from an isokinetic dynamometer and a load cell. Passive torque values that corresponded with the last 10° of dorsiflexion, verified by surface electromyographic amplitude, were analyzed for each device (θ1, θ2, θ3, …, θ10). Passive torque values measured with the load cell were greater (p ≤ 0.05) than the dynamometer torque values for θ4 through θ10. There were more statistical differentiations among joint angles for passive torque measured by the load cell, and the load cell measured a greater (p ≤ 0.01) increase in passive torque and PS than the isokinetic dynamometer. These findings suggested that when examining the angle-torque curves from passive dorsiflexion stretch tolerance tests, a load cell placed under the distal end of the foot may be more sensitive than the torque recorded from an isokinetic dynamometer. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

Effects of postnatal growth restriction and subsequent catch-up growth on neurodevelopment and glucose homeostasis in rats.

PubMed

Alexeev, Erica E; Lönnerdal, Bo; Griffin, Ian J

2015-06-05

There is increasing evidence that poor growth of preterm infants is a risk factor for poor long-term development, while the effects of early postnatal growth restriction are not well known. We utilized a rat model to examine the consequences of different patterns of postnatal growth and hypothesized that early growth failure leads to impaired development and insulin resistance. Rat pups were separated at birth into normal (N, n = 10) or restricted intake (R, n = 16) litters. At d11, R pups were re-randomized into litters of 6 (R-6), 10 (R-10) or 16 (R-16) pups/dam. N pups remained in litters of 10 pups/dam (N-10). Memory and learning were examined through T-maze test. Insulin sensitivity was measured by i.p. insulin tolerance test and glucose tolerance test. By d10, N pups weighed 20% more than R pups (p < 0.001). By d15, the R-6 group caught up to the N-10 group in weight, the R-10 group showed partial catch-up growth and the R-16 group showed no catch-up growth. All R groups showed poorer scores in developmental testing when compared with the N-10 group during T-Maze test (p < 0.05). Although R-16 were more insulin sensitive than R-6 and R-10, all R groups were more glucose tolerant than N-10. In rats, differences in postnatal growth restriction leads to changes in development and in insulin sensitivity. These results may contribute to better elucidating the causes of poor developmental outcomes in human preterm infants.

Application of damage tolerance methodology in certification of the Piaggio P-180 Avanti

NASA Technical Reports Server (NTRS)

Johnson, Jerry

1992-01-01

The Piaggio P-180 Avanti, a twin pusher-prop engine nine-passenger business aircraft was certified in 1990, to the requirements of FAR Part 23 and Associated Special Conditions for Composite Structure. Certification included the application of a damage tolerant methodology to the design of the composite forward wing and empennage (vertical fin, horizontal stabilizer, tailcone, and rudder) structure. This methodology included an extensive analytical evaluation coupled with sub-component and full-scale testing of the structure. The work from the Damage Tolerance Analysis Assessment was incorporated into the full-scale testing. Damage representing hazards such as dropped tools, ground equipment, handling, and runway debris, was applied to the test articles. Additional substantiation included allowing manufacturing discrepancies to exist unrepaired on the full-scale articles and simulated bondline failures in critical elements. The importance of full-scale testing in the critical environmental conditions and the application of critical damage are addressed. The implication of damage tolerance on static and fatigue testing is discussed. Good correlation between finite element solutions and experimental test data was observed.

Fludrocortisone does not prevent orthostatic hypotension in astronauts after spaceflight.

PubMed

Shi, Shang-Jin; South, Donna A; Meck, Janice V

2004-03-01

During stand/tilt tests after spaceflight, 20% of astronauts experience orthostatic hypotension and presyncope. Spaceflight-induced hypovolemia is a contributing factor. Fludrocortisone, a synthetic mineralocorticoid, has been shown to increase plasma volume and orthostatic tolerance in Earth-bound patients. The efficacy of fludrocortisone as a treatment for postflight hypovolemia and orthostatic hypotension in astronauts has not been studied. Our purpose was to test the hypothesis that astronauts who ingest fludrocortisone prior to landing would have less loss of plasma volume and greater orthostatic tolerance than astronauts who do not ingest fludrocortisone. There were 25 male astronauts who were randomized into 2 groups: placebo (n = 18) and fludrocortisone (n = 7), and participated in stand tests 10 d before launch and 2-4 h after landing. Subjects took either 0.3 mg fludrocortisone or placebo orally 7 h prior to landing. Supine plasma and red cell volumes, supine and standing HR, arterial pressure, aortic outflow, and plasma norepinephrine and epinephrine were measured. On landing day, 2 of 18 in the placebo group and 1 of 7 in the fludrocortisone group became presyncopal (chi2 = 0.015, p = 0.90). Plasma volumes were significantly decreased after flight in the placebo group, but not in the fludrocortisone group. During postflight stand tests, standing plasma norepinephrine was significantly less in the fludrocortisone group compared with the placebo group. Treatment with a single dose of fludrocortisone results in protection of plasma volume but no protection of orthostatic tolerance. Fludrocortisone is not recommended as a countermeasure for spaceflight-induced orthostatic intolerance.

Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans

PubMed Central

Sagoo, Pervinder; Perucha, Esperanza; Sawitzki, Birgit; Tomiuk, Stefan; Stephens, David A.; Miqueu, Patrick; Chapman, Stephanie; Craciun, Ligia; Sergeant, Ruhena; Brouard, Sophie; Rovis, Flavia; Jimenez, Elvira; Ballow, Amany; Giral, Magali; Rebollo-Mesa, Irene; Le Moine, Alain; Braudeau, Cecile; Hilton, Rachel; Gerstmayer, Bernhard; Bourcier, Katarzyna; Sharif, Adnan; Krajewska, Magdalena; Lord, Graham M.; Roberts, Ian; Goldman, Michel; Wood, Kathryn J.; Newell, Kenneth; Seyfert-Margolis, Vicki; Warrens, Anthony N.; Janssen, Uwe; Volk, Hans-Dieter; Soulillou, Jean-Paul; Hernandez-Fuentes, Maria P.; Lechler, Robert I.

2010-01-01

Identifying transplant recipients in whom immunological tolerance is established or is developing would allow an individually tailored approach to their posttransplantation management. In this study, we aimed to develop reliable and reproducible in vitro assays capable of detecting tolerance in renal transplant recipients. Several biomarkers and bioassays were screened on a training set that included 11 operationally tolerant renal transplant recipients, recipient groups following different immunosuppressive regimes, recipients undergoing chronic rejection, and healthy controls. Highly predictive assays were repeated on an independent test set that included 24 tolerant renal transplant recipients. Tolerant patients displayed an expansion of peripheral blood B and NK lymphocytes, fewer activated CD4+ T cells, a lack of donor-specific antibodies, donor-specific hyporesponsiveness of CD4+ T cells, and a high ratio of forkhead box P3 to α-1,2-mannosidase gene expression. Microarray analysis further revealed in tolerant recipients a bias toward differential expression of B cell–related genes and their associated molecular pathways. By combining these indices of tolerance as a cross-platform biomarker signature, we were able to identify tolerant recipients in both the training set and the test set. This study provides an immunological profile of the tolerant state that, with further validation, should inform and shape drug-weaning protocols in renal transplant recipients. PMID:20501943

Differential expression of benzodiazepine anticonvulsant cross-tolerance according to time following flurazepam or diazepam treatment.

PubMed

Rosenberg, H C

1995-01-01

In previous studies in which the anti-pentylenetetrazol (PTZ) effect of benzodiazepines was used to measure tolerance, the results depended on the benzodiazepine used for chronic treatment as well as the benzodiazepine given acutely to test for tolerance. In this study, the time course of tolerance reversal was studied in rats given two treatments known to cause anticonvulsant tolerance, 1-week flurazepam (FZP), and 3-week diazepam (DZP). Neither treatment altered convulsive threshold for IV PTZ, but both treatments decreased the convulsive threshold for bicuculline. Withdrawing DZP, but not FZP, treatment resulted in a loss of body weight. Twelve hours after 1-week FZP treatment, all benzodiazepines were significantly less effective, showing tolerance. Forty-eight hours after the 1-week FZP treatment, tolerance was still observed with DZP, FZP, and zolpidem, but was no longer present with clonazepam or bretazenil. After the 3-week DZP treatment, rats were tolerant to all benzodiazepines tested at 12 h of withdrawal, but had lost tolerance to all the drugs except bretazenil by 48 h. The results suggest differences in the way these benzodiazepines interact with their receptors, allowing differential expression of tolerance, and that chronic DZP and FZP treatments affected interactions of the benzodiazepines with their receptors, but not in the same fashion.

Effect of Surgical Curve Correction on Exercise Tolerance and Physical Capacities in Patients of Severe Spinal Deformity.

PubMed

Patil, Prateek C; Rathod, Ashok K; Borde, Mandar; Singh, Vishwajeet; Singh, Hemant U

2016-12-01

Traditionally, surgical intervention for patients with a spinal deformity has been considered for cosmetic benefits, but surgical intervention can alter the lung physiology or volumes and in turn leads to increase in physical capacity and exercise tolerance. Therefore, we conducted this to determine whether a surgical correction would restore the lung physiology, physical capacity and exercise tolerance in patients with kyphoscoliosis. To evaluate the usage of six-minute walk test scores and modified Borg scores as tools/measures for exercise tolerance in patients with spinal deformity and to study the effects of surgical correction of spinal deformity on exercise tolerance with above parameters as the measures. Thirty patients with spinal deformity, who had undergone surgery for deformity correction, were evaluated. All patients were investigated pre-operatively with x-rays of the spine (anteroposterior and lateral views). Clinical tests like breath holding time (after full inspiration) in number of seconds, modified Borg scores, six-minute walk test scores (heart rate, respiratory rate, maximum distance walked); were recorded as measures of exercise tolerance. The patients were followed up on the first, third, sixth and twelfth month post-operatively and tested clinically for breath holding time, modified Borg scores, six-minute walk test scores (heart rate, respiratory rate, maximum distance walked) and x-rays of the spine (anteroposterior and lateral views). In our study, breath holding time (p-value = 0.001) and modified Borg scores (p-value = 0.012) showed a significant improvement at 12 months post-operatively. We noted similar findings with heart rate, respiratory rate and maximum distance walked after a six-minute walk test. Improvements were noted in all the parameters, especially in the group of patients with greater than 60 degrees of cobb angle. However, the differences between the two groups (pre-operative cobb angle less than 60 degrees and pre-operative cobb angle more than 60 degrees) were not significant. The results were analysed and tested for significance using Student's t-test (paired and unpaired as appropriate) and Wilcoxon signed rank test. Surgical correction in cases of spinal deformity improves the cosmetic appearance and balance in the patients. Favourable results of surgical intervention were found in exercise tolerance with improvements in modified Borg scores, six-minute walk test results and breath holding time. The above parameters appear to be good tools for the assessment of physical capacity and exercise tolerance in patients with spinal deformity.

Nutritional equivalency evaluation of transgenic maize grain from event DP-O9814O-6 and transgenic soybeans containing event DP-356O43-5: laying hen performance and egg quality measures.

PubMed

McNaughton, J; Roberts, M; Rice, D; Smith, B; Hinds, M; Delaney, B; Iiams, C; Sauber, T

2011-02-01

The objective of this study was to compare the nutritional performance of laying hens fed maize grain from event DP-Ø9814Ø-6 (98140; gat4621 and zm-hra genes) and processed soybean meal from soybeans containing event DP-356Ø43-5 (356043; gat4601 and gm-hra genes), individually or in combination, with the performance of hens fed diets containing nontransgenic maize and soybean meal. Healthy pullets (n = 216) placed in cages (3 hens/cage) were randomly assigned to 9 dietary treatments (8 cages/treatment): nontransgenic controls 1, 2, and 3 (comparable genetic background controls for 98140, 356043, and 98140 + 356043, respectively); reference 1, reference 2, and reference 3 (commercially available nontransgenic maize-soybean meal sources); and 98140 (test 1), 356043 (test 2), and 98140 + 356043 (test 3). The experiment was divided into three 4-wk phases (24 to 28 wk, 28 to 32 wk, and 32 to 36 wk of age), during which time hens were fed mash diets. Performance (BW, feed intake, and egg production) and egg quality data were collected. Data were analyzed using a mixed model ANOVA; differences between the control and respective test group means were considered significant at P < 0.05. Data generated from the reference groups were used only in the estimation of experimental variability and in generating the tolerance interval. Body weight and BW gain, egg production, and production efficiency for hens fed the test diets were similar to the respective values for hens fed the corresponding control diets. Haugh unit measures and egg component weights were similar between the respective test and control groups, and no differences were observed in quality grades or crack measures. All observed values of the control and test groups were within the calculated tolerance intervals. This research indicates that the performance and egg quality of hens fed diets containing 98140 maize grain, 356043 soybean meal, or a combination of the 2 was comparable with that of hens fed diets formulated with nontransgenic maize grain or soybean meal control diets with comparable genetic backgrounds.

40 CFR Table E-2 to Subpart E of... - Spectral Energy Distribution and Permitted Tolerance for Conducting Radiative Tests

Code of Federal Regulations, 2010 CFR

2010-07-01

... Permitted Tolerance for Conducting Radiative Tests E Table E-2 to Subpart E of Part 53 Protection of... Reference Methods and Class I and Class II Equivalent Methods for PM2.5 or PM10â2.5 Pt. 53, Subpt. E, Table E-2 Table E-2 to Subpart E of Part 53—Spectral Energy Distribution and Permitted Tolerance for...

Optimal Design and Damage Tolerance Verification of an Isogrid Structure for Helicopter Application

NASA Technical Reports Server (NTRS)

Baker, Donald J.; Fudge, Jack; Ambur, Damodar R.; Kassapoglou, Christos

2003-01-01

A composite isogrid panel design for application to a rotorcraft fuselage is presented. An optimum panel design for the lower fuselage of the rotorcraft that is subjected to combined in-plane compression and shear loads was generated using a design tool that utilizes a smeared-stiffener theory in conjunction with a genetic algorithm. A design feature was introduced along the edges of the panel that facilitates introduction of loads into the isogrid panel without producing undesirable local bending gradients. A low-cost manufacturing method for the isogrid panel that incorporates these design details is also presented. Axial compression tests were conducted on the undamaged and low-speed impact damaged panels to demonstrate the damage tolerance of this isogrid panel. A combined loading test fixture was designed and utilized that allowed simultaneous application of compression and shear loads to the test specimen. Results from finite element analyses are presented for the isogrid panel designs and these results are compared with experimental results. This study illustrates the isogrid concept to be a viable candidate for application to the helicopter lower fuselage structure.

Clinical characteristics of people experiencing biochemical hypoglycaemia during an oral glucose tolerance test: cross-sectional analyses from a UK multi-ethnic population.

PubMed

Parekh, S; Bodicoat, D H; Brady, E; Webb, D; Mani, H; Mostafa, S; Levy, M J; Khunti, K; Davies, M J

2014-06-01

People who experience biochemical hypoglycaemia during an oral glucose tolerance test (OGTT) may be insulin resistant, but this has not been investigated robustly, therefore we examined this in a population-based multi-ethnic UK study. Cross-sectional data from 6478 diabetes-free participants (849 with fasting insulin data available) who had an OGTT in the ADDITION-Leicester screening study (2005-2009) were analysed. People with biochemical hypoglycaemia (2-h glucose <3.3mmol/l) were compared with people with normal glucose tolerance (NGT) or impaired glucose regulation (IGR) using regression methods. 359 participants (5.5%) had biochemical hypoglycaemia, 1079 (16.7%) IGR and 5040 (77.8%) NGT. Biochemical hypoglycaemia was associated with younger age (P<0.01), white European ethnicity (P<0.001), higher HDL cholesterol (P<0.01), higher insulin sensitivity (P<0.05), and lower body mass index (P<0.001), blood pressure (P<0.01), fasting glucose (P<0.001), HbA1C (P<0.01), and triglycerides (P<0.01) compared with NGT and IGR separately in both unadjusted and adjusted (age, sex, ethnicity, body mass index, smoking status) models. Biochemical hypoglycaemia during an OGTT in the absence of diabetes or IGR was not associated with insulin resistance, but instead appeared to be associated with more favourable glycaemic risk profiles than IGR and NGT. Thus, clinicians may not need to intervene due to biochemical hypoglycaemia on a 2-h OGTT. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Creatine Supplementation and Anterior Compartment Pressure During Exercise in the Heat in Dehydrated Men

PubMed Central

Hile, Amy M; Anderson, Jeffrey M; Fiala, Kelly A; Stevenson, J. Herb; Casa, Douglas J; Maresh, Carl M

2006-01-01

Context: Theoretically, the risk of compartment syndrome is increased during creatine monohydrate (CrM) supplementation because of intracellular fluid retention in muscle cells and the overall increased size of the muscle tissue. Whether this change in intracellular fluid is associated with an increase in anterior compartment pressure in the lower leg when subjects are under thermal stress is unknown. Objective: To assess the influence of CrM on the resting and postexercise anterior compartment pressure of the lower leg in mildly to moderately dehydrated males exercising in the heat. Design: Double-blind, randomized, crossover design. Setting: Human Performance Laboratory. Patients or Other Participants: Eleven well-trained, non– heat-acclimated, healthy males (age = 22 ± 2 years, height = 181.1 ± 7 cm, mass = 78.4 ± 4.2 kg, V̇o2max = 50.5 ± 3.4 mL·kg−1·min−1). Intervention(s): Subjects were supplemented with 21.6 g/d of CrM or placebo for 7 days. On day 7, they performed 2 hours of submaximal exercise, alternating 30 minutes of walking with 30 minutes of cycling in the heat, resulting in approximately 2% dehydration. This was followed by an 80-minute heat tolerance test (temperature = 33.5 ± 0.5°C, humidity = 41.0 ± 12%), which included 12 repetitions of a 3-minute walk (pace = 4.0 ± 0.1 miles/h, intensity = 37.1 ± 6.1% V̇o2max) alternating with a 1-minute, high-intensity run (pace = 11.8 ± 0.4 miles/h, intensity = 115.0 ± 5.6% V̇o2max), resulting in an additional 2% decrease in body weight. Main Outcome Measures: Before supplementation and on day 7 of supplementation, anterior compartment pressure was measured at rest, after dehydration, and at 1, 3, 5, 10, 15, and 60 minutes after the heat tolerance test. Analysis of variance with repeated measures was calculated to compare differences within the trials and time points and to identify any interaction between trial and time. Results: The CrM intake was associated with an increase in body weight (P < .05). A moderate effect size was noted for compartment pressures between the trials for the differences between predehydration and postdehydration (η2 = 0.414). This effect diminished substantially by 3 minutes after the heat tolerance test. Compared with the placebo trial, the change in anterior compartment pressure from rest to dehydration was greater, as was the change from rest to 1 minute after the heat tolerance test (P < .05) during the CrM trial. Conclusions: A 7-day loading dose of CrM increased anterior compartment pressures after dehydration and immediately after the heat tolerance tests, but the changes did not induce symptoms and the pressure changes were transient. PMID:16619092

Bioavailability of a Sustained Release Formulation of Curcumin

PubMed Central

Madhavi, Doddabele; Kagan, Daniel

2014-01-01

Context Curcumin has a number of beneficial effects, such as functioning as a potent antioxidant,1 anti-inflammatory, 2 and anticancer agent. Because of its poor oral bioavailability, very high oral doses and repeated dosing have been used to obtain effective plasma levels, with mixed results. High doses of curcumin may cause gastric disturbance, often resulting in poor patient compliance. Objective The objective of this study was to compare the relative bioavailability of MicroActive Curcumin—an advanced, micronized formulation of curcumin that is 25% curcuminoids in a sustained release matrix—with that of an unformulated, 95% pure curcumin powder. Design A dissolution study compared the solubility of the formulated and the unformulated curcumin. The research team also performed a single-dose, 12-h, crossover uptake study with 10 participants and a high-dose tolerability and accumulation study with 3 participants, comparing the 2 forms of curcumin. Setting The study was done in MAZE Laboratories (Purchase, NY, USA). Participants Ten healthy male and female volunteers, aged 21–66 y, took part in the single-dose study. Three participants, 2 female and 1 male aged 40–55 y, took part in the tolerability and accumulation study. The participants were people from the community. Intervention For the dissolution study, the research team filled hard gelatin capsules with unformulated 95% curcumin powder and the MicroActive Curcumin powder to the equivalent of 25 mg curcuminoids. For the single-dose study, participants received 500 mg of curcumin in 2 forms. MicroActive Curcumin capsules were administered after breakfast, and blood samples were drawn at 1, 2, 4, 8, and 12 h postdose. After a 7-d washout period, the protocol was repeated for unformulated, 95% curcumin powder capsules. For the tolerability study, the unformulated, 95% curcumin powder was given at a dose that provided 2 g of curcumin for 7 d followed by 5 g of curcumin for an additional 7 d. After a washout period of 14 d, the protocol was repeated with MicroActive Curcumin. Participants then continued to take the MicroActive Curcumin for >3 mo. Outcome Measures For the dissolution study, the curcumin was quantified at room temperature using reverse-phase, high-performance liquid chromatography (HPLC) with a Phenomenex Luna column (150 × 4.6 mm, 5 μm) (Phenomenex Inc, Torrance, CA, USA). For the single-dose and the tolerability studies, hydrolysis of conjugates and extraction of curcuminoids from the plasma were performed. The curcuminoids were quantified using reverse-phase HPLC with an ultraviolet-visible detector as described above. Results The dissolution study indicated that the sustained-release curcumin had greater dissolution for 12 h at all points tested, compared with the unformulated curcumin. Very little of the unformulated curcumin powder had been released at the end of the 12 h. The results of the single-dose uptake study indicated that the sustained-release formula was 9.7 × more bioavailable than the unformulated powder (P < .001, paired t test). Additionally, all participants showed uptake from the sustained-release formulation. That formulation also resulted in significant increases in the plasma demethoxylated curcuminoids, but the research team did not observe the same increases for the unformulated curcumin powder. The sustained-release formulation was well tolerated, without adverse effects in the high-dose tolerability study. Conclusions Formulation of micronized curcumin in a combination of surfactants, oils, and polymers improves the absorption of curcumin. In addition, the unique plasma demethylated curcuminoid profile may enhance the therapeutic effects of MicroActive Curcumin not observed with unformulated curcumin at moderate and well-tolerated doses. MicroActive Curcumin was well tolerated, without any adverse effects in a high-dose tolerability study. These properties have the potential to make high-dose curcumin supplementation more accessible through simplified incorporation into food and beverage preparations. PMID:26770097

Insulin resistance according to β-cell function in women with polycystic ovary syndrome and normal glucose tolerance.

PubMed

Song, Do Kyeong; Hong, Young Sun; Sung, Yeon-Ah; Lee, Hyejin

2017-01-01

Polycystic ovary syndrome (PCOS) is associated with insulin resistance (IR) and compensatory hyperinsulinemia. IR is recognized as a major risk factor for the development of type 2 diabetes mellitus. However, few studies have investigated IR in women with PCOS and normal glucose tolerance. The objective of this study was to evaluate IR and β-cell function in women with PCOS and normal glucose tolerance. Additionally, we sought to evaluate the usefulness of oral glucose tolerance test (OGTT)-derived IR indices in lean women with PCOS. We recruited 100 women with PCOS and normal glucose tolerance and 100 age- and BMI-matched women as controls. IR and insulin secretory indices, including the homeostasis-model assessment (HOMA)-IR, HOMA-M120, HOMA-F and the Stumvoll index, were calculated from an OGTT. Increased β-cell function was defined as>75th percentile for the HOMA-F in control women. Women with PCOS had higher values for post-load 2-hour glucose, fasting insulin, post-load 2-hour insulin, HOMA-IR, HOMA-M120, HOMA-F and lower values for the Stumvoll index than the controls (all Ps<0.05). Women with PCOS and increased β-cell function showed lower Stumvoll index values than the matched controls (P<0.05). The HOMA-F was significantly associated with the HOMA-M120 and Stumvoll index when adjusted for age and BMI in a multiple regression analysis (all Ps<0.05). The HOMA-M120 was positively correlated with triglycerides and free testosterone, and the Stumvoll index was negatively correlated with triglycerides and free testosterone in lean women with PCOS (all Ps<0.05). Women with PCOS and normal glucose tolerance showed higher IR than controls matched for age, BMI, and β-cell function. β-cell function was increased in women with PCOS when compared to the matched controls, but not when the lean subjects were compared to the matched controls separately. Therefore, early evaluation of IR in women with PCOS and normal glucose tolerance may be needed.

Insulin resistance according to β-cell function in women with polycystic ovary syndrome and normal glucose tolerance

PubMed Central

Hong, Young Sun; Sung, Yeon-Ah

2017-01-01

Background Polycystic ovary syndrome (PCOS) is associated with insulin resistance (IR) and compensatory hyperinsulinemia. IR is recognized as a major risk factor for the development of type 2 diabetes mellitus. However, few studies have investigated IR in women with PCOS and normal glucose tolerance. The objective of this study was to evaluate IR and β-cell function in women with PCOS and normal glucose tolerance. Additionally, we sought to evaluate the usefulness of oral glucose tolerance test (OGTT)-derived IR indices in lean women with PCOS. Methods We recruited 100 women with PCOS and normal glucose tolerance and 100 age- and BMI-matched women as controls. IR and insulin secretory indices, including the homeostasis-model assessment (HOMA)-IR, HOMA-M120, HOMA-F and the Stumvoll index, were calculated from an OGTT. Increased β-cell function was defined as>75th percentile for the HOMA-F in control women. Results Women with PCOS had higher values for post-load 2-hour glucose, fasting insulin, post-load 2-hour insulin, HOMA-IR, HOMA-M120, HOMA-F and lower values for the Stumvoll index than the controls (all Ps<0.05). Women with PCOS and increased β-cell function showed lower Stumvoll index values than the matched controls (P<0.05). The HOMA-F was significantly associated with the HOMA-M120 and Stumvoll index when adjusted for age and BMI in a multiple regression analysis (all Ps<0.05). The HOMA-M120 was positively correlated with triglycerides and free testosterone, and the Stumvoll index was negatively correlated with triglycerides and free testosterone in lean women with PCOS (all Ps<0.05). Conclusions Women with PCOS and normal glucose tolerance showed higher IR than controls matched for age, BMI, and β-cell function. β-cell function was increased in women with PCOS when compared to the matched controls, but not when the lean subjects were compared to the matched controls separately. Therefore, early evaluation of IR in women with PCOS and normal glucose tolerance may be needed. PMID:28542421

Is the Quantification of Antigen-Specific Basophil Activation a Useful Tool for Monitoring Oral Tolerance Induction in Children With Egg Allergy?

PubMed

Gamboa, P M; Garcia-Lirio, E; Gonzalez, C; Gonzalez, A; Martinez-Aranguren R M; Sanz María, L

2016-01-01

To assess modifications in baseline specific IgE- and anti-IgE- and antigen-specific-mediated basophil activation in egg-allergic children. The values were compared before and after the children completed specific oral tolerance induction (SOTI) with egg. We studied 28 egg-allergic children who completed SOTI with egg. The basophil activation test and specific IgE determinations with egg white, ovalbumin, and ovomucoid were performed in all 28 children. A decrease in antigen-specific activation with egg white, ovalbumin, and ovomucoid was observed only at the 2 lowest concentrations used (5 and 0.05 ng/mL). Baseline activation was higher in patients with multiple food allergies and in those who developed anaphylaxis during SOTI; this activation decreased in both groups after completion of SOTI. A significant decrease was also observed in specific IgE values for egg white, ovalbumin, and ovomucoid after tolerance induction. Food tolerance induction is a specific process for each food that can be mediated by immunologic changes such as a decrease in specific IgE values and in specific and spontaneous basophil activation.

Effects of methadone hydrochloride on the growth of organotypic cerebellar cultures prepared from methadone-tolerant and control rats.

PubMed

Willson, N J; Schneider, J F; Roizin, L; Fleiss, J F; Rivers, W; Demartini, J E

1976-11-01

Male and female Sprague-Dawley rats were given dl-methadone (5 mg/kg) for at least 3 months and then mated. The drug was continued throughout pregnancy and after delivery. The newly born pups were divided into two groups. One group was tested for in vivo methadone tolerance, while the animals in the othergroup were used to prepare organotypic cerebellar cultures. Various amounts of dl-methadone were added to the media of half of these cerebellum cultures. The effect of the drug in the medium was assessed by measuring explant outgrowth. Similar experiments were carried out with control animals. Statistical analysis of the data obtained in the in vivo portion of the experiment indicates that the pups of methadone-treated mothers tolerate methadone better than those of untreated mothers. The culture experiments revealed that the addition of methadone to the medium reduced explant outgrowth size and this was a dose-related effect. Also, there was significantly less outgrowth from explants prepared using pups of methadone-treated mothers as compared to the controls. There was no significant difference in the effect of methadone on the growth of cultures prepared from the methadone-tolerant and control animals.

Cellular mechanisms contributing to multiple stress tolerance in Saccharomyces cerevisiae strains with potential use in high-temperature ethanol fermentation.

PubMed

Kitichantaropas, Yasin; Boonchird, Chuenchit; Sugiyama, Minetaka; Kaneko, Yoshinobu; Harashima, Satoshi; Auesukaree, Choowong

2016-12-01

High-temperature ethanol fermentation has several benefits including a reduction in cooling cost, minimizing risk of bacterial contamination, and enabling simultaneous saccharification and fermentation. To achieve the efficient ethanol fermentation at high temperature, yeast strain that tolerates to not only high temperature but also the other stresses present during fermentation, e.g., ethanol, osmotic, and oxidative stresses, is indispensable. The C3253, C3751, and C4377 Saccharomyces cerevisiae strains, which have been previously isolated as thermotolerant yeasts, were found to be multiple stress-tolerant. In these strains, continuous expression of heat shock protein genes and intracellular trehalose accumulation were induced in response to stresses causing protein denaturation. Compared to the control strains, these multiple stress-tolerant strains displayed low intracellular reactive oxygen species levels and effective cell wall remodeling upon exposures to almost all stresses tested. In response to simultaneous multi-stress mimicking fermentation stress, cell wall remodeling and redox homeostasis seem to be the primary mechanisms required for protection against cell damage. Moreover, these strains showed better performances of ethanol production than the control strains at both optimal and high temperatures, suggesting their potential use in high-temperature ethanol fermentation.

Adaptation of Gammarus pulex to agricultural insecticide contamination in streams.

PubMed

Shahid, Naeem; Becker, Jeremias Martin; Krauss, Martin; Brack, Werner; Liess, Matthias

2018-04-15

Exposure to pesticides affects non-target aquatic communities, with substantial consequences on ecosystem services. Adaptation of exposed populations may reduce the effects of pesticides. However, it is not known under which conditions adaptation occurs when only a low toxic pressure from pesticides is present. Here, we show that Gammarus pulex, a dominant macroinvertebrate species in many agricultural streams, acquires increased tolerance to pesticides when recolonization from non-contaminated refuge areas is low. Populations in the field that were exposed to pesticides at concentrations several orders of magnitude below considerable acute effects showed almost 3-fold higher tolerance to the neonicotinoid insecticide clothianidin (mean EC 50 218μgL -1 ) compared with non-exposed populations (mean EC 50 81μgL -1 ). This tolerance of exposed populations increased from 2- to 4-fold with increasing distance to the next refuge area (0 to 10km). We conclude that the development of tolerance for non-target species may occur at very low concentrations, much below those affecting sensitive test organisms and also lower than those predicted to be safe by governmental risk assessment frameworks. Copyright © 2017 Elsevier B.V. All rights reserved.

Variation in waterlogging-triggered stomatal behavior contributes to changes in the cold acclimation process in prehardened Lolium perenne and Festuca pratensis.

PubMed

Jurczyk, Barbara; Pociecha, Ewa; Janowiak, Franciszek; Kabała, Dawid; Rapacz, Marcin

2016-12-01

According to predicted changes in climate, waterlogging events may occur more frequently in the future during autumn and winter at high latitudes of the Northern Hemisphere. If excess soil water coincides with the process of cold acclimation for plants, winter survival may potentially be affected. The effects of waterlogging during cold acclimation on stomatal aperture, relative water content, photochemical activity of photosystem II, freezing tolerance and plant regrowth after freezing were compared for two prehardened overwintering forage grasses, Lolium perenne and Festuca pratensis. The experiment was performed to test the hypothesis that changes in photochemical activity initiated by waterlogging-triggered modifications in the stomatal aperture contribute to changes in freezing tolerance. Principal component analysis showed that waterlogging activated different adaptive strategies in the two species studied. The increased freezing tolerance of F. pratensis was associated with increased photochemical activity connected with stomatal opening, whereas freezing tolerance of L. perenne was associated with a decrease in stomatal aperture. In conclusion, waterlogging-triggered stomatal behavior contributed to the efficiency of the cold acclimation process in L. perenne and F. pratensis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Does selection on increased cold tolerance in the adult stage confer resistance throughout development?

PubMed

Dierks, A; Kölzow, N; Franke, K; Fischer, K

2012-08-01

Artificial selection is a powerful approach to unravel constraints on genetic adaptation. Although it has been frequently used to reveal genetic trade-offs among different fitness-related traits, only a few studies have targeted genetic correlations across developmental stages. Here, we test whether selection on increased cold tolerance in the adult stage increases cold resistance throughout ontogeny in the butterfly Bicyclus anynana. We used lines selected for decreased chill-coma recovery time and corresponding controls, which had originally been set up from three levels of inbreeding (outbred control, one or two full-sib matings). Four generations after having terminated selection, a response to selection was found in 1-day-old butterflies (the age at which selection took place). Older adults showed a very similar although weaker response. Nevertheless, cold resistance did not increase in either egg, larval or pupal stage in the selection lines but was even lower compared to control lines for eggs and young larvae. These findings suggest a cost of increased adult cold tolerance, presumably reducing resource availability for offspring provisioning and thereby stress tolerance during development, which may substantially affect evolutionary trajectories. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

PtRu nanoparticles embedded in nitrogen doped carbon with highly stable CO tolerance and durability

NASA Astrophysics Data System (ADS)

Ling, Ying; Yang, Zehui; Yang, Jun; Zhang, Yunfeng; Zhang, Quan; Yu, Xinxin; Cai, Weiwei

2018-02-01

As is well known, the lower durability and sluggish methanol oxidation reaction (MOR) of PtRu alloy electrocatalyst blocks the commercialization of direct methanol fuel cells (DMFCs). Here, we design a new PtRu electrocatalyst, with highly stable CO tolerance and durability, in which the PtRu nanoparticles are embedded in nitrogen doped carbon layers derived from carbonization of poly(vinyl pyrrolidone). The newly fabricated electrocatalyst exhibits no loss in electrochemical surface area (ECSA) and MOR activity after potential cycling from 0.6-1.0 V versus reversible hydrogen electrode, while commercial CB/PtRu retains only 50% of its initial ECSA. Meanwhile, due to the same protective layers, the Ru dissolution is decelerated, resulting in stable CO tolerance. Methanol oxidation reaction (MOR) testing indicates that the activity of newly fabricated electrocatalyst is two times higher than that of commercial CB/PtRu, and the fuel cell performance of the embedded PtRu electrocatalyst was comparable to that of commercial CB/PtRu. The embedded PtRu electrocatalyst is applicable in real DMFC operation. This study offers important and useful information for the design and fabrication of durable and CO tolerant electrocatalysts.

A new model for low-dose food challenge in children with allergy to milk or egg.

PubMed

Devenney, Irene; Norrman, Gunilla; Oldaeus, Göran; Strömberg, Leif; Fälth-Magnusson, Karin

2006-09-01

Atopic eczema and food allergy are common in early childhood. Children seem to gradually develop tolerance to milk and egg, and it is a relief for families when their child can tolerate small amounts of these basic foods, even if larger doses may still cause symptoms. To develop a model for low-dose oral food challenge, facilitating re-/introduction of milk or egg. In 39 children sensitized to milk and/or egg, we performed 52 challenges using a new standardized model for low-dose oral food challenge. The recipes were validated for blinding with sensorial tests. Four children challenged to milk had a positive challenge outcome. There were no significant differences with respect to family history, associated atopic manifestations, nutritional supply, eczema severity, or skin-prick test compared with the non-reacting children, but total and specific IgE values were significantly higher. All but two of the non-reacting children were able to introduce milk and egg into their diet without problems. We report recipes and a protocol to be used for standardized open and double-blind placebo-controlled low-dose food challenge in young children, enabling the introduction of small amounts of egg and milk into the diet during tolerance development.

Stress tolerances of nullmutants of function-unknown genes encoding menadione stress-responsive proteins in Aspergillus nidulans.

PubMed

Leiter, Éva; Bálint, Mihály; Miskei, Márton; Orosz, Erzsébet; Szabó, Zsuzsa; Pócsi, István

2016-07-01

A group of menadione stress-responsive function-unkown genes of Aspergillus nidulans (Locus IDs ANID_03987.1, ANID_06058.1, ANID_10219.1, and ANID_10260.1) was deleted and phenotypically characterized. Importantly, comparative and phylogenetic analyses of the tested A. nidulans genes and their orthologs shed light only on the presence of a TANGO2 domain with NRDE protein motif in the translated ANID_06058.1 gene but did not reveal any recognizable protein-encoding domains in other protein sequences. The gene deletion strains were subjected to oxidative, osmotic, and metal ion stress and, surprisingly, only the ΔANID_10219.1 mutant showed an increased sensitivity to 0.12 mmol l(-1) menadione sodium bisulfite. The gene deletions affected the stress sensitivities (tolerances) irregularly, for example, some strains grew more slowly when exposed to various oxidants and/or osmotic stress generating agents, meanwhile the ΔANID_10260.1 mutant possessed a wild-type tolerance to all stressors tested. Our results are in line with earlier studies demonstrating that the deletions of stress-responsive genes do not confer necessarily any stress-sensitivity phenotypes, which can be attributed to compensatory mechanisms based on other elements of the stress response system with overlapping functions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recent progress in NASA Langley Research Center textile reinforced composites program

NASA Technical Reports Server (NTRS)

Dexter, H. Benson; Harris, Charles E.; Johnston, Norman J.

1992-01-01

Research was conducted to explore the benefits of textile reinforced composites for transport aircraft primary structures. The objective is to develop and demonstrate the potential of affordable textile reinforced composite materials to meet design properties and damage tolerance requirements of advanced aircraft structural concepts. Some program elements include development of textile preforms, processing science, mechanics of materials, experimental characterization of materials, and development and evaluation of textile reinforced composite structural elements and subcomponents. Textile 3-D weaving, 3-D braiding, and knitting and/or stitching are being compared with conventional laminated tape processes for improved damage tolerance. Through-the-thickness reinforcements offer significant damage tolerance improvements. However, these gains must be weighted against potential loss in in-plane properties such as strength and stiffness. Analytical trade studies are underway to establish design guidelines for the application of textile material forms to meet specific loading requirements. Fabrication and testing of large structural parts are required to establish the potential of textile reinforced composite materials.

Longitudinal analysis of the effect of academic failure tolerance on academic achievement fluctuation in medical school students.

PubMed

Chae, Su Jin; Kim, Miran; Chang, Ki Hong

2016-03-01

Academic failure tolerance (AFT) is one of the important psychological concepts in education, but its applications in medical education are rare. Thus, the purpose of this study was to investigate the effect of academic failure tolerance on academic achievement fluctuation among medical school students using a longitudinal research design. The subjects were 43 medical students who responded to the AFT test. This study analyzed the longitudinal data of achievement scores up to the 2nd academic year (2012-2013) among students who were divided into academic achievement improvement and decline groups. Comparing the improvement and decline groups' mean academic achievement fluctuation scores demonstrated that behavior and preferred task difficulty showed high scores whereas feeling scores were lower in the improvement group (p<0.05). In the improvement group, despite the higher negative feeling scores during academic failure, the students favored the more difficult subjects and were more assiduous in their studies. This will form an important basis for enhancing academic achievement among medical students.

Metabolic differences between short children with GH peak levels in the lower normal range and healthy children of normal height.

PubMed

Tidblad, Anders; Gustafsson, Jan; Marcus, Claude; Ritzén, Martin; Ekström, Klas

2017-06-01

Severe growth hormone deficiency (GHD) leads to several metabolic effects in the body ranging from abnormal body composition to biochemical disturbances. However, less is known regarding these parameters in short children with GH peak levels in the lower normal range during provocation tests. Our aim was to study the metabolic profile of this group and compare it with that of healthy children of normal height. Thirty-five pre-pubertal short children (<-2.5 SDS) aged between 7 and 10years, with peak levels of GH between 7 and 14μg/L in an arginine insulin tolerance test (AITT), were compared with twelve age- and sex-matched children of normal height. The metabolic profile of the subjects was analysed by blood samples, DEXA, frequently sampled intravenous glucose tolerance test, microdialysis and stable isotope examinations of rates of glucose production and lipolysis. There were no overall significant metabolic differences between the groups. However, in the subgroup analysis, the short children with GH peaks <10μg/L had significantly lower fasting insulin levels which also correlated to other metabolic parameters. The short pre-pubertal children with GH peak levels between 7 and 14μg/L did not differ significantly from healthy children of normal height but subpopulations within this group show significant metabolic differences. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of pitavastatin on walking capacity and CD34+/133+ cell number in patients with peripheral artery disease.

PubMed

Arao, Kenshiro; Yasu, Takanori; Endo, Yasuhiro; Funazaki, Toshikazu; Ota, Yoshimi; Shimada, Kazunori; Tokutake, Eiichi; Naito, Naoki; Takase, Bonpei; Wake, Minoru; Ikeda, Nahoko; Horie, Yasuto; Sugimura, Hiroyuki; Momomura, Shin-Ichi; Kawakami, Masanobu

2017-10-01

This multi-center prospective non-randomized comparative study investigated the effects of pitavastatin in patients with peripheral artery disease (PAD) in terms of exercise tolerance capacities and peripheral CD34 + /133 + cell numbers. At baseline, a peripheral blood test was administered to 75 patients with PAD, along with a treadmill exercise test using the Skinner-Gardner protocol to measure asymptomatic walking distance (AWD) and maximum walking distance (MWD). Each patient was assigned to a 6-month pitavastatin treatment group (n = 53) or a control group (n = 22), according to the patient's preference. The tests were repeated in both groups at 3 and 6 months. Baseline AWD and MWD correlated positively with the ankle-brachial pressure index (r = 0.342, p = 0.0032 and r = 0.324, p = 0.0054, respectively). Both AWD and MWD values improved at 3 and 6 months compared with baseline, and the degrees of their improvement were higher in the pitavastatin treatment group. CD34 + /133 + cell numbers did not change over time or between groups. Eighty-seven percent of patients in the treatment group attained low-density lipoprotein cholesterol levels below 100 mg/dL after 3 months. The study shows that pitavastatin may be effective in increasing exercise tolerance capacity in patients with PAD.

Screening for diabetes and prediabetes should be cost-saving in patients at high risk.

PubMed

Chatterjee, Ranee; Narayan, K M Venkat; Lipscomb, Joseph; Jackson, Sandra L; Long, Qi; Zhu, Ming; Phillips, Lawrence S

2013-07-01

Although screening for diabetes and prediabetes is recommended, it is not clear how best or whom to screen. We therefore compared the economics of screening according to baseline risk. Five screening tests were performed in 1,573 adults without known diabetes--random plasma/capillary glucose, plasma/capillary glucose 1 h after 50-g oral glucose (any time, without previous fast, plasma glucose 1 h after a 50-g oral glucose challenge [GCTpl]/capillary glucose 1 h after a 50-g oral glucose challenge [GCTcap]), and A1C--and a definitive 75-g oral glucose tolerance test. Costs of screening included the following: costs of testing (screen plus oral glucose tolerance test, if screen is positive); costs for false-negative results; and costs of treatment of true-positive results with metformin, all over the course of 3 years. We compared costs for no screening, screening everyone for diabetes or high-risk prediabetes, and screening those with risk factors based on age, BMI, blood pressure, waist circumference, lipids, or family history of diabetes. Compared with no screening, cost-savings would be obtained largely from screening those at higher risk, including those with BMI >35 kg/m(2), systolic blood pressure ≥130 mmHg, or age >55 years, with differences of up to -46% of health system costs for screening for diabetes and -21% for screening for dysglycemia110, respectively (all P < 0.01). GCTpl would be the least expensive screening test for most high-risk groups for this population over the course of 3 years. From a health economics perspective, screening for diabetes and high-risk prediabetes should target patients at higher risk, particularly those with BMI >35 kg/m(2), systolic blood pressure ≥130 mmHg, or age >55 years, for whom screening can be most cost-saving. GCTpl is generally the least expensive test in high-risk groups and should be considered for routine use as an opportunistic screen in these groups.

Screening obese children and adolescents for prediabetes and/or type 2 diabetes in pediatric practices: a validation study.

PubMed

Brar, Preneet C; Mengwall, Lisa; Franklin, Bonita H; Fierman, Arthur H

2014-07-01

Increased prevalence of type 2 diabetes mellitus (T2DM) makes it important for pediatricians to use effective screening tools for risk assessment of prediabetes/T2DM in children. Children (n = 149) who had an oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) were studied. American Diabetes Association recommended screening criteria-HbA1c ≥5.7% and fasting plasma glucose (FPG) ≥100 mg/dL-were compared against OGTT. The homeostatic model assessment of insulin resistance (HOMA-IR), a mathematical index derived from fasting insulin and glucose, was compared with OGTT. We studied whether combining screening tests (HbA1c and fasting glucose or HbA1c and HOMA-IR) improved accuracy of prediction of the OGTT. HbA1c of ≥5.7% had a sensitivity of 75% and specificity of 57% when compared with the OGTT. Combining screening tests (HbA1c ≥5.7% and FPG ≥100 mg/dL; HbA1c ≥5.7% and HOMA-IR ≥3.4) resulted in improved sensitivity (95.5% for each), with the HbA1c-FPG doing better than the HbA1c-HOMA-IR combination in terms of ability to rule out prediabetes (likelihood ratio [LR]) negative. 0.07 vs 0.14). HbA1c of ≥5.7% provided fair discrimination of glucose tolerance compared with the OGTT. The combination of HbA1c and FPG is a useful method for identifying children who require an OGTT. © The Author(s) 2014.

Relationship between fish size and upper thermal tolerance

USGS Publications Warehouse

Recsetar, Matthew S.; Zeigler, Matthew P.; Ward, David L.; Bonar, Scott A.; Caldwell, Colleen A.

2012-01-01

Using critical thermal maximum (CTMax) tests, we examined the relationship between upper temperature tolerances and fish size (fry-adult or subadult lengths) of rainbow trout Oncorhynchus mykiss (41-200-mm TL), Apache trout O. gilae apache (40-220-mm TL), largemouth bass Micropterus salmoides (72-266-mm TL), Nile tilapia Oreochromis niloticus (35-206-mm TL), channel catfish Ictalurus punctatus (62-264 mm-TL), and Rio Grande cutthroat trout O. clarkii virginalis (36-181-mm TL). Rainbow trout and Apache trout were acclimated at 18°C, Rio Grande cutthroat trout were acclimated at 14°C, and Nile tilapia, largemouth bass, and channel catfish were acclimated at 25°C, all for 14 d. Critical thermal maximum temperatures were estimated and data were analyzed using simple linear regression. There was no significant relationship (P > 0.05) between thermal tolerance and length for Nile tilapia (P = 0.33), channel catfish (P = 0.55), rainbow trout (P = 0.76), or largemouth bass (P = 0.93) for the length ranges we tested. There was a significant negative relationship between thermal tolerance and length for Rio Grande cutthroat trout (R2 = 0.412, P 2 = 0.1374, P = 0.028); however, the difference was less than 1°C across all lengths of Apache trout tested and about 1.3°C across all lengths of Rio Grande cutthroat trout tested. Because there was either no or at most a slight relationship between upper thermal tolerance and size, management and research decisions based on upper thermal tolerance should be similar for the range of sizes within each species we tested. However, the different sizes we tested only encompassed life stages ranging from fry to adult/subadult, so thermal tolerance of eggs, alevins, and larger adults should also be considered before making management decisions affecting an entire species.

Design, testing, and damage tolerance study of bonded stiffened composite wing cover panels

NASA Technical Reports Server (NTRS)

Madan, Ram C.; Sutton, Jason O.

1988-01-01

Results are presented from the application of damage tolerance criteria for composite panels to multistringer composite wing cover panels developed under NASA's Composite Transport Wing Technology Development contract. This conceptual wing design integrated aeroelastic stiffness constraints with an enhanced damage tolerance material system, in order to yield optimized producibility and structural performance. Damage tolerance was demonstrated in a test program using full-sized cover panel subcomponents; panel skins were impacted at midbay between stiffeners, directly over a stiffener, and over the stiffener flange edge. None of the impacts produced visible damage. NASTRAN analyses were performed to simulate NDI-detected invisible damage.

A whole-plant screening test to identify genotypes with superior freezing tolerance.

PubMed

Bertrand, Annick; Castonguay, Yves; Bourassa, Josée

2014-01-01

Freezing tolerance is a determinant factor of persistence of perennials grown in northern climate. Selection for winterhardiness in field nurseries is difficult because of the unpredictability of occurrence of test winters allowing the identification of hardy genotypes. Here we describe a whole-plant assay entirely performed indoor in growth chambers and walk-in freezers to identify genotypes with superior tolerance to freezing within populations of open pollinated species. Three successive freezing stresses are applied to progressively eliminate 90 % of the population and to retain only the 10 % best performing genotypes. This approach can be used to generate recurrently selected populations more tolerant to freezing in different species.

Damage Tolerance of Composites

NASA Technical Reports Server (NTRS)

Hodge, Andy

2007-01-01

Fracture control requirements have been developed to address damage tolerance of composites for manned space flight hardware. The requirements provide the framework for critical and noncritical hardware assessment and testing. The need for damage threat assessments, impact damage protection plans, and nondestructive evaluation are also addressed. Hardware intended to be damage tolerant have extensive coupon, sub-element, and full-scale testing requirements in-line with the Building Block Approach concept from the MIL-HDBK-17, Department of Defense Composite Materials Handbook.

Freezing and desiccation tolerance in entomopathogenic nematodes: diversity and correlation of traits.

PubMed

Shapiro-Ilan, David I; Brown, Ian; Lewis, Edwin E

2014-03-01

The ability of entomopathogenic nematodes to tolerate environmental stress such as desiccating or freezing conditions, can contribute significantly to biocontrol efficacy. Thus, in selecting which nematode to use in a particular biocontrol program, it is important to be able to predict which strain or species to use in target areas where environmental stress is expected. Our objectives were to (i) compare inter- and intraspecific variation in freeze and desiccation tolerance among a broad array of entomopathogenic nematodes, and (ii) determine if freeze and desiccation tolerance are correlated. In laboratory studies we compared nematodes at two levels of relative humidity (RH) (97% and 85%) and exposure periods (24 and 48 h), and nematodes were exposed to freezing temperatures (-2°C) for 6 or 24 h. To assess interspecific variation, we compared ten species including seven that are of current or recent commercial interest: Heterorhabditis bacteriophora (VS), H. floridensis, H. georgiana, (Kesha), H. indica (HOM1), H. megidis (UK211), Steinernema carpocapsae (All), S. feltiae (SN), S. glaseri (VS), S. rarum (17C&E), and S. riobrave (355). To assess intraspecific variation we compared five strains of H. bacteriophora (Baine, Fl1-1, Hb, Oswego, and VS) and four strains of S. carpocapsae (All, Cxrd, DD136, and Sal), and S. riobrave (355, 38b, 7-12, and TP). S. carpocapsae exhibited the highest level of desiccation tolerance among species followed by S. feltiae and S. rarum; the heterorhabditid species exhibited the least desiccation tolerance and S. riobrave and S. glaseri were intermediate. No intraspecific variation was observed in desiccation tolerance; S. carpocapsae strains showed higher tolerance than all H. bacteriophora or S. riobrave strains yet there was no difference detected within species. In interspecies comparisons, poor freeze tolerance was observed in H. indica, and S. glaseri, S. rarum, and S. riobrave whereas H. georgiana and S. feltiae exhibited the highest freeze tolerance, particularly in the 24-h exposure period. Unlike desiccation tolerance, substantial intraspecies variation in freeze tolerance was observed among H. bacteriophora and S. riobrave strains, yet within species variation was not detected among S. carpocapsae strains. Correlation analysis did not detect a relationship between freezing and desiccation tolerance.

Docking Studies, Synthesis and Biological Evaluation of β-aryl-β-hydroxy Propanoic Acids for Anti-inflammatory Activity.

PubMed

Savic, Jelena; Dilber, Sanda; Milenkovic, Marina; Kotur-Stevuljevic, Jelena; Markovic, Bojan; Vladimirov, Sote; Brboric, Jasmina

2017-01-01

Nonsteriodal anti-inflammatory drugs (NSAIDs) are numerous and widely used for more than 60 years, but there is still a strong need for developing novel selective NSAIDs. The need is justified by the fact that nonselective NSAIDs can produce serious gastric side effects and that some of the selective NSAID are withdrawn due to their cardiotoxic side effects. Eight β-hydroxy-β-arylpropanoic acids, which belong to the arylpropanoic acid class of compounds, structurally similar to some nonsteroidal anti-inflammatory drugs (NSAIDs), were docked into 3D catalytic site of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Seven out of those eight acids were synthesized using already published modification of Reformatsky reaction additionally optimized by increasing temperature. Synthesized compounds were tested in vivo in order to elucidate anti-inflammatory activity, gastric tolerability and impact on liver function of rats. Results of docking studies have indicated that all compounds have potential to selectively inhibit COX-2 isoform, but that the compounds containing polar substituents on phenyl ring are better inhibitors. Results of carrageenan-induced rat paw oedema test have shown that all compounds exhibit dose dependence and good gastric tolerability and none of the tested compounds have shown negative effect on liver function compared to ibuprofen. The compound containing polar nitro group in para position has shown the best docking results, anti-inflammatory activity, low hepatotoxicity and good gastric tolerability. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Multiple Heavy Metal Tolerance of Soil Bacterial Communities and Its Measurement by a Thymidine Incorporation Technique

PubMed Central

Díaz-Raviña, Montserrat; Bååth, Erland; Frostegård, Åsa

1994-01-01

A thymidine incorporation technique was used to determine the tolerance of a soil bacterial community to Cu, Cd, Zn, Ni, and Pb. An agricultural soil was artificially contaminated in our laboratory with individual metals at three different concentrations, and the results were compared with the results obtained by using the plate count technique. Thymidine incorporation was found to be a simple and rapid method for measuring tolerance. Data obtained by this technique were very reproducible. A linear relationship was found between changes in community tolerance levels obtained by the thymidine incorporation and plate count techniques (r = 0.732, P < 0.001). An increase in tolerance to the metal added to soil was observed for the bacterial community obtained from each polluted soil compared with the community obtained from unpolluted soil. The only exception was when Pb was added; no indication of Pb tolerance was found. An increase in the tolerance to metals other than the metal originally added to soil was also observed, indicating that there was multiple heavy metal tolerance at the community level. Thus, Cu pollution, in addition to increasing tolerance to Cu, also induced tolerance to Zn, Cd, and Ni. Zn and Cd pollution increased community tolerance to all five metals. Ni amendment increased tolerance to Ni the most but also increased community tolerance to Zn and, to lesser degrees, increased community tolerance to Pb and Cd. In soils polluted with Pb increased tolerance to other metals was found in the following order: Ni > Cd > Zn > Cu. We found significant positive relationships between changes in Cd, Zn, and Pb tolerance and, to a lesser degree, between changes in Pb and Ni tolerance when all metals and amendment levels were compared. The magnitude of the increase in heavy metal tolerance was found to be linearly related to the logarithm of the metal concentration added to the soil. Threshold tolerance concentrations were estimated from these linear relationships, and changes in tolerance could be detected at levels of soil contamination similar to those reported previously to result in changes in the phospholipid fatty acid pattern (Å. Frostegård, A. Tunlid, and E. Bååth, Appl. Environ. Microbiol. 59: 3605-3617, 1993). PMID:16349314

The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

PubMed

Márquez-Ibarra, Adriana; Huerta, Miguel; Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I; Cruzblanca, Humberto; Mancilla, Evelyn; Trujillo, Xóchitl

2016-01-01

Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin, in patients.

High intensity interval exercise is an effective alternative to moderate intensity exercise for improving glucose tolerance and insulin sensitivity in adolescent boys.

PubMed

Cockcroft, Emma J; Williams, Craig A; Tomlinson, Owen W; Vlachopoulos, Dimitris; Jackman, Sarah R; Armstrong, Neil; Barker, Alan R

2015-11-01

High-intensity interval exercise (HIIE) may offer a time efficient means to improve health outcomes compared to moderate-intensity exercise (MIE). This study examined the acute effect of HIIE compared to a work-matched bout of MIE on glucose tolerance, insulin sensitivity (IS), resting fat oxidation and exercise enjoyment in adolescent boys. Within-measures design with counterbalanced experimental conditions. Nine boys (14.2 ± 0.4 years) completed three conditions on separate days in a counterbalanced order: (1) HIIE; (2) work matched MIE, both on a cycle ergometer; and (3) rest (CON). An oral glucose tolerance test (OGTT) was performed after exercise or rest and the area under curve (AUC) responses for plasma [glucose] and [insulin] were calculated, and IS estimated (Cederholm index). Energy expenditure and fat oxidation were measured following the OGTT using indirect calorimetry. Exercise enjoyment was assessed using the Physical Activity Enjoyment Scale. The incremental AUC (iAUC) for plasma [glucose] was reduced following both MIE (-23.9%, P = 0.013, effect size [ES] = -0.64) and HIIE (-28.9%, P=0.008, ES = -0.84) compared to CON. The iAUC for plasma [insulin] was lower for HIIE (-24.2%, P = 0.021, ES = -0.71) and MIE (-29.1%, P = 0.012, ES = -0.79) compared to CON. IS increased by 11.2% after HIIE (P = 0.03, ES = 0.76) and 8.4% after MIE (P = 0.10, ES = 0.58). There was a trend for an increase in fat oxidation following HIIE (P = 0.097, ES = 0.70). Both HIIE and MIE were rated as equally enjoyable (P > 0.05, ES < 0.01). A single bout of time efficient HIIE is an effective alternative to MIE for improving glucose tolerance and IS in adolescent boys immediately after exercise. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Metabolic Capacity of Sinorhizobium (Ensifer) meliloti Strains as Determined by Phenotype MicroArray Analysis▿ †

PubMed Central

Biondi, Emanuele G.; Tatti, Enrico; Comparini, Diego; Giuntini, Elisa; Mocali, Stefano; Giovannetti, Luciana; Bazzicalupo, Marco; Mengoni, Alessio; Viti, Carlo

2009-01-01

Sinorhizobium meliloti is a soil bacterium that fixes atmospheric nitrogen in plant roots. The high genetic diversity of its natural populations has been the subject of extensive analysis. Recent genomic studies of several isolates revealed a high content of variable genes, suggesting a correspondingly large phenotypic differentiation among strains of S. meliloti. Here, using the Phenotype MicroArray (PM) system, hundreds of different growth conditions were tested in order to compare the metabolic capabilities of the laboratory reference strain Rm1021 with those of four natural S. meliloti isolates previously analyzed by comparative genomic hybridization (CGH). The results of PM analysis showed that most phenotypic differences involved carbon source utilization and tolerance to osmolytes and pH, while fewer differences were scored for nitrogen, phosphorus, and sulfur source utilization. Only the variability of the tested strain in tolerance to sodium nitrite and ammonium sulfate of pH 8 was hypothesized to be associated with the genetic polymorphisms detected by CGH analysis. Colony and cell morphologies and the ability to nodulate Medicago truncatula plants were also compared, revealing further phenotypic diversity. Overall, our results suggest that the study of functional (phenotypic) variability of S. meliloti populations is an important and complementary step in the investigation of genetic polymorphism of rhizobia and may help to elucidate rhizobial evolutionary dynamics, including adaptation to diverse environments. PMID:19561177

Use of Fatty Acid Methyl Ester Profiles to Compare Copper-Tolerant and Copper-Sensitive Strains of Pantoea ananatis.

PubMed

Nischwitz, C; Gitaitis, R; Sanders, H; Langston, D; Mullinix, B; Torrance, R; Boyhan, G; Zolobowska, L

2007-10-01

ABSTRACT A survey was conducted to evaluate differences in fatty acid methyl ester (FAME) profiles among strains of Pantoea ananatis, causal agent of center rot of onion (Allium cepa), isolated from 15 different onion cultivars in three different sites in Georgia. Differences in FAME composition were determined by plotting principal components (PCs) in two-dimensional plots. Euclidean distance squared (ED(2)) values indicated a high degree of similarity among strains. Plotting of PCs calculated from P. ananatis strains capable of growing on media amended with copper sulfate pentahydrate (200 mug/ml) indicated that copper-tolerant strains grouped into tight clusters separate from clusters formed by wild-type strains. However, unlike copper-sensitive strains, the copper-tolerant strains tended to cluster by location. A total of 80, 60, and 73% of the strains from Tift1, Tift2, and Tattnall, respectively, exhibited either confluent growth or partial growth on copper-amended medium. However, all strains were sensitive to a mixture of copper sulfate pentahydrate (200 mug/ml) and maneb (40 mug/ml). When copper-tolerant clones were analyzed and compared with their wild-type parents, in all cases the plotting of PCs developed from copper-tolerant clones formed tight clusters separate from clusters formed by the parents. Eigenvalues generated from these tests indicated that two components provided a good summary of the data, accounting for 98, 98, and 96% of the standardized variance for strains Pna 1-15B, Pna 1-12B, and Pna 2-5A, respectively. Furthermore, feature 4 (cis-9-hexadecenoic acid/2-hydroxy-13-methyltetradecanoic acid) and feature 7 (cis-9/trans-12/cis-7-octadecenoic acid) were the highest or second highest absolute values for PC1 in all three strains of the parents versus copper-tolerant clones, and hexadecanoic acid was the highest absolute value for PC2 in all three strains. Along with those fatty acids, dodecanoic acid and feature 3 (3-hydroxytetradecanoic acid/14-methylpentadecenoic acid) also had an impact on the differences observed between copper-sensitive parents and copper-resistant mutants. Finding these changes in bacterial fatty acid composition could lead to the development of a laboratory assay to identify copper-tolerant strains using gas chromatography as well as providing clues to further elucidate the mode of action of copper tolerance.

The Xenon Test Chamber Q-SUN® for testing realistic tolerances of fungi exposed to simulated full spectrum solar radiation.

PubMed

Dias, Luciana P; Araújo, Claudinéia A S; Pupin, Breno; Ferreira, Paulo C; Braga, Gilberto Ú L; Rangel, Drauzio E N

2018-06-01

The low survival of insect-pathogenic fungi when used for insect control in agriculture is mainly due to the deleterious effects of ultraviolet radiation and heat from solar irradiation. In this study, conidia of 15 species of entomopathogenic fungi were exposed to simulated full-spectrum solar radiation emitted by a Xenon Test Chamber Q-SUN XE-3-HC 340S (Q-LAB ® Corporation, Westlake, OH, USA), which very closely simulates full-spectrum solar radiation. A dendrogram obtained from cluster analyses, based on lethal time 50 % and 90 % calculated by Probit analyses, separated the fungi into three clusters: cluster 3 contains species with highest tolerance to simulated full-spectrum solar radiation, included Metarhizium acridum, Cladosporium herbarum, and Trichothecium roseum with LT 50  > 200 min irradiation. Cluster 2 contains eight species with moderate UV tolerance: Aschersonia aleyrodis, Isaria fumosorosea, Mariannaea pruinosa, Metarhizium anisopliae, Metarhizium brunneum, Metarhizium robertsii, Simplicillium lanosoniveum, and Torrubiella homopterorum with LT 50 between 120 and 150 min irradiation. The four species in cluster 1 had the lowest UV tolerance: Lecanicillium aphanocladii, Beauveria bassiana, Tolypocladium cylindrosporum, and Tolypocladium inflatum with LT 50  < 120 min irradiation. The QSUN Xenon Test Chamber XE3 is often used by the pharmaceutical and automotive industry to test light stability and weathering, respectively, but it was never used to evaluate fungal tolerance to full-spectrum solar radiation before. We conclude that the equipment provided an excellent tool for testing realistic tolerances of fungi to full-spectrum solar radiation of microbial agents for insect biological control in agriculture. Copyright © 2018 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Utility of antenatal clinical factors for prediction of postpartum outcomes in women with gestational diabetes mellitus (GDM).

PubMed

Ingram, Emily R; Robertson, Iain K; Ogden, Kathryn J; Dennis, Amanda E; Campbell, Joanne E; Corbould, Anne M

2017-06-01

Gestational diabetes mellitus (GDM) is associated with life-long increased risk of type 2 diabetes: affected women are advised to undergo oral glucose tolerance testing (OGTT) at 6-12 weeks postpartum, then glucose screening every 1-3 years. We investigated whether in women with GDM, antenatal clinical factors predicted postpartum abnormal glucose tolerance and compliance with screening. In women with GDM delivering 2007 to mid-2009 in a single hospital, antenatal/obstetric data and glucose tests at 6-12 weeks postpartum and during 5.5 years post-pregnancy were retrospectively collected. Predictors of return for testing and abnormal glucose tolerance were identified using multivariate analysis. Of 165 women, 117 (70.9%) returned for 6-12 week postpartum OGTT: 23 (19.6%) were abnormal. Smoking and parity, independent of socioeconomic status, were associated with non-return for testing. Fasting glucose ≥5.4 mmol/L on pregnancy OGTT predicted both non-return for testing and abnormal OGTT. During 5.5 years post-pregnancy, 148 (89.7%) women accessed glucose screening: nine (6.1%) developed diabetes, 33 (22.3%) had impaired fasting glucose / impaired glucose tolerance. Predictors of abnormal glucose tolerance were fasting glucose ≥5.4 mmol/L and 2-h glucose ≥9.3 mmol/L on pregnancy OGTT (~2.5-fold increased risk), and polycystic ovary syndrome (~3.4 fold increased risk). Risk score calculation, based on combined antenatal factors, did not improve predictions. Antenatal clinical factors were modestly predictive of return for testing and abnormal glucose tolerance post-pregnancy in women with GDM. Risk score calculations were ineffective in predicting outcomes: risk scores developed in other populations require validation. Ongoing glucose screening is indicated for all women with GDM. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Effect of N. sativa oil on impaired glucose tolerance and insulin insensitivity induced by high-fat-diet and turpentine-induced trauma.

PubMed

Alsaif, Mohammed A

2008-04-15

The aim of this study was to investigate the effect of N. sativa oil on impaired glucose tolerance and insulin insensitivity induced by high-fat diet and trauma. Three dietary groups were used in this study; Rat-Chow (RC), N. sativa oil diet (Combination 4% N. sativa oil and 16% butter oil) (NSOD) and 20% Butter Oil Diet (BOD). Each group was subdivided in two groups; control and trauma. Diets were supplemented for five consecutive weeks body weight increase per week was calculated. At end of the dietary treatments, single dose (2 mL kg(-1) body weight) of turpentine was injected in the dorso-lumber region. Intravenous glucose tolerance test (i.v. GTT) was performed, insulinogenic index and insulin sensitivity was measured. The results showed butter oil diet significantly increased the body weights and visceral fats compared other two groups, respectively. Fasting glucose levels did not change in trauma induced rats while insulin levels increased significantly and it found highest in butter oil diet fed animals. Impaired glucose tolerance was found sever in BOD fed traumatized rats. N. sativa oil diet protected impaired glucose tolerance and insulin insensitivity induced either via saturated fatty acids or injury. In conclusion, N. sativa oil may be used in post surgery diabetic patients to prevent the long going adverse effects from surgical trauma.

Induction of tolerance towards TNP entails down-regulation of an autoimmune attack.

PubMed Central

Zöller, M; Andrighetto, G

1988-01-01

In order to follow the process of induction and maintainance of tolerance, BALB/c mice were tolerized by free hapten, and effector and regulatory cell interactions were analysed by limiting-dilution (LD) cultures. Injection of trinitrobenzenesulphonic acid (TNBS) resulted, predominantly, in the activation and expansion of self-reactive cytotoxic T cells (CTL), which were observed transiently at frequencies comparable to allo-specific CTL. In addition, self-reactive helper T cells (Th) were activated and expanded in tolerized mice. TNP-specific reactivity was difficult to evaluate, since cytotoxic activity against haptenized self followed the pattern of self-reactivity throughout the test period. But in LD cultures determining proliferation, two populations of Th responding to TNP-self were observed, while only one Th population could be detected in response to self. Expansion/activation of Th and CTL precursors (CTLp) was followed by activation of suppressor T cells (Ts). The suppressor population could be divided into two subpopulations, one interfering with Th, the second interacting directly with CTL (veto cells). The results indicate that during the induction of tolerance, animals pass through an autoimmune attack, with expansion and activation of self-reactive clones (CTL, Th). The final status of non-responsiveness towards TNP is not due to the deletion of effector or regulatory cells, but results from the establishment of a steady state of dominance of self-reactive and TNP-self-reactive suppression. PMID:2965095

Improving glucose tolerance by muscle-damaging exercise.

PubMed

Ho, Chien-Te; Otaka, Machiko; Kuo, Chia-Hua

2017-04-01

Tissue damage is regarded as an unwanted medical condition to be avoided. However, introducing tolerable tissue damages has been used as a therapeutic intervention in traditional and complementary medicine to cure discomfort and illness. Eccentric exercise is known to cause significant necrosis and insulin resistance of skeletal muscle. The purpose of this study was to determine the magnitude of muscle damage and blood glucose responses during an oral glucose tolerance test (OGTT) after eccentric training in 21 young participants. They were challenged by 5 times of 100-meter downhill sprinting and 20 times of squats training at 30 pounds weight load for 3 days, which resulted in a wide spectrum of muscle creatine kinase (CK) surges in plasma, 48 h after the last bout of exercise. Participants were then divided into two groups according the magnitude of CK increases (low CK: +48% ± 0.3; high CK: +137% ± 0.5, P < 0.05). Both groups show comparable decreases in blood glucose levels in OGTT, suggesting that this muscle-damaging exercise does not appear to decrease but rather improve glycemic control in men. The result of the study rejects the hypothesis that eccentric exercise decreases glucose tolerance. Improved glucose tolerance with CK increase implicates a beneficial effect of replacing metabolically weaker muscle fibers by eccentric exercise in Darwinian natural selection fashion.

Evaluating the Metal Tolerance Capacity of Microbial Communities Isolated from Alberta Oil Sands Process Water

PubMed Central

Frankel, Mathew L.; Demeter, Marc A.; Lemire, Joe A.; Turner, Raymond J.

2016-01-01

Anthropogenic activities have resulted in the intensified use of water resources. For example, open pit bitumen extraction by Canada’s oil sands operations uses an estimated volume of three barrels of water for every barrel of oil produced. The waste tailings–oil sands process water (OSPW)–are stored in holding ponds, and present an environmental concern as they are comprised of residual hydrocarbons and metals. Following the hypothesis that endogenous OSPW microbial communities have an enhanced tolerance to heavy metals, we tested the capacity of planktonic and biofilm populations from OSPW to withstand metal ion challenges, using Cupriavidus metallidurans, a known metal-resistant organism, for comparison. The toxicity of the metals toward biofilm and planktonic bacterial populations was determined by measuring the minimum biofilm inhibitory concentrations (MBICs) and planktonic minimum inhibitory concentrations (MICs) using the MBEC ™ assay. We observed that the OSPW community and C. metallidurans had similar tolerances to 22 different metals. While thiophillic elements (Te, Ag, Cd, Ni) were found to be most toxic, the OSPW consortia demonstrated higher tolerance to metals reported in tailings ponds (Al, Fe, Mo, Pb). Metal toxicity correlated with a number of physicochemical characteristics of the metals. Parameters reflecting metal-ligand affinities showed fewer and weaker correlations for the community compared to C. metallidurans, suggesting that the OSPW consortia may have developed tolerance mechanisms toward metals present in their environment. PMID:26849649

Materials and processes laboratory composite materials characterization task, part 1. Damage tolerance

NASA Technical Reports Server (NTRS)

Nettles, A. T.; Tucker, D. S.; Patterson, W. J.; Franklin, S. W.; Gordon, G. H.; Hart, L.; Hodge, A. J.; Lance, D. G.; Russel, S. S.

1991-01-01

A test run was performed on IM6/3501-6 carbon-epoxy in which the material was processed, machined into specimens, and tested for damage tolerance capabilities. Nondestructive test data played a major role in this element of composite characterization. A time chart was produced showing the time the composite material spent within each Branch or Division in order to identify those areas which produce a long turnaround time. Instrumented drop weight testing was performed on the specimens with nondestructive evaluation being performed before and after the impacts. Destructive testing in the form of cross-sectional photomicrography and compression-after-impact testing were used. Results show that the processing and machining steps needed to be performed more rapidly if data on composite material is to be collected within a reasonable timeframe. The results of the damage tolerance testing showed that IM6/3501-6 is a brittle material that is very susceptible to impact damage.

Screening and selection of most potent diazotrophic cyanobacterial isolate exhibiting natural tolerance to rice field herbicides for exploitation as biofertilizer.

PubMed

Singh, Surendra; Datta, Pallavi

2006-01-01

Periodic applications of heavy dosages of herbicides in modern rice-agriculture are a necessary evil for obtaining high crop productivity. Such herbicides are not only detrimental to weeds but biofertilizer strains of diazotrophic cyanobacteria also. It is therefore, essential to screen and select such biofertilizer strains of diazotrophic cyanobacteria exhibiting natural tolerance to common rice-field herbicides that can be further improved by mutational techniques to make biofertilizer technology a viable one. Therefore, efforts have been made to screen five dominant diazotrophic cyanobacterial forms e.g. filamentous heterocystous Nostoc punctiforme , Nostoc calcicola , Anabaena variabilis and unicellular Gloeocapsa sp. and Aphanocapsa sp. along with standard laboratory strain Nostoc muscorum ISU against increasing concentrations (0-100 mg l(-1) of four commercial grade common rice-field herbicides i.e. Arozin, Butachlor, Alachlor and 2,4-D under diazotrophic growth conditions. The lethal and IGC(50) concentrations for all four herbicides tested were found highest for A. variabilis as compared to other test cyanobacteria. The lowest reduction in chlorophyll a content, photosynthetic oxygen evolution, and N(2)-fixation was found in A. variabilis as compared to other rice field isolates and standard laboratory strain N. muscorum ISU. On the basis of prolong survival potential and lowest reductions in vital metabolic activities tested at IGC(50) concentration of four herbicides, it is concluded that A. variabilis is the most potent and promising cyanobacterial isolate as compared with other forms. This could be further improved by mutational techniques for exploitation as most potential and viable biofertilizer strain.

Effect of eicosapentaenoic acid ethyl ester v. oleic acid-rich safflower oil on insulin resistance in type 2 diabetic model rats with hypertriacylglycerolaemia.

PubMed

Minami, Asako; Ishimura, Noriko; Sakamoto, Sadaichi; Takishita, Eiko; Mawatari, Kazuaki; Okada, Kazuko; Nakaya, Yutaka

2002-02-01

The purpose of the present study was to test whether hyperlipidaemia and insulin resistance in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats can be improved by dietary supplementation with purified eicosapentaenoic acid (EPA) or oleic acid (OA). Male OLETF rats were fed powdered chow (510 g fat/kg) alone (n 8) or chow supplemented with 10 g EPA- (n 8) or OA- (n 8) rich oil/kg per d from 5 weeks until 30 weeks of age. An oral glucose tolerance test and hyperinsulinaemic euglycaemic clamp was performed at 25 and 30 weeks of age. EPA supplementation resulted in significantly (P<0.05) reduced plasma lipids, hepatic triacylglycerols, and abdominal fat deposits, and more efficient in vivo glucose disposal compared with OA supplementation and no supplementation. OA supplementation was associated with significantly increased insulin response to oral glucose compared with EPA supplementation and no supplementation. Inverse correlation was noted between glucose uptake and plasma triacylglycerol levels (r -086, P<0.001) and abdominal fat volume (r -0.80, P<0.001). The result of oral glucose tolerance test study showed that the rats fed EPA tended to improve glucose intolerance, although this was not statistically significant. Levels of plasma insulin at 60 min after glucose was significantly increased in rats fed OA compared with the other two groups. The results indicate that long-term feeding of EPA might be effective in preventing insulin resistance in diabetes-prone rats, at least in part, due to improving hypertriacylglycerolaemia.

Electrical stimulation-evoked contractions blunt orthostatic hypotension in sub-acute spinal cord-injured individuals: two clinical case studies.

PubMed

Hamzaid, N A; Tean, L T; Davis, G M; Suhaimi, A; Hasnan, N

2015-05-01

Prospective study of two cases. To describe the effects of electrical stimulation (ES) therapy in the 4-week management of two sub-acute spinal cord-injured (SCI) individuals (C7 American Spinal Injury Association Impairment Scale (AIS) B and T9 AIS (B)). University Malaya Medical Centre, Kuala Lumpur, Malaysia. A diagnostic tilt-table test was conducted to confirm the presence of orthostatic hypotension (OH) based on the current clinical definitions. Following initial assessment, subjects underwent 4 weeks of ES therapy 4 times weekly for 1 h per day. Post-tests tilt table challenge, both with and without ES on their rectus abdominis, quadriceps, hamstrings and gastrocnemius muscles, was conducted at the end of the study (week 5). Subjects' blood pressures (BP) and heart rates (HR) were recorded every minute during pre-test and post-tests. Orthostatic symptoms, as well as the maximum tolerance time that the subjects could withstand head up tilt at 60°, were recorded. Subject A improved his orthostatic symptoms, but did not recover from clinically defined OH based on the 20-min duration requirement. With concurrent ES therapy, 60° head up tilt BP was 89/62 mm Hg compared with baseline BP of 115/71 mm Hg. Subject B fully recovered from OH demonstrated by BP of 105/71 mm Hg during the 60° head up tilt compared with baseline BP of 124/77 mm Hg. Both patients demonstrated longer tolerance time during head up tilt with concomitant ES (subject A: pre-test 4 min, post-test without ES 6 min, post-test with ES 12 min; subject B: pre-test 4 min, post-test without ES 28 min, post-test with ES 60 min). Weekly ES therapy had positive effect on OH management in sub-acute SCI individuals.

Predictive value of first fasting plasma glucose compared with admission plasma glucose for undiagnosed diabetes in a stable cardiology population.

PubMed

Wen, Zhu-zhi; Zhang, Xin-mei; Mai, Zun; Geng, Deng-feng; Wang, Jing-feng

2012-09-01

The study compared the predictive value of admission plasma glucose (APG) and first fasting plasma glucose (FPG) in stratifying patients meriting an oral glucose tolerance test (OGTT). Characteristics of APG, FPG and OGTT 2-hour glucose as well as other blood measurements, physical examinations and medical information were assessed in 994 patients without known diabetes. The prevalences of diabetes and impaired glucose tolerance were 24.6% and 37.9%, according to an OGTT, respectively. The first FPG demonstrated stronger predictive value in diagnosing diabetes than APG did both in overall and in patients with less clinical value. Compared to the first FPG, APG provided less value to coronary artery disease, hypertension and high-sensitivity C-reactive protein for diabetes screening. The first FPG exerted more predictive value than APG did and was still a preferable reference prior to APG in stratifying patients for undiagnosed diabetes by an OGTT. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Flight test results of the Strapdown hexad Inertial Reference Unit (SIRU). Volume 1: Flight test summary

NASA Technical Reports Server (NTRS)

Hruby, R. J.; Bjorkman, W. S.

1977-01-01

Flight test results of the strapdown inertial reference unit (SIRU) navigation system are presented. The fault-tolerant SIRU navigation system features a redundant inertial sensor unit and dual computers. System software provides for detection and isolation of inertial sensor failures and continued operation in the event of failures. Flight test results include assessments of the system's navigational performance and fault tolerance.

The X-38 Spacecraft Fault-Tolerant Avionics System

NASA Technical Reports Server (NTRS)

Kouba,Coy; Buscher, Deborah; Busa, Joseph

2003-01-01

In 1995 NASA began an experimental program to develop a reusable crew return vehicle (CRV) for the International Space Station. The purpose of the CRV was threefold: (i) to bring home an injured or ill crewmember; (ii) to bring home the entire crew if the Shuttle fleet was grounded; and (iii) to evacuate the crew in the case of an imminent Station threat (i.e., fire, decompression, etc). Built at the Johnson Space Center, were two approach and landing prototypes and one spacecraft demonstrator (called V201). A series of increasingly complex ground subsystem tests were completed, and eight successful high-altitude drop tests were achieved to prove the design concept. In this program, an unprecedented amount of commercial-off-the-shelf technology was utilized in this first crewed spacecraft NASA has built since the Shuttle program. Unfortunately, in 2002 the program was canceled due to changing Agency priorities. The vehicle was 80% complete and the program was shut down in such a manner as to preserve design, development, test and engineering data. This paper describes the X-38 V201 fault-tolerant avionics system. Based on Draper Laboratory's Byzantine-resilient fault-tolerant parallel processing system and their "network element" hardware, each flight computer exchanges information on a strict timescale to process input data, compare results, and issue voted vehicle output commands. Major accomplishments achieved in this development include: (i) a space qualified two-fault tolerant design using mostly COTS (hardware and operating system); (ii) a single event upset tolerant network element board, (iii) on-the-fly recovery of a failed processor; (iv) use of synched cache; (v) realignment of memory to bring back a failed channel; (vi) flight code automatically generated from the master measurement list; and (vii) built in-house by a team of civil servants and support contractors. This paper will present an overview of the avionics system and the hardware implementation, as well as the system software and vehicle command & telemetry functions. Potential improvements and lessons learned on this program are also discussed.

Orthostatic intolerance and motion sickness after parabolic flight

NASA Technical Reports Server (NTRS)

Schlegel, T. T.; Brown, T. E.; Wood, S. J.; Benavides, E. W.; Bondar, R. L.; Stein, F.; Moradshahi, P.; Harm, D. L.; Fritsch-Yelle, J. M.; Low, P. A.

2001-01-01

Because it is not clear that the induction of orthostatic intolerance in returning astronauts always requires prolonged exposure to microgravity, we investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy subjects before and after the brief micro- and hypergravity of parabolic flight. Concomitantly, we investigated the effect of parabolic flight-induced vomiting on orthostatic tolerance, R-wave-R-wave interval and arterial pressure power spectra, and carotid-cardiac baroreflex and Valsalva responses. After parabolic flight 1) 8 of 16 subjects could not tolerate 30 min of upright tilt (compared to 2 of 16 before flight); 2) 6 of 16 subjects vomited; 3) new intolerance to upright tilt was associated with exaggerated falls in total peripheral resistance, whereas vomiting was associated with increased R-wave-R-wave interval variability and carotid-cardiac baroreflex responsiveness; and 4) the proximate mode of new orthostatic failure differed in subjects who did and did not vomit, with vomiters experiencing comparatively isolated upright hypocapnia and cerebral vasoconstriction and nonvomiters experiencing signs and symptoms reminiscent of the clinical postural tachycardia syndrome. Results suggest, first, that syndromes of orthostatic intolerance resembling those developing after space flight can develop after a brief (i.e., 2-h) parabolic flight and, second, that recent vomiting can influence the results of tests of autonomic cardiovascular function commonly utilized in returning astronauts.

PTSD’s risky behavior criterion: Relation with DSM-5 PTSD symptom clusters and psychopathology

PubMed Central

Contractor, Ateka A.; Weiss, Nicole H.; Dranger, Paula; Ruggero, Camilo; Armour, Cherie

2017-01-01

A new symptom criterion of reckless and self-destructive behaviors (E2) was recently added to posttraumatic stress disorder’s (PTSD) diagnostic criteria in DSM-5, which is unsurprising given the well-established relation between PTSD and risky behaviors. Researchers have questioned the significance and incremental validity of this symptom criterion within PTSD’s symptomatology. Unprecedented to our knowledge, we aim to compare trauma-exposed groups differing on their endorsement status of the risky behavior symptom on several psychopathology constructs (PTSD, depression, distress tolerance, rumination, anger). The sample included 123 trauma-exposed participants seeking mental health treatment (M age=35.70; 68.30% female) who completed self-report questionnaires assessing PTSD symptoms, depression, rumination, distress tolerance, and anger. Results of independent samples t-tests indicated that participants who endorsed the E2 criterion at a clinically significant level reported significantly greater PTSD subscale severity; depression severity; rumination facets of repetitive thoughts, counterfactual thinking, and problem-focused thinking; and anger reactions; and significantly less absorption and regulation (distress tolerance facets) compared to participants who did not endorse the E2 criterion at a clinically significant level. Results indicate the utility of the E2 criterion in identifying trauma-exposed individual with greater posttraumatic distress, and emphasize the importance of targeting such behaviors in treatment. PMID:28285248

A Basic Helix-Loop-Helix Transcription Factor, PtrbHLH, of Poncirus trifoliata Confers Cold Tolerance and Modulates Peroxidase-Mediated Scavenging of Hydrogen Peroxide1[C][W

PubMed Central

Huang, Xiao-San; Wang, Wei; Zhang, Qian; Liu, Ji-Hong

2013-01-01

The basic helix-loop-helix (bHLH) transcription factors are involved in a variety of physiological processes. However, plant bHLHs functioning in cold tolerance and the underlying mechanisms remain poorly understood. Here, we report the identification and functional characterization of PtrbHLH isolated from trifoliate orange (Poncirus trifoliata). The transcript levels of PtrbHLH were up-regulated under various abiotic stresses, particularly cold. PtrbHLH was localized in the nucleus with transactivation activity. Overexpression of PtrbHLH in tobacco (Nicotiana tabacum) or lemon (Citrus limon) conferred enhanced tolerance to cold under chilling or freezing temperatures, whereas down-regulation of PtrbHLH in trifoliate orange by RNA interference (RNAi) resulted in elevated cold sensitivity. A range of stress-responsive genes was up-regulated or down-regulated in the transgenic lemon. Of special note, several peroxidase (POD) genes were induced after cold treatment. Compared with the wild type, POD activity was increased in the overexpression plants but decreased in the RNAi plants, which was inversely correlated with the hydrogen peroxide (H2O2) levels in the tested lines. Treatment of the transgenic tobacco plants with POD inhibitors elevated the H2O2 levels and greatly compromised their cold tolerance, while exogenous replenishment of POD enhanced cold tolerance of the RNAi line. In addition, transgenic tobacco and lemon plants were more tolerant to oxidative stresses. Yeast one-hybrid assay and transient expression analysis demonstrated that PtrbHLH could bind to the E-box elements in the promoter region of a POD gene. Taken together, these results demonstrate that PtrbHLH plays an important role in cold tolerance, at least in part, by positively regulating POD-mediated reactive oxygen species removal. PMID:23624854

In Vivo Assessment of Cold Tolerance through Chlorophyll-a Fluorescence in Transgenic Zoysiagrass Expressing Mutant Phytochrome A

PubMed Central

Gururani, Mayank Anand; Venkatesh, Jelli; Ganesan, Markkandan; Strasser, Reto Jörg; Han, Yunjeong; Kim, Jeong-Il; Lee, Hyo-Yeon; Song, Pill-Soon

2015-01-01

Chlorophyll-a fluorescence analysis provides relevant information about the physiology of plants growing under abiotic stress. In this study, we evaluated the influence of cold stress on the photosynthetic machinery of transgenic turfgrass, Zoysia japonica, expressing oat phytochrome A (PhyA) or a hyperactive mutant phytochrome A (S599A) with post-translational phosphorylation blocked. Biochemical analysis of zoysiagrass subjected to cold stress revealed reduced levels of hydrogen peroxide, increased proline accumulation, and enhanced specific activities of antioxidant enzymes compared to those of control plants. Detailed analyses of the chlorophyll-a fluorescence data through the so-called OJIP test exhibited a marked difference in the physiological status among transgenic and control plants. Overall, these findings suggest an enhanced level of cold tolerance in S599A zoysiagrass cultivars as reflected in the biochemical and physiological analyses. Further, we propose that chlorophyll-a fluorescence analysis using OJIP test is an efficient tool in determining the physiological status of plants under cold stress conditions. PMID:26010864

VKOR variant and sex are the main influencing factors on bromadiolone tolerance of the house mouse (Mus musculus L.).

PubMed

Šćepović, Tanja; Jokić, Goran; Esther, Alexandra; Kataranovski, Dragan; Vukša, Petar; Đedović, Suzana; Vukša, Marina

2016-03-01

After reports of management problems in practice, a survey was conducted to determine the presence of bromadiolone-resistant animals in different house mouse (Mus musculus L.) populations in Serbia. A 21 day no-choice feeding test was carried out to examine the resistance of house mice to bromadiolone. Eighty house mice collected from four locations (ten males and ten females per location) were tested for bromadiolone tolerance. Surviving animals and their F1 offspring were screened for mutations. The influence of VKOR variant, zygosity and sex on bromadiolone tolerance was analysed. Bait intake and changes in body weight revealed different animal responses regarding susceptibility or resistance. Leu128Ser, Tyr139Cys and a new Ala21Thr polymorphism were detected in wild-born survivors and their F1 generation. However, not every individual with the polymorphisms Leu128Ser and Tyr139Cys survived the feeding test. VKOR variants and sex caused variations in bromadiolone tolerance. For the first time it was shown that the VKOR variant, along with sex, is responsible for bromadiolone tolerance in house mice. Other factors influencing bromadiolone tolerance, including sex-specific factors, cannot be excluded. The tolerance levels of VKOR variants should be determined in further studies in order to evaluate the effectiveness of bromadiolone in sustainable management. © 2015 Society of Chemical Industry.

Multi-version software reliability through fault-avoidance and fault-tolerance

NASA Technical Reports Server (NTRS)

Vouk, Mladen A.; Mcallister, David F.

1989-01-01

A number of experimental and theoretical issues associated with the practical use of multi-version software to provide run-time tolerance to software faults were investigated. A specialized tool was developed and evaluated for measuring testing coverage for a variety of metrics. The tool was used to collect information on the relationships between software faults and coverage provided by the testing process as measured by different metrics (including data flow metrics). Considerable correlation was found between coverage provided by some higher metrics and the elimination of faults in the code. Back-to-back testing was continued as an efficient mechanism for removal of un-correlated faults, and common-cause faults of variable span. Software reliability estimation methods was also continued based on non-random sampling, and the relationship between software reliability and code coverage provided through testing. New fault tolerance models were formulated. Simulation studies of the Acceptance Voting and Multi-stage Voting algorithms were finished and it was found that these two schemes for software fault tolerance are superior in many respects to some commonly used schemes. Particularly encouraging are the safety properties of the Acceptance testing scheme.

Acute tolerance to alcohol impairment of behavioral and cognitive mechanisms related to driving: drinking and driving on the descending limb.

PubMed

Weafer, Jessica; Fillmore, Mark T

2012-04-01

Alcohol effects on behavioral and cognitive mechanisms influence impaired driving performance and decisions to drive after drinking (Barry 1973; Moskowitz and Robinson 1987). To date, research has focused on the ascending limb of the blood alcohol curve, and there is little understanding of how acute tolerance to impairment of these mechanisms might influence driving behavior on the descending limb. To provide an integrated examination of the degree to which alcohol impairment of motor coordination and inhibitory control contributes to driving impairment and decisions to drive on the ascending and descending limbs of the blood alcohol curve. Social-drinking adults (N = 20) performed a testing battery that measured simulated driving performance and willingness to drive, as well as mechanisms related to driving: motor coordination (grooved pegboard), inhibitory control (cued go/no-go task), and subjective intoxication. Performance was tested in response to placebo and a moderate dose of alcohol (0.65 g/kg) twice at comparable blood alcohol concentrations: once on the ascending limb and again on the descending limb. Impaired motor coordination and subjective intoxication showed acute tolerance, whereas driving performance and inhibitory control showed no recovery from impairment. Greater motor impairment was associated with poorer driving performance under alcohol, and poorer inhibitory control was associated with more willingness to drive. Findings suggest that acute tolerance to impairment of motor coordination is insufficient to promote recovery of driving performance and that the persistence of alcohol-induced disinhibition might contribute to risky decisions to drive on the descending limb.

Acute tolerance to alcohol impairment of behavioral and cognitive mechanisms related to driving: drinking and driving on the descending limb

PubMed Central

Weafer, Jessica

2015-01-01

Rationale Alcohol effects on behavioral and cognitive mechanisms influence impaired driving performance and decisions to drive after drinking (Barry 1973; Moskowitz and Robinson 1987). To date, research has focused on the ascending limb of the blood alcohol curve, and there is little understanding of how acute tolerance to impairment of these mechanisms might influence driving behavior on the descending limb. Objectives To provide an integrated examination of the degree to which alcohol impairment of motor coordination and inhibitory control contributes to driving impairment and decisions to drive on the ascending and descending limbs of the blood alcohol curve. Methods Social-drinking adults (N=20) performed a testing battery that measured simulated driving performance and willingness to drive, as well as mechanisms related to driving: motor coordination (grooved pegboard), inhibitory control (cued go/no-go task), and subjective intoxication. Performance was tested in response to placebo and a moderate dose of alcohol (0.65 g/kg) twice at comparable blood alcohol concentrations: once on the ascending limb and again on the descending limb. Results Impaired motor coordination and subjective intoxication showed acute tolerance, whereas driving performance and inhibitory control showed no recovery from impairment. Greater motor impairment was associated with poorer driving performance under alcohol, and poorer inhibitory control was associated with more willingness to drive. Conclusions Findings suggest that acute tolerance to impairment of motor coordination is insufficient to promote recovery of driving performance and that the persistence of alcohol-induced disinhibition might contribute to risky decisions to drive on the descending limb. PMID:21960182

GABA dramatically improves glucose tolerance in streptozotocin-induced diabetic rats fed with high-fat diet.

PubMed

Sohrabipour, Shahla; Sharifi, Mohammad Reza; Talebi, Ardeshir; Sharifi, Mohammadreza; Soltani, Nepton

2018-05-05

Skeletal muscle, hepatic insulin resistance, and beta cell dysfunction are the characteristic pathophysiological features of type 2 diabetes mellitus. GABA has an important role in pancreatic islet cells. The present study attempted to clarify the possible mechanism of GABA to improve glucose tolerance in a model of type 2 diabetes mellitus in rats. Fifty Wistar rats were divided into five groups: NDC that was fed the normal diet, CD which received a high-fat diet with streptozotocin, CD-GABA animals that received GABA via intraperitoneal injection, plus CD-Ins1 and CD-Ins2 groups which were treated with low and high doses of insulin, respectively. Body weight and blood glucose were measured weekly. Intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (ITT), urine volume, amount of water drinking, and food intake assessments were performed monthly. The hyperinsulinemic euglycemic clamp was done for assessing insulin resistance. Plasma insulin and glucagon were measured. Abdominal fat was measured. Glucagon receptor, Glucose 6 phosphatase, Phosphoenolpyruvate carboxykinase genes expression were evaluated in liver and Glucose transporter 4 (GLUT4) genes expression and protein translocation were evaluated in the muscle. GABA or insulin therapy improved blood glucose, insulin level, IPGTT, ITT, gluconeogenesis pathway, Glucagon receptor, body weight and body fat in diabetic rats. GLUT4 gene and protein expression increased. GABA whose beneficial effect was comparable to that of insulin, also increased glucose infusion rate during an euglycemic clamp. GABA could improve insulin resistance via rising GLUT4 and also decreasing the gluconeogenesis pathway and Glucagon receptor gene expression. Copyright © 2018. Published by Elsevier B.V.

Design, assembly, and metrology of an oil-immersion microscope objective with long working distance

NASA Astrophysics Data System (ADS)

Peng, Wei-Jei; Lin, Wen-Lung; Kuo, Hui-Jean; Ho, Cheng-Fang; Hsu, Wei-Yao

2016-10-01

The design, tolerance sensitivity reduction, assembly, and optical bench test for an oil-immersion microscope objective with long working distance employed in a lattice light-sheet microscope is presented in this paper. In this application, the orthogonal excitation and detection objectives are dipped in an oil medium. The excitation objective focuses the incident laser beam to generate fluorescence on specimen for collecting by detection objective. The excitation objective is custom-designed to meet the requirement specification such as oil-immersion, the long working distance, and numerical aperture (NA) of 0.5, etc. To produce an acceptable point spread function (PSF) for effective excitation, the performance of the objective needs to be close to diffraction limit. Because the tolerance of the modulation transfer function (MTF) is more and more sensitive at higher spatial frequency, it is extremely critical to keep the performance after manufacture. Consequently, an insensitive optical design is very important for relaxing tolerance. We compare the design with and without tolerance sensitivity reduction, and the as-built MTF shows the result. Furthermore, the method for sensitivity reduction is presented. The opto-mechanical design and assembly method are also discussed. Eventually, the objective with five spherical lenses was fabricated. In optical bench test, the depth of the oil is sensitive to MTF, and it leads to the complicated adjustment. For solving this issue, we made an index-matching lens to replace oil for measurement easily. Finally, the measured MTF of the excitation objective can accomplish the requirement specification and successfully employed in a lattice light-sheet microscope.

Insulin secretion and insulin resistance in Korean women with gestational diabetes mellitus and impaired glucose tolerance.

PubMed

Yang, Sae Jeong; Kim, Tae Nyun; Baik, Sei Hyun; Kim, Tae Sun; Lee, Kwan Woo; Nam, Moonsuk; Park, Yong Soo; Woo, Jeong-Teak; Kim, Young Seol; Kim, Sung-Hoon

2013-05-01

The aim was to compare the insulin sensitivity and secretion index of pregnant Korean women with normal glucose tolerance (NGT), gestational impaired glucose tolerance (GIGT; only one abnormal value according to the Carpenter and Coustan criteria), and gestational diabetes mellitus (GDM). A cross-sectional study was performed with 1,163 pregnant women with positive (1-hour plasma glucose ≥ 7.2 mmol/L) in a 50-g oral glucose challenge test (OGCT). The 100-g oral glucose tolerance test (OGTT) was used to stratify the participants into three groups: NGT (n = 588), GIGT (n = 294), and GDM (n = 281). The GDM group had higher homeostasis model assessment of insulin resistance and lower insulin sensitivity index (ISOGTT), quantitative insulin sensitivity check index, homeostasis model assessment for estimation of index β-cell secretion (HOMA-B), first and second phase insulin secretion, and insulin secretion-sensitivity index (ISSI) than the NGT group (p ≤ 0.001 for all). Moreover, the GIGT group had lower ISOGTT, HOMA-B, first and second phase insulin secretion, and ISSI than the NGT group (p < 0.001 for all). Among the GIGT subjects, the 1-hour plasma glucose abnormal levels group showed significantly greater weight gain during pregnancy and higher values in the 50-g OGCT than the other two groups. Moreover, the 1-hour and 2-hour abnormal levels groups had poorer insulin secretion status than the 3-hour abnormal levels group. Korean women with GDM show impairments of both insulin secretion and insulin sensitivity. In addition, GIGT is associated with both β-cell dysfunction and insulin resistance.

Chicken-based formula is better tolerated than extensively hydrolyzed casein formula for the management of cow milk protein allergy in infants.

PubMed

Jirapinyo, Pipop; Densupsoontorn, Narumon; Kangwanpornsiri, Channagan; Wongarn, Renu

2012-01-01

The effective treatment of cow milk allergy in infants consists of elimination of cow milk protein and the introduction of formulas based on an extensively hydrolyzed protein formula or an amino acid-based formula. However, about 10% of these infants are still allergic to an extensively hydrolyzed protein formula and an amino acid-based formula is very expensive. We conducted a study to verify whether the new chicken-based formula will be better tolerated than an extensively hydrolyzed protein formula for the treatment of cow milk allergy in infants. One hundred infants, diagnosed with cow milk allergy by double-blind, placebo-controlled food challenge tests, were enrolled in a double-blind, randomized, cross-over study to compare a response to an extensively hydrolyzed protein formula and the chicken-based formula. Subjects were randomly given one of the two formulas for 2 weeks. There was a 2-week washout period of taking an amino acid-based formula before being switched to the other formula for another 2 weeks. If the subjects showed allergic symptoms during the 2 weeks of test formula, they would be announced as intolerance or allergic to that formula. Sixty seven of 80 confirmed subjects agreed to enroll their infants. Fifty-eight subjects completed the study. Twenty and 33 infants were tolerant whereas and 38 and 25 infants were intolerant to an extensively hydrolyzed protein formula and the chicken-based formula, respectively. The chicken-based formula showed significantly better tolerance than an extensively hydrolyzed protein formula in the management of cow milk allergy in infants.

Early genetic testing of coastal Douglas-fir for Swiss needle cast tolerance.

Treesearch

Fatih Temel; G.R. Johnson; W.T. Adams

2005-01-01

The possibility of early testing coastal Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco) for Swiss needle cast (SNC; caused by Phaeocryptopus gaeumannii (Rohde) Petrak) tolerance was investigated using 55 Douglas-fir families from western Oregon. Seedlings were inoculated with P...

Comparative genomic and proteomic analyses of Clostridium acetobutylicum Rh8 and its parent strain DSM 1731 revealed new understandings on butanol tolerance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bao, Guanhui; University of Chinese Academy of Sciences, Beijing; Dong, Hongjun

Highlights: • Genomes of a butanol tolerant strain and its parent strain were deciphered. • Comparative genomic and proteomic was applied to understand butanol tolerance. • None differentially expressed proteins have mutations in its corresponding genes. • Mutations in ribosome might be responsible for the global difference of proteomics. - Abstract: Clostridium acetobutylicum strain Rh8 is a butanol-tolerant mutant which can tolerate up to 19 g/L butanol, 46% higher than that of its parent strain DSM 1731. We previously performed comparative cytoplasm- and membrane-proteomic analyses to understand the mechanism underlying the improved butanol tolerance of strain Rh8. In this work,more » we further extended this comparison to the genomic level. Compared with the genome of the parent strain DSM 1731, two insertion sites, four deletion sites, and 67 single nucleotide variations (SNVs) are distributed throughout the genome of strain Rh8. Among the 67 SNVs, 16 SNVs are located in the predicted promoters and intergenic regions; while 29 SNVs are located in the coding sequence, affecting a total of 21 proteins involved in transport, cell structure, DNA replication, and protein translation. The remaining 22 SNVs are located in the ribosomal genes, affecting a total of 12 rRNA genes in different operons. Analysis of previous comparative proteomic data indicated that none of the differentially expressed proteins have mutations in its corresponding genes. Rchange Algorithms analysis indicated that the mutations occurred in the ribosomal genes might change the ribosome RNA thermodynamic characteristics, thus affect the translation strength of these proteins. Take together, the improved butanol tolerance of C. acetobutylicum strain Rh8 might be acquired through regulating the translational process to achieve different expression strength of genes involved in butanol tolerance.« less

Factors predicting early postpartum glucose intolerance in Japanese women with gestational diabetes mellitus: decision-curve analysis.

PubMed

Kondo, M; Nagao, Y; Mahbub, M H; Tanabe, T; Tanizawa, Y

2018-04-29

To identify factors predicting early postpartum glucose intolerance in Japanese women with gestational diabetes mellitus, using decision-curve analysis. A retrospective cohort study was performed. The participants were 123 Japanese women with gestational diabetes who underwent 75-g oral glucose tolerance tests at 8-12 weeks after delivery. They were divided into a glucose intolerance and a normal glucose tolerance group based on postpartum oral glucose tolerance test results. Analysis of the pregnancy oral glucose tolerance test results showed predictive factors for postpartum glucose intolerance. We also evaluated the clinical usefulness of the prediction model based on decision-curve analysis. Of 123 women, 78 (63.4%) had normoglycaemia and 45 (36.6%) had glucose intolerance. Multivariable logistic regression analysis showed insulinogenic index/fasting immunoreactive insulin and summation of glucose levels, assessed during pregnancy oral glucose tolerance tests (total glucose), to be independent risk factors for postpartum glucose intolerance. Evaluating the regression models, the best discrimination (area under the curve 0.725) was obtained using the basic model (i.e. age, family history of diabetes, BMI ≥25 kg/m 2 and use of insulin during pregnancy) plus insulinogenic index/fasting immunoreactive insulin <1.1. Decision-curve analysis showed that combining insulinogenic index/fasting immunoreactive insulin <1.1 with basic clinical information resulted in superior net benefits for prediction of postpartum glucose intolerance. Insulinogenic index/fasting immunoreactive insulin calculated using oral glucose tolerance test results during pregnancy is potentially useful for predicting early postpartum glucose intolerance in Japanese women with gestational diabetes. © 2018 Diabetes UK.

Tolerance response of multidrug-resistant Salmonella enterica strains to habituation to Origanum vulgare L. essential oil

PubMed Central

Monte, Daniel F. M.; Tavares, Adassa G.; Albuquerque, Allan R.; Sampaio, Fábio C.; Oliveira, Tereza C. R. M.; Franco, Octavio L.; Souza, Evandro L.; Magnani, Marciane

2014-01-01

Multidrug-resistant Salmonella enterica isolates from human outbreaks or from poultry origin were investigated for their ability to develop direct-tolerance or cross-tolerance to sodium chloride, potassium chloride, lactic acid, acetic acid, and ciprofloxacin after habituation in subinhibitory amounts ( of the minimum inhibitory concentration – (MIC) and of the minimum inhibitory concentration – MIC) of Origanum vulgare L. essential oil (OVEO) at different time intervals. The habituation of S. enterica to OVEO did not induce direct-tolerance or cross-tolerance in the tested strains, as assessed by the modulation of MIC values. However, cells habituated to OVEO maintained or increased susceptibility to the tested antimicrobials agents, with up to fourfold double dilution decrease from previously determined MIC values. This study reports for the first time the non-inductive effect of OVEO on the acquisition of direct-tolerance or cross-tolerance in multidrug-resistant S. enterica strains to antimicrobial agents that are largely used in food preservation, as well as to CIP, the therapeutic drug of salmonellosis. PMID:25566231

Timing and Frequency of Sublethal Exposure Modifies the Induction and Retention of Increased Insecticide Tolerance in Wood Frogs (Lithobates sylvaticus).

PubMed

Jones, Devin K; Yates, Erika K; Mattes, Brian M; Hintz, William D; Schuler, Matthew S; Relyea, Rick A

2018-05-22

While the paradigm for increased tolerance to pesticides has been by selection on constitutive (naïve) traits, recent research has shown it can also occur through phenotypic plasticity. However, the time period in which induction can occur, the duration of induced tolerance, and the influence of multiple induction events remain unknown. We hypothesized that the induction of increased pesticide tolerance is limited to early sensitive periods, the magnitude of induced tolerance depends on the number of exposures, and the retention of induced tolerance depends on the time elapsed after an exposure and the number of exposures. To test these hypotheses, we exposed wood frog tadpoles to either a no-carbaryl control (water) or 0.5 mg/L carbaryl at four time periods, and later tested their tolerance to carbaryl using time-to-death assays. We discovered that tadpoles induced increased tolerance early and midway, but not late, in our experiment and their constitutive tolerance increased with age. We found no difference in the magnitude of induced tolerance following one or two exposures. Lastly, induced pesticide tolerance was reversed within 6 d, but was retained only when tadpoles experienced all four consecutive exposures. Phenotypic plasticity provides an immediate response for sensitive amphibian larvae to early pesticide exposures and reduces phenotypic mismatches in aquatic environments contaminated by agrochemicals. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

135-Day Interventions of Yam Dioscorin and the Dipeptide Asn-Trp (NW) To Reduce Weight Gains and Improve Impaired Glucose Tolerances in High-Fat Diet-Induced C57BL/6 Mice.

PubMed

Wu, Guang-Cheng; Lin, Shyr-Yi; Liang, Hong-Jen; Hou, Wen-Chi

2018-01-24

The C57BL/6J mice were fed a 135-day normal diet or a high-fat diet (HFD) without, or concurrent with, a single yam dioscorin (80 mg/kg) or dipeptide NW (40 mg/kg) intervention every day. The final body weights (g) of mice were 26.1 ± 1.4, 34.97 ± 2.1, 31.75 ± 2.6, and 31.66 ± 3.1, respectively, for normal diet-fed, HFD-fed, dioscorin-intervened, and NW-intervened group. The mice in both intervened groups showed similar less weight gains and had significant differences (P < 0.05) compared to those in the HFD group under the same cumulative HFD intakes. The blood biochemical index of mice with dioscorin interventions showed significantly lower contents in total cholesterol and low-density lipoprotein, and NW interventions showed significantly lower total triglyceride contents compared to those of the HFD group (P < 0.05). Both intervened mice exhibited similar reductions in total visceral lipid contents and have significant differences compared to those of the HFD group (P < 0.05). The dioscorin intervention was better than NW interventions in lowering blood glucose levels by oral glucose tolerance tests and both showed significant differences (P < 0.05) compared to those in the HFD group. Yam dioscorin or dipeptide NW will potentially be used for preventive functional foods of less body weight gains and impaired glucose tolerance controls, which require further clinical trial investigations.

Assessment of the antidandruff activity of a new shampoo: a randomized, double-blind, controlled study by clinical and instrumental evaluations.

PubMed

Sparavigna, Adele; Setaro, Michele; Caserini, Maurizio; Bulgheroni, Anna

2013-01-01

The aim of this randomized, double-blind, controlled study was to evaluate the antidandruff activity exerted by a new shampoo on patients affected by dandruff and/or mild seborrheic dermatitis by means of both D-squame technique coupled with image analysis and clinical assessments. Thirty-four patients were enrolled and 1:1 randomly assigned to either a test shampoo or a comparative shampoo group. Treatment schedule was twice a week for 4 weeks. The D-squame technique was shown to be able to objectively record variations in scalp desquamation both between test and comparative groups and within the same group over time. The results obtained with this instrumental approach showed a statistically significant reduction by 52% vs baseline after 2 weeks of treatment. There was an even greater reduction after 4 weeks (-66%). This reduction was statistically significant compared with the comparative group at the same time points. The analysis of all the other parameters (except Wood's lamp) confirmed the superiority of the test vs the comparative shampoo. The test shampoo proved to be safe, well tolerated, and accepted by the patients for cosmetic acceptability and efficacy. The study confirmed the antidandruff efficacy of the test shampoo and its superiority vs the comparative shampoo.

Comparison of 70 deg tilt, LBNP, and passive standing as measures of orthostatic tolerance

NASA Technical Reports Server (NTRS)

Hyatt, K. H.; Jacobson, L. B.; Schneider, V. S.

1975-01-01

The present study was performed to assess the reliability of lower body negative pressure (LBNP) as a test of orthostatic tolerance. The need for this assessment arose from the prior observation in this laboratory that some subjects show wide day-to-day variation in heart rate responses to LBNP. The extent of these variations was so great as to raise a serious question as to the value of LBNP as a measure of study-induced alterations (e.g., those produced by bedrest or weightlessness) in orthostatic tolerance. Five healthy volunteers were subjected to a series of tests, consisting of 70 deg tilt, LBNP, and passive standing, on three occasions preceding and three occasions following a 2-week period of bedrest. Study results show that it is possible to subdivide the volunteers into subgroups which show either great or little day-to-day variability in any of the three tests. All three tests revealed bedrest-induced alterations in orthostatic tolerance quite adequately. Of the three tests studied, LBNP most frequently resulted in the largest test-induced heart rate alterations, followed by quiet standing and, finally 70 deg tilt.

Tolerance limit value of brightness and contrast adjustment on digitized radiographs

NASA Astrophysics Data System (ADS)

Utami, S. N.; Kiswanjaya, B.; Syahraini, S. I.; Ustriyana, P.

2017-08-01

The aim of this study was to measure the tolerance limit value of brightness and contrast adjustment on digitized radiograph with apical periodontitis and early apical abscess. Brightness and contrast adjustment on 60 periapical radiograph with apical periodontitis and early apical abscess made by 2 observers. Reliabilities tested by Cohen’s Kappa Coefficient and significance tested by wilcoxon test. Tolerance limit value of brightness and contrast adjustment for apical periodontitis is -5 and +5, early apical abscess is -10 and +10, and both is -5 and +5. Brightness and contrast adjustment which not appropriate can alter the evaluation and differential diagnosis of periapical lesion.

Further investigation of relationships between membrane fluidity and ethanol tolerance in Saccharomyces cerevisiae.

PubMed

Ishmayana, Safri; Kennedy, Ursula J; Learmonth, Robert P

2017-11-27

Membrane lipid unsaturation index and membrane fluidity have been related to yeast ethanol stress tolerance in published studies, however findings have been inconsistent. In this study, viability reduction on exposure to 18% (v/v) ethanol was compared to membrane fluidity determined by laurdan generalized polarization. Furthermore, in the determination of viability reduction, we examined the effectiveness of two methods, namely total plate count and methylene violet staining. We found a strong negative correlation between ethanol tolerance and membrane fluidity, indicated by negative Pearson correlation coefficients of - 0.79, - 0.65 and - 0.69 for Saccharomyces cerevisiae strains A12, PDM and K7, respectively. We found that lower membrane fluidity leads to higher ethanol tolerance, as indicated by decreased viability reduction and higher laurdan generalized polarization in respiratory phase compared to respiro-fermentative phase cells. Total plate count better differentiated ethanol tolerance of yeast cells in different growth phases, while methylene violet staining was better to differentiate ethanol tolerance of the different yeast strains at a particular culture phase. Hence, both viability assessment methods have their own advantages and limitations, which should be considered when comparing stress tolerance in different situations.

Comparative Metabolomic Analyses of Ipomoea lacunosa Biotypes with Contrasting Glyphosate Tolerance Captures Herbicide-Induced Differential Perturbations in Cellular Physiology.

PubMed

Maroli, Amith S; Nandula, Vijay K; Duke, Stephen O; Gerard, Patrick; Tharayil, Nishanth

2018-02-28

Glyphosate-tolerant Ipomoea lacunosa is emerging as a problematic weed in the southeastern United States. Metabolomic profiling was conducted to examine the innate physiology and the glyphosate induced perturbations in two biotypes of I. lacunosa (WAS and QUI) that had contrasting glyphosate tolerance. Compared to the less tolerant QUI-biotype, the innate metabolism of the more tolerant WAS-biotype was characterized by a higher abundance of amino acids, and pyruvate; whereas the sugar profile of the QUI biotype was dominated by the transport sugar sucrose. Glyphosate application (80 g ae/ha) caused similar shikimate accumulation in both biotypes. Compared to QUI, in WAS, the content of aromatic amino acids was less affected by glyphosate treatment, and the content of Ala, Val, Ile, and Pro increased. However, the total sugars decreased by ∼75% in WAS, compared to ∼50% decrease in QUI. The innate, higher proportional abundance, of the transport-sugar sucrose in QUI coud partly explain the higher translocation and greater sensitivity of this biotype to glyphosate. The decrease in sugars, accompanied by an increase in amino acids could delay feedback regulation of upstream enzymes of the shikimate acid pathway in WAS, which could contribute to a greater glyphosate tolerance. Our study, through a metabolomics approach, provides complementary data that elucidates the cellular physiology of herbicide tolerance in Ipomoea lacunosa biotypes.

Cardiorespiratory assessment of 24-hour crash-diet effects on altitude, +Gz, and fatigue tolerances.

DOT National Transportation Integrated Search

1981-02-01

Eleven male surrogates of general aviation pilots, 25-40 years old, were tested for altitude, +Gz, and fatigue tolerances with and without previous fasting for 24 h. Testing included 2 min of lower body negative pressure (LBNP) at -40 torr (equivalen...

77 FR 56782 - Bifenthrin; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-14

..., hay. Interregional Research Project Number 4 (IR-4) requested these tolerances under the Federal Food... OCSPP test guidelines referenced in this document electronically, please go to http://www.epa.gov/ocspp and select ``Test Methods and Guidelines.'' C. How can I file an objection or hearing request? Under...

78 FR 55635 - Prometryn; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-11

.... Interregional Research Project Number 4 (IR-4) requested these tolerances under the Federal Food, Drug, and... test guidelines referenced in this document electronically, please go to http://www.epa.gov/ocspp and select ``Test Methods and Guidelines. C. How can I file an objection or hearing request? Under FFDCA...

Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs.

PubMed

Sachs, B; Al Masaoudi, T; Merk, H F; Erdmann, S

2004-10-01

Amino-penicillins are a major cause of delayed-type reactions to penicillins. The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.

Effect of resin on impact damage tolerance of graphite/epoxy laminates

NASA Technical Reports Server (NTRS)

Williams, J. G.; Rhodes, M. D.

1982-01-01

Twenty-four different epoxy resin systems were evaluated by a variety of test techniques to identify materials that exhibited improved impact damage tolerance in graphite/epoxy composite laminates. Forty-eight-ply composite panels of five of the material systems were able to sustain 100 m/s impact by a 1.27-cm-diameter aluminum projectile while statically loaded to strains of 0.005. Of the five materials with the highest tolerance to impact, two had elastomeric additives, two had thermoplastic additives, and one had a vinyl modifier; all the five systems used bisphenol A as the base resin. An evaluation of test results shows that the laminate damage tolerance is largely determined by the resin tensile properties, and that improvements in laminate damage tolerance are not necessarily made at the expense of room-temperature mechanical properties. The results also suggest that a resin volume fraction of 40 percent or greater may be required to permit the plastic flow between fibers necessary for improved damage tolerance.

Tolerability of 2.5% Lidocaine/Prilocaine Hydrogel in Children Undergoing Cryotherapy for Molluscum Contagiosum.

PubMed

Gobbato, André A M; Babadópulos, Tainah; Gobbato, Cintia A R S; Moreno, Ronilson A; Gagliano-Jucá, Thiago; De Nucci, Gilberto

2016-05-01

The tolerability of a 2.5% lidocaine/prilocaine hydrogel (Nanorap, Biolab Indústria Farmacêutica Ltd., Sao Paulo, Brazil) was evaluated in 20 children ages 2 to 11 years undergoing cryotherapy for molluscum contagiosum (MC). The product was well tolerated, with only two children presenting with eczema at the application site. These adverse reactions were considered unlikely to be related to the test product, because a patch test was negative in one of the individuals and the other event occurred in only one of the two treated areas. Nanorap is an efficacious and well-tolerated option for topical anesthesia in children undergoing cryotherapy for MC. © 2016 Wiley Periodicals, Inc.

Is the OJIP Test a Reliable Indicator of Winter Hardiness and Freezing Tolerance of Common Wheat and Triticale under Variable Winter Environments?

PubMed Central

Rapacz, Marcin; Sasal, Monika; Kalaji, Hazem M.; Kościelniak, Janusz

2015-01-01

OJIP analysis, which explores changes in photosystem II (PSII) photochemical performance, has been used as a measure of plant susceptibility to stress. However, in the case of freezing tolerance and winter hardiness, which are highly environmentally variable, the use of this method can give ambiguous results depending on the species as well as the sampling year and time. To clarify this issue, we performed chlorophyll fluorescence measurements over three subsequent winters (2010/11, 2011/12 and 2012/13) on 220 accessions of common winter wheat and 139 accessions of winter triticale. After freezing, leaves were collected from cold-acclimated plants in the laboratory and field-grown plants. Observations of field survival in seven locations across Poland and measurements of freezing tolerance of the studied plants were also recorded. Our results confirm that the OJIP test is a reliable indicator of winter hardiness and freezing tolerance of common wheat and triticale under unstable winter environments. Regardless of species, the testing conditions giving the most reliable results were identical, and the reliability of the test could be easily checked by analysis of some relationships between OJIP-test parameters. We also found that triticale is more winter hardy and freezing tolerant than wheat. In addition, the two species were characterized by different patterns of photosynthetic apparatus acclimation to cold. PMID:26230839

Is the OJIP Test a Reliable Indicator of Winter Hardiness and Freezing Tolerance of Common Wheat and Triticale under Variable Winter Environments?

PubMed

Rapacz, Marcin; Sasal, Monika; Kalaji, Hazem M; Kościelniak, Janusz

2015-01-01

OJIP analysis, which explores changes in photosystem II (PSII) photochemical performance, has been used as a measure of plant susceptibility to stress. However, in the case of freezing tolerance and winter hardiness, which are highly environmentally variable, the use of this method can give ambiguous results depending on the species as well as the sampling year and time. To clarify this issue, we performed chlorophyll fluorescence measurements over three subsequent winters (2010/11, 2011/12 and 2012/13) on 220 accessions of common winter wheat and 139 accessions of winter triticale. After freezing, leaves were collected from cold-acclimated plants in the laboratory and field-grown plants. Observations of field survival in seven locations across Poland and measurements of freezing tolerance of the studied plants were also recorded. Our results confirm that the OJIP test is a reliable indicator of winter hardiness and freezing tolerance of common wheat and triticale under unstable winter environments. Regardless of species, the testing conditions giving the most reliable results were identical, and the reliability of the test could be easily checked by analysis of some relationships between OJIP-test parameters. We also found that triticale is more winter hardy and freezing tolerant than wheat. In addition, the two species were characterized by different patterns of photosynthetic apparatus acclimation to cold.

A modeling intervention in heart failure.

PubMed

Maddison, Ralph; Prapavessis, Harry; Armstrong, Guy P; Hill, Caleb

2008-08-01

Peak oxygen uptake (VO(2)) testing is commonly used to assess chronic heart failure (CHF) patients' exercise tolerance. The test requires maximal effort; however, many participants have low confidence (self-efficacy) to perform optimally. This randomized controlled trial examined the effectiveness of a modeling intervention to increase Peak VO(2) (PVO(2)) and self-efficacy in people diagnosed with CHF. Twenty participants with a diagnosis of CHF were randomized to either an intervention (modeling DVD) or a control group. Both groups completed a measure of self-efficacy prior to performing two PVO(2) tests, each separated by 7 days. After completing the first test (T1) the intervention group watched a 10-min coping model DVD. All participants returned 1 week later (T2) to complete identical study procedures. Analysis of covariance results showed that compared with the participants in the control group, those assigned to the modeling intervention had higher PVO(2) at T2, F (1, 19) = 4.38, p = 0.05, eta (2) = 0.21 and self-efficacy, F (1, 19) = 5.80, p < 0.05, eta (2) = 0.25. Only partial support was found for change in self-efficacy mediating treatment outcome (PVO(2)). Watching a modeling video is associated with increased PVO(2) and self-efficacy. These results have implications for testing patients in a clinical setting to maximize exercise tolerance test results.

An Efficient Implementation of Fixed Failure-Rate Ratio Test for GNSS Ambiguity Resolution.

PubMed

Hou, Yanqing; Verhagen, Sandra; Wu, Jie

2016-06-23

Ambiguity Resolution (AR) plays a vital role in precise GNSS positioning. Correctly-fixed integer ambiguities can significantly improve the positioning solution, while incorrectly-fixed integer ambiguities can bring large positioning errors and, therefore, should be avoided. The ratio test is an extensively used test to validate the fixed integer ambiguities. To choose proper critical values of the ratio test, the Fixed Failure-rate Ratio Test (FFRT) has been proposed, which generates critical values according to user-defined tolerable failure rates. This contribution provides easy-to-implement fitting functions to calculate the critical values. With a massive Monte Carlo simulation, the functions for many different tolerable failure rates are provided, which enriches the choices of critical values for users. Moreover, the fitting functions for the fix rate are also provided, which for the first time allows users to evaluate the conditional success rate, i.e., the success rate once the integer candidates are accepted by FFRT. The superiority of FFRT over the traditional ratio test regarding controlling the failure rate and preventing unnecessary false alarms is shown by a simulation and a real data experiment. In the real data experiment with a baseline of 182.7 km, FFRT achieved much higher fix rates (up to 30% higher) and the same level of positioning accuracy from fixed solutions as compared to the traditional critical value.

Flight test results of the strapdown hexad inertial reference unit (SIRU). Volume 2: Test report

NASA Technical Reports Server (NTRS)

Hruby, R. J.; Bjorkman, W. S.

1977-01-01

Results of flight tests of the Strapdown Inertial Reference Unit (SIRU) navigation system are presented. The fault tolerant SIRU navigation system features a redundant inertial sensor unit and dual computers. System software provides for detection and isolation of inertial sensor failures and continued operation in the event of failures. Flight test results include assessments of the system's navigational performance and fault tolerance. Performance shortcomings are analyzed.

Low HDL-cholesterol among normal weight, normoglycemic offspring of individuals with type 2 diabetes mellitus.

PubMed

Praveen, Edavan P; Kulshreshtha, Bindu; Khurana, Madan L; Sahoo, Jayaprakash; Gupta, Nandita; Kumar, Guresh; Ammini, Ariachery; Knadgawat, Rajech

2011-01-01

Offspring of type 2 diabetics have an increased risk of dyslipidemia, glucose intolerance and obesity. The aim of this study was to assess the lipid levels in the offspring of diabetics with normal glucose tolerance and normal body weight. Normal weight offspring of patients with type 2 diabetes mellitus (DM) who had normal glucose tolerance, and healthy gender matched controls of comparable age without a family history of diabetes mellitus, were the subjects of this study. Lipid profiles were determined in cases and controls. The study included 114 subjects (64 males and 50 females) in each group, aged (mean ± SD) 24.0 ± 7.9 in cases and 24.1 ± 8.0 years in controls. The body mass index (BMI) was 20.8 ± 3.0 and 20.2 ± 3.1 kg/m2 in cases and controls, respectively. Serum total cholesterol, triglycerides, plasma glucose, fasting insulin, C-peptide and proinsulin levels were comparable in cases and controls. Serum high density lipoprotein (HDL) cholesterol was lower (p <0.001), whilst the serum triglyceride/HDL ratio, low density lipoprotein (LDL) cholesterol and area under the curve for insulin and proinsulin during an oral glucose tolerance test were higher in cases compared to controls. HDL cholesterol showed no significant correlation with plasma glucose, insulin or proinsulin. Plasma HDL cholesterol is low among normal weight, normoglycemic offspring of subjects with type 2 diabetes mellitus. The implications of this finding are not apparent.

The conditional indirect effect model of women's union participation: the moderating effect of perceived union tolerance for sexual harassment.

PubMed

Mellor, Steven; Golay, Leslie M

2014-01-01

We tested a theoretically trimmed model of union participation presented by Tetrick, Shore, McClurg, and Vandenberg (2007), in which perceived union instrumentality is expected to influence participation through perceived union support. This testing was accomplished as a precursor to testing a conditional indirect effect model of women's participation--in which perceived union tolerance for sexual harassment was expected to moderate the influence of perceived support on willingness to participate in union activities. In a sample of 326 women from multiple unions, we found support for the conditional model; the influence of perceived instrumentality on willingness to participate through perceived support was moderated by perceived tolerance for harassment; specifically, the influence through perceived support was weak when perceived tolerance was high. The implications of our results are discussed in reference to need support and women's participation.

Wind selectivity and partial compensation for wind drift among nocturnally migrating passerines

PubMed Central

McLaren, James D.

2012-01-01

A migrating bird’s response to wind can impact its timing, energy expenditure, and path taken. The extent to which nocturnal migrants select departure nights based on wind (wind selectivity) and compensate for wind drift remains unclear. In this paper, we determine the effect of wind selectivity and partial drift compensation on the probability of successfully arriving at a destination area and on overall migration speed. To do so, we developed an individual-based model (IBM) to simulate full drift and partial compensation migration of juvenile Willow Warblers (Phylloscopus trochilus) along the southwesterly (SW) European migration corridor to the Iberian coast. Various degrees of wind selectivity were tested according to how large a drift angle and transport cost (mechanical energy per unit distance) individuals were willing to tolerate on departure after dusk. In order to assess model results, we used radar measurements of nocturnal migration to estimate the wind selectivity and proportional drift among passerines flying in SW directions. Migration speeds in the IBM were highest for partial compensation populations tolerating at least 25% extra transport cost compared to windless conditions, which allowed more frequent departure opportunities. Drift tolerance affected migration speeds only weakly, whereas arrival probabilities were highest with drift tolerances below 20°. The radar measurements were indicative of low drift tolerance, 25% extra transport cost tolerance and partial compensation. We conclude that along migration corridors with generally nonsupportive winds, juvenile passerines should not strictly select supportive winds but partially compensate for drift to increase their chances for timely and accurate arrival. PMID:22936843

Wind selectivity and partial compensation for wind drift among nocturnally migrating passerines.

PubMed

McLaren, James D; Shamoun-Baranes, Judy; Bouten, Willem

2012-09-01

A migrating bird's response to wind can impact its timing, energy expenditure, and path taken. The extent to which nocturnal migrants select departure nights based on wind (wind selectivity) and compensate for wind drift remains unclear. In this paper, we determine the effect of wind selectivity and partial drift compensation on the probability of successfully arriving at a destination area and on overall migration speed. To do so, we developed an individual-based model (IBM) to simulate full drift and partial compensation migration of juvenile Willow Warblers (Phylloscopus trochilus) along the southwesterly (SW) European migration corridor to the Iberian coast. Various degrees of wind selectivity were tested according to how large a drift angle and transport cost (mechanical energy per unit distance) individuals were willing to tolerate on departure after dusk. In order to assess model results, we used radar measurements of nocturnal migration to estimate the wind selectivity and proportional drift among passerines flying in SW directions. Migration speeds in the IBM were highest for partial compensation populations tolerating at least 25% extra transport cost compared to windless conditions, which allowed more frequent departure opportunities. Drift tolerance affected migration speeds only weakly, whereas arrival probabilities were highest with drift tolerances below 20°. The radar measurements were indicative of low drift tolerance, 25% extra transport cost tolerance and partial compensation. We conclude that along migration corridors with generally nonsupportive winds, juvenile passerines should not strictly select supportive winds but partially compensate for drift to increase their chances for timely and accurate arrival.

Transient improvement after brief antiepileptic drug withdrawal in the epilepsy monitoring unit--possible relationship to AED tolerance.

PubMed

Azar, Nabil J; Lagrange, Andre H; Wang, Lily; Song, Yanna; Abou-Khalil, Bassel W

2010-05-01

A drug holiday seems to produce seizure interval prolongation (SIP) after reinstitution of antiepileptic drugs (AEDs). This effect was demonstrated mainly with carbamazepine. We evaluated SIP with newer AEDs and tested the relationship of SIP to history of AED tolerance. We prospectively studied patients with refractory epilepsy admitted to the Vanderbilt epilepsy monitoring unit (EMU) over a period of 12 months. We included only patients on levetiracetam, lamotrigine, or oxcarbazepine who had their AEDs withdrawn on admission and reinstituted without change upon discharge. We defined SIP as the interval from EMU discharge to first seizure minus the interval between the last two seizures before EMU admission. A total of 43 patients completed the study; 15 were on monotherapy. SIP was greater than zero in this patient group (p < 0.0001), with a mean prolongation of 19.4 +/- 28.0 days. The average SIP was higher (p = 0.01) in patients on monotherapy (29.7 +/- 23.8 days) than patients on polytherapy (13.9 +/- 29.0 days). SIP tended to be greater in patients with a prior history of AED tolerance (25.7 +/- 36.8 days) compared to patient with no prior history of AED tolerance (14.0 +/- 16.3 days). SIP does occur after brief AED withdrawal. This effect is greater in patients on monotherapy and tends to be larger in patients with a history of AED tolerance. The SIP effect may be related to the phenomenon of tolerance, clinically seen as resistance to AED therapeutic effect.

Biological profile and bioavailability of imidazoline compounds on morphine tolerance modulation.

PubMed

Caprioli, Giovanni; Mammoli, Valerio; Ricciutelli, Massimo; Sagratini, Gianni; Ubaldi, Massimo; Domi, Esi; Mennuni, Laura; Sabatini, Chiara; Galimberti, Chiara; Ferrari, Flora; Milia, Chiara; Comi, Eleonora; Lanza, Marco; Giannella, Mario; Pigini, Maria; Del Bello, Fabio

2015-12-15

Tolerance to opioid administration represents a serious medical alert in different chronic conditions. This study compares the effects of the imidazoline compounds 1, 2, and 3 on morphine tolerance in an animal model of inflammatory pain in the rat. 1, 2, and 3 have been selected in that, although bearing a common scaffold, preferentially bind to α2-adrenoceptors, imidazoline I2 receptors, or both systems, respectively. Such compounds have been tested in vivo by measuring the paw withdrawal threshold to mechanical pressure after complete Freund's adjuvant injection. To determine the ligand levels in rat plasma, an HPLC-mass spectrometry method has been developed. All the compounds significantly reduced the induction of morphine tolerance, showing different potency and duration of action. Indeed, the selective imidazoline I2 receptor interaction (2) restored the analgesic response by maintaining the same time-dependent profile observed after a single morphine administration. Differently, the selective α2C-adrenoceptor activation (1) or the combination between α2C-adrenoceptor activation and imidazoline I2 receptor engagement (3) promoted a change in the temporal profile of morphine analgesia by maintaining a mild but long lasting analgesic effect. Interestingly, the kinetics of compounds in rat plasma supported the pharmacodynamic data. Therefore, this study highlights that both peculiar biological profile and bioavailability of such ligands complement each other to modulate the reduction of morphine tolerance. Based on these observations, 1-3 can be considered useful leads in the design of new drugs able to turn off the undesired tolerance induced by opioids. Copyright © 2015 Elsevier B.V. All rights reserved.

Talk, Silence and Anxiety during One-To-One Tutorials: A Cross-Cultural Comparative Study of Japan and UK Undergraduates' Tolerance of Silence

ERIC Educational Resources Information Center

King, Jim; Aono, Atsuko

2017-01-01

This paper discusses the issue of tolerance of silence within university tutorials from a cross-cultural, comparative perspective. A mixed methods, quasi-experimental approach was employed to measure the length of silence which individual students from samples in Japan and the UK tolerated during a one-to-one staged encounter with their…

Nickel detoxification and plant growth promotion by multi metal resistant plant growth promoting Rhizobium species RL9.

PubMed

Wani, Parvaze Ahmad; Khan, Mohammad Saghir

2013-07-01

Pollution of the biosphere by heavy metals is a global threat that has accelerated dramatically since the beginning of industrial revolution. The aim of the study is to check the resistance of RL9 towards the metals and to observe the effect of Rhizobium species on growth, pigment content, protein and nickel uptake by lentil in the presence and absence of nickel. The multi metal tolerant and plant growth promoting Rhizobium strain RL9 was isolated from the nodules of lentil. The strain not only tolerated nickel but was also tolerant o cadmium, chromium, nickel, lead, zinc and copper. The strain tolerated nickel 500 μg/mL, cadmium 300 μg/mL, chromium 400 μg/mL, lead 1,400 μg/mL, zinc 1,000 μg/mL and copper 300 μg/mL, produced good amount of indole acetic acid and was also positive for siderophore, hydrogen cyanide and ammonia. The strain RL9 was further assessed with increasing concentrations of nickel when lentil was used as a test crop. The strain RL9 significantly increased growth, nodulation, chlorophyll, leghaemoglobin, nitrogen content, seed protein and seed yield compared to plants grown in the absence of bioinoculant but amended with nickel The strain RL9 decreased uptake of nickel in lentil compared to plants grown in the absence of bio-inoculant. Due to these intrinsic abilities strain RL9 could be utilized for growth promotion as well as for the remediation of nickel in nickel contaminated soil.

Hyaluronic acid improves "pleasantness" and tolerability of nebulized hypertonic saline in a cohort of patients with cystic fibrosis.

PubMed

Buonpensiero, Paolo; De Gregorio, Fabiola; Sepe, Angela; Di Pasqua, Antonio; Ferri, Pasqualina; Siano, Maria; Terlizzi, Vito; Raia, Valeria

2010-11-01

Inhaled hypertonic saline improves lung function and decreases pulmonary exacerbations in people with cystic fibrosis. However, side effects such as cough, narrowing of airways and saltiness cause intolerance of the therapy in 8% of patients. The aim of our study was to compare the effect of an inhaled solution of hyaluronic acid and hypertonic saline with hypertonic solution alone on safety and tolerability. A total of 20 patients with cystic fibrosis aged 6 years and over received a single treatment regimen of 7% hypertonic saline solution or hypertonic solution with 0.1% hyaluronate for 2 days nonconsecutively after a washout period in an open crossover study. Cough, throat irritation, and salty taste were evaluated by a modified ordinal score for assessing tolerability; "pleasantness" was evaluated by a five-level, Likert-type scale. Forced expiratory volume in 1 second was registered before and after the end of the saline inhalations. All 20 patients (nine males, 11 females, mean age 13 years, range 8.9-17.7) completed the study. The inhaled solution of 0.1% hyaluronic acid and hypertonic saline significantly improved tolerability and pleasantness compared to hypertonic saline alone. No major adverse effects were observed. No difference was documented in pulmonary function tests between the two treatments. Hyaluronic acid combined with hypertonic saline solution may contribute to improved adherence to hypertonic saline therapy. Further clinical trials are needed to confirm our findings. Considering the extraordinary versatility of hyaluronic acid in biological reactions, perspective studies could define its applicability to halting progression of lung disease in cystic fibrosis.

The horizontal computerized rotational impulse test.

PubMed

Furman, Joseph M; Shirey, Ian; Roxberg, Jillyn; Kiderman, Alexander

2016-01-01

Whole-body impulsive rotations were used to overcome several limitations associated with manual head impulse testing. A computer-controlled rotational chair delivered brief, whole-body, earth-vertical axis yaw impulsive rotations while eye movements were measured using video-oculography. Results from an unselected group of 20 patients with dizziness and a group of 22 control subjects indicated that the horizontal computerized rotational head impulse test (crHIT) is well-tolerated and provides an estimate of unidirectional vestibulo-ocular reflex gain comparable to results from caloric testing. This study demonstrates that the horizontal crHIT is a new assessment tool that overcomes many of the limitations of manual head impulse testing and provides a reliable laboratory-based measure of unilateral horizontal semicircular canal function.

Gestational diabetes mellitus screening, management and outcomes in the Cook Islands.

PubMed

Aung, Yin Yin May; Sowter, Martin; Kenealy, Timothy; Herman, Josephine; Ekeroma, Alec

2015-04-17

To describe current practices for screening for gestational diabetes mellitus in the Cook Islands and consider the implications of alternative screening strategies. Eligible women had antenatal care from January 2009 to December 2012. A non-fasting 50 g glucose challenge between 24 and 28 weeks gestation (positive if 1-hour glucose greater than or equal to 7.8 mmol/L) was followed by a 75 g oral glucose tolerance test (gestational diabetes mellitus diagnosed if fasting glucose greater than or equal to 5.2 mmol/L or 2-hour glucose greater than or equal to 8.0 mmol/L; pregnancy impaired glucose tolerance if positive screen and negative diagnostic test). Uptake of the screening programme rose from 49.0% to 99.6% by the end of the study period. 646 women had a glucose challenge; for 186/646 (28.8%) the challenge was positive; 183 had an oral glucose tolerance test; 89/646 (13.8%) had pregnancy impaired glucose tolerance; 94/646 (13.9%) had gestational diabetes mellitus. Median maternal weight gain was 6 kg (gestational diabetes mellitus) and 10 kg (normal glucose tolerance); caesarean section rates were 25% and 11% respectively; baby birthweights were not significantly different. 59 women with gestational diabetes mellitus had a post-natal glucose tolerance test at their 6-week check and 21 (35.6%) had diabetes confirmed. The gestational diabetes mellitus screening programme has a high uptake and current management appears effective in reducing maternal and fetal weight gain. A proposed new screening programme is outlined.

Test and analysis results for composite transport fuselage and wing structures

NASA Technical Reports Server (NTRS)

Deaton, Jerry W.; Kullerd, Susan M.; Madan, Ram C.; Chen, Victor L.

1992-01-01

Automated tow placement (ATP) and stitching of dry textile composite preforms followed by resin transfer molding (RTM) are being investigated by researchers at NASA LaRC and Douglas Aircraft Company as cost-effective manufacturing processes for obtaining damage tolerant fuselage and wing structures for transport aircraft. The Douglas work is being performed under a NASA contract entitled 'Innovative Composites Aircraft Primary Structures (ICAPS)'. Data are presented in this paper to assess the damage tolerance of ATP and RTM fuselage elements with stitched-on stiffeners from compression tests of impacted three-J-stiffened panels and from stiffener pull-off tests. Data are also presented to assess the damage tolerance of RTM wing elements which had stitched skin and stiffeners from impacted single stiffener and three blade-stiffened compression tests and stiffener pull-off tests.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Angers, Crystal Plume; Bottema, Ryan; Buckley, Les

Purpose: Treatment unit uptime statistics are typically used to monitor radiation equipment performance. The Ottawa Hospital Cancer Centre has introduced the use of Quality Control (QC) test success as a quality indicator for equipment performance and overall health of the equipment QC program. Methods: Implemented in 2012, QATrack+ is used to record and monitor over 1100 routine machine QC tests each month for 20 treatment and imaging units ( http://qatrackplus.com/ ). Using an SQL (structured query language) script, automated queries of the QATrack+ database are used to generate program metrics such as the number of QC tests executed and themore » percentage of tests passing, at tolerance or at action. These metrics are compared against machine uptime statistics already reported within the program. Results: Program metrics for 2015 show good correlation between pass rate of QC tests and uptime for a given machine. For the nine conventional linacs, the QC test success rate was consistently greater than 97%. The corresponding uptimes for these units are better than 98%. Machines that consistently show higher failure or tolerance rates in the QC tests have lower uptimes. This points to either poor machine performance requiring corrective action or to problems with the QC program. Conclusions: QATrack+ significantly improves the organization of QC data but can also aid in overall equipment management. Complimenting machine uptime statistics with QC test metrics provides a more complete picture of overall machine performance and can be used to identify areas of improvement in the machine service and QC programs.« less

40 CFR 172.3 - Scope of requirement.

Code of Federal Regulations, 2010 CFR

2010-07-01

... experimental use permit (EUP) is generally required for testing of any unregistered pesticide or any registered... testing for more than one target pest occurs at the same time and in the same locality, the 10 acre... experimental animals unless an appropriate tolerance or exemption from a tolerance has been established under...

40 CFR 172.3 - Scope of requirement.

Code of Federal Regulations, 2012 CFR

2012-07-01

... experimental use permit (EUP) is generally required for testing of any unregistered pesticide or any registered... testing for more than one target pest occurs at the same time and in the same locality, the 10 acre... experimental animals unless an appropriate tolerance or exemption from a tolerance has been established under...

Advanced information processing system - Status report. [for fault tolerant and damage tolerant data processing for aerospace vehicles

NASA Technical Reports Server (NTRS)

Brock, L. D.; Lala, J.

1986-01-01

The Advanced Information Processing System (AIPS) is designed to provide a fault tolerant and damage tolerant data processing architecture for a broad range of aerospace vehicles. The AIPS architecture also has attributes to enhance system effectiveness such as graceful degradation, growth and change tolerance, integrability, etc. Two key building blocks being developed by the AIPS program are a fault and damage tolerant processor and communication network. A proof-of-concept system is now being built and will be tested to demonstrate the validity and performance of the AIPS concepts.

A novel system for in situ determination of heat tolerance of plants: first results on alpine dwarf shrubs

PubMed Central

2013-01-01

Background Heat stress and heat damage to plants gain globally increasing importance for crop production and plant survival in endangered habitats. Therefore the knowledge of heat tolerance of plants is of great interest. As many heat tolerance measurement procedures require detachment of plants and protocols expose samples to various heat temperatures in darkness, the ecological relevance of such results may be doubted. To overcome these constraints we designed a novel field compatible Heat Tolerance Testing System (HTTS) that opens the opportunity to induce controlled heat stress on plants in situ under full natural solar irradiation. Subsequently, heat tolerance can be evaluated by a variety of standard viability assays like the electrolyte leakage test, chlorophyll fluorescence measurements and visual assessment methods. Furthermore, recuperation can be studied under natural environmental conditions which is impossible when detached plant material is used. First results obtained on three alpine dwarf - shrubs are presented. Results When heat tolerance of Vaccinium gaultherioides Bigelow was tested with the HTTS in situ, the visual assessment of leaves showed 50% heat injury (LT50) at 48.3°C, while on detached leaves where heat exposure took place in small heat chambers this already happened at 45.8°C. Natural solar irradiation being applied during heat exposure in the HTTS had significantly protective effects: In Loiseleuria procumbens L. (Desv.), if heat exposure (in situ) took place in darkness, leaf heat tolerance was 50.6°C. In contrast, when heat exposure was conducted under full natural solar irradiation heat tolerance was increased to 53.1°C. In Rhododendron ferrugineum L. heat tolerance of leaves was 42.5°C if the exposure took place ex situ and in darkness, while it was significantly increased to 45.8°C when this happened in situ under natural solar irradiation. Conclusions The results obtained with the HTTS tested in the field indicate a mitigating effect of natural solar irradiation during heat exposure. Commonly used laboratory based measurement procedures expose samples in darkness and seem to underestimate leaf heat tolerance. Avoidance of detachment by the use of the HTTS allows studying heat tolerance and recuperation processes in the presence of interacting external abiotic, biotic and genetic factors under field conditions. The investigation of combined effects of heat exposure under full solar irradiation, of recuperation and repair processes but also of possible damage amplification into the results with the HTTS appears to be particularly useful as it allows determining heat tolerance of plants with a considerably high ecological significance. PMID:23497517

Effect of a viscous fiber bar on postprandial glycemia in subjects with type 2 diabetes.

PubMed

Flammang, Ann M; Kendall, David M; Baumgartner, C John; Slagle, Trish D; Choe, Yong S

2006-10-01

To compare the effect of an experimental viscous fiber (VF) crispy bar on the postprandial glucose, insulin, and C-peptide response in adult subjects with type 2 diabetes to two commercially available control crispy bars. The study was a randomized, double-blinded, three period, crossover study. The study was conducted at two sites: Park Nicollet Institute, International Diabetes Center, Minneapolis, MN, and Radiant Research, Inc., Minneapolis, MN. A total of 60 adults with type 2 diabetes taking oral antihyperglycemic medication participated in the study. After an overnight fast, subjects consumed a test meal containing an equicaloric amount (300 kcal) of an experimental VF crispy bar or one of two commercially available crispy bars at each of three test visits, followed by a four hour meal tolerance test. Subjects also completed gastrointestinal (GI) response records for the 24 hours following each test visit. The VF crispy bars produced significantly lower glucose (p < 0.0001), insulin (p < 0.0001), and C-peptide (p < 0.0001) responses (as measured by positive area under the curve) in subjects with type 2 diabetes, as compared with the two commercially available bars. Intensity (p < 0.05) and frequency (p < 0.05) of flatulence were significantly higher with the VF bar as compared with the 2 commercial bars. While the VF bar produced significant subjective GI tolerance scoring values, the mean value was below 3 on a scale of 0 (no effect) to 10 (most severe effect) for all tested materials. The incorporation of VF into a crispy bar provided a means to improve blood glucose levels by reducing postprandial glucose, insulin, and C-peptide responses in subjects with type 2 diabetes. Though associated with some GI symptoms, VF may have application in improving the postprandial glycemic response in people with diabetes attempting intensive glucose control.

Effect of metal-tolerant plant growth-promoting Rhizobium on the performance of pea grown in metal-amended soil.

PubMed

Wani, Parvaze Ahmad; Khan, Md Saghir; Zaidi, Almas

2008-07-01

The nickel- and zinc-tolerant plant growth-promoting (PGP) Rhizobium sp. RP5 was isolated from nodules of pea, grown in metal-contaminated Indian soils. The PGP potentials of strain RP5 was assessed under in vitro conditions. Strain RP5 displayed a high level of tolerance to nickel (350 microg ml(-1)) and zinc (1500 microg ml(-1)) and showed PGP activity under in vitro conditions. The PGP activity of this strain was further assessed with increasing concentrations of nickel and zinc, using pea as a test crop. The bio-inoculant enhanced the dry matter, nodule numbers, root N, shoot N, leghemoglobin, seed yield, and grain protein (GP) by 19%, 23%, 26%, 47%, 112%, 26%, and 8%, respectively, at 290 mg Ni kg(-1) while at 4890 mg Zn kg(-1) soil, it increased the dry matter, nodule numbers, leghemoglobin, seed yield, GP, and root and shoot N by 18%, 23%, 78%, 26%, 7%, 25%, and 42%, respectively, compared to plants grown in soil amended with metal only. The bio-inoculant increased the glutathione reductase activity of roots and nodules by 46% and 65% at 580 mg Ni kg(-1) and 47% and 54% at 9780 mg Zn kg(-1) soil, respectively, compared to uninoculated plants. The inoculated strain decreased the concentration of nickel and zinc in plant organs. The intrinsic abilities of nitrogen fixation, growth promotion, and the ability to reduce the toxicity of nickel and zinc of the tested strain could be of practical importance in augmenting the growth and yield of pea, in nickel- and zinc-polluted soils.

A Comparative Study of Eating Habits and Food Intake in Women with Gestational Diabetes according to Early Postpartum Glucose Tolerance Status

PubMed Central

Hwang, You Jeong; Park, Bo Kyung

2011-01-01

Background Women with gestational diabetes mellitus (GDM) are at high risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD); continuous life-style intervention, especially diet, is central to managing T2DM and CVD. However, little is known about the dietary patterns of women with GDM after delivery. The goal of this study was to compare the eating habits and food intakes of women diagnosed with GDM during the early postpartum period. Methods We performed a 75 g oral glucose tolerance test (OGTT) in 184 women with GDM between 6 and 12 weeks after delivery. Based on the results of the OGTT, the subjects were divided into three groups according to the American Diabetes Association criteria; normal glucose tolerance (NGT) (n=100), pre-diabetes (n=73), and diabetes mellitus (DM) (n=11). Eating habits and usual food intake after delivery were investigated using a questionnaire, based on 24 hour-recall, which was administered by a trained dietitian. The daily intake data were analyzed using CAN Pro 3.0. Blood tests were performed pre- and post-delivery. Results Eating habits were not significantly different among the three groups. However, animal fat consumption was significantly different among the three groups. The intake ratio of fat calories to total calories was also significantly higher in the pre-diabetes and DM groups. Conclusion Although diet in the period 6 to 12 weeks postpartum did not influence glucose level, it may be important to educate women with GDM about the risks of excessive animal fat intake during pregnancy and the postpartum period in order to prevent later onset of T2DM. PMID:21977455

[Indicators of dynamic work tolerability in healthy subjects].

PubMed

Capodaglio, E M; Capodaglio, P

1997-01-01

This paper reports a study on the dynamics of tolerability in performing dynamic cycling in healthy subjects. Data on individually tolerable levels (power x duration) was obtained from 9 subjects by means of three submaximal tests on an ergometric bicycle lasting < or = 40 minutes, with constant load (50%, 65% and 80% of maximum VO2 reached during a previous test of increasing difficulty within the limits of the symptoms). During performance of the test we monitored heart rate and subjective perception of fatigue (Borg's 10-point scale). We then defined the individual functions of "isoperception", which expressed the individual trend of the product "power x duration" at identical subjective perception score. On the basis of the metabolic parameters monitored, the individual isoperceptive functions at a "moderate" level of fatigue (3 on the Borg scale) were defined as "tolerability) threshold" for prolonged dynamic cycling. The product "power x duration" defined by the isoperceptive curves at a "moderate" level of fatigue does in fact reflect the individual aerobic capacity that can be sustained for prolonged dynamic activity (under 60 minutes). In order to validate the hypothesis of tolerability of the functions identified, three further short tests were performed (duration < or = 8.5 minutes) on an ergometric bicycle, with measurement of ventilatory and metabolic parameters.

Modeling and Simulation Reliable Spacecraft On-Board Computing

NASA Technical Reports Server (NTRS)

Park, Nohpill

1999-01-01

The proposed project will investigate modeling and simulation-driven testing and fault tolerance schemes for Spacecraft On-Board Computing, thereby achieving reliable spacecraft telecommunication. A spacecraft communication system has inherent capabilities of providing multipoint and broadcast transmission, connectivity between any two distant nodes within a wide-area coverage, quick network configuration /reconfiguration, rapid allocation of space segment capacity, and distance-insensitive cost. To realize the capabilities above mentioned, both the size and cost of the ground-station terminals have to be reduced by using reliable, high-throughput, fast and cost-effective on-board computing system which has been known to be a critical contributor to the overall performance of space mission deployment. Controlled vulnerability of mission data (measured in sensitivity), improved performance (measured in throughput and delay) and fault tolerance (measured in reliability) are some of the most important features of these systems. The system should be thoroughly tested and diagnosed before employing a fault tolerance into the system. Testing and fault tolerance strategies should be driven by accurate performance models (i.e. throughput, delay, reliability and sensitivity) to find an optimal solution in terms of reliability and cost. The modeling and simulation tools will be integrated with a system architecture module, a testing module and a module for fault tolerance all of which interacting through a centered graphical user interface.

Tolerability of aztreonam and carbapenems in patients with IgE-mediated hypersensitivity to penicillins.

PubMed

Gaeta, Francesco; Valluzzi, Rocco Luigi; Alonzi, Cristiana; Maggioletti, Michela; Caruso, Cristiano; Romano, Antonino

2015-04-01

Studies performed on samples larger than 100 subjects with a documented IgE-mediated hypersensitivity to penicillins have demonstrated a cross-reactivity rate of approximately 1% between penicillins and both imipenem and meropenem, whereas a single study found a cross-reactivity rate of 6.2% with aztreonam in 16 such subjects. To assess the cross-reactivity and tolerability of aztreonam and 3 carbapenems (imipenem-cilastatin, meropenem, and ertapenem) in patients with documented IgE-mediated hypersensitivity to penicillins. A total of 212 consecutive subjects with immediate reactions to penicillins and positive results on skin tests to at least 1 penicillin reagent underwent skin tests with aztreonam and carbapenems; subjects with negative results were challenged with escalating doses of aztreonam and carbapenems. All subjects displayed negative skin test results to both aztreonam and carbapenems; 211 accepted challenges and tolerated them. Challenges were not followed by full therapeutic courses. These data indicate the tolerability of both aztreonam and carbapenems in penicillin-allergic subjects. In those who especially require these alternative β-lactams, however, we recommend pretreatment skin tests, both because rare cases of cross-reactivity have been reported and because negative results indicate tolerability. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chronic voluntary alcohol consumption results in tolerance to sedative/hypnotic and hypothermic effects of alcohol in hybrid mice

PubMed Central

Ozburn, Angela Renee; Harris, R. Adron; Blednov, Yuri A.

2013-01-01

The continuous two bottle choice test is the most common measure of alcohol consumption but there is remarkably little information about the development of tolerance or dependence with this procedure. We showed that C57BL/6JxFVB/NJ and FVB/NJxC57BL/6J F1 hybrid mice demonstrate greater preference for and consumption of alcohol than either parental strain. In order to test the ability of this genetic model of high alcohol consumption to produce neuroadaptation, we examined development of alcohol tolerance and dependence after chronic self-administration using a continuous access two-bottle choice paradigm. Ethanol-experienced mice stably consumed about 16–18 g/kg/day of ethanol. Ethanol-induced withdrawal severity was assessed (after 59 days of drinking) by scoring handling-induced convulsions; withdrawal severity was minimal and did not differ between ethanol-experienced and -naïve mice. After 71 days of drinking, the rate of ethanol clearance was similar for ethanol-experienced and -naïve mice. After 77 days of drinking, ethanol-induced loss of righting reflex (LORR) was tested daily for 5 days. Ethanol-experienced mice had a shorter duration of LORR. For both ethanol-experienced and -naïve mice, blood ethanol concentrations taken at gain of righting reflex were greater on day 5 than on day 1, indicative of tolerance. After 98 days of drinking, ethanol-induced hypothermia was assessed daily for 3 days. Both ethanol-experienced and –naïve mice developed rapid and chronic tolerance to ethanol-induced hypothermia, with significant group differences on the first day of testing. In summary, chronic, high levels of alcohol consumption in F1 hybrid mice produced rapid and chronic tolerance to both the sedative/hypnotic and hypothermic effects of ethanol; additionally, a small degree of metabolic tolerance developed. The development of tolerance supports the validity of using this model of high alcohol consumption in genetic studies of alcoholism. PMID:23313769

Validation of antibiotic residue tests for dairy goats.

PubMed

Zeng, S S; Hart, S; Escobar, E N; Tesfai, K

1998-03-01

The SNAP test, LacTek test (B-L and CEF), Charm Bacillus sterothermophilus var. calidolactis disk assay (BsDA), and Charm II Tablet Beta-lactam sequential test were validated using antibiotic-fortified and -incurred goat milk following the protocol for test kit validations of the U.S. Food and Drug Administration Center for Veterinary Medicine. SNAP, Charm BsDA, and Charm II Tablet Sequential tests were sensitive and reliable in detecting antibiotic residues in goat milk. All three assays showed greater than 90% sensitivity and specificity at tolerance and detection levels. However, caution should be taken in interpreting test results at detection levels. Because of the high sensitivity of these three tests, false-violative results could be obtained in goat milk containing antibiotic residues below the tolerance level. Goat milk testing positive by these tests must be confirmed using a more sophisticated methodology, such as high-performance liquid chromatography, before the milk is condemned. LacTek B-L test did not detect several antibiotics, including penicillin G, in goat milk at tolerance levels. However, LacTek CEF was excellent in detecting ceftiofur residue in goat milk.

Vibration and Operational Characteristics of a Composite-Steel (Hybrid) Gear

NASA Technical Reports Server (NTRS)

Handschuh, Robert F.; LaBerge, Kelsen E.; DeLuca, Samuel; Pelagalli, Ryan

2014-01-01

Hybrid gears have been tested consisting of metallic gear teeth and shafting connected by composite web. Both free vibration and dynamic operation tests were completed at the NASA Glenn Spur Gear Fatigue Test Facility, comparing these hybrid gears to their steel counterparts. The free vibration tests indicated that the natural frequency of the hybrid gear was approximately 800 Hz lower than the steel test gear. The dynamic vibration tests were conducted at five different rotational speeds and three levels of torque in a four square test configuration. The hybrid gears were tested both as fabricated (machined, composite layup, then composite cure) and after regrinding the gear teeth to the required aerospace tolerance. The dynamic vibration tests indicated that the level of vibration for either type of gearing was sensitive to the level of load and rotational speed.

Results of a Phase 2, Randomized,Vehicle-Controlled Study Evaluating the Efficacy,Tolerability, and Safety of Daily or Twice Daily SB204 for the Treatment of Acne Vulgaris.

PubMed

Eichenfield, Lawrence F; Gold, Linda Stein; Nahm, Walter K; Cook-Bolden, Fran E; Pariser, David M

2016-12-01

This randomized, double-blind, placebo-controlled, Phase 2 study compared efficacy, tolerability, and safety of SB204 once or twice daily to vehicle in the treatment of acne vulgaris. Eligible subjects were to be between 12 and 40 years old, have facial acne vulgaris with 25 to 70 non-inflammatory lesions, 20 to 40 inflammatory lesions, no more than 2 nodules, and a baseline Investigator's Global Assessment (IGA) score of moderate or severe. The co-primary efficacy endpoints were the absolute change in inflammatory and non-inflammatory lesion counts and IGA success rate (baseline to week 12). Safety assessments included reported adverse events (AEs), physical examinations, and laboratory testing. Tolerability was evaluated by the investigators based on the occurrence and severity of erythema, scaling, dryness, pruritus, and burning/stinging. A total of 213 subjects were randomized: 27 subjects to vehicle once daily; 29 subjects to vehicle twice daily; 53 subjects to SB204 2% twice daily; 52 subjects to SB204 4% once daily; and 52 subjects to SB204 4% twice daily. When compared to vehicle, treatment with all 3 SB204 regimens significantly reduced the absolute inflammatory lesion count and SB204 4% once daily reduced the absolute non-inflammatory lesion count. Treatment with SB204 4% once daily demonstrated a significant reduction in percent inflammatory lesions by week 4. There were no significant differences in the IGA success rates between groups at the end of treatment. All treatment regimens of SB204 were found to be safe and well tolerated. When compared to vehicle, SB204 2% and SB204 4% significantly decreased the absolute inflammatory lesion count and SB204 4% once daily also significantly decreased the absolute non-inflammatory lesion count in subjects with acne vulgaris treated for 12 weeks. Treatment with SB204 2% and 4% was found to be safe and well tolerated. J Drugs Dermatol. 2016;15(12):1496-1502.

Survival of thermophilic and hyperthermophilic microorganisms after exposure to UV-C, ionizing radiation and desiccation.

PubMed

Beblo, Kristina; Douki, Thierry; Schmalz, Gottfried; Rachel, Reinhard; Wirth, Reinhard; Huber, Harald; Reitz, Günther; Rettberg, Petra

2011-11-01

In this study, we investigated the ability of several (hyper-) thermophilic Archaea and phylogenetically deep-branching thermophilic Bacteria to survive high fluences of monochromatic UV-C (254 nm) and high doses of ionizing radiation, respectively. Nine out of fourteen tested microorganisms showed a surprisingly high tolerance against ionizing radiation, and two species (Aquifex pyrophilus and Ignicoccus hospitalis) were even able to survive 20 kGy. Therefore, these species had a comparable survivability after exposure to ionizing radiation such as Deinococcus radiodurans. In contrast, there was nearly no difference in survival of the tested strains after exposure to UV-C under anoxic conditions. If the cells had been dried in advance of UV-C irradiation, they were more sensitive to UV-C radiation compared with cells irradiated in liquid suspension; this effect could be reversed by the addition of protective material like sulfidic ores before irradiation. By exposure to UV-C, photoproducts were formed in the DNA of irradiated Archaea and Bacteria. The distribution of the main photoproducts was species specific, but the amount of the photoproducts was only partly dependent on the applied fluence. Overall, our results show that tolerance to radiation seems to be a common phenomenon among thermophilic and hyperthermophilic microorganisms.

Improvement of Glucose Metabolism in Patients with Impaired Glucose Tolerance or Diabetes by Long-Term Administration of a Palatinose-Based Liquid Formula as a Part of Breakfast

PubMed Central

Sakuma, Masae; Arai, Hidekazu; Mizuno, Akira; Fukaya, Makiko; Matsuura, Motoi; Sasaki, Hajime; Yamanaka-Okumura, Hisami; Yamamoto, Hironori; Taketani, Yutaka; Doi, Toshio; Takeda, Eiji

2009-01-01

A palatinose-based liquid formula (palatinose-formula), suppresses postprandial plasma glucose and insulin levels in healthy men. The objective of this study was to investigate the effects of long-term palatinose-formula ingestion on glucose metabolism in patients with impaired glucose tolerance (IGT) or type 2 diabetes. Two patients with IGT and 7 patients with type 2 diabetes participated in the palatinose-formula and dextrin-based liquid formula (dextrin-formula) loading test and long-term palatinose-formula administration study. After a 3-month control period, palatinose-formula (1046 kJ) was ingested daily by patients as a part of breakfast for 5 months. In the loading test, palatinose-formula suppressed postprandial plasma glucose and insulin levels and areas under the curve compared with those after dextrin-formula ingestion. In the long-term study, glycated hemoglobin levels (after 3 months and 5 months of treatment) and serum 8-hydroxydeoxyguanosine levels (after 5 months of treatment) were markedly decreased comparing with those at baseline. Intake of 1046 kJ palatinose-formula as a part of breakfast over a long-term period may be effective for improvement of glucose metabolism in patients with IGT or type 2 diabetes. PMID:19794923

Long-term and acute effects of temperature and oxygen on metabolism, food intake, growth and heat tolerance in a freshwater gastropod.

PubMed

Hoefnagel, K Natan; Verberk, Wilco C E P

2017-08-01

Temperature affects the physiology and life-history of ectothermic animals, often increasing metabolic rate and decreasing body size. Oxygen limitation has been put forward as a mechanism to explain thermal responses of body size and the ability to survive stress. However the time-scales involved in growth performance and heat tolerance differ radically. In order to increase our understanding of oxygen and temperature effects on body size and heat tolerance and the time scale involved, we reared Lymnaea stagnalis under six combinations of temperature and oxygen tension from hatching up to an age of 300 days and recorded shell length during this whole period. At the end of this period, we determined scope for growth by measuring food intake rate, assimilation efficiency, respiration rate and ammonium excretion rate at two different temperatures. We also measured the snails' ability to survive heat stress (CTmax), both at normoxia and hypoxia. We found that scope for growth and long term growth performance were much more affected by interactions of chronic oxygen and temperature conditions during rearing than by acute conditions during testing. Furthermore, our study shows that individual variation in growth performance can be traced back to individual differences in rates of food and oxygen consumption. Developmental acclimation also gave rise to differences in CTmax, but these were relatively small and were only expressed when CTmax was tested under hypoxia. The large effects of rearing oxygen conditions on growth and other physiological rates compared to modest effects of test oxygen conditions on CTmax suggest that small effects of hypoxia on the short term (e.g. heat tolerance) may nevertheless have large repercussions on the long term (e.g. growth and reproduction), even in a pulmonate snail that can compensate for hypoxia to some extent by aerial respiration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Variable content and distribution of arabinogalactan proteins in banana (Musa spp.) under low temperature stress.

PubMed

Yan, Yonglian; Takáč, Tomáš; Li, Xiaoquan; Chen, Houbin; Wang, Yingying; Xu, Enfeng; Xie, Ling; Su, Zhaohua; Šamaj, Jozef; Xu, Chunxiang

2015-01-01

Information on the spatial distribution of arabinogalactan proteins (AGPs) in plant organs and tissues during plant reactions to low temperature (LT) is limited. In this study, the extracellular distribution of AGPs in banana leaves and roots, and their changes under LT stress were investigated in two genotypes differing in chilling tolerance, by immuno-techniques using 17 monoclonal antibodies against different AGP epitopes. Changes in total classical AGPs in banana leaves were also tested. The results showed that AGP epitopes recognized by JIM4, JIM14, JIM16, and CCRC-M32 antibodies were primarily distributed in leaf veins, while those recognized by JIM8, JIM13, JIM15, and PN16.4B4 antibodies exhibited predominant sclerenchymal localization. Epitopes recognized by LM2, LM14, and MAC207 antibodies were distributed in both epidermal and mesophyll cells. Both genotypes accumulated classical AGPs in leaves under LT treatment, and the chilling tolerant genotype contained higher classical AGPs at each temperature treatment. The abundance of JIM4 and JIM16 epitopes in the chilling-sensitive genotype decreased slightly after LT treatment, and this trend was opposite for the tolerant one. LT induced accumulation of LM2- and LM14-immunoreactive AGPs in the tolerant genotype compared to the sensitive one, especially in phloem and mesophyll cells. These epitopes thus might play important roles in banana LT tolerance. Different AGP components also showed differential distribution patterns in banana roots. In general, banana roots started to accumulate AGPs under LT treatment earlier than leaves. The levels of AGPs recognized by MAC207 and JIM13 antibodies in the control roots of the tolerant genotype were higher than in the chilling sensitive one. Furthermore, the chilling tolerant genotype showed high immuno-reactivity against JIM13 antibody. These results indicate that several AGPs are likely involved in banana tolerance to chilling injury.

Variable content and distribution of arabinogalactan proteins in banana (Musa spp.) under low temperature stress

PubMed Central

Yan, Yonglian; Takáč, Tomáš; Li, Xiaoquan; Chen, Houbin; Wang, Yingying; Xu, Enfeng; Xie, Ling; Su, Zhaohua; Šamaj, Jozef; Xu, Chunxiang

2015-01-01

Information on the spatial distribution of arabinogalactan proteins (AGPs) in plant organs and tissues during plant reactions to low temperature (LT) is limited. In this study, the extracellular distribution of AGPs in banana leaves and roots, and their changes under LT stress were investigated in two genotypes differing in chilling tolerance, by immuno-techniques using 17 monoclonal antibodies against different AGP epitopes. Changes in total classical AGPs in banana leaves were also tested. The results showed that AGP epitopes recognized by JIM4, JIM14, JIM16, and CCRC-M32 antibodies were primarily distributed in leaf veins, while those recognized by JIM8, JIM13, JIM15, and PN16.4B4 antibodies exhibited predominant sclerenchymal localization. Epitopes recognized by LM2, LM14, and MAC207 antibodies were distributed in both epidermal and mesophyll cells. Both genotypes accumulated classical AGPs in leaves under LT treatment, and the chilling tolerant genotype contained higher classical AGPs at each temperature treatment. The abundance of JIM4 and JIM16 epitopes in the chilling-sensitive genotype decreased slightly after LT treatment, and this trend was opposite for the tolerant one. LT induced accumulation of LM2- and LM14-immunoreactive AGPs in the tolerant genotype compared to the sensitive one, especially in phloem and mesophyll cells. These epitopes thus might play important roles in banana LT tolerance. Different AGP components also showed differential distribution patterns in banana roots. In general, banana roots started to accumulate AGPs under LT treatment earlier than leaves. The levels of AGPs recognized by MAC207 and JIM13 antibodies in the control roots of the tolerant genotype were higher than in the chilling sensitive one. Furthermore, the chilling tolerant genotype showed high immuno-reactivity against JIM13 antibody. These results indicate that several AGPs are likely involved in banana tolerance to chilling injury. PMID:26074928

Oral glucose tolerance test significantly impacts the prevalence of abnormal glucose tolerance among Indian women with polycystic ovary syndrome: lessons from a large database of two tertiary care centers on the Indian subcontinent.

PubMed

Ganie, Mohd Ashraf; Dhingra, Atul; Nisar, Sobia; Sreenivas, Vishnubhatla; Shah, Zaffar Amin; Rashid, Aafia; Masoodi, Shariq; Gupta, Nandita

2016-01-01

To estimate the prevalence of abnormal glucose tolerance (AGT) among Indian women with polycystic ovary syndrome (PCOS) and analyze the role of oral glucose tolerance (OGTT) test on its estimation. Cross-sectional clinical study. Tertiary care center. A total of 2,014 women with PCOS diagnosed on the basis of the Rotterdam 2003 criteria were enrolled, and the data of 1,746 subjects were analyzed. In addition to recording clinical, biochemical, and hormone parameters, a 75 g OGTT was administered. Prevalence of AGT and impact of age, body mass index (BMI), family history, and OGTT on its prevalence. The mean age of subjects was 23.8 ± 5.3 years, with a mean BMI of 24.9 ± 4.4 kg/m(2). The overall prevalence of AGT was 36.3% (6.3% diabetes and 30% impaired fasting plasma glucose/impaired glucose tolerance) using American Diabetes Association criteria. The glucose intolerance showed a rising trend with advancing age (30.3%, 35.4%, 51%, and 58.8% in the second, third, fourth, and fifth decades, respectively) and increasing BMI. Family history of diabetes mellitus was present in 54.6% (953/1,746) subjects, and it did not correlate with any of the studied parameters except waist circumference and BMI. Sensitivity was better with 2-hour post-OGTT glucose values as compared with fasting plasma glucose, since using fasting plasma glucose alone would have missed the diagnosis in 107 (6.1%) subjects. We conclude that AGT is high among young Indian women with PCOS and that it is not predicted by family history of type 2 DM. OGTT significantly improves the detection rate of AGT among Indian women with PCOS. Copyright © 2016. Published by Elsevier Inc.

Prediabetes in patients treated with antipsychotic drugs.

PubMed

Manu, Peter; Correll, Christoph U; van Winkel, Ruud; Wampers, Martien; De Hert, Marc

2012-04-01

In 2010, the American Diabetes Association (ADA) proposed that individuals with fasting glucose level of 100-125 mg/dL (5.6-6.9 mmol/L) or glucose level of 140-199 mg/dL (7.8-11.0 mmol/L) 2 hours after a 75-g oral glucose tolerance test or hemoglobin A(1c) 5.7%-6.4% be classified as prediabetic, indicating increased risk for the emergence of diabetes mellitus. At the same time, the ADA formulated guidelines for the use of metformin for the treatment of prediabetes. To determine the prevalence of prediabetes in a cohort of psychiatrically ill adults receiving antipsychotics and to compare the clinical and metabolic features of prediabetic patients with those of patients with normal glucose tolerance and those with diabetes mellitus. The 2010 ADA criteria were applied to a large, consecutive, single-site European cohort of 783 adult psychiatric inpatients (mean age: 37.6 years) without a history of diabetes who were receiving antipsychotics. All patients in this cross-sectional study underwent measurement of body mass index (BMI), waist circumference, oral glucose tolerance test, and fasting insulin and lipids from November 2003 through July 2007. 413 patients (52.8%) had normal glucose tolerance, 290 (37.0%) had prediabetes, and 80 (10.2%) had diabetes mellitus. The fasting glucose and/or hemoglobin A(1c) criteria were met by 89.7% of prediabetic patients. A statistically significant intergroup gradient from normal glucose tolerance to prediabetes and from prediabetes to diabetes mellitus was observed for waist circumference, triglycerides, fasting insulin levels, and frequency of metabolic syndrome (P = .02 to P < .0001). Only 19/290 prediabetic patients (6.6%) met the 2010 ADA criteria for treatment with metformin. Prediabetes is highly prevalent in adults treated with antipsychotic drugs and correlates with markers of increased intraabdominal adiposity, enhanced lipolysis, and insulin resistance. Criteria for using metformin to prevent the emergence of diabetes mellitus may need to be revised for this population. © Copyright 2012 Physicians Postgraduate Press, Inc.

Biosentinel: Improving Desiccation Tolerance of Yeast Biosensors for Deep-Space Missions

NASA Technical Reports Server (NTRS)

Dalal, Sawan; Santa Maria, Sergio R.; Liddell, Lauren; Bhattacharya, Sharmila

2017-01-01

BioSentinel is one of 13 secondary payloads to be deployed on Exploration Mission 1 (EM-1) in 2019. We will use the budding yeast Saccharomyces cerevisiae as a biosensor to determine how deep-space radiation affects living organisms and to potentially quantify radiation levels through radiation damage analysis. Radiation can damage DNA through double strand breaks (DSBs), which can normally be repaired by homologous recombination. Two yeast strains will be air-dried and stored in microfluidic cards within the payload: a wild-type control strain and a radiation sensitive rad51 mutant that is deficient in DSB repairs. Throughout the mission, the microfluidic cards will be rehydrated with growth medium and an indicator dye. Growth rates of each strain will be measured through LED detection of the reduction of the indicator dye, which correlates with DNA repair and the amount of radiation damage accumulated. Results from BioSentinel will be compared to analog experiments on the ISS and on Earth. It is well known that desiccation can damage yeast cells and decrease viability over time. We performed a screen for desiccation-tolerant rad51 strains. We selected 20 re-isolates of rad51 and ran a weekly screen for desiccation-tolerant mutants for five weeks. Our data shows that viability decreases over time, confirming previous research findings. Isolates L2, L5 and L14 indicate desiccation tolerance and are candidates for whole-genome sequencing. More time is needed to determine whether a specific strain is truly desiccation tolerant. Furthermore, we conducted an intracellular trehalose assay to test how intracellular trehalose concentrations affect or protect the mutant strains against desiccation stress. S. cerevisiae cell and reagent concentrations from a previously established intracellular trehalose protocol did not yield significant absorbance measurements, so we tested varying cell and reagent concentrations and determined proper concentrations for successful protocol use.

Desiccation tolerance, longevity and seed-siring ability of entomophilous pollen from UK native orchid species.

PubMed

Marks, Timothy R; Seaton, Philip T; Pritchard, Hugh W

2014-09-01

Pollinator-limited seed-set in some terrestrial orchids is compensated for by the presence of long-lived flowers. This study tests the hypothesis that pollen from these insect-pollinated orchids should be desiccation tolerant and relatively long lived using four closely related UK terrestrial species; Anacamptis morio, Dactylorhiza fuchsii, D. maculata and Orchis mascula. Pollen from the four species was harvested from inflorescences and germinated in vitro, both immediately and also after drying to simulate interflower transit. Their tolerance to desiccation and short-term survival was additionally assessed after 3 d equilibration at a range of relative humidities (RHs), and related to constructed sorption isotherms (RH vs. moisture content, MC). Ageing of D. fuchsii pollen was further tested over 2 months against temperature and RH, and the resultant survival curves were subjected to probit analysis, and the distribution of pollen death in time (σ) was determined. The viability and siring ability, following artificial pollinations, were determined in D. fuchsii pollen following storage for 6 years at -20 °C. The pollen from all four species exhibited systematic increases in germinability and desiccation tolerance as anthesis approached, and pollen from open flowers generally retained high germinability. Short-term storage revealed sensitivity to low RH, whilst optimum survival occurred at comparable RHs in all species. Similarly, estimated pollen life spans (σ) at differing temperatures were longest under the dry conditions. Despite a reduction in germination and seeds per capsule, long-term storage of D. fuchsii pollen did not impact on subsequent seed germination in vitro. Substantial pollen desiccation tolerance and life span of the four entomophilous orchids reflects a resilient survival strategy in response to unpredictable pollinator visitation, and presents an alternative approach to germplasm conservation. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hypoglycaemic effect of Musa sapientum L. in alloxan-induced diabetic rats.

PubMed

Pari, L; Maheswari, J U

1999-12-15

Musa sapientum L. ('Ney Poovan') commonly known as 'banana' is mainly used in Indian folk medicine for the treatment of diabetes mellitus. Oral administration of 0.15, 0.20 and 0.25 g/kg of chloroform extract of the Musa sapientum flowers (MSFEt) for 30 days resulted in a significant reduction in blood glucose, glycosylated haemoglobin and an increase in total haemoglobin, but in the case of 0.25 g/kg the effect was highly significant. It also prevents decrease in body weight. Oral glucose tolerance test was also performed in experimental diabetic rats in which there was a significant improvement in glucose tolerance in animals treated with MSFEt and the effect was compared with glibenclamide. Thus the study shows that MSFEt has hypoglycaemic action.

Identifying a maximum tolerated contour in two-dimensional dose-finding

PubMed Central

Wages, Nolan A.

2016-01-01

The majority of Phase I methods for multi-agent trials have focused on identifying a single maximum tolerated dose combination (MTDC) among those being investigated. Some published methods in the area have been based on the notion that there is no unique MTDC, and that the set of dose combinations with acceptable toxicity forms an equivalence contour in two dimensions. Therefore, it may be of interest to find multiple MTDC's for further testing for efficacy in a Phase II setting. In this paper, we present a new dose-finding method that extends the continual reassessment method to account for the location of multiple MTDC's. Operating characteristics are demonstrated through simulation studies, and are compared to existing methodology. Some brief discussion of implementation and available software is also provided. PMID:26910586

7 CFR 801.12 - Design requirements incorporated by reference.

Code of Federal Regulations, 2010 CFR

2010-01-01

... reference: General Code (1.10.) G-S.5.5. Money Values, Mathematical Agreement G-T.1. Acceptance Tolerances G.... Tolerance Values T.3. For Test Weight Per Bushel Indications or Recorded Representations UR.3.2. Other... Standards and Technology's (NIST) Handbook 44, “Specifications, Tolerances, and Other Technical Requirements...

Fuel Cycle Research and Development Accident Tolerant Fuels Series 1 (ATF-1) Irradiation Testing FY 2016 Status Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Core, Gregory Matthew

This report contains a summary of irradiation testing of Fuel Cycle Research and Development (FCRD) Accident Tolerant Fuels Series 1 (ATF 1) experiments performed at Idaho National Laboratory (INL) in FY 2016. ATF 1 irradiation testing work performed in FY 2016 included design, analysis, and fabrication of ATF-1B drop in capsule ATF 1 series experiments and irradiation testing of ATF-1 capsules in the ATR.

Agent Based Fault Tolerance for the Mobile Environment

NASA Astrophysics Data System (ADS)

Park, Taesoon

This paper presents a fault-tolerance scheme based on mobile agents for the reliable mobile computing systems. Mobility of the agent is suitable to trace the mobile hosts and the intelligence of the agent makes it efficient to support the fault tolerance services. This paper presents two approaches to implement the mobile agent based fault tolerant service and their performances are evaluated and compared with other fault-tolerant schemes.

Diagnostic tools for post-gastric bypass hypoglycaemia.

PubMed

Emous, M; Ubels, F L; van Beek, A P

2015-10-01

In spite of its evident success, several late complications can occur after gastric bypass surgery. One of these is post-gastric bypass hypoglycaemia. No evidence-based guidelines exist in the literature on how to confirm the presence of this syndrome. This study aims to describe and compare the tests aimed at making a diagnosis of post-gastric bypass hypoglycaemia and to provide a diagnostic approach based upon the available evidence. A search was conducted in PubMed, Cochrane and Embase. A few questionnaires have been developed to measure the severity of symptoms in post-gastric bypass hypoglycaemia but none has been validated. The gold standard for provocation of a hypoglycaemic event is the oral glucose tolerance test or the liquid mixed meal tolerance test. Both show a high prevalence of hypoglycaemia in post-gastric bypass patients with and without hypoglycaemic complaints as well as in healthy volunteers. No uniformly established cut-off values for glucose concentrations are defined in the literature for the diagnosis of post-gastric bypass hypoglycaemia. For establishing an accurate diagnosis of post-gastric bypass hypoglycaemia, a validated questionnaire, in connection with the diagnostic performance of provocation tests, is the most important thing missing. Given these shortcomings, we provide recommendations based upon the current literature. © 2015 World Obesity.

A comparison of the herbicide tolerances of rare and common plants in an agricultural landscape.

PubMed

Egan, J Franklin; Graham, Ian M; Mortensen, David A

2014-03-01

Declining plant biodiversity in agroecosystems has often been attributed to escalating use of chemical herbicides, but other changes in farming systems, including the clearing of seminatural habitat fragments, confound the influence of herbicides. The present study introduces a new approach to evaluate the impacts of herbicide pollution on plant communities at landscape or regional scales. If herbicides are in fact a key factor shaping agricultural plant diversity, one would expect to see the signal of past herbicide impacts in the current plant community composition of an intensively farmed region, with common, successful species more tolerant to widely used herbicides than rare or declining species. Data from an extensive field survey of plant diversity in Lancaster County, Pennsylvania, USA, were compared with herbicide bioassay experiments in a greenhouse to test the hypothesis that common species possess higher herbicide tolerances than rare species. Five congeneric pairs of rare and common species were treated with 3 commonly used herbicide modes of action in bioassay experiments, and few significant differences were found in the tolerances of rare species relative to common species. These preliminary results suggest that other factors beyond herbicide exposure may be more important in shaping the distribution and abundance of plant species diversity across an agricultural landscape. © 2014 SETAC.

Effect of mild intermittent hypoxia on glucose tolerance, muscle morphology and AMPK-PGC-1alpha signaling.

PubMed

Chen, Chung-Yu; Tsai, Ying-Lan; Kao, Chung-Lan; Lee, Shin-Da; Wu, Ming-Chieh; Mallikarjuna, K; Liao, Yi-Hung; Ivy, John L; Kuo, Chia-Hua

2010-02-28

The main goal of this study was to investigate the long-term effect of daily 8-hour mild intermittent hypoxia (14-15% O2) on glucose tolerance and muscle morphology of Sprague-Dawley rats. The involvement of AMPK-PGC-1alpha-VEGF signaling pathways in the skeletal muscle was also determined during the first 8 hours of hypoxia. We found that mRNA levels of VEGF and PGC-1alpha were significantly increased above control after 8-h mild hypoxia without a change in AMPK phosphorylation. After 8 weeks of mild intermittent hypoxia treatment, plasma glucose and insulin levels in oral glucose tolerance test (OGTT), epididymal fat mass, and body weight were significantly lower compared to the control group. While soleus muscle weight was not changed, capillary and fiber densities in the hypoxia group were 33% and 35% above the control suggesting reorganization of muscle fibers. In conclusion, our data provide strong evidence that long-term mild intermittent hypoxia decreases the diffusion distance of glucose and insulin across muscle fibers, and decreases adiposity in rats. These changes may account for the improved glucose tolerance observed following the 8-week hypoxia treatment, and provides grounds for investigating the development of a mild non-pharmacological intervention in the treatment of obesity and type 2 diabetes.

New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies.

PubMed

Yanagida, Noriyuki; Okada, Yu; Sato, Sakura; Ebisawa, Motohiro

2016-04-01

A number of studies have suggested that a large subset of children (approximately 70%) who react to unheated milk or egg can tolerate extensively heated forms of these foods. A diet that includes baked milk or egg is well tolerated and appears to accelerate the development of regular milk or egg tolerance when compared with strict avoidance. However, the indications for an oral food challenge (OFC) using baked products are limited for patients with high specific IgE values or large skin prick test diameters. Oral immunotherapies (OITs) are becoming increasingly popular for the management of food allergies. However, the reported efficacy of OIT is not satisfactory, given the high frequency of symptoms and requirement for long-term therapy. With food allergies, removing the need to eliminate a food that could be consumed in low doses could significantly improve quality of life. This review discusses the importance of an OFC and OIT that use low doses of causative foods as the target volumes. Utilizing an OFC or OIT with a low dose as the target volume could be a novel approach for accelerating the tolerance to causative foods. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Habitat segregation and ecological character displacement in cryptic African malaria mosquitoes

PubMed Central

Tene Fossog, Billy; Ayala, Diego; Acevedo, Pelayo; Kengne, Pierre; Ngomo Abeso Mebuy, Ignacio; Makanga, Boris; Magnus, Julie; Awono-Ambene, Parfait; Njiokou, Flobert; Pombi, Marco; Antonio-Nkondjio, Christophe; Paupy, Christophe; Besansky, Nora J; Costantini, Carlo

2015-01-01

Understanding how divergent selection generates adaptive phenotypic and population diversification provides a mechanistic explanation of speciation in recently separated species pairs. Towards this goal, we sought ecological gradients of divergence between the cryptic malaria vectors Anopheles coluzzii and An. gambiae and then looked for a physiological trait that may underlie such divergence. Using a large set of occurrence records and eco-geographic information, we built a distribution model to predict the predominance of the two species across their range of sympatry. Our model predicts two novel gradients along which the species segregate: distance from the coastline and altitude. Anopheles coluzzii showed a ‘bimodal’ distribution, predominating in xeric West African savannas and along the western coastal fringe of Africa. To test whether differences in salinity tolerance underlie this habitat segregation, we assessed the acute dose–mortality response to salinity of thirty-two larval populations from Central Africa. In agreement with its coastal predominance, Anopheles coluzzii was overall more tolerant than An. gambiae. Salinity tolerance of both species, however, converged in urban localities, presumably reflecting an adaptive response to osmotic stress from anthropogenic pollutants. When comparing degree of tolerance in conjunction with levels of syntopy, we found evidence of character displacement in this trait. PMID:25926878

The Role of the Environment in the Evolution of Tolerance and Resistance to a Pathogen.

PubMed

Zeller, Michael; Koella, Jacob C

2017-09-01

Defense against parasites can be divided into resistance, which limits parasite burden, and tolerance, which reduces pathogenesis at a given parasite burden. Distinguishing between the two and understanding which defense is favored by evolution in different ecological settings are important, as they lead to fundamentally different evolutionary trajectories of host-parasite interactions. We let the mosquito Aedes aegypti evolve under different food levels and with either no parasite, a constant parasite, or a coevolving parasite (the microsporidian Vavraia culicis). We then tested tolerance and resistance of the evolved lines on a population level at the two food levels. Exposure to parasites during evolution increased resistance and tolerance, but there were no differences between the lines evolved with coevolving or constant parasites. Mosquitoes that had evolved with food restriction had higher resistance than those evolved with high food but similar tolerance. The mosquitoes that had restricted food when being tested had lower tolerance than those with normal food, but there was no difference in resistance. Our results emphasize the complexity and dependence on environmental conditions of the evolution and expression of resistance and tolerance and help to evaluate some of the predictions about the evolution of host defense against parasites.

Ocular tolerance of preservatives on the murine cornea.

PubMed

Furrer, P; Mayer, J M; Plazonnet, B; Gurny, R

1999-03-01

We investigated the effects of instilling 13 commonly used preservatives on the murine cornea in vivo. Due to the instillation of preservatives, micro-lesions are formed on the cornea and can be selectively marked by fluorescein. The sum of the resulting fluorescent areas was measured using an episcopic microscope coupled to an image processing system. All the tested preservatives proved to be well-tolerated by the eye at commonly used concentrations. However, in some cases, increased concentrations of preservatives or combinations resulted in significant increase of the amount of corneal damage. With increasing the concentration, corneal lesion increased the most in the case of cetylpyridinium. While a combination of chlorobutanol 0.5% and phenylethylalcohol 0.5% did not result in an increase in corneal damage (when compared to the use of each separately), the associations of thiomersal 0.02% and phenylethylalcohol 0.4% on one hand and of edetate disodium (EDTA) 0.1% and benzalkonium 0.01% on the other, resulted in significant increases in the amount of corneal damage. However, in none of the tested combinations, the increase in the observed damage exceed the limit of ocular intolerance we had defined beforehand: thus, they were all deemed relatively well-tolerated. In the last part of the study, we investigated the effects of combining several preservatives, at usual concentrations, with an anesthetic solution of oxybuprocaine and found no notable increase in ocular damage.

Continuous glucose monitoring system in the screening of early glucose derangements in children and adolescents with cystic fibrosis.

PubMed

Franzese, Adriana; Valerio, Giuliana; Buono, Pietro; Spagnuolo, Maria Immacolata; Sepe, Angela; Mozzillo, Enza; De Simone, Ilaria; Raia, Valeria

2008-02-01

In cystic fibrosis (CF), diabetes mellitus (DM) is associated with progression of pulmonary disease and nutritional impairment. To compare oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS) in patients with CF with early glucose derangements. Thirty-two patients with CF (5-20 years) with intermediate glucose values > 7.7 mmol/l during OGTT received a CGMS registration. Patients were classified into those with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and DM, according to glucose values at 120 min of OGTT and during CGMS. Furthermore BMI z-scores, forced expiratory volume in 1 second (FEV1%), number of respiratory infections/year, enzyme supplementation, and HbA1c were evaluated. OGTT and CGMS derangements were in agreement in 43.7% of the patients. BMI z-scores, FEV1%, number of respiratory infections/ year, enzyme supplementation, and HbA1c did not differ among the three groups. HbA1c, correlated positively with 120 min OGTT (r = 0.34; p = 0.059), CGMS area (r = 0.35; p = 0.048) and the number of respiratory infections, and negatively with FEV1%. Intermediate glucose values during OGTT should be considered as a screening test in patients with CF. CGMS can be useful in studying the early occurrence of glucose derangements in selected patients.

Direct Reading Particle Counters: Calibration Verification and Multiple Instrument Agreement via Bump Testing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jankovic, John; Zontek, Tracy L.; Ogle, Burton R.

We examined the calibration records of two direct reading instruments designated as condensation particle counters in order to determine the number of times they were found to be out of tolerance at annual manufacturer's recalibration. For both instruments were found to be out of tolerance more times than within tolerance. And, it was concluded that annual calibration alone was insufficient to provide operational confidence in an instrument's response. Thus, a method based on subsequent agreement with data gathered from a newly calibrated instrument was developed to confirm operational readiness between annual calibrations, hereafter referred to as bump testing. The methodmore » consists of measuring source particles produced by a gas grille spark igniter in a gallon-size jar. Sampling from this chamber with a newly calibrated instrument to determine the calibrated response over the particle concentration range of interest serves as a reference. Agreement between this reference response and subsequent responses at later dates implies that the instrument is performing as it was at the time of calibration. Side-by-side sampling allows the level of agreement between two or more instruments to be determined. This is useful when simultaneously collected data are compared for differences, i.e., background with process aerosol concentrations. A reference set of data was obtained using the spark igniter. The generation system was found to be reproducible and suitable to form the basis of calibration verification. Finally, the bump test is simple enough to be performed periodically throughout the calibration year or prior to field monitoring.« less

Direct Reading Particle Counters: Calibration Verification and Multiple Instrument Agreement via Bump Testing

DOE PAGES

Jankovic, John; Zontek, Tracy L.; Ogle, Burton R.; ...

2015-01-27

We examined the calibration records of two direct reading instruments designated as condensation particle counters in order to determine the number of times they were found to be out of tolerance at annual manufacturer's recalibration. For both instruments were found to be out of tolerance more times than within tolerance. And, it was concluded that annual calibration alone was insufficient to provide operational confidence in an instrument's response. Thus, a method based on subsequent agreement with data gathered from a newly calibrated instrument was developed to confirm operational readiness between annual calibrations, hereafter referred to as bump testing. The methodmore » consists of measuring source particles produced by a gas grille spark igniter in a gallon-size jar. Sampling from this chamber with a newly calibrated instrument to determine the calibrated response over the particle concentration range of interest serves as a reference. Agreement between this reference response and subsequent responses at later dates implies that the instrument is performing as it was at the time of calibration. Side-by-side sampling allows the level of agreement between two or more instruments to be determined. This is useful when simultaneously collected data are compared for differences, i.e., background with process aerosol concentrations. A reference set of data was obtained using the spark igniter. The generation system was found to be reproducible and suitable to form the basis of calibration verification. Finally, the bump test is simple enough to be performed periodically throughout the calibration year or prior to field monitoring.« less

Tolerance to the antinociceptive effects of chronic morphine requires c-Jun N-terminal kinase.

PubMed

Marcus, David J; Zee, Michael; Hughes, Alex; Yuill, Matthew B; Hohmann, Andrea G; Mackie, Ken; Guindon, Josée; Morgan, Daniel J

2015-06-12

Morphine and fentanyl are opioid analgesics in wide clinical use that act through the μ-opioid receptor (MOR). However, one limitation of their long-term effectiveness is the development of tolerance. Receptor desensitization has been proposed as a putative mechanism driving tolerance to G protein-coupled receptor (GPCR) agonists. Recent studies have found that tolerance to morphine is mediated by the c-Jun N-terminal Kinase (JNK) signaling pathway. The goal of the present study was to test the hypotheses that: 1) JNK inhibition will be antinociceptive on its own; 2) JNK inhibition will augment morphine antinociception and; 3) JNK mediates chronic tolerance for the antinociceptive effects of morphine using acute (hotplate and tail-flick), inflammatory (10 μl of formalin 2.5%) and chemotherapy (cisplatin 5 mg/kg ip once weekly)-induced neuropathic pain assays. We found that JNK inhibition by SP600125 (3 mg/kg) produces a greater antinociceptive effect than morphine (6 mg/kg) alone in the formalin test. Moreover, co-administration of morphine (6 mg/kg) with SP600125 (3 mg/kg) produced a sub-additive antinociceptive effect in the formalin test. We also show that pre-treatment with SP600125 (3 or 10 mg/kg), attenuates tolerance to the antinociceptive effects of morphine (10 mg/kg), but not fentanyl (0.3 mg/kg), in the tail-flick and hotplate tests. Pre-treatment with SP600125 also attenuates tolerance to the hypothermic effects of both morphine and fentanyl. We also examined the role of JNK in morphine tolerance in a cisplatin-induced model of neuropathic pain. Interestingly, treatment with SP600125 (3 mg/kg) alone attenuated mechanical and cold allodynia in a chemotherapy-induced pain model using cisplatin. Strikingly, SP600125 (3 mg/kg) pre-treatment prolonged the anti-allodynic effect of morphine by several days (5 and 7 days for mechanical and cold, respectively). These results demonstrate that JNK signaling plays a crucial role in mediating antinociception as well as chronic tolerance to the antinociceptive effects of morphine in acute, inflammatory, and neuropathic pain states. Thus, inhibition of JNK signaling pathway, via SP600125, represents an efficacious pharmacological approach to delay tolerance to the antinociceptive effects of chronic morphine in diverse pain models.

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single Enantiomer (+)-Mefloquine Compared with Racemic Mefloquine in Healthy Persons

PubMed Central

Tansley, Robert; Lotharius, Julie; Priestley, Anthony; Bull, Fiona; Duparc, Stephan; Möhrle, Jörg

2010-01-01

Racemic mefloquine is a highly effective antimalarial whose clinical utility has been compromised by its association with neuropsychiatric and gastrointestinal side effects. It is hypothesized that the cause of the side effects may reside in the (−) enantiomer. We sought to compare the safety, tolerability and pharmacokinetic profile of (+)-mefloquine with racemic mefloquine in a randomized, ascending-dose, double-blind, active and placebo-controlled, parallel cohort study in healthy male and female adult volunteers. Although differing in its manifestations, both study drugs displayed a substantially worse tolerability profile compared with placebo. The systemic clearance was slower for (−)-mefloquine than (+)-mefloquine. Thus, (+)-mefloquine has a different safety and tolerability profile compared with racemic mefloquine but its global safety profile is not superior and replacement of the currently used antimalarial drug with (+)-mefloquine is not warranted. PMID:21118921

In polycystic ovary syndrome, adrenal steroids are regulated differently in the morning versus in response to nutrient intake

USDA-ARS?s Scientific Manuscript database

The objective of this study was to investigate adrenal steroid regulation in Polycystic Ovary Syndrome (PCOS). A 5-h oral glucose tolerance test (OGTT) and a 3-h frequently sampled-intravenous glucose tolerance test (FSIVGTT) were administered to 30 patients with PCOS. Anthropometric parameters (hei...

PRN 2007-2: Guidance on Small-Scale Field Testing and Low-level Presence in Food of Plant-Incorporated Protectants (PIPs)

EPA Pesticide Factsheets

This notice clarifies how EPA ensures the safety of residues of PIPs possibly present in food or feed and when a tolerance or tolerance exemption would be required for field tests for biotechnology-derived food and feed crop plants containing PIPs.

Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive.

PubMed

Ayoub, R; Page, S T; Swerdloff, R S; Liu, P Y; Amory, J K; Leung, A; Hull, L; Blithe, D; Christy, A; Chao, J H; Bremner, W J; Wang, C

2017-03-01

Dimethandrolone (DMA, 7α,11β-dimethyl-19-nortestosterone) has both androgenic and progestational activities, ideal properties for a male hormonal contraceptive. In vivo, dimethandrolone undecanoate (DMAU) is hydrolyzed to DMA. We showed previously that single oral doses of DMAU powder in capsule taken with food are well tolerated and effective at suppressing both LH and testosterone (T), but absorption was low. We compared the pharmacokinetics and pharmacodynamics of two new formulations of DMAU, in castor oil and in self-emulsifying drug delivery systems (SEDDS), with the previously tested powder formulation. DMAU was dosed orally in healthy adult male volunteers at two academic medical centers. For each formulation tested in this double-blind, placebo-controlled study, 10 men received single, escalating, oral doses of DMAU (100, 200, and 400 mg) and two subjects received placebo. All doses were evaluated for both fasting and with a high fat meal. All three formulations were well tolerated without clinically significant changes in vital signs, blood counts, or serum chemistries. For all formulations, DMA and DMAU showed higher maximum (p < 0.007) and average concentrations (p < 0.002) at the 400 mg dose, compared with the 200 mg dose. The powder formulation resulted in a lower conversion of DMAU to DMA (p = 0.027) compared with both castor oil and SEDDS formulations. DMAU in SEDDS given fasting resulted in higher serum DMA and DMAU concentrations compared to the other two formulations. Serum LH and sex hormone concentrations were suppressed by all formulations of 200 and 400 mg DMAU when administered with food, but only the SEDDS formulation was effectively suppressed serum T when given fasting. We conclude that while all three formulations of oral DMAU are effective and well tolerated when administered with food, DMAU in oil and SEDDS increased conversion to DMA, and SEDDS may have some effectiveness when given fasting. These properties might be advantageous for the application of DMAU as a male contraceptive. © 2016 American Society of Andrology and European Academy of Andrology.

Liver microRNA profile of induced allograft tolerance

PubMed Central

Vitalone, Matthew James; Wai, Liang; Fujiki, Masato; Lau, Audrey H.; Littau, Erik; Esquivel, Carlos; Martinez, Olivia M.; Krams, Sheri M.

2016-01-01

Introduction Although the liver is less immunogenic than other solid organs, most liver transplant recipients receive lifelong immunosuppression. In both experimental models and clinical transplantation, total Lymphoid Irradiation (TLI) has been shown to induce allograft tolerance. Our goal was to identify the microRNAs (miRNAs) expressed in tolerant liver allograft recipients in an experimental model of TLI-induced tolerance. Methods To identify the miRNAs associated with TLI-induced tolerance we examined syngeneic recipients (Lewis→Lewis) and allogeneic recipients (DA→Lewis) of orthotropic liver transplants that received post-transplant TLI, allogeneic recipients that were not treated post-transplantation and experienced acute rejection, and native DA livers. QPCR miRNA array cards were used to profile liver grafts. Results We identified 12 miRNAs that were specifically and significantly increased during acute rejection. In early tolerance, 33 miRNAs were altered compared to syngeneic livers, with 80% of the miRNAs increased. In established tolerance 42 miRNAs were altered. In addition, miR-142-5p and miR-181a demonstrated increased expression in tolerant livers (both early and established tolerance) as compared to syngeneic livers. A principal component analysis of all miRNAs assayed, demonstrated a profile in established tolerance that was closely related to that seen in syngeneic livers. Conclusions The miRNA profile of established tolerant allografts is very similar to syngeneic grafts suggesting tolerance may be a return to an immunological state of quiescence. PMID:26950716

Exposure to low level of arsenic and lead in drinking water from Antofagasta city induces gender differences in glucose homeostasis in rats.

PubMed

Palacios, Javier; Roman, Domingo; Cifuentes, Fredi

2012-08-01

Populations chronically exposed to arsenic in drinking water often have increased prevalence of diabetes mellitus. The purpose of this study was to compare the glucose homeostasis of male and female rats exposed to low levels of heavy metals in drinking water. Treated groups were Sprague-Dawley male and female rats exposed to drinking water from Antofagasta city, with total arsenic of 30 ppb and lead of 53 ppb for 3 months; control groups were exposed to purified water by reverse osmosis. The two treated groups in both males and females showed arsenic and lead in the hair of rats. The δ-aminolevulinic acid dehydratase was used as a sensitive biomarker of arsenic toxicity and lead. The activity of δ-aminolevulinic acid dehydratase was reduced only in treated male rats, compared to the control group. Treated males showed a significantly sustained increase in blood glucose and plasma insulin levels during oral glucose tolerance test compared to control group. The oral glucose tolerance test and the homeostasis model assessment of insulin resistance demonstrated that male rats were insulin resistant, and females remained sensitive to insulin after treatment. The total cholesterol and LDL cholesterol increased in treated male rats vs. the control, and triglyceride increased in treated female rats vs. the control. The activity of intestinal Na+/glucose cotransporter in male rats increased compared to female rats, suggesting a significant increase in intestinal glucose absorption. The findings indicate that exposure to low levels of arsenic and lead in drinking water could cause gender differences in insulin resistance.

Likelihood of myocardial infarction during stroke rehabilitation preceded by cardiovascular screening and an exercise tolerance test: the Locomotor Experience Applied Post-Stroke (LEAPS) trial.

PubMed

Nadeau, Stephen E; Rose, Dorian Kay; Dobkin, Bruce; Wu, Samuel S; Dai, Yufeng E; Schofield, Richard; Duncan, Pamela W

2014-12-01

Coronary artery disease is highly prevalent in patients with stroke, but because revascularization does not improve major clinical outcomes in patients with stable coronary artery disease relative to intensive medical therapy, routine evaluation for this disease is not warranted in stroke patients. However, it might be warranted in patients destined to undergo vigorous physical therapy. The Locomotor Experience Applied Post-Stroke study, a randomized controlled trial of 408 participants that tested the relative efficacy of two rehabilitation techniques on functional walking level, provided the opportunity to address this question. The study aims to test the efficacy of screening for cardiovascular disease and an exercise tolerance test in assuring safety among patients undergoing vigorous rehabilitation for gait impairment. All participants were screened for serious cardiovascular and pulmonary conditions. At six-weeks poststroke, they also completed a cardiovascular screening inventory and underwent an exercise tolerance test involving bicycle ergometry. Participants received 36, 90-min sessions of a prescribed physical therapy (three per week), initiated at either two-months or six-months poststroke. Twenty-nine participants were excluded on the basis of the cardiac screening questionnaire, and 15 failed the exercise tolerance test for cardiovascular reasons. No participant experienced a cardiac event during a treatment session. Two participants experienced myocardial infarctions, but continued in the trial. In three additional participants, myocardial infarctions caused or contributed to death. The combination of a negative cardiac screen and the absence of exercise tolerance test failure appeared to have a high negative predictive value for cardiac events during treatment, despite the likelihood of a high prevalence of coronary artery disease in our population. © 2014 World Stroke Organization.

Alcohol-impaired speed and accuracy of cognitive functions: a review of acute tolerance and recovery of cognitive performance.

PubMed

Schweizer, Tom A; Vogel-Sprott, Muriel

2008-06-01

Much research on the effects of a dose of alcohol has shown that motor skills recover from impairment as blood alcohol concentrations (BACs) decline and that acute tolerance to alcohol impairment can develop during the course of the dose. Comparable alcohol research on cognitive performance is sparse but has increased with the development of computerized cognitive tasks. This article reviews the results of recent research using these tasks to test the development of acute tolerance in cognitive performance and recovery from impairment during declining BACs. Results show that speed and accuracy do not necessarily agree in detecting cognitive impairment, and this mismatch most frequently occurs during declining BACs. Speed of cognitive performance usually recovers from impairment to drug-free levels during declining BACs, whereas alcohol-increased errors fail to diminish. As a consequence, speed of cognitive processing tends to develop acute tolerance, but no such tendency is shown in accuracy. This "acute protracted error" phenomenon has not previously been documented. The findings pose a challenge to the theory of alcohol tolerance on the basis of physiological adaptation and raise new research questions concerning the independence of speed and accuracy of cognitive processes, as well as hemispheric lateralization of alcohol effects. The occurrence of alcohol-induced protracted cognitive errors long after speed returned to normal is identified as a potential threat to the safety of social drinkers that requires urgent investigation.

Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial.

PubMed

Butchart, Joseph; Brook, Laura; Hopkins, Vivienne; Teeling, Jessica; Püntener, Ursula; Culliford, David; Sharples, Richard; Sharif, Saif; McFarlane, Brady; Raybould, Rachel; Thomas, Rhodri; Passmore, Peter; Perry, V Hugh; Holmes, Clive

2015-05-26

To determine whether the tumor necrosis factor α inhibitor etanercept is well tolerated and obtain preliminary data on its safety in Alzheimer disease dementia. In a double-blind study, patients with mild to moderate Alzheimer disease dementia were randomized (1:1) to subcutaneous etanercept (50 mg) once weekly or identical placebo over a 24-week period. Tolerability and safety of this medication was recorded including secondary outcomes of cognition, global function, behavior, and systemic cytokine levels at baseline, 12 weeks, 24 weeks, and following a 4-week washout period. This trial is registered with EudraCT (2009-013400-31) and ClinicalTrials.gov (NCT01068353). Forty-one participants (mean age 72.4 years; 61% men) were randomized to etanercept (n = 20) or placebo (n = 21). Etanercept was well tolerated; 90% of participants (18/20) completed the study compared with 71% (15/21) in the placebo group. Although infections were more common in the etanercept group, there were no serious adverse events or new safety concerns. While there were some interesting trends that favored etanercept, there were no statistically significant changes in cognition, behavior, or global function. This study showed that subcutaneous etanercept (50 mg/wk) was well tolerated in this small group of patients with Alzheimer disease dementia, but a larger more heterogeneous group needs to be tested before recommending its use for broader groups of patients. This study shows Class I evidence that weekly subcutaneous etanercept is well tolerated in Alzheimer disease dementia. © 2015 American Academy of Neurology.

A randomized controlled trial for the effect of passive stretching on measures of hamstring extensibility, passive stiffness, strength, and stretch tolerance.

PubMed

Marshall, Paul W M; Cashman, Anthony; Cheema, Birinder S

2011-11-01

To measure hamstring extensibility, stiffness, stretch tolerance, and strength following a 4-week passive stretching program. Randomized controlled trial. Twenty-two healthy participants were randomly assigned to either a 4-week stretching program consisting of 4 hamstring and hip stretches performed 5 times per week, or a non-stretching control group. Hamstring extensibility and stiffness were measured before and after training using the instrumented straight leg raise test (iSLR). Stretch tolerance was measured as the pain intensity (visual analog scale; VAS) elicited during the maximal stretch. Hamstring strength was measured using isokinetic dynamometry at 30 and 120° s(-1). Hamstring extensibility increased by 20.9% in the intervention group following 4 weeks of training (p<0.001; d=0.86). Passive stiffness was reduced by 31% in the intervention group (p<0.05; d=-0.89). Stretch tolerance VAS scores were not different between groups at either time point, and no changes were observed following training. There were no changes in hamstring concentric strength measured at 30 and 120° s(-1). Passive stretching increases hamstring extensibility and decreases passive stiffness, with no change in stretch tolerance defined by pain intensity during the stretch. Compared to previous research, the volume of stretching was higher in this study. The volume of prescribed stretching is important for eliciting the strong clinical effect observed in this study. Copyright © 2011 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Localization and Quantification of Callose in the Streptophyte Green Algae Zygnema and Klebsormidium: Correlation with Desiccation Tolerance

PubMed Central

Herburger, Klaus; Holzinger, Andreas

2015-01-01

Freshwater green algae started to colonize terrestrial habitats about 460 million years ago, giving rise to the evolution of land plants. Today, several streptophyte green algae occur in aero-terrestrial habitats with unpredictable fluctuations in water availability, serving as ideal models for investigating desiccation tolerance. We tested the hypothesis that callose, a β-d-1,3-glucan, is incorporated specifically in strained areas of the cell wall due to cellular water loss, implicating a contribution to desiccation tolerance. In the early diverging genus Klebsormidium, callose was drastically increased already after 30 min of desiccation stress. Localization studies demonstrated an increase in callose in the undulating cross cell walls during cellular water loss, allowing a regulated shrinkage and expansion after rehydration. This correlates with a high desiccation tolerance demonstrated by a full recovery of the photosynthetic yield visualized at the subcellular level by Imaging-PAM. Furthermore, abundant callose in terminal cell walls might facilitate cell detachment to release dispersal units. In contrast, in the late diverging Zygnema, the callose content did not change upon desiccation for up to 3.5 h and was primarily localized in the corners between individual cells and at terminal cells. While these callose deposits still imply reduction of mechanical damage, the photosynthetic yield did not recover fully in the investigated young cultures of Zygnema upon rehydration. The abundance and specific localization of callose correlates with the higher desiccation tolerance in Klebsormidium when compared with Zygnema. PMID:26412780

The DIAMIND study: postpartum SMS reminders to women who have had gestational diabetes mellitus to test for type 2 diabetes: a randomised controlled trial - study protocol.

PubMed

Heatley, Emer; Middleton, Philippa; Hague, William; Crowther, Caroline

2013-04-12

Postpartum follow up of women who have been found to have gestational diabetes during pregnancy is essential because of the strong association of gestational diabetes with subsequent type 2 diabetes. Postal reminders have been shown to increase significantly attendance for oral glucose tolerance testing postpartum. It is possible that a short message service (text) reminder system may also be effective. This trial aims to assess whether a text message reminder system for women who have experienced gestational diabetes in their index pregnancy will increase attendance for oral glucose tolerance testing within six months after birth. Single centre (Women's and Children's Hospital, South Australia), parallel group randomised controlled trial. Women diagnosed with gestational diabetes in their index pregnancy (oral glucose tolerance test with fasting glucose ≥ 5.5 mmol/L and/or two hour glucose ≥ 7.8 mmol/L), with access to a mobile phone, whose capillary blood glucose profile measurements prior to postnatal discharge are all normal (fasting glucose < 6.0 mmol/L, postprandial glucoses < 8.0 mmol/L). Pregestational diabetes mellitus, triplet/higher order multiple birth or stillbirth in the index pregnancy, requirement for interpreter.Trial entry and randomisation: Allocation to intervention will be undertaken using a telephone randomisation service (computer-generated random number sequence generation, with balanced variable blocks, and stratification by insulin requirement).Study groups: Women in the intervention group will receive a text reminder to attend for an oral glucose tolerance test at 6 weeks postpartum, with further reminders at 3 months and 6 months if they do not respond to indicate test completion. Women in the control group will receive a single text message reminder at 6 months postpartum.Blinding: Baseline data collection will be undertaken blinded. Blinding of participants and blinded collection of primary outcome data will not be possible for this study.Primary study outcome: Attendance for the oral glucose tolerance test within 6 months postpartum. 276 subjects will be required to show an 18% absolute increase in the rate of attendance (α=0.05 two tailed, β=80%, 5% loss to follow up) from 37% to 55% in the intervention group. Given the heightened risk of impaired glucose tolerance and type 2 diabetes in women who have had gestational diabetes, ensuring the highest possible rate of attendance for postpartum glucose tolerance testing, so that early diagnosis and intervention can occur, is important. A text message reminder system may prove to be an effective method for achieving improved attendance for such testing. This randomised controlled trial will assess whether such a system will increase rates of attendance for postpartum oral glucose tolerance testing in women who have experienced gestational diabetes. Australian New Zealand Clinical Trials Registry - ACTRN12612000621819.

Fluoride-sensitivity of growth and acid production of oral Actinomyces: comparison with oral Streptococcus.

PubMed

Kawashima, Junko; Nakajo, Kazuko; Washio, Jumpei; Mayanagi, Gen; Shimauchi, Hidetoshi; Takahashi, Nobuhiro

2013-12-01

Actinomyces are predominant oral bacteria; however, their cariogenic potential in terms of acid production and fluoride sensitivity has not been elucidated in detail and compared with that of other caries-associated oral bacteria, such as Streptococcus. Therefore, this study aimed to elucidate and compare the acid production and growth of Actinomyces and Streptococcus in the presence of bicarbonate and fluoride to mimic conditions in the oral cavity. Acid production from glucose was measured by pH-stat at pH 5.5 and 7.0 under anaerobic conditions. Growth rate was assessed by optical density in anaerobic culture. Although Actinomyces produced acid at a lower rate than did Streptococcus, their acid production was more tolerant of fluoride (IDacid production 50 = 110-170 ppm at pH 7.0 and 10-13 ppm at pH 5.5) than that of Streptococcus (IDacid production 50 = 36-53 ppm at pH 7.0 and 6.3-6.5 ppm at pH 5.5). Bicarbonate increased acid production by Actinomyces with prominent succinate production and enhanced their fluoride tolerance (IDacid production 50 = 220-320 ppm at pH 7.0 and 33-52 ppm at pH 5.5). Bicarbonate had no effect on these variables in Streptococcus. In addition, although the growth rate of Actinomyces was lower than that of Streptococcus, Actinomyces growth was more tolerant of fluoride (IDgrowth 50 = 130-160 ppm) than was that of Streptococcus (IDgrowth 50 = 27-36 ppm). These results indicate that oral Actinomyces are more tolerant of fluoride than oral Streptococcus, and bicarbonate enhances the fluoride tolerance of oral Actinomyces. Because of the limited number of species tested here, further study is needed to generalize these findings to the genus level. © 2013 The Societies and Wiley Publishing Asia Pty Ltd.

Gene therapy enhances chemotherapy tolerance and efficacy in glioblastoma patients.

PubMed

Adair, Jennifer E; Johnston, Sandra K; Mrugala, Maciej M; Beard, Brian C; Guyman, Laura A; Baldock, Anne L; Bridge, Carly A; Hawkins-Daarud, Andrea; Gori, Jennifer L; Born, Donald E; Gonzalez-Cuyar, Luis F; Silbergeld, Daniel L; Rockne, Russell C; Storer, Barry E; Rockhill, Jason K; Swanson, Kristin R; Kiem, Hans-Peter

2014-09-01

Temozolomide (TMZ) is one of the most potent chemotherapy agents for the treatment of glioblastoma. Unfortunately, almost half of glioblastoma tumors are TMZ resistant due to overexpression of methylguanine methyltransferase (MGMT(hi)). Coadministration of O6-benzylguanine (O6BG) can restore TMZ sensitivity, but causes off-target myelosuppression. Here, we conducted a prospective clinical trial to test whether gene therapy to confer O6BG resistance in hematopoietic stem cells (HSCs) improves chemotherapy tolerance and outcome. We enrolled 7 newly diagnosed glioblastoma patients with MGMT(hi) tumors. Patients received autologous gene-modified HSCs following single-agent carmustine administration. After hematopoietic recovery, patients underwent O6BG/TMZ chemotherapy in 28-day cycles. Serial blood samples and tumor images were collected throughout the study. Chemotherapy tolerance was determined by the observed myelosuppression and recovery following each cycle. Patient-specific biomathematical modeling of tumor growth was performed. Progression-free survival (PFS) and overall survival (OS) were also evaluated. Gene therapy permitted a significant increase in the mean number of tolerated O6BG/TMZ cycles (4.4 cycles per patient, P < 0.05) compared with historical controls without gene therapy (n = 7 patients, 1.7 cycles per patient). One patient tolerated an unprecedented 9 cycles and demonstrated long-term PFS without additional therapy. Overall, we observed a median PFS of 9 (range 3.5-57+) months and OS of 20 (range 13-57+) months. Furthermore, biomathematical modeling revealed markedly delayed tumor growth at lower cumulative TMZ doses in study patients compared with patients that received standard TMZ regimens without O6BG. These data support further development of chemoprotective gene therapy in combination with O6BG and TMZ for the treatment of glioblastoma and potentially other tumors with overexpression of MGMT. Clinicaltrials.gov NCT00669669. R01CA114218, R01AI080326, R01HL098489, P30DK056465, K01DK076973, R01HL074162, R01CA164371, R01NS060752, U54CA143970.

Elevated 1-h post-challenge plasma glucose levels in subjects with normal glucose tolerance or impaired glucose tolerance are associated with whole blood viscosity.

PubMed

Marini, Maria Adelaide; Fiorentino, Teresa Vanessa; Andreozzi, Francesco; Mannino, Gaia Chiara; Perticone, Maria; Sciacqua, Angela; Perticone, Francesco; Sesti, Giorgio

2017-08-01

It has been suggested that glucose levels ≥155 mg/dl at 1-h during an oral glucose tolerance test (OGTT) may predict development of type 2 diabetes and cardiovascular events among adults with normal glucose tolerance (NGT 1 h-high). Studies showed a link between increased blood viscosity and type 2 diabetes. However, whether blood viscosity is associated with dysglycemic conditions such as NGT 1 h-high, impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) is unsettled. 1723 non-diabetic adults underwent biochemical evaluation and OGTT. A validated formula based on hematocrit and total plasma proteins was employed to estimate whole blood viscosity. Subjects were categorized into NGT with 1 h glucose <155 mg/dL (NGT-1 h-low), NGT-1 h-high, IFG and/or IGT. Hematocrit and blood viscosity values appeared significantly higher in individuals with NGT 1 h-high, IFG and/or IGT as compared to NGT 1 h-low subjects. Blood viscosity was significantly correlated with age, waist circumference, blood pressure, HbA1c, fasting, 1- and 2-h post-challenge insulin levels, total cholesterol and low-density lipoprotein, triglycerides, fibrinogen, white blood cell, and inversely correlated with high-density lipoprotein and insulin sensitivity. Of the four glycemic parameters, 1-h post-challenge glucose showed the strongest correlation with blood viscosity (β = 0.158, P < 0.0001) in a multivariate regression analysis model including several atherosclerosis risk factors. Our results demonstrate a positive relationship between blood viscosity and 1-h post-challenge plasma glucose. They also suggest that a subgroup of NGT individuals with 1-h post-challenge plasma >155 mg/dl have increased blood viscosity comparable to that observed in subjects with IFG and/or IGT.

Shuttle filter study. Volume 3: Appendix

NASA Technical Reports Server (NTRS)

1974-01-01

Test data obtained from flow resistance and contaminant tolerance tests on the various porous media evaluated in the different fluids are presented in both graphical and tabular forms. Test procedures for both flow resistance and contaminant tolerance testing are presented, and the development of a system for continuously adding contaminant at a predetermined rate to a flowing fluid stream is described. Also included is a section describing the development effort of the self-indexing filter. This concept was adapted during this program for various shuttle applications.

Randomized double-blind comparison of cognitive and EEG effects of lacosamide and carbamazepine.

PubMed

Meador, Kimford J; Loring, David W; Boyd, Alan; Echauz, Javier; LaRoche, Suzette; Velez-Ruiz, Naymee; Korb, Pearce; Byrnes, William; Dilley, Deanne; Borghs, Simon; De Backer, Marc; Story, Tyler; Dedeken, Peter; Webster, Elizabeth

2016-09-01

Differential effectiveness of antiepileptic drugs (AEDs) is more commonly determined by tolerability than efficacy. Cognitive effects of AEDs can adversely affect tolerability and quality of life. This study evaluated cognitive and EEG effects of lacosamide (LCM) compared with carbamazepine immediate-release (CBZ-IR). A randomized, double-blind, double-dummy, two-period crossover, fixed-dose study in healthy subjects compared neuropsychological and EEG effects of LCM (150mg, b.i.d.) and CBZ-IR (200mg, t.i.d.). Testing was conducted at screening, predrug baseline, the end of each treatment period (3-week titration; 3-week maintenance), and the end of each washout period (4weeks after treatment). A composite Z-score was derived for the primary outcome variable (computerized cognitive tests and traditional neuropsychological measures) and separately for the EEG measures. Other variables included individual computer, neuropsychological, and EEG scores and adverse events (AEs). Subjects included 60 healthy adults (57% female; mean age: 34.4years [SD: 10.5]); 44 completed both treatments; 41 were per protocol subjects. Carbamazepine immediate-release had worse scores compared with LCM for the primary composite neuropsychological outcome (mean difference=0.33 [SD: 1.36], p=0.011) and for the composite EEG score (mean difference=0.92 [SD: 1.77], p=0.003). Secondary analyses across the individual variables revealed that CBZ-IR was statistically worse than LCM on 36% (4/11) of the neuropsychological tests (computerized and noncomputerized) and 0% of the four EEG measures; none favored CBZ-IR. Drug-related AEs occurred more with CBZ-IR (49%) than LCM (22%). Lacosamide had fewer untoward neuropsychological and EEG effects and fewer AEs and AE-related discontinuations than CBZ-IR in healthy subjects. Lacosamide exhibits a favorable cognitive profile. Copyright © 2016 Elsevier Inc. All rights reserved.

Isolation, identification and expression analysis of salt-induced genes in Suaeda maritima, a natural halophyte, using PCR-based suppression subtractive hybridization

PubMed Central

Sahu, Binod B; Shaw, Birendra P

2009-01-01

Background Despite wealth of information generated on salt tolerance mechanism, its basics still remain elusive. Thus, there is a need of continued effort to understand the salt tolerance mechanism using suitable biotechnological techniques and test plants (species) to enable development of salt tolerant cultivars of interest. Therefore, the present study was undertaken to generate information on salt stress responsive genes in a natural halophyte, Suaeda maritima, using PCR-based suppression subtractive hybridization (PCR-SSH) technique. Results Forward and reverse SSH cDNA libraries were constructed after exposing the young plants to 425 mM NaCl for 24 h. From the forward SSH cDNA library, 429 high quality ESTs were obtained. BLASTX search and TIGR assembler programme revealed overexpression of 167 unigenes comprising 89 singletons and 78 contigs with ESTs redundancy of 81.8%. Among the unigenes, 32.5% were found to be of special interest, indicating novel function of these genes with regard to salt tolerance. Literature search for the known unigenes revealed that only 17 of them were salt-inducible. A comparative analysis of the existing SSH cDNA libraries for NaCl stress in plants showed that only a few overexpressing unigenes were common in them. Moreover, the present study also showed increased expression of phosphoethanolamine N-methyltransferase gene, indicating the possible accumulation of a much studied osmoticum, glycinebetaine, in halophyte under salt stress. Functional categorization of the proteins as per the Munich database in general revealed that salt tolerance could be largely determined by the proteins involved in transcription, signal transduction, protein activity regulation and cell differentiation and organogenesis. Conclusion The study provided a clear indication of possible vital role of glycinebetaine in the salt tolerance process in S. maritima. However, the salt-induced expression of a large number of genes involved in a wide range of cellular functions was indicative of highly complex nature of the process as such. Most of the salt inducible genes, nonetheless, appeared to be species-specific. In light of the observations made, it is reasonable to emphasize that a comparative analysis of ESTs from SSH cDNA libraries generated systematically for a few halophytes with varying salt exposure time may clearly identify the key salt tolerance determinant genes to a minimum number, highly desirable for any genetic manipulation adventure. PMID:19497134

Discrepancy between stimulus response and tolerance of pain in Alzheimer disease

PubMed Central

Werner, Mads U.; Jensen, Troels Staehelin; Ballegaard, Martin; Andersen, Birgitte Bo; Høgh, Peter; Waldemar, Gunhild

2015-01-01

Background: Affective-motivational and sensory-discriminative aspects of pain were investigated in patients with mild to moderate Alzheimer disease (AD) and healthy elderly controls using the cold pressor test tolerance and repetitive stimuli of warmth and heat stimuli, evaluating the stimulus-response function. Methods: A case-control design was applied examining 33 patients with mild to moderate AD dementia and 32 healthy controls with the cold pressor test (4°C). Warmth detection threshold (WDT) and heat pain threshold (HPT) were assessed using 5 stimulations. A stimulus-response function was estimated using 4 incrementally increasing suprathreshold heat stimuli. Results: Cold pressor tolerance was lower in patients with AD dementia than in controls (p = 0.027). There were no significant differences between groups regarding WDT and HPT. Significant successive increases in HPT assessments indicated habituation (p < 0.0001), which was similar in the 2 groups (p = 0.85). A mixed model for repeated measures demonstrated that pain rating of suprathreshold stimuli depended on HPT (p = 0.0004) and stimulus intensity (p < 0.0001). Patients with AD dementia had significantly lower increases in pain ratings than controls during suprathreshold stimulation (p = 0.0072). Conclusion: Our results indicate that AD dementia is not associated with a propensity toward development of sensitization or a lack of habituation, suggesting preservation of sensory-discriminative aspects of pain perception. The results further suggest that the attenuated cold pressor pain tolerance may relate to impairment of coping abilities. Paradoxically, we found an attenuated stimulus-response function, compared to controls, suggesting that AD dementia interferes with pain ratings over time, most likely due to memory impairment. PMID:25788560

Hysterosalpingo-foam sonography (HyFoSy): Tolerability, safety and the occurrence of pregnancy post-procedure.

PubMed

Tanaka, Keisuke; Chua, Jackie; Cincotta, Robert; Ballard, Emma L; Duncombe, Gregory

2018-02-01

Fallopian tube patency testing is an essential part of infertility evaluation. Hysterosalpingo-contrast sonography (HyCoSy) has been described as reliable, well tolerated and safe compared to other modalities such as laparoscopy and a dye test or hysterosalpingography. Limited availability of the previously used contrast has led to the introduction of a foam contrast agent as an alternative. To assess the tolerability, safety and occurrence of pregnancy post-procedure of hysterosalpingo-foam sonography (HyFoSy). A retrospective cohort study of women who had a HyFoSy at Queensland Ultrasound for Women from March 2013 to February 2015. A questionnaire was sent to their referring doctor to identify any complications or subsequent pregnancies with or without artificial reproductive technology (ART) within six months of the HyFoSy. Of 200 women, four cases were abandoned due to difficulty introducing the intracervical catheter, severe discomfort or a vasovagal episode. Response from referring doctors for 155 women reported no post-procedural complication. One hundred and eleven women were followed up for at least six months. Twenty-four out of 59 women (40.7%) who had ART and 24 out of 52 women (46.2%) who did not have ART conceived. Fifty percent of women who were nulligravida at the time of investigation, found to have at least one patent fallopian tube, whose partner had a normal semen analysis, spontaneously conceived within the time of follow up. HyFoSy is well tolerated and safe. A preponderance of pregnancies in the first month after HyFoSy suggests that a therapeutic effect may exist. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Epigenetics of drought-induced trans-generational plasticity: consequences for range limit development

PubMed Central

Alsdurf, Jacob; Anderson, Cynthia; Siemens, David H.

2016-01-01

Genetic variation gives plants the potential to adapt to stressful environments that often exist beyond their geographic range limits. However, various genetic, physiological or developmental constraints might prevent the process of adaptation. Alternatively, environmentally induced epigenetic changes might sustain populations for several generations in stressful areas across range boundaries, but previous work on Boechera stricta, an upland mustard closely related to Arabidopsis, documented a drought-induced trans-generational plastic trade-off that could contribute to range limit development. Offspring of parents who were drought treated had higher drought tolerance, but lower levels of glucosinolate toxins. Both drought tolerance and defence are thought to be needed to expand the range to lower elevations. Here, we used methylation-sensitive amplified fragment length polymorphisms to determine whether environmentally induced DNA methylation and thus epigenetics could be a mechanism involved in the observed trans-generational plastic trade-off. We compared 110 offspring from the same self-fertilizing lineages whose parents were exposed to experimental drought stress treatments in the laboratory. Using three primer combinations, 643 polymorphic epi-loci were detected. Discriminant function analysis (DFA) on the amount of methylation detected resulted in significant combinations of epi-loci that distinguished the parent drought treatments in the offspring. Principal component (PC) and univariate association analyses also detected the significant differences, even after controlling for lineage, planting flat, developmental differences and multiple testing. Univariate tests also indicated significant associations between the amount of methylation and drought tolerance or glucosinolate toxin concentration. One epi-locus that was implicated in DFA, PC and univariate association analysis may be directly involved in the trade-off because increased methylation at this site on the genome decreased drought tolerance, but increased glucosinolate concentration. PMID:26685218

Insulin secretion and insulin resistance in Korean women with gestational diabetes mellitus and impaired glucose tolerance

PubMed Central

Yang, Sae Jeong; Kim, Tae Nyun; Baik, Sei Hyun; Kim, Tae Sun; Lee, Kwan Woo; Nam, Moonsuk; Park, Yong Soo; Woo, Jeong-Teak; Kim, Young Seol

2013-01-01

Background/Aims The aim was to compare the insulin sensitivity and secretion index of pregnant Korean women with normal glucose tolerance (NGT), gestational impaired glucose tolerance (GIGT; only one abnormal value according to the Carpenter and Coustan criteria), and gestational diabetes mellitus (GDM). Methods A cross-sectional study was performed with 1,163 pregnant women with positive (1-hour plasma glucose ≥ 7.2 mmol/L) in a 50-g oral glucose challenge test (OGCT). The 100-g oral glucose tolerance test (OGTT) was used to stratify the participants into three groups: NGT (n = 588), GIGT (n = 294), and GDM (n = 281). Results The GDM group had higher homeostasis model assessment of insulin resistance and lower insulin sensitivity index (ISOGTT), quantitative insulin sensitivity check index, homeostasis model assessment for estimation of index β-cell secretion (HOMA-B), first and second phase insulin secretion, and insulin secretion-sensitivity index (ISSI) than the NGT group (p ≤ 0.001 for all). Moreover, the GIGT group had lower ISOGTT, HOMA-B, first and second phase insulin secretion, and ISSI than the NGT group (p < 0.001 for all). Among the GIGT subjects, the 1-hour plasma glucose abnormal levels group showed significantly greater weight gain during pregnancy and higher values in the 50-g OGCT than the other two groups. Moreover, the 1-hour and 2-hour abnormal levels groups had poorer insulin secretion status than the 3-hour abnormal levels group. Conclusions Korean women with GDM show impairments of both insulin secretion and insulin sensitivity. In addition, GIGT is associated with both β-cell dysfunction and insulin resistance. PMID:23682224