Does midazolam inhibit the development of acute tolerance to the analgesic effect of alfentanil?

Alfentanil-midazolam analgesic interactions were studied in rats with continuous infusions or bolus injections of the drugs. Analgesia was determined by measuring the threshold of motor response to noxious pressure. The continous constant-rate infusion of alfentanil demonstrated that after an initial peak, the analgesia profoundly declined due to the development of acute tolerance. When alfentanil (250 μg·kg⁻¹·h⁻¹) was given together with midazolam (3 mg·kg⁻¹·h⁻¹), the decline in the analgesic effect of alfentanil was attenuated. Following the 4 h period of the constant-rate (250 μg·kg⁻¹·h⁻¹) infusion of alfentanil, when acute tolerance was already developed, midazolam (3 mg·kg⁻¹) given as a bolus injection enhanced the alfentanil-induced anesthesia. At the same time, when alfentanil was given as a bolus injection (30 μg·kg⁻¹) with or without midazolam (3 mg·kg⁻¹) also by bolus injection, no changes were seen to indicate an enhancement of the analgesic effect of alfentanil by midazolam. The results suggest that midazolam attenuates the development of acute tolerance to the analgesic effect of alfentanil.     

More diversity,less tolerance? The effect of type of cultural diversity on the erosion of tolerance in Swiss municipalities

Immigration and the ways in which host societies receive newcomers pose challenges for modern civil societies. This article contributes to the ongoing discussion about how ethnic diversity influences tolerance towards immigrants. Compared to previous studies, we analyse tolerance as a sequential concept in order to uncover the effects of contextual diversity on attitudes towards immigrants and the granting of certain rights to this group. Moreover, we distinguish different shares of ethnic groups based on their ethnic and cultural origins both on the independent and dependent variable. The analysis relies on a subnational survey of sixty municipalities in Switzerland, revealing that only certain ethnic groups are seen as an economic and cultural threat.     

Does the treatment of primary hyperaldosteronism influence glucose tolerance?

Primary hyperaldosteronism (PH) is frequently considered to be a secondary form of diabetes mellitus (DM). In our previous study we attempted to evaluate the prevalence of DM among patients with PH compared to control subjects with essential hypertension (EH). We have noted a relatively high prevalence of DM and impaired glucose tolerance in PH, but the differences between the PH and EH groups did not reach statistical significance. We performed this study to assess whether the effective treatment of PH (surgical and conservative) would improve the glucose tolerance. We have studied 24 patients with PH of the following two subtypes: aldosterone-producing adenoma (APA) treated with adrenalectomy and idiopathic hyperaldosteronism (IHA) treated with spironolactone. No significant changes of glucose levels were found in the 60th and 120th min of the oral glucose tolerance test (OGTT) in the APA group. On the other hand, fasting glucose levels were decreased significantly after adrenalectomy. Plasma glucose levels were significantly increased in the 60th min, but no differences were found in fasting values and in the 120th min in the IHA group. There was a significantly higher incidence of impaired glucose tolerance (36 per cent before, 45 per cent after treatment) and DM (9 per cent, 18 per cent) in the IHA group compared to the APA group (8 per cent, 32 per cent; DM 0 per cent, 0 per cent). In conclusion, the treatment of PH does not improve glucose tolerance. Mild worsening of glucose tolerance after treatment could be explained by an increase of the body mass index. These data, in accordance with our previous study, do not support the idea that PH is a secondary form of diabetes mellitus.     

Can the function of the extirpated amygdaloid complex be compensated for by the transplantation of embryonic nerve tissue?

In 20 white rats bilateral coagulation of the amygdalar complex was produced; on the fifth day to one half of them transplantation was performed by introducing stereotaxically on the left side 0.2-0.5 mm3 of the brain embryonal tissue from the corresponding area of the amygdala of 20-days embryo; in control saline was administered. After two months the rats were sacrificed to determine the activity of antiradical defense by superoxide dismutase (SOD) and the level of lipids peroxide oxidation (LPO) in the cerebral cortex. The transplantation decreased LPO even more and increased SOD as compared to amygdalectomy, e. i. caused still greater deviations from the norm (in this meaning--paradoxal effect), what apparently corresponds to intensification of adaptative-compensatory processes caused by amygdalectomy. The transplantation did not reverse the rats behaviour to the initial one and did not eliminate memory defect in the test of conditioned reaction of passive avoidance (like pyrazetam); it had different direction influence on "drinking under current" in conflict situation, only in particular cases approaching it to the norm.     

Breeding for salt tolerance in crop plants — the role of molecular biology

Salinity in soil affects about 7 % of the land’s surface and about 5 % of cultivated land. Most importantly, about 20 % of irrigated land has suffered from secondary salinisation and 50 % of irrigation schemes are affected by salts. In many hotter, drier countries of the world salinity is a concern in their agriculture and could become a key issue. Consequently, the development of salt resistant crops is seen as an important area of research. Although there has been considerable research into the effects of salts on crop plants, there has not, unfortunately, been a commensurate release of salt tolerant cultivars of crop plants. The reason is likely to be the complex nature of the effect of salts on plants. Given the rapid increase in molecular biological techniques, a key question is whether such techniques can aid the development of salt resistance in plants. Physiological and biochemical research has shown that salt tolerance depends on a range of adaptations embracing many aspects of a plant’s physiology: one of these the compartmentation of ions. Introducing genes for compatible solutes, a key part of ion compartmentation, in salt-sensitive species is, conceptually, a simple way of enhancing tolerance. However, analysis of the few data available suggests the consequences of transformation are not straightforward. This is not unexpected for a multigenic trait where the hierarchy of various aspects of tolerance may differ between and within species. The experimental evaluation of the response of transgenic plants to stress does not always match, in quality, the molecular biology. We have advocated the use of physiological traits in breeding programmes as a process that can be undertaken at the present while more knowledge of the genetic basis of salt tolerance is obtained. The use of molecular biological techniques might aid plant breeders through the development of marker aided selection.     

Effects of NO 3 − -N on the growth and salinity tolerance of Tamarix laxa Willd

The influence of NO ₃ ^? -N on growth and osmotic adjustment was studied in Tamarix laxa Willd., a halophyte with salt glands on its twigs. Seedlings of T. laxa Willd. were exposed to 1 mM (control) or 300 mM NaCl, with 0.05, 1 or 10 mM NO ₃ ^? -N for 24 days. The relative growth rate of seedlings at 300 mM NaCl was lower than that of control plants at all NO ₃ ^? -N levels, but the concentrations of organic N and total N in the twigs did not differ between the two NaCl treatments. Increasing NO ₃ ^? supply under 300 mM NaCl improved the growth of T. laxa, indicating that NO ₃ ^? played positive roles in improving salt resistance of the plant. The twigs of T. laxa Willd. accumulated mainly inorganic ions, especially Na⁺ and Cl^?, to lower osmotic potential (Ψs): the contributions of Na⁺ and Cl^? to Ψs were estimated at 31% and 27% respectively, at the highest levels of supply of both NaCl and NO ₃ ^? -N. The estimated contribution of NO ₃ ^? -N to Ψs was as high as 20% in the twigs in these conditions, indicating that NO ₃ ^? was also involved in osmotic adjustment in the twigs. Furthermore, increases in tissue NO ₃ ^? were accompanied by decreases in tissue Cl^? and proline under 300 mM NaCl. The estimated contribution of proline to Ψs declined as with NO ₃ ^? -N supply increased from 1 to 10 mM, while the contributions of nitrate to Ψs were enhanced under 300 mM NaCl. This suggested that higher accumulation of nitrate in the vacuole alleviated the effects of salinity stress on the plant by balancing the osmotic potential. In conclusion, NO ₃ ^? -N played both nutritional and osmotic roles in T. laxa Willd. in saline conditions.     

Immobilization of the α-amylase of Bacillus amyloliquifaciens TSWK1-1 for the improved biocatalytic properties and solvent tolerance

The α-amylase of Bacillus amyloliquifaciens TSWK1-1 (GenBank Number, GQ121033) was immobilized by various methods, including ionic binding with DEAE cellulose, covalent coupling with gelatin and entrapment in polyacrylamide and agar. The immobilization of the purified enzyme was most effective with the DEAE cellulose followed by gelatin, agar and polyacrylamide. The K _m increased, while V _max decreased upon immobilization on various supports. The temperature and pH profiles broadened, while thermostability and pH stability enhanced after immobilization. The immobilized enzyme exhibited greater activity in various non-ionic surfactants, such as Tween-20, Tween-80 and Triton X-100 and ionic surfactant, SDS. Similarly, the enhanced stability of the immobilized α-amylase in various organic solvents was among the attractive features of the study. The reusability of the immobilized enzyme in terms of operational stability was assessed. The DEAE cellulose immobilized α-amylase retained its initial activity even after 20 consequent cycles. The DEAE cellulose immobilized enzyme hydrolyzed starch with 27 % of efficiency. In summary, the immobilization of B. amyloliquifaciens TSWK1-1 α-amylase with DEAE cellulose appeared most suitable for the improved biocatalytic properties and stability.     

Different population responses of three sympatric rodent species to acorn masting—the role of tannin tolerance

Rodent population dynamics are predicted to respond positively to the masting of acorns, but diverging results have been published. This study tested the hypothesis that population responses to acorn masting vary depending on differences in the tolerance to tannins of different rodent species. The effects of acorn abundance on the rodent population densities were analyzed using a dataset obtained in Hokkaido, Japan. Specifically, population fluctuations of three rodent species (Apodemus speciosus, A. argenteus, and Myodes rufocanus) and the abundance of Quercus crispula acorns have been monitored since 1992. Acorn production in previous years had a positive effect on the annual population growth rates of A. speciosus; however, this trend was not clear in the other two species. Tannin tolerance, assessed by body weight changes in an acorn feeding experiment, exhibited clear differences among the rodent species; namely, the body weight of A. speciosus increased, whereas that of the other two species decreased. The observed responses to acorn masting of populations of the three sympatric rodent species reflected tannin tolerance. It suggests that only populations of species with high tannin tolerance positively respond to acorn masting. Previous studies tend to overlook species-specific abilities of coping with tannins in acorns. Our results emphasize the necessity of evaluating the tannin tolerance of rodents and the tannin content of acorns to understand how rodent population dynamics and acorn production are related.     

Acquisition of tolerance to Δ-9-THC as measured by the response of a cellular function

The development of tolerance to delta-9-tetrahydrocannabinol (Δ-9-THC) was investigated by measuring respiration in brain tissue after acute or chronic administration. Mice were given either single or seven daily repeated intraperitoneal injections of 50 mg/Kg of delta-9-tetrahydrocannabinol (Δ-9-THC) or control vehicle. The final injection for all drug treated animals included radiolabeled ³H-Δ-9-THC. The mice were sacrificed at 1 hour, 2 hours, 4 hours, 24 hours, and 7 days after the final injection. Δ-9-THC depressed respiration, but after repeated injections was significantly less effective in this regard, indicating acquisition of tolerance to Δ-9-THC. Because the concentration of radiolabeled cannabinoids in brain tissue from each group is not appreciably different, a cellular as opposed to distributional mode of tolerance is suggested.     

Shape of glucose, insulin, C-peptide curves during a 3-h oral glucose tolerance test: any relationship with the degree of glucose tolerance?

We aimed to analyze the shape of the glucose, insulin, and C-peptide curves during a 3-h oral glucose tolerance test (OGTT). Another aim was defining an index of shape taking into account the whole OGTT pattern. Five-hundred ninety-two OGTT curves were analyzed, mainly from women with former gestational diabetes, with glycemic concentrations characterized by normal glucose tolerance (n = 411), impaired glucose metabolism (n = 134), and Type 2 diabetes (n = 47). Glucose curves were classified according to their shape (monophasic, biphasic, triphasic, and 4/5-phases), and the metabolic condition of the subjects, divided according to the glucose shape stratification, was analyzed. Indices of shape based on the discrete second-order derivative of the curve patterns were also defined. We found that the majority of the glucose curves were monophasic (n = 262). Complex shapes were less frequent but not rare (n = 37 for the 4/5-phases shape, i.e., three peaks). There was a tendency toward the amelioration of the metabolic condition for increasing complexity of the shape, as indicated by lower glucose concentrations, improved insulin sensitivity and β-cell function. The shape index computed on C-peptide, WHOSH(CP) (WHole-Ogtt-SHape-index-C-peptide), showed a progressive increase [monophasic: 0.93 ± 0.04 (dimensionless); 4/5-phases: 1.35 ± 0.14], and it showed properties typical of β-cell function indices. We also found that the type of glucose shape is often associated to similar insulin and C-peptide shape. In conclusion, OGTT curves can be characterized by high variability, and complex OGTT shape is associated with better glucose tolerance. WHOSH(CP) (WHole-Ogtt-SHape-index) may be a powerful index of β-cell function much simpler than model-based indices.     

On the salinity tolerance of eggs and young larvae of Phryganea grandis Linné (Trichoptera)

Summary The salinity tolerance of eggs and recently hatched larvae of Phryganea grandis Linné (Trichoptera) from brackish-water in the Baltic Sea was investigated. Freshly deposited eggs will not develop to hatching in salinities above 7 More mature eggs will hatch even in 20 \% but the larvae die soon after emerging. Larvae have the same tolerance range as freshly deposited eggs (distilled water to 7 \%) in accordance with the actual distribution of the species. The high tolerance of mature eggs is probably due to changes in the egg-membranes or in the jelly of the egg-masses.Case building becomes abnormal in salinities above 10

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Résumé La tolérance de sel des oeufs et des larves récemment écloses de Phryganea grandis Linné (Trichoptera) de l'eau saumâtre de la Baltique a été examinée. Des oeufs nouvellement pondus ne se développeront pas jusqu'à éclosion dans une salinité de 7 Des oeufs plus mûrs sortiront de l'oeuf même dans une salinité de 20 \%, mais les larves meurent bientôt. Les larves ont la même limite de tolérance que des oeufs nouvellement pondus (de l'eau distillee de 7 \%), conformément à la distribution actuelle des espèces. La haute tolérance des oeufs mûrs est probablement conditionnée par des changements dans les membranes des oeufs ou dans la gelèe des masses d'oeufs. La construction des fourreaux devient anormale dans des salinités au-dessus de 10

     

What affects the desiccation tolerance threshold of Brazilian Eugenia (Myrtaceae) seeds?

Desiccation sensitive (DS) seeds are shed at high water contents (WC) and metabolically active, but WC thresholds vary broadly among species even in the same genus. Eugenia is an important ecological genus that has high occurrence in several Brazilian morphoclimatic domains. In this study, we assessed seed desiccation tolerance of five Eugenia species collected in specific meteorological conditions. We reported the species geographical ranges and verified the rainfall and temperature of species sites in the year prior to seed collection. We also assessed initial WC, seed germination and vigor and seedling growth upon desiccation. Eugenia uniflora was the widest spread among the five species, while E. astringens was the most restricted. In this specific study, widespread species showed a higher WC threshold than restricted species. In the same way, the WC of fresh seeds was not correlated to the desiccation tolerance threshold. Seed desiccation tolerance was species dependent and correlated with the environmental status of seed collection sites. Wetter and warmer conditions were correlated to the E. uniflora higher DS threshold. Low rainfall and temperature corresponded to a lower desiccation sensitivity of E. astringens seeds. Seeds of the five species lost half viability between 0.44 and 0.25 g H₂O g DW^??1 and after 65–270 h of desiccation. Our results indicate that abiotic factors impact plant populations during the seed production season and can drive seed desiccation tolerance threshold and physiological behavior. These results should be taken into account in ex-situ plant conservation programs and tropical species management.

     

How the biliary tree maintains immune tolerance?

The liver is a vital organ with distinctive anatomy, histology and heterogeneous cell populations. These characteristics are of particular importance in maintaining immune homeostasis within the liver microenvironments, notably the biliary tree. Cholangiocytes are the first line of defense of the biliary tree against foreign substances, and are equipped to participate through various immunological pathways. Indeed, cholangiocytes protect against pathogens by TLRs-related signaling; maintain tolerance by expression of IRAK-M and PPARγ; limit immune response by inducing apoptosis of leukocytes; present antigen by expressing human leukocyte antigen molecules and costimulatory molecules; recruit leukocytes to the target site by expressing cytokines and chemokines. However, breach of tolerance in the biliary tree results in various cholangiopathies, exemplified by primary biliary cholangitis, primary sclerosing cholangitis and biliary atresia. Lessons learned from immune tolerance of the biliary tree will provide the basis for the development of effective therapeutic approaches against autoimmune biliary tract diseases. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.     

Genetic analysis of physiological components of salt tolerance conferred by Solanum rootstocks. What is the rootstock doing for the scion?

Grafting desirable crop varieties on stress-tolerant rootstocks provides an opportunity to increase crop salt tolerance. Here, a commercial hybrid tomato variety was grafted on two populations of recombinant inbred lines developed from a salt-sensitive genotype of Solanum lycopersicum var. cerasiforme, as female parent, and two salt-tolerant lines, as male parents, from S. pimpinellifolium, the P population, and S. cheesmaniae, the C population, to identify an easy screening method for identifying rootstocks conferring salt tolerance in terms of fruit yield. Potential physiological components of salt tolerance were assessed in the scion: leaf biomass, [Na⁺], nutrition, water relations and xylem ABA concentration. A significant correlation between scion fruit yield and scion leaf fresh weight, water potential or the ABA concentration was found in the C population under salinity, but the only detected QTL did not support this relationship. The rootstocks of the P population clearly affected seven traits related to the sodium, phosphorous and copper concentrations and water content of the scion leaf, showing heritability estimates around 0.4 or higher. According to heritability estimates in the P population, up to five QTLs were detected per trait. QTLs contributing over 15% to the total variance were found for P and Cu concentrations and water content of the scion leaf, and the proportion of fresh root weight. Correlation and QTL analysis suggests that rootstock-mediated improvement of fruit yield in the P population under salinity is mainly explained by the rootstock’s ability to minimise perturbations in scion water status.     

Application of the β-expectation tolerance interval to method validation of the M30 and M65 ELISA cell death biomarker assays

Method validation should focus on demonstrating that an assay is fit for its intended purpose. We have applied the β-expectation tolerance interval - a statistical approach that predicts the accuracy of assay measurements in the future - to the validation of two different cell death biomarker assays, the M30 and M65 ELISAs. A meta-analysis was conducted on a total of 57 different M30 and M65 assays run over a 2 year period. All code utilised in calculations was developed using MATLAB. The optimal fit to the calibration curve for the M30 assay was shown to be a quartic curve which yielded a β-expectation tolerance interval of +20.5% and -23.6% at β=95% over a wide range of QC standards (88-810 U/L). However, such a fit required at least 7 points to avoid problems with over fitting. A linear fit to the M65 calibration curve normally produced a tolerance interval of less than ±20%, however, marked inter-batch variations were evident. Amelioration of batch to batch variations was accomplished by fitting M65 calibration data preferably to a 4-parameter logistic function or a cubic spline. The minimum number of QC replicates and different assays required to produce reliable accuracy profiles was determined. The β-expectation tolerance interval approach has resulted in further optimisation of the M30 and M65 ELISAs as biomarker assays that should translate into greater accuracy in results generated from clinical trials samples.     

Effect of glucose on Listeria monocytogenes biofilm formation,and assessment of the biofilm’s sanitation tolerance

Listeria monocytogenes is an important cause of human foodborne infections and its ability to form biofilms is a serious concern to the food industry. To reveal the effect of glucose conditions on biofilm formation of L. monocytogenes, 20 strains were investigated under three glucose conditions (0.1, 1.0, and 2.0% w v^–1) by quantifying the number of cells in the biofilm and observing the biofilm structure after incubation for 24, 72, and 168 h. In addition, the biofilms were examined for their sensitivity to sodium hypochlorite. It was found that high concentrations of glucose reduced the number of viable cells in the biofilms and increased extracellular polymeric substance production. Moreover, biofilms formed at a glucose concentration of 1.0 or 2.0% were more resistant to sodium hypochlorite than those formed at a glucose concentration of 0.1%. This knowledge can be used to help design the most appropriate sanitation strategy.