Greater Increase In Resistance Research Articles

CFD Analysis of Biofouling Effect on Submarine Resistance and Wake

It is well known that biofouling increases a ship’s resistance and nominal wake. For submarines, any change to the circumferential variation of the nominal wake in the propeller plane will affect the variation of the flow over the propeller blade, and hence the fluctuating forces, and noise, generated by the propeller. The ANSYS FLUENT commercial Reynolds-Averaged Navier Stokes Computational Fluid Dynamics solver was used to investigate the influence of both the longitudinal and vertical distribution of biofouling on the resistance and wake, including the circumferential variation of the nominal wake, on a submarine, using the well-known Suboff standard submarine. For the present work, the k-ε turbulence model was selected, as this is commonly used in this field and is generally considered acceptable. To handle different boundary layer thicknesses in the flow fields, the whole y+ formulation was employed, enabling automatic switching between low and high Reynolds boundary wall models. The numerical solver used for the simulations is based on the finite volume method, which discretizes the RANS equations. In this approach, a segregated model was utilized in the solver, and the convection terms were discretized using the second-order upwind scheme to enhance solution accuracy. The criteria for the near wall are between 30 and 100, and the value of y+ for the present case is 84. It is shown that fouling over only the forward third of the submarine results in a greater increase in resistance than fouling over only the aft third. Fouling over only the lower half of the submarine results in greater resistance than fouling over only the forward third, but less than fouling over the whole of the hull. Fouling over only the forward third of the hull has less influence on the circumferential variation of the wake than fouling over the aft third only of the hull. The results show the importance of keeping the forward area of the hull clean when considering resistance only, whereas keeping the aft area of the hull clean is important when considering the uniformity of the nominal wake into the propeller.

Resistance of Aluminide Coatings on Austenitic Stainless Steel in a Nitriding Atmosphere.

A new slurry cementation method was used to produce silicide-aluminide protective coatings on austenitic stainless steel 1.4541. The slurry cementation processes were carried out at temperatures of 800 and 1000 °C for 2 h with and without an additional oxidation process at a temperature of 1000 °C for 5 min. The microstructure and thickness of the coatings were studied by scanning electron microscopy (SEM). The intention was to produce coatings that would increase the heat resistance of the steel in a nitriding atmosphere. For this reason, the produced coatings were subjected to gas nitriding at a temperature of 550–570 °C in an atmosphere containing from 40 to 60% of ammonia. The nitriding was carried out using four time steps: 16, 51, 124, and 200 h, and microstructural observations using SEM were performed after each step. Analysis of the chemical composition of the aluminide coatings and reference sample was performed using wavelength (WDS) and energy (EDS) dispersive X-ray microanalysis, and phase analysis was carried out using X-ray diffraction (XRD). The resistance of the aluminide coatings in the nitriding atmosphere was found to depend strongly on the phase composition of the coating. The greatest increase in resistance to gas corrosion under nitriding atmosphere conditions was achieved using a manufacturing temperature of 1000 °C.

Effect of Substrate Strain, Aluminum Thickness and Corona Pretreatment on the Electrical Resistance of Physical Vapor Deposited Aluminum Coatings

Aluminum coatings applied to polymer films by physical vapor deposition should be defect-free for applications such as packaging and electronic devices. However, cracks can appear in the aluminum coating as the polymer film stretches, becoming manifest as an increase in resistance. We evaluated the effect of different aluminum thicknesses (10–85 nm), polymer films (polyethylene terephthalate or polypropylene), and corona doses (0–280 W∙min/m2) on the relative increase in resistance during stretching (strain = 0–100%). We found that the thickness of the aluminum coating was inversely related to the increase in resistance. Corona pretreatment led to an increase in surface energy (≤40 mN/m for polypropylene; ≤50 mN/m for polyethylene terephthalate) although high corona doses resulted in overtreatment, which limited the adhesion of aluminum to the substrate and led to a greater increase in resistance. Varying the coating thickness had a much greater effect than the corona pretreatment, suggesting that thicker aluminum coatings are more effective than corona pretreatment as a strategy to increase coating stability. The effect of aluminum thickness and strain on resistance was described using a fit function containing three fit factors.

Biochemical mechanism, inheritance and cross-resistance to cyromazine in a non-target Chrysoperla carnea: A potential predator of whiteflies and aphids

Developing an eco-friendly Integrated Pest Management (IPM) approach is only possible by minimizing the use of insecticides and their effects on non-targets such as natural enemies. Chrysoperla carnea is a potential predator of several economic pests including whiteflies and aphids. C. carnea selected with cyromazine for 15 generations indicated a great increase in resistance to this Insect Growth Regulator (IGR). There was no cross-resistance to chlorpyrifos, cypermethrin and nitenpyram in Cyro-SEL population. Inheritance to cyromazine was autosomal, incompletely dominant, and polygenic. A high realized heritability (h2) value (0.37) confirmed more genetic variability. Synergists piperonyl butoxide (PBO) and S,S,S-tributylphosphorotrithioate (DEF) showed a significant involvement of P-450 monooxygenase and esterase in cyromazine resistance development. These findings are helpful to design a natural enemy-friendly IPM strategy resulting in increased survival and performance of C. carnea controlling economic pests.

Spatio-temporal dynamics of Varroa destructor resistance to tau-fluvalinate in Czechia, associated with L925V sodium channel point mutation.

Extensive application of pyrethroids to control Varroa destructor, an invasive mite devastating bee colonies, has resulted in a global spread of resistant mite populations. In this study, we analyzed the spatio-temporal dynamics of resistant V. destructor populations in Czechia, stemming from the L925V mutation. Mites were collected during 2011-2018 directly or from winter beeswax debris, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and densitometry was used to detect the L925V mutation. Pooled samples of 10 mites were classified, based on their PCR-RFLP patterns, as tau-fluvalinate-sensitive (56%), resistant (9%), or mixed (35%), with the latter including sensitive and resistant homo- and heterozygotes. We identified two zones with higher frequencies of resistance, one in southern Moravia and the other in Bohemia. The mutant populations were evenly distributed throughout the monitored districts, with a few temporal and spatial local fluctuations. The greatest increase in resistance was observed in 2016, following massive losses of bee colonies in the winter of 2015. This event appeared to be closely associated with fluctuations in resistant mite populations and their dispersion. Two outbreaks of resistance were detected in Czechia; however, the amount of applied tau-fluvalinate was not correlated with the frequency of resistance in mites. There was no remarkable increase in mite resistance in 2011-2018, although the use of tau-fluvalinate increased 40-fold between 2011 and 2015. PCR-RFLP analysis, performed on mites present in beeswax debris, is a suitable method for monitoring the L925V mutation in V. destructor. © 2018 Society of Chemical Industry.

CHANGES OF BLOOD PRESSURE DURING ORTHOSTATISM AND ITS HEMODYNAMIC PROFILE IN PATIENTS IN DIALYSIS

Objective: 1- Analyze whether increases/decreases in BP during orthostatism are associated with characteristic hemodynamic profiles at rest 2-To establish whether increases/decreases in BP during orthostatism are associated with specific hemodynamic changes by standing 3-Determine independent hemodinamic predictors of orthostatic hypotension and hypertension Design and method: We studied 74 patients within a program of cardiovascular evaluation of patients on dialysis of CEMIC (PRECADIA). BP and hemodynamics were determined by impedance cardiography in the supine position and after the third minute of standing. Patients were classified into 3 groups according to the presence of orthostatic hypotension,orthostatic hypertension and stable behavior of blood pressure. The hemodynamic variables were analyzed according to: 1- basal conditions and 2-differences (Delta standing-lying), in each of them, according to the pressure changes with standing (ANOVA, Tukey). Iindependent hemodynamic predictors for orthostatic hypotension and orthostatic hypertension were determined. Results: In the supine position, the HypertOrt group was significantly younger (p = 0.018),SBP and DBP much lower (p = 0.00067andp = 0.05). I also present significantly less ejection period than the other two groups, accompanied by a tendency to a higher heart rate (p = 0.06). The HipotOrt group presented SBP and DBP significantly higher than the other two groups. Before standing, the HipotOrt group showed a general fall of the Delta-SVRI (p = 0.0182). The HypertOrt group, on the other hand, presented a greater increase Delta-SVRI. There were no significant differences in volume changes as well as in heart rate. In the logistic regressions, SBP turned out to be the only hemodynamic variable predictive of orthostatic hypotension (Odds ratio = 1.0288, p = 0.0019). Predictors of orthostatic hypertension were age (OR = 0.922, 95% CI = 0.8669–0.9802) and SBP (OR = 0.958, p = 0,0001). Conclusions: In basal conditions, patients with orthostatic hypotension showed a typical profile of supine hypertension-orthostatic hypotension, with a fall in vascular resistance during standing, commonly associated with dysautonomia. The orthostatic hypertension group presented a hyperdynamic tendency, with an increased heart rate with a lower ejection period, this associated with a greater increase in resistance during standing. This would justify the increase in blood pressure when standing.

Bortezomib Resistance Is Mediated by Increased Signaling through the Insulin-Like Growth Factor-1/Akt Axis.

Abstract 2739Poster Board II-715 Background:Inhibition of the proteasome as an anti-cancer strategy was first validated with the approval of bortezomib (VELCADE®), which is now a standard of care in relapsed and/or refractory multiple myeloma, and is also being used in the front-line setting, where it has shown improved efficacy compared to previously available induction therapies. However, myeloma remains incurable, and the use of bortezomib up-front may limit its later utility in the relapsed setting. Indeed, response rates on retreatment of patients with previously bortezomib-sensitive disease have been as low as 23%, indicating the rapid development of resistance. The mechanisms by which plasma cells survive and become resistant to bortezomib therapy have not been fully characterized, in part due to a lack of appropriate model systems. Discovery of these resistance mechanisms will facilitate the development of strategies to circumvent them, and help to identify potential novel therapies for the treatment of patients with disease showing resistance to bortezomib. Methods:To improve our understanding of the mechanisms responsible for bortezomib resistance, we developed cell line models of interleukin (IL)-6-dependent (ANBL-6 and KAS-6/1) and –independent (RPMI 8226 and OPM-2) bortezomib-resistant (BR) myeloma by continuously exposing drug-naïve cells to increasing bortezomib concentrations. One of these pooled lines derived from RPMI 8226 cells was then subjected to single-cell cloning, and all of the lines where characterized by gene expression profiling to identify potential mechanisms of resistance. Results:Cell lines resistant to bortezomib, such as RPMI 8226.BR, retained their viability, and did not demonstrate increased Annexin V staining compared to drug-naïve cells in the presence of 50 nM or more of this proteasome inhibitor. Calculations of the degree of resistance revealed values of up to 4.3 or more. Bortezomib resistance was a stable phenotype, since these cells remained unaffected by bortezomib treatment even after a one month period of drug withdrawal. Mutation of the binding site of the β5 proteasome subunit has been reported as one mechanism of bortezomib resistance, but the chymotrypsin-like proteasome activity in RPMI 8226.BR cells could still be suppressed by bortezomib even in the face of increased β5 expression in some subclones. Increased drug clearance has also been proposed as a resistance pathway, but studies by mass spectrometry indicated increased intracellular concentrations of bortezomib and its metabolites in RPMI 8226.BR cells, suggesting that neither of these mechanisms contributed to resistance in our models. Gene expression profiling revealed evidence of up-regulation of insulin-like growth factor (IGF)-1 transcripts by up to 5.2-fold, along with increased expression of phosphoinositide 3-kinase (by up to 4.4-fold) and protein kinase B/Akt (up to 3.2-fold), but suppression of phosphatase and tensin homolog (by up to 5.3-fold). RPMI 8226.BR clones secreted increased levels of IGF-1 into their media leading, in combination with the above gene expression changes, to increased levels of cellular activated, phosphorylated IGF-1 receptor (IGF-1R) and Akt. Addition of exogenous IGF-1 did reduce bortezomib sensitivity in drug-naïve myeloma cells, but induced a much greater increase in resistance in the BR clones even greater than that present in un-supplemented media. In contrast, inhibition of the IGF-1/IGF-1R/Akt axis using picropodophyllin, a pharmacologic inhibitor of IGF-1R; LY294002, a PI3K inhibitor; or NVP-BEZ-235, a novel Akt inhibitor, enhanced sensitivity to bortezomib, and this enhancement was greatest in the BR clones. Similarly, suppression of IGF-1R expression using Lentiviral-mediated delivery of specific shRNAs re-sensitized bortezomib-resistant cells to bortezomib-induced apoptosis, and indeed returned their sensitivity to that of their drug-naïve counterparts. Conclusions:Our data support the hypothesis that increased signaling through the IGF-1/Akt axis mediated by enhanced plasma cell secretion of IGF-1, and enhanced expression of PI3K and Akt, is another mechanism that mediates stable bortezomib resistance in vitro. Moreover, if validated by ongoing studies of primary patient samples, they provide a rationale for the introduction of combination therapies with bortezomib and either Akt or IGF-1 inhibitors to overcome or prevent the emergence of bortezomib resistance in the clinic. Disclosures:No relevant conflicts of interest to declare.

Overexpression of polyphenol oxidase in transgenic tomato plants results in enhanced bacterial disease resistance.

Polyphenol oxidases (PPOs; EC 1.10.3.2 or EC 1.14.18.1) catalyzing the oxygen-dependent oxidation of phenols to quinones are ubiquitous among angiosperms and assumed to be involved in plant defense against pests and pathogens. In order to investigate the role of PPO in plant disease resistance, we made transgenic tomato ( Lycopersicon esculentum Mill. cv. Money Maker) plants that overexpressed a potato ( Solanum tuberosum L.) PPO cDNA under control of the cauliflower mosaic virus 35S promoter. The transgenic plants expressed up to 30-fold increases in PPO transcripts and 5- to 10-fold increases in PPO activity and immunodetectable PPO. As expected, these PPO-overexpressing transgenic plants oxidized the endogenous phenolic substrate pool at a higher rate than control plants. Three independent transgenic lines were selected to assess their interaction with the bacterial pathogen Pseudomonas syringae pv. tomato. The PPO-overexpressing tomato plants exhibited a great increase in resistance to P. syringae. Compared with control plants, these transgenic lines showed less severity of disease symptoms, with over 15-fold fewer lesions, and strong inhibition of bacterial growth, with over 100-fold reduction of bacterial population in the infected leaves. These results demonstrate the importance of PPO-mediated phenolic oxidation in restricting plant disease development.

Airway reactivity following repeated milk aspiration in rabbits.

Asthma and gastroesophageal reflux (GER) are commonly associated disorders. Microaspiration is one possible link between these processes. The purpose of this study was to assess methacholine reactivity following repeated small-volume aspiration such as may occur with GER. This was also correlated with airway cytology. Five weekly intratracheal instillations of either milk (N = 8) or saline sham controls (N = 7) in volumes of 0.25 mL/kg were performed in anesthetized rabbits. Transpulmonary pressure, flow, tidal volume, central airways resistance, and dynamic lung compliance were measured in anesthetized and paralyzed animals at baseline, after 2 and 5 weeks of instillation, and 3 weeks after the last instillation. Doubling concentrations of methacholine were given until a 50% or greater increase in resistance occurred (PC50R). Bronchial washings for cytological evaluation were performed after the physiologic measurements and before each instillation. There were no significant differences in airway reactivity between baseline and all subsequent observation points within each of the two groups. However, methacholine responsiveness was significantly higher in the milk group before the final instillation (PC50R = 5.84 vs. 12.97 mg/mL, P = 0.03) and at recovery (PC50R = 6.40 vs. 10.56 mg/mL, P = 0.047) when compared to saline controls. This was associated with a higher neutrophil percentage (P = 0.01) at 5 weeks, and eosinophil percentage (P = 0.05) at recovery in the bronchial wash specimens from the milk group. These results show that repeated small-volume aspiration of milk in rabbits causes persistent inflammation and is associated with greater airway reactivity when compared to sham controls. This inflammation was accompanied by either increased neutrophils or eosinophils in bronchial lavage specimens. These findings lend support to a possible role of microaspiration in association with increased airway reactivity in patients with GER.

Airway reactivity following repeated milk aspiration in rabbits

Asthma and gastroesophageal reflux (GER) are commonly associated disorders. Microaspiration is one possible link between these processes. The purpose of this study was to assess methacholine reactivity following repeated small-volume aspiration such as may occur with GER. This was also correlated with airway cytology. Five weekly intratracheal instillations of either milk (N = 8) or saline sham controls (N = 7) in volumes of 0.25 mL/kg were performed in anesthetized rabbits. Transpulmonary pressure, flow, tidal volume, central airways resistance, and dynamic lung compliance were measured in anesthetized and paralyzed animals at baseline, after 2 and 5 weeks of instillation, and 3 weeks after the last instillation. Doubling concentrations of methacholine were given until a 50% or greater increase in resistance occurred (PC50R). Bronchial washings for cytological evaluation were performed after the physiologic measurements and before each instillation. There were no significant differences in airway reactivity between baseline and all subsequent observation points within each of the two groups. However, methacholine responsiveness was significantly higher in the milk group before the final instillation (PC50R = 5.84 vs. 12.97 mg/mL, P = 0.03) and at recovery (PC50R = 6.40 vs. 10.56 mg/mL, P = 0.047) when compared to saline controls. This was associated with a higher neutrophil percentage (P = 0.01) at 5 weeks, and eosinophil percentage (P = 0.05) at recovery in the bronchial wash specimens from the milk group. These results show that repeated small-volume aspiration of milk in rabbits causes persistent inflammation and is associated with greater airway reactivity when compared to sham controls. This inflammation was accompanied by either increased neutrophils or eosinophils in bronchial lavage specimens. These findings lend support to a possible role of microaspiration in association with increased airway reactivity in patients with GER. Pediatr Pulmonol. 2000; 29:113–119. © 2000 Wiley-Liss, Inc.

The prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in young women

Four hundred and fifty-two urine isolates from women with acute uncomplicated cystitis and a positive urine culture presenting to a sexually transmitted disease clinic were collected during 1989–1991, and 213 specimens were collected over 1995–1997. The predominant species was Escherichia coli, representing 68% of the isolates; others included Staphylococcus saprophyticus (8%), Group B streptococci (7%), Proteus spp. (6%), Klebsiella spp. (4%) and Enterococcus spp. (3%). More than 10% of the E. coli isolates were resistant to ampicillin, cephalothin, tetracycline and trimethoprim–sulfamethoxazole (TMP–SMX ) during both study periods, with the greatest increase in resistance to ampicillin and TMP/SMX between the two periods. Six hundred and four urinary tract infection isolates, including 83% E. coli, 7% S. saprophyticus, 3% Klebsiella spp. 2% Proteus spp., 2% enterococci, 1% Enterobacter spp. and 2% other organisms, were collected from women with acute cystitis attending a university student health service during 1995. Among E. coli isolates, 25% were resistant to ampicillin, 24% to tetracycline and 11% to TMP–SMX. Resistance to fluoroquinolones was essentially absent among gram-negative pathogens. Continued evaluation of susceptibility patterns of pathogens causing acute uncomplicated cystitis to traditional as well as new antimicrobials in well defined populations is necessary to ascertain the optimal empiric therapy.

The enzymological basis for resistance of herpesvirus DNA polymerase mutants to acyclovir: relationship to the structure of alpha-like DNA polymerases.

Acyclovir (ACV), like many antiviral drugs, is a nucleoside analog. In vitro, ACV triphosphate inhibits herpesvirus DNA polymerase by means of binding, incorporation into primer/template, and dead-end complex formation in the presence of the next deoxynucleoside triphosphate. However, it is not known whether this mechanism operates in vivo. To address this and other questions, we analyzed eight mutant polymerases encoded by drug-resistant viruses, each altered in a region conserved among alpha-like DNA polymerases. We measured Km and kcat values for dGTP and ACV triphosphate incorporation and Ki values of ACV triphosphate for dGTP incorporation for each mutant. Certain mutants showed increased Km values for ACV triphosphate incorporation, suggesting a defect in inhibitor binding. Other mutants showed reduced kcat values for ACV triphosphate incorporation, suggesting a defect in incorporation of inhibitor into DNA, while the rest of the mutants exhibited both altered km and kcat values. In most cases, the fold increase in Ki of ACV triphosphate for dGTP incorporation relative to wild-type polymerase was similar to fold resistance conferred by the mutation in vivo; however, one mutation conferred a much greater increase in resistance than in Ki. The effects of mutations on enzyme kinetics could be explained by using a model of an alpha-like DNA polymerase active site bound to primer/template and inhibitor. The results have implications for mechanisms of action and resistance of antiviral nucleoside analogs in vivo, in particular for the importance of incorporation into DNA and for the functional roles of conserved regions of polymerases.

Asymmetry in reflex responses of nasal muscles in anesthetized guinea pigs

Nasal reflexes elicited by mechanical or electrical stimulation of nasal afferents were studied in anesthetized guinea pigs. Probing the nasal cavity of one side evoked a greater activation of the contralateral than the ipsilateral nasal muscles and, occasionally, sneezing. Similarly, electrical stimulation of the ethmoidal nerve often caused sneezing, with a greater activation of the nasal muscles and a greater increase in resistance on the contralateral side. Asymmetrical activation of the nasal muscles in response to mechanical stimuli induces asymmetrical airflows, especially during sneezing, between the two sides of the nasal cavity. Most of the expired air is forcibly blown out through the ipsilateral nostril, thus improving the elimination of irritants from the nose.

Bond strengths of maxillary anterior base metal resin-bonded retainers with different thicknesses

Purpose. This study evaluated the effect of three different thicknesses of base metal resin-bonded retainers on retention/resistance. Material and methods. Three ivorine teeth, a central incisor, lateral incisor, and canine, were prepared to receive resin bonded retainers. Fifteen metal replicas of prepared teeth were made (five for each tooth morphotype). A total of 45 metal retainers were cast in three different thicknesses, 0.3, 0.5, and 0.7 mm, with 15 for each thickness. Retainers were cemented to metal die replicas with Panavia EX luting agent. After 24 hours, forces to dislodge the retainers were applied at 45 degrees to the vertical mesiodistal plane at the proximolingual line angle. Results. An increase in thicknesses resulted in elevation of dislodging forces that were almost linear for the three thicknesses of canine retainers. The central incisor exhibited the greatest increase in resistance to dislodgment between retainers that were 0.3 and 0.5 mm thick, whereas increased thickness for the lateral incisor retainer resulted in minimal or no benefit. (J Prosthet Dent 1997;78:281-5.)

The Effects of Chemical Pollution on Antibiotic Resistance of Escherichia coli and Salmonella enteritidis in Sea Water

Minimum inhibitory concentraitons of ceftazidime, gentamicin, rifampicin and streptomycin for Escherichia coli and Salmonella enteritidis were determined under the effects of chemical pollution in sea water. Cells were either pretreated with hydrogen peroxide, ethanol, nitrobenzene and toluene and then released into sea water microcosms, or added directly to the sea water. Antibiotic susceptibility of E. coli and S. enteritidis was altered following chemical treatments. Antibiotic resistance was increased in E. coli cells with all chemical treatments, but ethanol and nitrobenzene treatment yielded the greatest increase in resistance. Similar trends were observed both in pretreated cells and in those surviving in the presence of chemical treatments. However, S. enteritidis cells showed a more marked increase in resistance in the presence of chemicals than pretreated cells.

The Effect of Dust Loading on Penetration and Resistance of Glass Fiber Filters

ABSTRACT As glass fiber filters become loaded with solid particles, their resistance to airflow increases and penetration at a given flow rate decreases. In the present study, we measured the effect of loading on resistance and penetration for three types of loading dust with Mass Median Aerodynamic Diameter (MMAD) from 0.8 to 7.5 μm, and mass loading up to 2.2 mg/cm2. Penetration as a function of particle size and resistance measurements were made for five loading conditions, seven face velocities (0.04–3.38 cm/s), and 12 particle sizes (0.137–3.65 μm). As expected, loading modified filter performance to give greater resistance and lower penetration. Unit mass loading by the finer loading dust caused a greater increase in resistance and a greater decrease in penetration than did the coarser dusts. A computer model to predict the effect of loading on resistance and penetration was prepared. The model uses modified single-fiber filtration theory to estimate resistance and penetration. It assumes that solid...

The effect of trace additions of tellurium on oxidation and some other properties of aluminium-lithium base alloys

Alloys of various chemical compositions with and without tellurium (Te) have been prepared in this research. Several types of tests were carried out, namely, tensile, ageing (hardness versus ageing time), erosion-corrosion, and oxidation, in addition to the evaluation of oxidation resistance by thermal shock. X-ray diffraction was also used to analyse the oxidation scales built on the samples. The microstructures of the alloys and oxides have been studied as well. It was found that the addition of small amounts (0.2 and 0.4 wt %) of Te led to drastic increases in oxidation resistance compared to the corresponding Te free alloy at both testing temperatures (300 and 500 °C). The great increase in resistance to environmental attack displayed by Te containing alloys was due to impediment of the interaction of Li with oxygen and enhancement of oxide plasticity and adhesion. Oxides grown on Te containing alloys remained intact when subjected to thermal shock. Te containing alloys also showed a great improvement in corrosion-erosion resistance compared to the other investigated Te free alloy. It was also noticed that Te enhanced the ductility of the base alloys themselves.

Investigation of impaired coronary vasodilator reserve in the guinea pig heart with pressure induced hypertrophy.

Impaired coronary reserve and increased minimal coronary resistance have been documented in several animal models of left ventricular hypertrophy. There is controversy whether the increased minimal coronary resistance is due to vascular or extravascular causes. To test the hypothesis that pressure-overloaded left ventricular hypertrophy (LVH) is associated with a vascular defect, studies were performed using isolated buffer-perfused guinea pig hearts taken 72 +/- 6 days post-aortic banding (LVH n = 13) and compared to sham-operated controls (n = 12). The pressure flow relationship was determined over the range 30-70 mmHg. We defined an extravascular compression index as the percentage increase in flow during maximal arteriolar dilation when systolic forces were excluded during prolonged diastole (2 +/- 0.2 s). In LVH, coronary reserve was reduced (141 +/- 5.5% v 231.7 +/- 24.1%) P less than 0.01 and minimal coronary resistance was increased (4.55 +/- 0.44 v 3.70 +/- 0.37 mmHg.ml-1.min-1.g-1) P less than 0.05. The extravascular compression index was increased in LVH (36.8 +/- 1.4 v 30.5 +/- 2.3%) P less than 0.05. Systole caused a greater increase in resistance in the LVH group than in controls (1.73 +/- 0.26 v 0.95 +/- 0.14 mmHg.ml-1.min-1.g-1) P less than 0.05. These data indicate that during diastole there is impaired minimal coronary resistance of vascular origin. Systole impaired flow to a greater extent in hypertrophied hearts, further reducing the coronary reserve.

Expression of recombinant glutathione S-transferase pi, Ya, or Yb1 confers resistance to alkylating agents.

Increased levels of glutathione S-transferase (GST; RX:glutathione R-transferase; EC 2.5.1.18) mRNA, protein, and activity in tumor biopsy samples and in drug-resistant cultured cells are associated with resistance to anticancer drugs. We report that each of three full-length cloned GST cDNAs, that for pi (acidic), Ya (basic), and Yb1 (neutral), can confer drug resistance when expressed in cultured mammalian cells. In one approach, stably transfected mouse C3H/10T1/2 cells that express GST pi, Ya, or Yb1 were cloned and analyzed for drug resistance in colony-forming assays. Transiently transfected COS cells that were sorted on a fluorescence-activated cell sorter were used in the second approach to avoid interclonal variation in factors other than the recombinant GST and to show that reversion of transient GST expression correlated with loss of drug resistance. A sorting technique, developed to separate the 20% of the electroporated COS cell population that transiently expressed GST pi, Ya, or Yb1 from the nonexpressing population, was based on a GST-catalyzed intracellular conjugation of glutathione to the fluorescent labeling reagent monochlorobimane. GST Ya conferred the greatest increase in resistance to chlorambucil and melphalan (1.3- to 2.9-fold), Yb1 conferred the greatest increase in resistance to cisplatin (1.5-fold), and pi conferred the greatest increase in resistance to a racemic mixture of 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a] pyrene and 7 alpha,8 beta-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene and doxorubicin (1.5- and 1.3-fold) relative to controls. These resistance values to alkylating agents are commensurate with values observed clinically. Cytotoxicity curves representing recombinant GST+ populations were significantly different from their controls with P values ranging from 0.005 to 0.0001. No resistance to vinblastine was detected. Conferred drug resistance was proportional to the magnitude of GST Ya expression, and reversion of transient expression in GST Ya+ COS cell clones to a GST Ya- phenotype was associated with total loss of drug resistance.

Serosal bicarbonate protects against acid injury to rabbit esophagus

The role of serosal bicarbonate ions (HCO3−) in protection against acid injury was investigated in rabbit esophageal mucosa mounted in Ussing chambers. Luminal acidification reduced potential difference and resistance in tissues exposed serosally to HCO3− or (unbuffered) HCO3-free solution. Whereas resistance declined similarly in both groups, potential difference declined less in HCO3− solution. After washout, HCO3-bathed tissues also had a greater increase in resistance, lower permeability to mannitol, and less histologic damage. Furthermore, as protection by HCO3− was not blocked by pretreatment with either the anion exchange blocker, 4 acetamido-4′-isothiocyanatostilbene 2-2′-disulfonic acid, or the carbonic anhydrase inhibitor, acetazolamide, and replacement of HCO3− with N-2-hydroxy-ethylpiperazine-N′-2-ethane sulfonic acid, a buffer impermeant to cells, was protective, an extracellular site for protection by HCO3− was likely. Where in the extracellular space HCO3− buffers H+ is unclear, but the absence of change in luminal pH and the inability to prevent the acid-induced increase in permeability in HCO3-bathed tissues argue against a luminal (preepithelial) site. Also, rapid repair was not demonstrated, indicating that a luminal site for protection after surface cell damage was unlikely. We conclude that serosal HCO3− is important in esophageal protection against acid damage by buffering H+ within the intercellular compartment of the extracellular space.