Concentration Of 10-4M Research Articles

Synthesis, structural characterization and anticorrosion properties of a new hexafunctional epoxy prepolymer based on urea and phosphorus trichloride for E24 carbon steel in 1.0 M HCl

Our goal is to set up a synthetic method to produce the hexaglycidyl amine tri-urea phosphoric acid (HGATUP), a novel hexafunctional prepolymer. We created this prepolymer by phosphorylating urea in two processes. Next, to generate the new prepolymer, we added epichlorohydrin. In addition, we focused on its microscopic characterization using FTIR and NMR. The novel HGATUP prepolymer was utilized as a corrosion inhibitor for E24 carbon steel in a 1.0M hydrochloric acid (HCl) solution. PDP, EIS, EFM, DFT, Monte Carlo (MC), and molecular dynamic (MD) simulations were used in this study. SEM/EDS and XPS studies were also used to investigate the surface morphology. These methods allowed us to examine the sample's surface characteristics and chemical composition, which added to our understanding of the adsorption along with corrosion prevention processes. The electrochemical tests' outcomes also showed that the concentration of HGATUP enhanced inhibitory performance. PDP results indicated that HGATUP at a concentration of 10-3M had a corrosion inhibition efficiency of 97.6% at 298K ambient temperature. The polarization curve confirmed that the HGATUP was a mixed type of inhibitor that could inhibit steel anodic and cathodic reactions. The Langmuir model predicted that an epoxy prepolymer protected the surface of E24 carbon steel. Calculated thermodynamic kinetic parameters were used to analyze the inhibitor adsorption processes.

Effect of molecular structure of two fluorescein molecules on the corrosion inhibition of mild steel in 1 M HCl solution

2-(6-hydroxy-3-oxo-3H-xanthen-9-yl) benzoic acid (opened form of Fluorescein) (NAR4) were investigated and compared to 3,6-dihydroxy-3H Spiro[isobenzofuran-1,9-xanthen]-3-one (Closed form of Fluorescein) (FLUO) using experimental and theoretical approaches. The theoretical methods used were DFT method at B3LYP/6-311G (d. p) and Monte Carlo simulation. The toxicity test was evaluated in vivo and the results indicate that the molecules showed good ecological behavior. Furthermore, FLUO was investigated as an eco-friendly corrosion inhibitor of mild steel in acidic medium using various experimental methods (electrochemical techniques and surface analysis). The opened form of Fluorescein derivative gave a high inhibition effect compared to the close form reaching an inhibition efficiency of 88% at optimum concentration of 10-4M. Moreover, the adsorption phenomenon of studied inhibitors obeys El-Awady, Florry-Huggins and Temkin isotherms. In addition, surface analysis and UV–Visible spectroscopy were also employed to confirm the inhibition performance of Fluorescein derivatives on the mild steel surface.

Computational and experimental studies of the inhibitory effect of imidazole derivatives for the corrosion of copper in an acid medium

The inhibitory efficiencies of the molecules tested are determined using weight loss measurements, potentiodynamic polarization and electrochemical impedance (EIS). The adsorption of 1-Methylimidazole and 1H-benzimidazole on metallic surface reinforced with SEM-EDS and UV–Visible analysis of copper surface. These imidazole derivatives are heterocyclic organic compounds containing nitrogen atoms and are of great interest because of their multiple pharmacological activities. A theoretical simulation is achieved for the series of systems studied using density functional theory (DFT) to determine their electronic, structural and energetic properties. Monte Carlo simulation was performed to know well of the relationship between the inhibition ability and molecular structure of imidazole derivatives, the results of the potentiodynamic polarization indicate that the imidazole derivatives are mixed type inhibitors. These reduce the speed of the corrosion process for an optimal concentration of 10-3M. Electrochemical impedance spectroscopy (EIS) shows the presence of a single capacitive loop in favor of the charge transfer mechanism, the corrosion inhibition efficiency of 1-Methylimidazole and and 1H-benzimidazole exceeds approximately 66% 80% respectively. The adsorption of the compounds was found to obey Langmuir adsorption isotherm. A good agreement is observed between the results obtained by the different experimental techniques. Theory-experience correlations are established.

Assessment of phytostabilization potential of two Salix L. clones based on the effects of heavy metals on the root anatomical traits.

Willow species (Salix L.) are a useful tool for assessing phytostabilization of the sites polluted by heavy metals. Phytostabilization potential of two willow genotypes (Salix alba L. clone '68/53/1' and Salix nigra Marshall clone '0408') has been evaluated in a 45-day hydroponic experiment, using stem cuttings (diameter 12 to 14mm, length 20cm) exposed to two concentrations (10-4M and 10-5M) of individually applied Cd, Ni, and Pb. Metals were diluted in 25% Hoagland's solution, in forms of CdCl2·H2O, NiSO4·6H2O, and Pb-EDTA. The control group of cuttings was grown in 25% Hoagland's solution without heavy metals. High Cd concentrations in willow roots, 8637mg/kg (clone '68/53/1') and 6728mg/kg of dry weight (clone '0408'), have indicated a high phytostabilization potential. However, detailed analyses of cross-sectional area of the root cortex and the central cylinder revealed that the excess concentration of Cd led to a significant reduction of measured anatomical root's traits of clone '68/53/1' in comparison with the control samples. Excessive concentration of Ni and Pb in nutrient solution increased the values of quantitatively measured root's traits of clone '0408', implying stimulatory effects of the applied concentrations. Concentration of 10-4M of each metal had more negative effects on the roots' anatomical traits, notably on parenchymal and exodermal cells and vessels. Deposits of metals were observed in root tissues. Clone '0408' demonstrated an increased tolerance to heavy metals, which could potentially make this clone useful in phytostabilization.

SUN-101 Support for a New Therapeutic Approach of Using a Low-Dose FGFR Tyrosine Kinase Inhibitor (Infigratinib) for Achondroplasia

Background: Achondroplasia (ACH) is the most common non-lethal skeletal dysplasia. Fibroblast growth factor receptor 3 (FGFR3) plays a crucial role in bone elongation, demonstrated by FGFR3 gain-of-function mutations in individuals with ACH and hypochondroplasia. Multiple therapeutic strategies have been considered for ACH, the most advanced is to employ an analog of C-type Natriuretic Peptide (CNP), which antagonizes the MAP kinase (MAPK) pathway. Here, we evaluated a therapeutic strategy that targets all pathways downstream of FGFR3 (e.g., STAT1), not just MAPK. We hypothesized that a very low dose of the oral selective FGFR1-3 tyrosine kinase inhibitor (TKI) infigratinib (BGJ398) would be able to improve defective bone elongation. We also hypothesized that infigratinib would have greater potency at lower concentrations in an ACH cell line than a CNP analog (e.g., vosoritide) given its effects on multiple downstream pathways. Methods: A mouse model (Fgfr3Y367C/+) mimicking ACH was treated with subcutaneous injections of infigratinib daily (0.2 or 0.5 mg/kg/day) or intermittently (1 mg/kg, every 3 days) for a treatment duration of 15 days (PND1-15). In vivo results were compared with vehicle-treated mutant mice. TAN 4-18-chondrocytes, a human chondrocyte line expressing a heterozygous Y373C FGFR3 mutation, were treated with multiple concentrations of infigratinib and vosoritide and MAPK levels were measured. Results: We observed a significant improvement of the upper (humerus +7%, ulna +11%) and lower (femur +11%, tibia +16%) limbs at 0.5 mg/kg/day, and improvement in the foramen magnum. The effect of infigratinib on bone elongation was reduced with a lower dose (0.2 mg/kg), confirming a dose-response relationship. With intermittent injections of infigratinib (1 mg/kg, every 3 days), gain of growth was significant for all the long bones (+7%) and the size of the foramen magnum was increased. Modification of the growth plate structure, displaying better organization, was also seen. In cell line data, compared with FGF18-treated TAN 4-18-chondrocytes, concentrations of 10-6M to 10-10M infigratinib led to statistically significant (p<0.05) improvements. With vosoritide treatment, a concentration of 10-4M led to statistically significant improvements compared with FGF18-treated chondrocytes (p<0.05), although this was not seen at 10-5M. Conclusions: Preclinical ACH mouse model data indicate that low, as well as intermittent, doses of infigratinib promote growth and can improve the foramen magnum. No apparent toxicity of infigratinib was observed, suggesting that TKI therapy has the potential to be a valuable and relevant option for children with ACH. Furthermore, cell line data indicate that infigratinib showed superior potency over a CNP analog, suggesting that inhibition of multiple FGFR3-related pathways vs MAPK inhibition alone may lead to increased efficacy.

Study of a Polymeric Nanofilm Formed By PSP/PAH (Poly(Sodium Phosphate) and Poly(Allylamine Hydrochloride)) Based on Its Roughness for Optical Fiber Sensors Development

Introduction Nanofilms surfaces with a high roughness are relevant to develop optical fiber sensors (OFS). It has been reported, in previous publications [1], that this type of structures has been used in several applications to detect parameters as for example, gases and VOCs. One of the most important features of these sensors, based on this type of nanofilms, is the high surface/volume ratio; thanks to this fact, the molecules of the parameter to be measured can interact in a better way, with the rough surface improving the final sensitivity. Moreover, in most of the cases, these structures can be functionalized to make the final sensor more selective.This is the case of the structure proposed in this work formed by PAH (Poly(Allylamine Hydrochloride)) / PSP (Poly(Sodium Phosphate)) when it is deposited along the optical fiber by means of the technique Layer-by-Layer (LbL) nano assembly. The main idea of LbL technique consists of the nanoassembly of oppositely electrically charged polyelectrolytes: PAH is the material used as polycation and PSP is the inorganic compound employed as polyanion. It has been studied and exposed in [2] that the final nanofilm obtained with both polymers yields into an increasing roughness as the thickness does so making it use very interesting for humidity sensing. Nano Film Construction and experimental set up As it can be mentioned above, LbL nano assembly technique was employed with the goal of obtaining a specific roughness for the PSP/PAH nanofilm (Sensor A). The roughness surface developed enables the interaction between the PSP/PAH thin film and the evanescent field of the light guided and, due to the surface/volume ratio obtained, the molecules of water can penetrate through the nanofilm deposited improving in this manner the sensitivity. Different constructions with a distinct number of pair of layers (15 for sensor A and 100 for sensor B) and were carried out with polyelectrolyte concentrations of 10-3M along the core of a 200 μm-core optical fiber using a robotic arm (Nadetech S.L.). Another construction with a polyelectrolyte concentration of 10-2 M was made (Sensor C: 15 pair of layers). Firstly, the optical fibers were cleaned by immersing them for 20 minutes in each one of the following solutions: soap, ultrapure water, potassium hydroxide (KOH) and ultrapure water. After that, in order to facilitate the deposition of the first layer of PSP, an anchoring layer of Poly(ethyleneimine) (PEI) was deposited during another 20 minutes. Every sensor was exposed to different concentrations of relative humidity (RH) and their responses were recorded and studied.For sensor characterization, a transmission architecture was employed. For humidity sensing, the interrogation was carried out with a halogen broadband source (HL-2000-FHSA) connected to one end of the optical fiber and a spectrometer (USB2000+XR1) connected to the other one (see Figure 1). The sensors were placed in a climatic chamber where changes in the RH, from 20% to 90%, were performed. This cycle of RH variations was repeated several times and the responses of the sensors were recorded every minute. Results and Conclusions The responses of the sensors towards RH were carried out by monitoring the signal power level at 600 nm. As Figures 2 and 3 show, the optical power variations of Sensor A (0,6 dB), when the RH changes from 20% to 90%, are higher than Sensor B variations (0,18 dB); this is because with a low number of pair of layers, the final nanofilm thickness enables a better interaction between the evanescent field of the optical fiber and Sensor A nanofilm. Both factors lead to increased sensitivity. On the other hand, the value of the nanofilm roughness, as with the thickness, of Sensor B is higher than Sensor A; thanks to this fact, the molecules of H2O can penetrate and spread more in its structure. As it can be appreciated in Figure 3, the consequence of this fact is the reduction of the noise component of the sensor B response. Finally, Figure 4 shows the response of the Sensor C towards HR. In this case, due to the polyelectrolyte concentration used (10-2M), the roughness obtained was the lowest and consequently, the response of the sensor C is the worst. Therefore, this fact proves that roughness is a very important factor in the sensitivity optimization process of this type of nanofilms. Acknowledgements This work was carried out with the financial support of MINECO (Spain) through TEC2016-79367-C2-2-R (AEI/FEDER, UE) as well as Public University of Navarre PhD grants program.

Seleksi dan Optimasi Karakter Fisik Bakteri Penghasil Fitase yang Diisolasi dari Sumber Air Panas di Guci, Tegal

&lt;p&gt;The aimed of this study to isolate, select and characterize physically phytase-producing bacteria&lt;br /&gt;from hot springs in the Guci, Tegal. Isolation and enrichment of bacteria using Lurya Betani media&lt;br /&gt;with 2% of phytic acid substrate. Extraction of extracellular phytase thus obtained extract coarse and&lt;br /&gt;optimization by loking at the relative activity at the difference in the resulting product. Phytaseproducing&lt;br /&gt;bacteria can be isolated from the hot springs of the Guci, Tegal with the highest relative&lt;br /&gt;activity in AG2 and AG2-1 colonies. The highest relative activity at a temperature of 55°C, pH 6, the&lt;br /&gt;incubation time of 90 minutes, the substrate concentration of 3% and a metal cofactor Ca2+ at a&lt;br /&gt;concentration of 10-4M. Phytase-producing bacteria can be isolated from a hot spring in Guci, Tegal&lt;br /&gt;and have certain physical characteristics.&lt;/p&gt;

Influence of β2- and β3-adrenoceptor agonists on contractile activity of the porcine myometrium in the luteal phase and the first days of pregnancy.

This study analysed the relaxant properties of salbutamol (β2-adrenoceptors agonist) and BRL 37344 (β3-adrenoceptors agonist) regarding the contractility of porcine myometrium on days 10-14 of the oestrous cycle (cyclic group; n = 10) and on days 3-5 of pregnancy (early pregnant group; n = 6). The activity of myometrial strips (tension, frequency and amplitude) was recorded under isometric conditions using force transducers. The contractility was assessed further following the administration of increasing concentrations of the agonists (10-9-10-4 M), both with and without β-adrenoceptor antagonists (butaxamine - a selective β2- adrenoceptor antagonist, propranolol- a non-selective β1- and β2-adrenoceptor antagonist and bupranolol - a non-selective β1-, β2- and β3-adrenoceptor antagonist) at a concentration of 10-4 M. Although neither salbutamol nor BRL 37344 caused changes in the tension, at the highest concentrations they decreased the frequency and amplitude of contractions. These changes were more evident after salbutamol treatment and in the early pregnant group. Antagonists given alone did not cause changes in the parameters examined but changed some activity of the agonists. Butoxamine reduced the decrease in frequency and amplitude induced by salbutamol and produced a decrease in the tension after BRL 37344 treatment in the early pregnant group. Propranolol reduced the decrease in frequency and amplitude induced by salbutamol in both examined groups and did not cause significant changes in BRL 37344 activity. The administration of bupranolol before salbutamol treatment caused an increase in the tension and reduced the decrease in the frequency in the cyclic group. Moreover, bupranolol eliminated a decrease in frequency and induced an increase in amplitude caused by BRL 37344 in both groups and these changes were more evident in the early pregnant group. The data indicates that both β2- and β3-adenoreceptors are involved in the regulation of the contractility in both groups, but the changes after agonists and antagonists treatment are more evident in the early pregnant myometrium.

EFFECT OF CADMIUM AND LEAD IONS ON THE GROWTH AND CONTENT OF PROLINE IN PLANTS OF TRITICALE (Triticosecale Wittm.)

We studied the effect of CdSO4 and Pb(NO3)2 salts in 10-5M, 10-4M and 10-3M concentrations on some physiological indices of growth and development in plants of triticale (Triticosecale Wittm.) cultivar PRAG-530. It is shown that both of the metal salts inhibited germination energy and this effect increased along with salt concentration. It was found that the changes in growth rates, biomass accumulation and accumulation of proline by above- and underground organs of plants cannot be described as a monotonic dose-response dependence, but they are consistent with the paradoxical effect that an increase in the metal dose resulted in a decrease of its damaging effects, whereas a reduction of the metal dose, on the contrary, increased its damaging effect. In particular, it was found that the exposure of triticale plants for 8 days in Pb(NO3)2 solutions stimulated growth processes in terms of length and weight of the shoot and the root system. Interestingly, the toxic 10-4M lead concentration was more favorable for the seedlings than the 10-5M concentration. The response of triticale seedlings grown on CdSO4 solutions was the same, except for the salt concentration of 10-3M, when growth in shoots was inhibited and that in roots was completely suppressed. It is shown that the plants responded to stress caused by lead and cadmium metal salts with substantial accumulation of proline in leaves and roots, and the compound had the protective function. These results indicate that triticale plants are resistant to heavy metals, lead and cadmium, and that cadmium is more toxic to them than lead.

Differences in wheat and triticale seed germination in the presence of natural and synthetic plant growth regulators

A simple, fast and easy-to-perform method was carried out for the quantification of the effects of plant growth regulators on wheat and triticale. The method uses seed germination, root elongation and hypocotil growth in the plants as parameters in the presence of varying concentration of giberrellic acid (GA3), indol acetic acid (IAA), potassium nitrate (KNO3), magnesium sulfate (MgSO4) and AMO 1618. The highest germination rate was found in the seed treated with KNO3, 90% of wheat seeds germinated at concentration 10- 5M, while for triticale was 77.77% at a concentration of 10-4M. Longest roots were recorded in solutions of MgSO4, and the greatest impact on hypocotyl had GA3, for both wheat and triticale seeds. For both taxa retardant AMO 1618 was, at a concentration of 10-3M, led to complete inhibition of germination.

GW24-e2104 Epinephrine enhanced LPS-induced pro-inflammatory cytokines release by BMMCs: a cross-talking between catecholamine, circadian rhythm and inflammation

ObjectivesOccurring of acute coronary syndromes (ACSs) displayed circadian rhythms as well as the levels of catecholamines and pro-inflammatory cytokines in vivo. Such circadian rhythms were proved to exist also in...

Zmiany potencjału proliferacyjnego fibroblastów pochodzących z polipów nosowych, w hodowlach in vitro, pod wpływem pochodnych wit. D

Recurrent polyposis in the same patient resulting in the necessity of repeated surgeries forced to search for new pharmacological therapeutic methods. At present, locally acting glycocorticosteroids have the greatest value in the treatment of nasal polyposis. Polyps grow is connected with inflammation process and proliferation of fibroblasts. An evaluation of calcitriol and tacalcitol influence on proliferation of fibroblasts extracted from nasal polyps. consisted of 9 tissue samples coming from nasal polyps sampled during polypectomies. The testing was performed on the polyps fibroblasts after the sixth passage after the primary culture was established. Three days after the culture was started the cells were poured with nutrient medium without serum added and after further 24 hours was replaced by nutrient medium with takalcitol and calcitriol in the defined concentrations. The expression of the genes coding histone H3 was evaluated with the use of RT-PCR technique. Tacalcitiol and calcitriol in vitro decrease proliferation of fibroblasts sampled from nasal polyps. Inhibition is most effective for the concentration of 10-4M. Tacalcitiol and calcitriol also inhibit level of histone H3 gene expression. Experimental data suggest tacalcitiol to be more effective in the same concentration. Present studies may indicate the direction of further investigation in the potential pharmacological treatment on nasal polyps.

Electrochemical behaviour of Cu–Ni alloy in 3%NaCl medium polluted by sulphides: effect of aminotriazole

AbstractThe behaviour of 70/30 Cu–Ni alloy in 3%NaCl medium, both pure and contaminated by 1 ppm S2-ions, has been studied in the absence and in the presence of aminotriazole at a concentration of 10-4M. Potentiodynamic and electrochemical impedance measurements showed that sulphides accelerate the corrosion of the alloy in 3%NaCl. The aminotriazole inhibited both anodic and cathodic corrosion processes. The inhibiting effect was higher when the solution contained the S2-ions. Analysis by scanning electron microscopy (SEM) showed that the inhibitor acts by establishing a very thin film on the metal surface. This film behaves as a barrier to the diffusion of dissolved oxygen and to the transport of the metal ions from the melt to the solution.

Gathering of Charged Colloid Particles Near Like Charged Entities.

Negatively charged polymer colloid particles were found to gather near a like charged glass plate in deionized dispersions. The particle distribution near the glass plate was observed using a confocal laser scanning microscope. The number of particles about 5-10μm from the glass plate was about two times larger than that in the bulk dispersion and decreased gradually with distance. The tail of the peak in the particle distribution profile reached about 50μm from the glass plate, a very long distance compared with the range of ordinary electrostatic interaction. The 'positive adsorption' of the particles could be observed even in density matched H2O-D2O mixtures. It could not be observed at an NaCl concentration of 10-4M. These results show that the driving force for the positive adsorption is not sedimentation of the particles, but an electrostatic interaction. The positive adsorption increased with the number of charges on the particles and the glass surface. This indicates that the driving force of the positive adsorption is an electrostatic attraction between like charged particles and glass plate.

Induction of metamorphosis in larvae of the oyster Crassostrea gigas using neuroactive compounds

Chemical (neuroactive compounds at different concentrations and exposure times) and physical (water agitation, light) factors with potential effects on the metamorphosis of larvae of the oyster Crassostrea gigas (Thunberg) larvae have been studied. The neurotransmitters l-dihydroxyphenylalanine (DO), epinephrine (EP), norepinephrine (NE), and acetylcholine (AC) have been identified as very active inducers of metamorphosis, whilst serotonin (SE), dopamine (DA) and potassium (K) were less effective inducers. The γ-aminobutyric acid (GA) and ammonium (AM) were found ineffective at the concentrations tested. Exposure to 10-4 M EP for 15 min was sufficient to promote >80% metamorphosis within 48 h, whereas NE required 2 h to exert comparable induction. Maximum induction by DO (>50%) was achieved after 2 h exposure to 10-4 M. However, unlike EP and NE, DO was lethal at that concentration in the long term. Maximum induction by AC (∼30% metamorphosis) was achieved at a concentration of 10-4 M. In contrast to other neurotransmitters, AC induced settlement behaviour, cementation and eventual metamorphosis, yielding postlarvae which were all attached to the substratum. EP and NE triggered the morphogenetic changes, by-passing settlement and leading to postlarvae not cemented to the substratum. DO induced mostly attached spat at low concentrations (10-5 M) and unattached spat at high concentrations (10-4 M), and a similar pattern was apparent for the weaker inducers SE and DA. Regarding physical factors, a highly reflectant surface significantly increased the percentage of attached spat obtained, compared to a dark bottom. No consistent effect of water current or light was detected on the production of unattached spat. The three different forms of induction are discussed in relation to different regulatory pathways of settlement and metamorphosis.

関節リウマチ滑膜の各種ｃｙｔｏｋｉｎｅ産生能に対する疾患修飾性抗リウマチ剤の影響

We investigated the production of IL-1β, IL-6 and TNF-α by cultured synovial cells, and the effect of disease modifying antirheumatic drugs (DMARDs) on the production of those cytokines. Sulfasalazine (SASP), amethopterin (MTX), gold sodium thiomalate (GST), and bucillamine (BU) were used as DMARDs. Dexamethasone (DEX) and lipopolysaccharide (LPS) were used as negative and positive controls.IL-1β and IL-6 were detected in the culture supernatant but TNF-α was not. LPS stimulated the production of IL-6 while DEX suppressed it. They did not modulate the production of IL-1β, GST suppressed the production of IL-1β at a concentration of 10-3M. SASP and GST suppressed the production of IL-6 at the same concentration.This result showed that SASP, MTX, GST and BU could not supress synovial cells to produce IL-6 and IL-1β at the level of clinical dosages.

Effect of the maternal serum of cigarette smokers on placental xenobiotic metabolic potential in the first trimester placenta in vitro

The calcium salts of the mono- and diesters of [4-(1,1,3,3-tetramethylbutyl)phenyl phosphoric acid] have been prepared, and the individual esters as well as mixtures of the esters have been used with several varieties of polyvinyl chloride to construct macro membrane electrodes selective to calcium ions. These electrodes have been calibrated by using solutions of CaCl2 and Ca ion buffers. The mixed ester electrodes showed Nernstian response in the concentration range 10-1 to 10-7M; the diester electrodes showed Nernstian response down to 7.9 x 10-8M. The detection limit of the mixed ester electrode was 10-8M, whereas that of the diester electrode was 7.9 x 10-9M. Contrary to these results, the monoester electrodes showed unsatisfactory behavior. The responses of both the mixed ester and diester electrodes to calcium ions were not affected by the presence of sodium, potassium, or other divalent ions. Only ferric and lanthanum ions showed interferences with the electrode response to calcium ions. p]The electrode response was independent of pH in the approximate range 5–8 at a CaCl2 concentration of 10-4M. As the Ca ion concentration was increased, the range of pH independence widened to approximately 4–8. The dynamic response time constant of the mixed ester electrode was in the range 0.7–1.5 sec, whereas that of the diester electrode was in the range 0.5–0.75 sec.

Immunomodulatory effect of cimetidine on the proliferative responses of splenocytes from T. cruzi-infected rats

The immunomodulatory effect of cimetidine (CIM), a histamine type-2 receptor antagonist, was evaluated in respect to the blastogenic response to Con A of Wistar Furth (WF) rats infected by the Y strain of Trypanosoma cruzi (T. cruzi). Enhancement of blastogenesis of normal splenocytes was observed at a concentration of 10(3) M. However, the splenocytes from infected animals responded to concentrations of CIM ranging from 10(-8) to 10(-3) M. The mitogenic response to Con A of cells from infected animals was restored in the presence of CIM. The results show that CIM modulates the "in vitro" proliferative response of cells from T. cruzi-infected rats and suggest an immunoregulatory role of histamine and/or of cells that express H2 receptors in this infection.

Action of noradrenaline on isolated proximal and distal coronary arteries of rat: selective release of endothelium‐derived relaxing factor in proximal arteries

1. The effect of noradrenaline (NA) on the vascular smooth muscle and endothelial cells in isolated ring segments from the proximal and distal part of the left coronary artery (LCA) in rats was examined. 2. NA had a weak concentration-dependent contractile effect on proximal but relaxed distal segments of the LCA. The maximal NA-induced contraction of the proximal segments was doubled while the relaxation of the distal LCA segments was converted to a contraction after blockade of beta-adrenoceptors with propranolol 3 x 10(-6) M, thus indicating the presence of both alpha- and beta-adrenoceptors in the arteries, with dominance of alpha-adrenoceptors and of beta-adrenoceptors in the proximal and distal segments of the LCA, respectively. 3. The contractile effect of NA (beta-adrenoceptors blocked) was doubled in the proximal LCA segments after the endothelium was removed. Endothelial denudation had, in contrast, no potentiating effect on the contractile response of the distal arteries to NA. Both proximal and distal segments became more sensitive to the contractile action of NA after removal of the endothelium. 4. The spontaneous myogenic tone increased in both proximal and distal LCAs after endothelial removal, indicating spontaneous release of a relaxing endothelial factor in the vessels. 5. Following contraction with prostaglandin F2 alpha (PGF2 alpha), and in the presence of propranolol, 3 x 10(-6) M, and prazosin, 10(-6) M, NA induced an endothelium-dependent relaxation of only proximal but not distal segments of the precontracted LCA. The NA-induced relaxation of the proximal segments of the LCA was not altered by indomethacin 10- M but was completely abolished after incubation with methylene blue, 3 x 10-6 M, or following endothelium removal. These results are compatible with NA-induced release of EDRF in these arteries. 6. The selective alpha 2-adrenoceptor agonist, B-HT 933, only induced a weak relaxation of PGF2 alpha,-precontracted proximal (endothelium intact) LCA segments at a concentration of 10-4M. The NA-induced relaxation of these vessels was unaffected by incubating the vessels with 10- IM B-HT 933. The NA relaxation response curve was shifted ca 1.1 log unit to the right by rauwolscine, 1o- 6M, giving an estimated pA2-value of 7.12. The receptor through which NA activates the endothelium appears to be of an atypical alpha 2-subtype.

塩酸ビフェメランの抗血小板作用

We investigated the erect of bifemelane hydrochloride on human platelet aggregation and platelet cyclic nucleotide metabolism in order to elucidate its mechanism. Bifemelane inhibited platelet aggregation induced by collagen and ADP with an IC50 value of 6.6×10-5M and 1.2×10-4M, respectively. The inhibitive effects of the agent on platelet aggregation increased in the presence of 10-9M PGI2. Bifemelane significantly increased platelet adenylate cyclase activity in concentrations of 10-5M and 10-4M and inhibited cyclic AMP phosphodiesterase activity with an IC50 value of 6.6×10-4M. Cyclic AMP accumulation in intact platelets in response to bifemelane alone significantly increased only in high concentrations of 10-3M. However, a synergistic effect on cyclic AMP accumulation was found between the bifemelane and PGI2. Although a concentration of 10-4M of bifemelane had no effect on guanylate cyclase activity it did attenuate activity at 10-3M. Bifemelane inhibited cyclic GMP phosphodiesterase activity with an IC50 value similar to cyclic AMP phosphodiesterase (4.5×10-4M). Bifemelane up to a concentration of 10-4M, did not alter cyclic GMP accumulation. However, bifemelane in a concentration 10-4M did decrease activity.We conclude that bifemelane hydrochloride inhibits human platelet aggregation by modulating the cyclic AMP metabolism. Synergism between bifemelane and prostacyclin may also contribute to the enhancement of the antiplatelet action of bifemelane in vivo.