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The perchlorate discharge test for examining thyroid function in rats.

A perchlorate discharge test was developed for rats to detect changes in the thyroidal iodide accumulation and organification mechanisms. Rats were pretreated with compounds that alter thyroid function by different mechanisms: SK&F 93479 (an H2-antagonist that enhances pituitary thyroid stimulating hormone drive by increasing thyroid hormone clearance) and propylthiouracil (an inhibitor of iodide organification). Six hours following administration of 125I, either potassium perchlorate (10 mg/kg x 2.5 min) or saline was given i.p. Perchlorate significantly reduced the thyroid: blood 125I ratio in propylthiouracil-treated rats but had no effect in those pretreated with SK&F 93479, indicating an iodide organification block in the former. At the same time thyroidal radioiodide accumulation in SK&F 93479-treated rats (no perchlorate) was enhanced, whereas that in propylthiouracil-treated animals (no perchlorate) was depressed.

Animals↗

Tetradecanoylphorbol acetate and terbutaline stimulate surfactant secretion in alveolar type II cells without changing the membrane potential.

Alveolar type II cells were isolated from adult rat lungs after tissue dissociation with elastase. The effect of known secretagogues on transmembrane potential was examined in freshly isolated cells (day 0 cells) and in cells after one day of primary culture (day 1 cells). Freshly isolated type II cells were incubated with 3,3'-dipentyloxacarbocyanine (di-O-C5(3)) or 3,3'-dipropylthiadicarbocyanine (di-S-C3(5)), dyes whose intracellular fluorescence intensity is a direct function of the cellular transmembrane potential. Fluorescence was continuously recorded by fluorescence spectrophotometry. Type II cells rapidly incorporated the dyes, and the addition of gramicidin (1 microgram/ml) depolarized the cells as indicated by a change in fluorescence. Neither 12-O-tetradecanoylphorbol 13-acetate (TPA) nor terbutaline plus 3-isobutyl-1-methylxanthine (IBMX), which stimulate surfactant secretion from isolated alveolar type II cells, changed the transmembrane potential. The lipophilic cation triphenylmethylphosphonium (TPMP+) was used to quantitate the transmembrane potential of type II cells cultured for one day. Addition of TPA or terbutaline plus IBMX induced surfactant secretion but did not alter the transmembrane potential. To study further the relationship of secretion to the transmembrane potential, secretion was also determined in the presence of high extracellular potassium which depolarizes the cells and in the presence of choline in place of sodium. High potassium enhanced the basal secretion of phosphatidylcholine from 1.8% to 3.4% (P less than 0.01, n = 7). Substitution of sodium chloride by choline chloride had no effect on basal secretion but enhanced TPA-induced secretion (P less than 0.01). We conclude that high extracellular potassium induces membrane depolarization and stimulates surfactant secretion, but TPA or terbutaline plus IBMX stimulates secretion without detectable membrane depolarization and stimulation of secretion by TPA does not require extracellular sodium.

Animals↗

Vesicular dopamine release elicits an inhibitory postsynaptic current in midbrain dopamine neurons.

Synchronous activation of dopamine neurons, for instance upon presentation of an unexpected rewarding stimulus, results in the release of dopamine from both terminals in projection areas and somatodendritic sites within the ventral midbrain. This report describes an inhibitory postsynaptic current (IPSC) that was elicited by dopamine in slices from mouse midbrain. The IPSC was tetrodotoxin sensitive, calcium dependent, and blocked by a D2 receptor antagonist. Inhibition of monoamine transporters prolonged the IPSC, indicating that the time course of dopamine neurotransmission is tightly regulated by reuptake. Changing the stimulus intensity altered the amplitude but not the time course of the IPSC, whose onset was faster than could be reproduced with iontophoresis. The results indicate a rapid rise in dopamine concentration at the D2 receptors, suggesting that dopamine that is released by a train of action potentials acts in a localized area rather than in a manner consistent with volume transmission.

Action Potentials↗

Study on fluorination of 2,3-dideoxy-2,3-(N-tosylepimino)-alpha-D-allopyranosides, and synthesis of 3'-deoxy-3'-fluorokanamycin B and 3',4'-dideoxy-3'-fluorokanamycin B.

Reaction of the structurally rigid methyl 2,3-dideoxy-4,6-O-isopropylidene-2,3-(N-tosylepimino)-alpha-D-a llopyranoside (6) with KHF2 in DMF at 150 degrees gave initially methyl 2,3-dideoxy-2-fluoro-4,6-O-isopropylidene-3-tosylamido-alpha-D-altrop yranoside (10) by N-tosylepimine-ring opening, and 10 was gradually converted into the stable methyl 2,3-dideoxy-3-fluoro-4,6-O-isopropylidene-2-tosylamido-alpha-D-glucopyra noside (11). A reversible mechanism involving 6 and 10 has been proposed. In the mobile methyl 2,3-dideoxy-2,3-(N-tosylepimino)-alpha-D-allopyranoside (7) and the corresponding 4,6-di-O-acetyl (8) and -di-O-methyl derivatives (9), reactions with KHF2 proceeded comparatively rapidly giving the corresponding 3-deoxy-3-fluoro-alpha-D-glucopyranosides as the major products. A slightly different reaction mechanism for the mobile compounds has been proposed. By application of this study, 3'-deoxy-3'-fluorokanamycin B was prepared by treatment of 4",6"-O-cyclohexylidene-2'-deamino-3'-deoxy-3'-epi-6'-N-methoxycarbonyl- 1,3, 3"-tri-N-tosyl-2',3'-(N-tosylepimino)kanamycin B (21) with KHF2 as the key reaction. 3',4'-Dideoxy-3'-fluorokanamycin B was also prepared. Both compounds were active against resistant bacteria producing 3'-modifying enzymes.

Carbohydrate Sequence↗

Strengthening of feldspathic porcelain by ion exchange and tempering.

This study investigated the effectiveness of tempering and ion-exchange treatments on crack growth and bi-axial flexural strength of seven feldspathic porcelains. The results showed that tempering treatment was more effective in strengthening porcelain than was the ion-exchange process as measured by the bi-axial flexural strength. However, the results of initial crack size induced by a microhardness tester showed that ion-exchange yielded a surface that was more resistant to crack initiation than was that yielded by the tempering treatment. EDX and microprobe analyses showed that there was evidence of exchange between Na+ within the porcelain surface and K+ from the ion-exchange agent applied on the surface.

Aluminum Silicates↗

[Potassium-sparing diuretics (spironolactone, triamterene, amylorid)].

The group of drugs, so-called "potassium sparing diuretics" represent an important part of our modern therapeutic arsenal. Their "weak diuretic" properties are especially beneficial in cirrhotic patients with ascites, when highly effective loop diuretics may be hazardous. Potassium sparing diuretics have not only the advantage of avoiding potassium loss, but can potentiate the effects of diuretics acting in distal tubules and Henle's loop also. They may be combined by each other or ACE inhibitors too, taking the necessary precautions and laboratory monitoring. Their indications include the hypertension and special diseases as Conn's, Bartter's, Liddle syndromes and hirsutism. The broad clinical usefulness justifies the drug inventory ambition to develop new, more effective potassium sparing compounds without side effects. Authors overview their main clinicofarmacological properties, therapeutical indications alone or in combinations and their potential side effects.

Amiloride↗

Effect of sodium content on the crystallization behavior of fluoramphibole glass-ceramics.

The purpose of this study was to evaluate the effect of sodium content on the crystallization behavior of glass-ceramics in the system SiO(2)-MgO-CaO-Na(2)O-K(2)O-F. Five glass compositions were prepared with increasing sodium content. The compositions were melted at 1400 degrees C for 2 h and cast into 60 x 12-mm ingots. Differential thermal analyses were performed on the glasses up to 1400 degrees C. Discs (1.5 x 12 mm) were cut from the ingots, nucleated in the temperature range 600-650 degrees C for 1-2 h, and crystallized in the temperature range 900-1000 degrees C for 0.5-4 h. The crystalline phases were analyzed by x-ray diffraction. The microstructure was investigated by scanning electron microscopy. Differential thermal analyses showed that the crystallization exotherm occurred in the temperature range 600-750 degrees C. There was a linear relationship between the amount of sodium and the transformation temperatures. X-ray diffraction revealed the presence of mica and diopside as major crystalline phases in the sodium-free composition. Mica, diopside, and fluorrichterite were present in all other glass-ceramics. The microstructure of the sodium-free glass-ceramic was characterized by the presence of hexagonal mica crystals and prismatic diopside crystals. All other compositions exhibited needle-shaped fluorrichterite crystals (2-5 microm in length) in addition to mica and diopside crystals.

Aluminum Silicates↗

Systematic investigations of the contrast results of histochemical stainings of neurons and glial cells in the human brain by means of image analysis.

The investigation of neurohistological specimens by image analysis has become an important tool in morphological neuroscience. The problems which arise during the processing of these images are non-trivial, especially if a pattern recognition of cells in the imaged tissue is intended. One of the major problems faced concerns the segmentation of structures of interest, whether cells or other histologic structures. The segmentation problem is often the result of an inappropriate staining procedure. For serious image analysis to be performed, the material under investigation must be optimally prepared. Spatially complex patterns, e.g. fuzzy-like neighbouring neurons, are easy to recognize for humans. But the integrative and associative performance of current artificial neuronal network schemes is too low to achieve the same recognition quality as humans do. Therefore, a general analysis of staining characteristics was performed, especially with respect to those stains which are relevant to object segmentation. Although most image analytical investigations of tissues are based on stained samples, a study of this type has not been previously conducted. Of the stains and procedures evaluated, the gallocyanin chrome alum combination staining provided the best stain contrast. Furthermore, this staining method shows sufficient constancy within different parts of the human brain. Even the fine nuclear textures are differentiable and can be used for further pattern recognition procedures.

Adult↗

Factors affecting the action of guanethidine on adrenergic neurones.

1. The uptake of guanethidine by adrenergic neurones has been studied indirectly by testing the ability of various procedures to prevent or reverse adrenergic neurone blockade in the periarterially stimulated isolated ileum preparation.2. Adrenergic neurone blockade was prevented but not reversed by equilibration with guanethidine (3.3 x 10(-6)M) at low temperatures (10 degrees C), in the absence of sodium or in the presence of tetrodotoxin (0.3 x 10(-6)M) or noradrenaline (1.2 x 10(-3)M).3. Calcium (5 x 10(-2)M) both prevented and, to some extent, reversed the adrenergic neurone blocking action of guanethidine.4. Equilibration with guanethidine in the presence of mersalyl (0.6 x 10(-7)M) or in the absence of potassium or calcium could neither prevent nor reverse adrenergic neurone blockade.

Animals↗

Coextraction during reactive extraction of phenylalanine using Aliquat 336: modeling extraction equilibrium.

Reactive liquid-liquid extraction can be used to recover hydrophilic fermentation products that would not otherwise partition into nonpolar solvents through an ion-exchange reaction at the two-phase interface. However, the ion-exchange reagent may not be specific to the solute of interest and other compounds present may also be extracted. In this study, the effect on solute extraction of other compounds present in the extraction medium was investigated for phenylalanine extraction using Aliquat 336. The extent of extraction at equilibrium was modeled using the equilibrium constants for the reactions present in the process. The interaction of different species within a multicomponent medium was examined using the model and experimental results. It was found that the extent of extraction and coextraction is controlled by the thermodynamics of each extraction reaction and, due to the formation of a common product, the interaction between each of the reactions. The main competition to reactive extraction will come from hydrophobic anionic compounds that will be present in fermentation broth.

Actinomycetales↗

The involvement of nucleosomes in Giemsa staining of chromosomes. A new hypothesis on the banding mechanism.

A new hypothesis is proposed on the involvement of nucleosomes in Giemsa banding of chromosomes. Giemsa staining as well as the concomitant swelling can be explained as an insertion of the triple charged hydrophobic dye complex between the negatively-charged super-coiled helical DNA and the denatured histone cores of the nucleosomes still present in the fixed chromosomes. New cytochemical data and recent results from biochemical literature on nucleosomes are presented in support of this hypothesis. Chromosomes are stained by the Giemsa procedure in a purple (magenta) colour. Giemsa staining of DNA and histone (isolated or in a simple mixture) in model experiments results in different colours, indicating that a higher order configuration of these chromosomal components lies at the basis of the Giemsa method. Cytophotometry of Giemsa dye absorbance of chromosomes shows that the banding in the case of saline pretreatment is due to a relative absence of the complex in the faintly coloured bands (interbands). Pretreatment with trypsin results in an increase in Giemsa dye uptake in the stained bands. Cytophotometric measurements of free phosphate groups before and after pretreatment with saline, reveal a blocking of about half of the free phosphate groups indicating that a substantial number of free amino groups is still present in the fixed chromosomes. Glutaraldehyde treatment inhibited Giemsa-banding irreversibly while the formaldehyde-induced disappearance of the bands could be restored by a washing procedure. These results correlate with those of biochemical nucleosome studies using the same aldehydes. Based on these findings and on the known properties of nucleosomes, a mechanism is proposed that explains the collapse of the chromosome structure when fixed chromosomes are transferred to aqueous buffer solutions. During homogeneous Giemsa staining reswelling of the unpretreated chromosome is explained by insertion of the hydrophobic Giemsa complex between the hydrophobic nucleosome cores and the superhelix DNA. Selective Giemsa staining of the AT-enriched bands after saline pretreatment is thought to be due to the, biochemically well-documented, higher affinity of arginine-rich proteins present in the core histones for GC-enriched DNA, which prevents the insertion of the Giemsa complex in the interbands. Production of Giemsa bands by trypsin pretreatment can be related to the action of this enzyme on the H1 histones and subsequent charge rearrangements.(ABSTRACT TRUNCATED AT 400 WORDS)

Azure Stains↗

Effect of bromidehypochlorite bactericides on microorganisms.

A new principle in compounding stable, granular bactericidal products led to unique combinations of a water-soluble inorganic bromide salt with a hypochlorite-type disinfectant of either inorganic or organic type. Microbiological results are shown for an inorganic bactericide composed of chlorinated trisodium phosphate containing 3.1% "available chlorine" and 2% potassium bromide, and for an organic bactericide formulated from sodium dichloroisocyanurate so as to contain 13.4% "available chlorine" and 8% potassium bromide. Comparison of these products with their nonbromide counterparts are reported for Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Streptococcus lactis, Aerobacter aerogenes, and Proteus vulgaris. Test methods employed were the Chambers test, the A.O.A.C. Germicidal and Detergent Sanitizer-Official test, and the Available Chlorine Germicidal Equivalent Concentration test. The minimal killing concentrations for the bromide-hypochlorite bactericides against this variety of organisms were reduced by a factor 2 to 24 times those required for similar hypochlorite-type disinfectants not containing the bromide.

Anti-Bacterial Agents↗

Dioxouranium(VI)--carboxylate complexes. Interaction with dicarboxylic acids in aqueous solution: speciation and structure.

In this paper we report the results of an investigation performed by potentiometric (H+-glass electrode) and visible spectrophotometric measurements on the interaction of UO2(2+) ion towards some carboxylic ligands (acetate, malonate, succinate, azelate). The measurements were carried out at T= 25 degrees C in different ionic media (KNO3 and NaCl) at different ionic strengths (0.1 < or = I/mol L(-1) < or = 1.0, NaCl; I/mol L(-1) = 0.1, KNO3). The dependence on ionic strength of formation constants was taken into account by using both a simple Debye-Hückel type equation and the SIT (Specific ion Interaction Theory) approach. Different speciation models (depending on concentration of reagents, ionic strength, pH-range) both for different carboxylates and different ionic media have been obtained. Linear combinations between formation constants, stoichiometric coefficients and length of alkyl chain of dicarboxylates have been observed and predicted formation constants at I= 0 mol L(-1) are reported for the interaction of UO2(2+) with HOOC-(CH2)n-COOH with 1 < or = n < or = 7. Finally, a visible absorption spectrum for each complex reaching a significant percentage of formation in solution (KNO3 medium) has been calculated to characterise the compounds found by pH-metric refinement.

Dicarboxylic Acids↗

Intracellular acidosis protects cultured hepatocytes from the toxic consequences of a loss of mitochondrial energization.

Cultured rat hepatocytes were treated with potassium cyanide, an inhibitor of cytochrome oxidase; valinomycin, a K+ ionophore; carbonyl cyanide m-chlorophenylhydrazone (CCCP), a protonophore; and the ATP synthetase inhibitor oligomycin. The effect of these agents on the viability of the cells was related to changes in ATP content and the deenergization of the mitochondria. The ATP content was reduced by over 90% by each inhibitor. All of the agents except oligomycin killed the cells within 4 h. With the exception of oligomycin, the mitochondrial membrane potential as measured by the distribution of [3H]triphenylmethylphosphonium collapsed with each of the agents. Monensin, a H+/Na+ ionophore, potentiated the toxicity of cyanide and CCCP, whereas the toxicity of valinomycin was reduced. The effect of cyanide and monesin on the cytoplasmic pH of cultured hepatocytes was measured with the fluorescent probe, 2',7'-biscarboxyethyl-5,6-carboxyfluorescein. Cyanide promptly acidified the cytosol, and the addition of 10 microM monensin caused a rapid alkalinization of the cytosol. A reduction of pH of the culture medium from 7.4 to 6.6 and 6.0 prevented the cell killing both by cyanide alone and by cyanide in the presence of monensin. However, neither monensin nor extracellular acidosis had any effect on the loss of mitochondrial energization in the presence of cyanide. It is concluded that ATP depletion per se is insufficient to explain the cell killing with cyanide, CCCP, and valinomycin. Rather, cell killing is better correlated with a loss of mitochondrial energization. With cyanide an intracellular acidosis interferes with the mechanism that couples collapse of the mitochondrial membrane potential to lethal cell injury.

Adenosine Triphosphate↗