Aluminium overload, a predisposing condition for epileptic seizures in renal-transplant patients treated with cyclosporin?
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Biomedical subjects
Publications and source records attributed to A Attramadal.
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In the present study we have examined adenylate cyclase (AC) activity, the stimulation by isoproterenol and inhibition by propranolol, in endomyocardial biopsies from eleven patients with suspected cardiomyopathy. Biopsies were obtained by heart catheterization from the right endomyocardial surface of the interventricular septum. Three biopsies were taken from each patient (mean weight, 2.1 mg; range, 1.2-4.0 mg). One biopsy was studied by light microscopy. The two other biopsies were homogenized and AC activity in the homogenates was determined in the presence of different concentrations of isoproterenol and isoproterenol (5 micrograms/ml) combined with different concentrations of propranolol. Thus stimulation and inhibition curves were established for a pair of biopsies from each patient. Appropriate biopsy material was obtained in triplicate from only seven patients. In these patients the variance in maximal receptor stimulation (by isoproterenol) and inhibition (by propranolol) was significantly smaller in pairs of biopsies compared to the variance between all biopsies (p values from less than 0.05 to less than 0.025). Hence it is possible to determine AC activity, and adrenergic receptor function, in very small endomyocardial biopsies. New diagnostic possibilities could thereby be introduced.
The cytosol from rat ventral prostates contains two estrogen-binding components that can be separated in a glycerol gradient: a high-affinity (KD = 4.2 X 10(-10) M), low-capacity (110 fmole/mg DNA) species that runs in the 8S region of the gradient, and a lower-affinity (KD = 2.4 X 10(-9) M), higher-capacity (410 fmole/mg DNA) 4S protein. Separation of prostate tissue into stromal- and epithelial-enriched fractions was associated with the disappearance of the latter component. When compared per milligram DNA stromal- and epithelial-enriched fractions contained similar amounts of the high-affinity 8S-binding protein. In vivo estrogen treatment caused a time-related disappearance of the protein from the intact cytosol presumably as a result of translocation. No major differences in the degree of binding to the high-affinity component were observed in rats of different ages. Estrogens seem to exert direct effects on both stromal and epithelial tissues of the prostate.
Prostatic secretory and basal or stem cells were isolated from rat ventral prostate lobes by collagenase dispersion and density centrifugation in a Percoll gradient. The membrane-bound adenylyl cyclase of secretory cells could be activated in a dose-dependent manner by vasoactive intestinal peptide (VIP ED50 10(-7)M) but not thyrotropin-releasing hormone (TRH). Conversely, only TRH could significantly stimulate the adenylyl cyclase in basal cell membranes (ED50 5 X 10(-7). In two separate studies enzyme activity was stimulated seven- and 13-fold by this peptide. This action of TRH on prostatic basal cells supports previous reports that high levels of immunologically active TRH have been found in prostate tissue and that TRH stimulates the growth of prostatic cancer cells in vitro.
The antibacterial effect of oral rinses with stannous fluoride and stannous chloride solutions, and of the use of a toothpaste containing stannous fluoride and stannous pyrophosphate was tested by recording the bacterial viable counts on the oral mucous membrane. Stannous chloride had no antibacterial effect, while stannous fluoride drastically reduced the viable counts up to 4 h. Calculations demonstrated that 25% of the tin content in 10 ml rinsing solutions was retained in the mouth, and analyses showed a raised tin level in saliva up to 4 h after rinsing or toothbrushing. It is suggested that most of the retained tin is bound to the oral mucosa.
This article describes some of the techniques and approaches currently in use in prostatic research which hopefully will provide new information and perspectives on the etiology of prostatic pathology. These techniques include a variety of methods for visualizing and quantitating protein hormone receptors, protein electrophoresis of prostatic tissue and fluids for protein markers, cell separation of the different cell populations of the prostate so that their interaction can be evaluated, and tests for the influence of low molecular weight peptides on prostatic function. Examples of the type of information which can be derived from each of the approaches are included and discussed.
A clinical model was introduced to study the ability of chlorhexidine, tannic acid, and iron to discolor dental plaque formed on acrylic resin surfaces. None of the agents caused discoloration when applied individually five times daily during a 5-day period. However, exposure of the dental plaque to either chlorhexidine or tannic acid before the iron applications produced marked staining. Possible mechanisms, among which denaturation appears to be significant, are discussed. The use of a strong oxidizing agent, peroxymonosulfate, completely bleached the established discolorations.
Saliva coated hydroxyapatite was used as a model to study iron adsorption to pellicle material. The uptake of iron was markedly influenced by its concentration in the medium. Denaturation of the protein film by chlorhexidine, tannic acid, or heating up to 70 degrees C increased the adsorption significantly.
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Extrinsic discoloration of teeth following a large consumption of tannin-containing beverages or a prolonged use of chlorhexidine mouthrinses is a well known observation. Tannins as well as chlorhexidine are denaturing agents. Based on preliminary studies revealing the presence of iron in chlorhexidine discolored pellicle material, the ability of iron to stain the integument after pretreatment with the two denaturants was studied in a human model. The denaturing effect of an acidic environment was also included. Enamel slabs fixed to acrylic appliances were carried in the oral cavity and alternately exposed to the test solutions in different sequences in vitro. Pretreatment with chlorhexidine or tannic acid led to marked discoloration upon iron application during 5-d tests, whereas the compounds individually had no such effect. A large content of the metal was found in the stained material. Stannous fluoride appeared to reduce the formation of the pigments, and strong oxidation completely bleached the established color. Possible mechanisms underlying the phenomena observed are discussed.
Progesterone and corticosterone have a similar effect on the production of growth hormone (GH) and prolactin (Prl) by pituitary tumour cells (GH3 cells) in culture. Previously we have shown that progesterone has a high affinity for the glucocorticoid receptors in these cells. Progesterone may therefore exert its effects through binding to the glucocorticoid receptor. The aim of the present study was to investigate if the GH3 tumour cells and an oestrogen induced pituitary tumours, which also produce GH and Prl, possess specific receptors for progesterone. Both the GH3 tumours and the oestrogen induced pituitary tumour were in fact found to possess cytoplasmatic receptor molecules for progesterone by using the potent progestin R5020 as a marker. Isoelectric focusing revealed one binding component (pH 5.9), which was of protein nature. The binding was of high affinity (KD 2 X 10(-9) mol/l). In the oestrogen induced tumour, the maximal binding was 70 fmol/mg cytosol protein. In female rats with GH3 tumours the binding was 55 fmol/mg cytosol protein. Priming of the animals with 1 mg oestradiol-valerate increased the binding to 116 fmol/mg cytosol protein, whereas very little binding was found in GH3 tumours from rats castrated 7 days before sacrifice. The receptors in the oestrogen induced pituitary tumour and the GH3 tumours exhibited high affinity for R5020 and progesterone, whereas corticosterone had no significant affinity for the receptors. Using exchange assay, it was demonstrated that the cytoplasmic progestin receptors could be translocated to the nucleus after administration of progesterone to the animals. Thus, the presence of specific progesterone receptors, different from the glucocorticoid receptors, strongly indicates that athe effects of progesterone on GH and Prl production are mediated through the progesterone receptors.
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The present paper describes some physiocochemical properties of the soluble 3 alpha-oxidoreductases in the rat testis and prostate, and comparison with rat epididymal 3 alpha-oxidoreductase, published previously (Hastings & Hansson 1979). The testicular enzyme shows properties very similar to that in the epididymis (size, stability, pH optium) except for minor differences in charge (iso-electric point). The prostatic enzyme revealed a slightly higher molecular weight, and was more sensitive to heating than those in the testis and epididymis, whereas the iso-electric point was the same as that in the testis (pI-5.25). The enzymes in all tissues exhibit very similar shapes (f/fo 1.14-1.17). The similar properties of the testicular and prostate 3 alpha-oxidoreductases to those previously reported for that in the epididymis may indicate that these enzymes represent identical peptide chains. The small differences observed in size, temperature stability and change may be due to their presence in different environments.
The present paper demonstrates the presence of at least two 3-hydroxysteroid oxidoreductases (3-HSO) in rat testis, prostate, and epididymis cytosol preparations. The enzymes were either NADH or NDAPH dependent. Further investigation by Sephadex G-200 chromatogrphy revealed the presence of enzyme activities in the void volume (peak 1) and also eluting close to the methyl-carbonic anhydrase standard (mol wt, 34,000; peak 2). Enzyme activity in peak 1 was predominantly stimulated by NADH and that in peak 2 was stimulated mainly by NADPH. Both 3 alpha- and 3 beta-HSO activities were observed in testicular eluates from 1; 3 beta-Adiol accounted for up to 50% of the 5 alpha-androstanediols formed. In peak 2,3 alpha-HSO constituted more than 90% of the enzyme activity. In contrast, the prostatic and epididymal eluates revealed only 3 alpha-HSO activity; 3 beta-Adiol constituted less than 5% of the 5 alpha-androstanediols formed in either peak 1 or 2. The apparent Km values for enzyme activation reveal differences in sensitivity to cofactors for enzymes in peaks 1 and 2 and also among testis, epididymis, and prostate. NADH caused a very similar activation of enzyme activity in peak 1 or the prostate and epididymis (Km 50-100 micro M), whereas the enzyme in the testis was activated by much lower cofactor concentration (Km approximately 5 microM). It is possible that this enzyme activity may represent microsomal contamination. The enzyme activity in peak 2 revealed very similar sensitivity to NADPH in all three organs (Km, 0.6-1.7 microM), confirming previous studies from our laboratory that the soluble. NADPH-dependent enzymes in all three tissues are very similar, if not identical.
The uptake of tin by S. mutans from stannous fluoride or stannous chloride solutions was determined by atomic absorption spectroscopy. The uptake occurred rapidly, and the microorganism was shown to have a greater capacity and higher affinity to uptake of tin than of other metal ions tested. In 10 mM solutions, bound tin amounted to 17.5 per cent of the cellular dry mass. The tin uptake was independent of cell metabolism. The cell bound tin could not be washed out with water or saline, but 84 per cent was removed by ethylenediaminetetraacetic acid solutions. When pH was lowered by low 2, increasing loss of bound tin occurred. It is suggested that the binding occurs to polyanionic structural polymers in the cell wall and the cell capsule.
Sixteen patients with prostatic carcinoma were treated with 200 mg of Cyproterone acetate daily. No other kind of hormonal treatment was given. Transrectal biopsies of the prostate were taken before the treatment was started, and at regular intervals afterwards. The treatment period lasted from 3 to 16 months, with an average of 9 months. A thorough examination of multiple sections from all specimens revealed no convincing signs of cellular involution. The study has demonstrated no specific or significant atrophic changes following Cyproterone acetate therapy. Some possible explanations regarding the effect of Cyproterone acetate on human malignant prostatic tissue are discussed.
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