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Biomedical subjects

C Ioannides

Publications and source records attributed to C Ioannides.

At least 163 records · Page 9Linked to original sources
PubMed1988

Replacement of the damaged interarticular disc of the TMJ.

Meniscectomy should be abandoned and the removed, damaged disc of the TMJ should be replaced in patients suffering from internal derangement of the TMJ. In seventeen patients the disc which was removed, was replaced with fresh autogenous auricular cartilage. The follow-up period ranged from one to six years with a mean of almost three years. From the analysis of the results we concluded that all patients showed a postoperative improvement in their symptoms and joint function and that the use of intermaxillary fixation for a short period postoperatively had a significant effect on the subsequent increase in mouth opening.

Adult↗
PubMed1988

Lyophilized auricular cartilage as a replacement for the interarticular disc of the craniomandibular joint. An experimental study in guinea pigs.

Meniscectomy has major disadvantages and should be abandoned. Replacement of the removed interarticular disc is mandatory. As the harvesting of autogenous transplants requires the creation of a donor site defect, the use of preserved allogenic material seems justified. The interarticular disc of six young adult albino guinea pigs was replaced with preserved allogenic auricular cartilage. From the clinical and histological results we concluded that the postoperative clinical course of all animals paralleled the histological appearance of the joints. The transplants showed marked degree of resorption, but were replaced by fibrous connective tissue with focal cartilage formation. This newly formed structure resembled the original disc and protected the articular components of the joints, which, 24 weeks postoperatively, hardly differed from the controls. The role of the synovia in the formation of the "new disc" was quite evident.

Animals↗
PubMed1988

Replacement of the interarticular disc of the craniomandibular joint with fresh autogenous sternal or auricular cartilage. An experimental study in guinea pigs.

Meniscectomy has proved to be a disadvantageous therapeutic method for the surgical treatment of patients with internal derangement of the TMJ. A few authors have reported on the replacement of the removed disc with dermis, fascia and auricular cartilage in clinical reports. To the best of our knowledge no experimental work has ever been published on this subject. The interarticular disc of six young adult albino guinea pigs was removed and replaced with fresh autogenous sternal cartilage and in nine others with fresh autogenous auricular cartilage. After having been followed clinically, the animals were sacrificed after 3, 6, 12 and 24 weeks. Transplantation of sternal cartilage resulted clinically in moderate to marked discomfort. However, histologically no spectacular changes in the joints were found. The auricular cartilage transplants clinically did rather well. Histologically, some changes were found which became less pronounced with time. The use of sternal cartilage is not advisable as a replacement material because of technical reasons. The protective role of the auricular transplants could not be fully evaluated because of their tendency to warp and become displaced, although they retained their original microscopic structure and did not show reactive or resorptive changes. Further studies using larger groups of experimental animals and intermaxillary fixation are justified.

Animals↗
PubMed1988

A comparison of bisoprolol and atenolol in the treatment of mild to moderate hypertension.

1. Fourteen patients (mean age 56.0, range 37-61 years; eight females) with mild essential hypertension (DBP greater than 90 mm Hg on placebo) completed a randomised, double-blind placebo controlled crossover study comparing the hypotensive effects of bisoprolol (10-20 mg) and atenolol (50-100 mg) each taken once daily. 2. Bisoprolol had a significantly greater antihypertensive effect than atenolol, reducing sitting blood pressures by 15.9 mm Hg (diastolic) and 21.9 mm Hg (systolic) compared with placebo. Corresponding figures for atenolol were 10.7 and 5.7 mm Hg respectively. Bisoprolol reduced standing blood pressures by 15.9 mm Hg (diastolic) and 22.8 mm Hg (systolic) compared with 7.3 and 8.6 mm Hg respectively for atenolol. 3. Examination of the pharmacokinetic data showed that bisoprolol had a median elimination half-life of 11.2 h during chronic dosing, compared with 6.4 h for atenolol. For bisoprolol, the median clearance fell from 264 ml min-1 after a single dose to 212 ml min-1 during chronic dosing, although clinically significant accumulation would not be expected during chronic administration. 4. Overall, the results suggest that bisoprolol may be a more effective antihypertensive agent than atenolol but larger studies are necessary to confirm these findings.

Adrenergic beta-Antagonists↗
PubMed1988

Effect of vitamin A on rat hepatic mixed-function oxidases, glutathione transferase activity and generations of oxygen radicals.

Rat hepatic microsomal mixed-function oxidase activities were not significantly affected by vitamin A deficiency. Similarly cytosolic glutathione S-transferase and glutathione reductase activities as well as total glutathione levels were unaffected by the vitamin A status. Induction of the mixed-function oxidases by 3-methylcholanthrene or phenobarbitone was independent of the vitamin A status. No significant differences in microsomal chemiluminescence, before and following challenge with tertiary butyl hydroperoxide, were evident between the vitamin-A-deficient animals and those maintained on vitamin-A-supplemented diets. The present findings indicate that the protective action of vitamin A against chemical carcinogens is unlikely to involve modulation of the enzyme systems responsible for their metabolism.

Animals↗
PubMed1988

Metabolic activation of carcinogens and toxic chemicals.

1. The spatial parameters and electronic structures of 100 exogenous and endogenous chemicals have been determined by computer graphics, from which their oxidative metabolism by the cytochrome P-448 (activation) or the other families of cytochromes P-450 (generally detoxication) have been predicted. 2. The spatial parameters of these chemicals primarily determine the family of cytochrome P-450 by which the chemicals are metabolized and the electronic structures primarily determine their ease of oxidative metabolism. 3. The role of oxidative metabolism of xenobiotics by the cytochromes P-448, and their binding to the cytosolic Ah receptor, are considered in relationship to the mechanisms of chemical toxicity, mutagenicity, carcinogenicity, and co-carcinogenicity. 4. The mechanisms of chemical toxicity and carcinogenesis are considered in respect of activation through cytochrome P-448-mediated, conformationally-hindered oxygenation to reactive intermediates which, unlike most cytochrome P-450-oxygenated metabolites, are not acceptable substrates for conjugation and detoxication and therefore react with essential intracellular macromolecules. 5. The computer graphic method of determining the molecular conformations and electronic structures of molecules is a rapid, scientifically-based procedure for evaluation of the potential toxicity, mutagenicity and carcinogenicity of chemicals.

Biotransformation↗
PubMed1988

Inhibition of the rat hepatic mixed-function oxidases by in vivo administration of clotrimazole.

The ability of the 1-substituted imidazole antifungal agent clotrimazole to inhibit the rat hepatic microsomal mixed-function oxidases was investigated in rats pretreated with either phenobarbital or 3-methylcholanthrene. When administered to 3-methylcholanthrene-pretreated animals, clotrimazole inhibited the O-deethylations of ethoxyresorufin and ethoxycoumarin. An even more marked inhibition of the dealkylation of pentoxyresorufin and O-deethylation of ethoxycoumarin was observed in phenobarbital-pretreated rats. It is concluded that administration of clotrimazole to rats gives rise to a marked inhibition of the hepatic mixed-function oxidases, and especially of the cytochrome P450 II B family of haemoproteins.

Animals↗
PubMed1987

Anthraflavic acid is a potent and specific inhibitor of cytochrome P-448 activity.

Consideration of the computer-optimised dimensions of anthraflavic acid indicates that it is essentially a planar molecule with a large area/depth ratio, that would preferentially interact with the polycyclic aromatic hydrocarbon-induced family of cytochrome P-450 proteins (cytochromes P-448). Anthraflavic acid was a potent inhibitor of the O-deethylations of ethoxycoumarin and ethoxyresorufin, both catalysed primarily by cytochromes P-448, in Arochlor-1254-induced hepatic microsomes. Similarly anthraflavic acid markedly inhibited the mutagenicity of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-I) in the Ames test. In contrast, it has no effect on the dealkylation of pentoxyresorufin, a reaction catalysed primarily by the phenobarbital-induced cytochromes P-450, and NADPH-dependent reduction of cytochrome c. It is concluded that anthraflavic acid is a potent and specific inhibitor of cytochrome P-448 activity.

Animals↗
PubMed1987

Interactions of imidazole antifungal agents with purified cytochrome P-450 proteins.

The imidazole N-substituted antifungal agents ketoconazole, miconazole and clotrimazole have been shown to be potent inhibitors of oxidative metabolism by both a phenobarbital-induced cytochrome P-450 (P-450b) and a 3-methylcholanthrene-induced cytochrome P-448-protein (P-450c) in reconstituted systems. All three compounds inhibited the cytochrome P-450b-dependent 7-pentoxyresorufin-O-dealkylase and the cytochrome P-450c-dependent 7-ethoxyresorufin-O-deethylase activities. When 7-benzyloxyresorufin and 7-ethoxycoumarin were employed as substrates with both cytochrome preparations, all three antifungal compounds exhibited selective inhibition of the cytochrome P-450b preparation; ketoconazole was always the weakest inhibitor. The three antifungal agents were also shown to elicit a type II difference spectral interaction with both isoenzymes, the magnitude of the spectral interaction being greater with the cytochrome P-450b preparation.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1987

Structural requirements for substrates of cytochromes P-450 and P-448.

Distinct and different molecular structural features are manifested by substrates, inhibitors and inducers of the two families of liver microsomal enzymes, the phenobarbital-induced cytochromes P-450 and the 3-methylcholanthrene-induced cytochromes P-448. In a theoretical study based on molecular orbital calculations and molecular graphics, it is established that cytochrome P-448 substrates contain fused aromatic or heteroaromatic rings giving rise to overall molecular planarity with relatively small molecular depth. In contrast, substrates of the cytochromes P-450 have greater conformational freedom and an ability to bind at more than one point of attachment, as a result of possession of certain characteristic functions, namely, a carbonyl and/or amine moiety coupled with an iso-propyl group, or similar function of equivalent shape and hydrophobicity. The implications are that the binding sites of cytochromes P-448 contain a number of hydrophobic aromatic amino acid residues orientated so as to allow occupation by similar substrates containing co-planar aromatic rings, whereas those of the phenobarbital-induced cytochromes P-450 contain hydrophilic amino acid residues capable of hydrogen bonding to greater than C = O moieties and at least one leucine or valine residue, as these contain the complementary isopropyl function. The corollary of these findings is the possibility of prediction of the toxicity of new chemicals on the basis of their molecular dimensions.

Binding Sites↗
PubMed1987

Effect of syngeneic anti-idiotypic antibody on influenza virus neuraminidase antibody response.

Influenza viruses possess two major surface glycoproteins - hemagglutinin (HA) and neuraminidase (NA). Py203, a monoclonal antibody (Ab) specific for the neuraminidase of the PR8 (H1N1) influenza virus, was used to prepare syngeneic monoclonal anti-idiotypic (anti-Id) Abs. From a BALB/c mouse immunized with Py203 (anti-N1), we obtained RM1, a monoclonal anti-Id Ab. The Py203-Id was detected in a significant fraction of immunoglobulins (Igs) in the primary and secondary responses elicited by PR8 (H1N1) and X31 (H3N2) viruses. In animals injected with minute amounts of RM1 and subsequently boosted with an identical dose of RM1, no detectable anti-NA activity was noted, but a significant increase in Py203-Id-bearing Igs was observed. In the sera of animals injected with minute amounts of RM1 and subsequently boosted with PR8 (H1N1) or X31 (H3N2) viruses, an increase in anti-NA activity and in the level of Py203-Id was noted. Animals injected with large amounts of RM1 and boosted with PR8 and X31 showed a marked suppression of the Py203-Id but no alteration in the anti-NA response. The anti-Id recognizes an idiotope (the Py203 idiotope) shared by antibodies specific for the N1 and N2 neuraminidase variants.

Animals↗
PubMed1987

Bioactivation of N-nitrosopiperidine to mutagens: role of hepatic cytochrome P-450 proteins and contribution of cytosolic fraction.

In the present study the role of two families of cytochrome P-450 proteins and the contribution of the cytosolic fraction in the activation of N-nitrosopiperidine to mutagens in the Ames test were investigated. The bioactivation of this nitrosamine was preferentially catalysed by the phenobarbitone-induced cytochromes P-450, in contrast to the 3-methylcholanthrene-induced cytochromes P-448. The mutagenicity of nitrosopiperidine catalysed by microsomes, in the absence of cytosol, was lower when compared with that observed with S9 fractions. Cytosol itself could not activate nitrosopiperidine but potentiated the microsome-mediated mutagenicity of the carcinogen. The cytosolic potentiation was still evident when microsomal metabolism was terminated, indicating that cytosolic enzyme(s) can further convert the microsome-generated metabolites to more potent mutagens. The cytosolic enzyme(s) was inducible by prior treatment of the rats with phenobarbitone or Arochlor 1254 but not 3-methylcholanthrene. The microsome-mediated activation of nitrosopiperidine could be supported by NADH in the absence of NADPH. It is therefore concluded that the activation of nitrosopiperidine to mutagen(s) involves, in addition to NADH- and NADPH-dependent microsomal enzymes, cytosolic proteins.

Animals↗
PubMed1987

The single dose pharmacokinetics of bisoprolol (10 mg) in renal insufficiency: the clinical significance of balanced clearance.

The pharmacokinetics of the beta-blocking agents presently available render some subject to accumulation in renal or hepatic failure. Bisoprolol is one of the beta blockers possessing balanced clearance (both renal and hepatic clearance) which prevents such accumulation even in the case of complete failure of kidneys or liver. The single dose pharmacokinetics of bisoprolol were studied in patients with varying degrees of renal impairment and in healthy controls. Correlations were demonstrated between creatinine clearance and elimination half-life, mean residence time, area under the curve, total clearance and maximum concentration in those with renal dysfunction. The elimination half-life increased by a factor of 1.96 in those with severe renal dysfunction. Because of its balanced clearance, it is unlikely that accumulation of bisoprolol would occur beyond a factor of 2 on dosing to a steady state. The 48 hour plasma levels in the patients on dialysis were similar to those of the patients with severe renal dysfunction. This suggest that accumulation is unlikely, even in end stage renal failure. Bisoprolol may be used safely in patients with renal dysfunction. No adjustment of dose is necessary for those with mild to moderate dysfunction, but in severe or end stage renal failure the dose should not exceed 10 mg once daily.

Administration, Oral↗
PubMed1987

Single oral dose pharmacokinetics of bisoprolol 10 mg in liver disease.

The pharmacokinetic profile of an oral single dose of the new cardioselective beta-blocking agent, bisoprolol, was studied in patients with moderate and severe liver disease (Pugh group B and C, respectively) and normal subjects. In patients with liver disease a significant increase in the drug elimination half-life, mean residence time, area under the curve, and time to reach maximum plasma concentration (Tmax) was observed with a significant reduction in the oral clearance compared with the control population. There was significant positive correlation between the Pugh Score (an objective measurement of hepatic dysfunction) and the volume of distribution. The drug was well tolerated although a rise in blood urea and creatinine of over 50% was observed in 4 of 9 patients with severe liver disease. In conclusion, the delayed absorption in these patients results in lower plasma concentrations and indicates that dose adjustment is not necessary but it is recommended that the upper limit for the daily dose should be set at 10 mg; this also applies under chronic dosing of bisoprolol.

Administration, Oral↗
PubMed1987

Effect of tryptamine on the mutagenic activity of 2-amino-3-methylimidazo(4,5-f) quinoline (IQ) and related azaarenes in the Ames test.

The bioactivation of the azaarenes 2-amino-3-methylimidazo(4,5-f) quinoline (IQ), 2-amino-3,4-dimethylimidazo(4,5-f) quinoline (MeIQ) and 2-amino-3,8-dimethylimidazo(4,5-f) quinoxaline (MeIQx) to mutagens by hepatic S9 preparations derived from Aroclor-pretreated Wistar rats was inhibited by tryptamine (2-50 microM). However, with similar preparations derived from Sprague-Dawley rats, bioactivation of IQ and MeIQx was less markedly inhibited by tryptamine while metabolic activation of MeIQ was enhanced. In the absence of cytosol, activation of IQ by microsomal preparations of both rat strains was inhibited by tryptamine. Cytosolic fractions from both rat strains were incapable of activation of IQ per se but increased the mutagenicity of the microsomal metabolite(s). This potentiation of the mutagenic activity by cytosol derived from Wistar rats was also inhibited by tryptamine whereas no significant inhibition was observed with cytosolic preparations from Sprague-Dawley rats. There appear to be two alternative pathways of microsomal metabolism of IQ: a tryptamine-sensitive pathway, probably involving the formation of the N-hydroxymetabolite; and a tryptamine-insensitive pathway producing weakly mutagenic or non-mutagenic metabolites which are activated to a potent mutagen by the cytosol. The tryptamine-insensitive pathway appears to be the major route of activation of the azaarenes in microsomal preparations from Sprague-Dawley rats and the principal activation route for MeIQ in both rat strains.

Animals↗
PubMed1987

Cytosolic potentiation of the rat hepatic microsome mediated mutagenicity of benzidine.

The role of the cytosolic fraction in the S9-mediated metabolic activation of benzidine to mutagens in the Ames test was investigated using hamster and rat hepatic preparations. Rat microsomes alone were poor activators of benzidine compared to hamster microsomes, at least partly explaining the well known superiority of S9 preparations from the latter species in activating this amine. Supplementation of rat microsomal preparations with the cytosolic fraction from hamsters and to a lesser extent from rats enhanced the bioactivation of benzidine. When hamster microsomal preparations were supplemented with rat or hamster cytosolic fractions no significant effect was observed. Cytosolic fractions from either species could not activate benzidine to mutagens in the absence of microsomes. The cytosolic potentiation of the microsome-mediated activation of the amine was not inducible by Aroclor 1254. Similarly, the microsome-mediated activation of benzidine was not enhanced by Aroclor 1254 pre-treatment of the rats, when mutagenicity is expressed per nmol of cytochrome P-450. It is concluded that (i) the cytosolic fraction may play an important role in the metabolic activation by S9 preparations of chemical carcinogens such as benzidine, and (ii) the Aroclor-induced isozymes of cytochrome P-450 do not catalyse the N-hydroxylation of benzidine.

Animals↗
PubMed1987

Induction of the hepatic mixed-function oxidases by Aroclor 1254 in the hamster: comparison of Aroclor-induced rat and hamster preparations in the activation of pre-carcinogens in the Ames test.

Hepatic microsomal mixed-function oxidase activities and the metabolic activation of chemical carcinogens to mutagens in the Ames test were investigated using Aroclor 1254-induced rat and hamster preparations. Benzphetamine N-demethylase, NADPH-cytochrome c reductase and cytochromes P-450 and b5 were induced in both animals to the same extent by pre-treatment with Aroclor. However, the O-deethylation of ethoxyresorufin was markedly induced in the rat (147-fold) but only modestly in the hamster (3-fold). 1,2-Benzanthracene and 4-aminobiphenyl were more efficiently activated by the rat preparations while, in contrast, 2-acetylaminofluorene, 2-aminoanthracene, nitrosopiperidine, nitrosopyrrolidine, cyclophosphamide and phenacetin were more efficiently activated by the hamster preparations. No significant difference was observed in the activation of 3-methylcholanthrene, benzo[a]pyrene and 2-aminofluorene. It is concluded that (a) the hamster is relatively refractive to cytochrome P-448 induction, and (b) Aroclor 1254-induced rat and hamster S9 preparations differ in their ability to convert chemical carcinogens to mutagens in the Ames test.

Animals↗