In vitro effect of L-tryptophan and its metabolites on dimethylaminoazobenzene reductase activity of rat liver.

The exact role of azodye reductase, a liver microsmal enzyme, and its influence on the hepatocarcinogenicity of 4-dimethylaminoazobenzene (DAB) are uncertain. The effect of DAB is depressed by many nutritional factors, including trytophan. Therefore, the effects of o-aminophenol and of L-tryptophan and its metabolites L-kynurenine, anthranilic acid, kynurenic acid, quinaldic acid, 3-hydroxy-DL-kynurenine, 3-hydroxyanthranilic acid, xanthurenic acid, quinolinic acid, N-methylnicotinamide, and N′-methylnicotin-amide on rat liver azoreductase activity were determined, using DAB as substrate. Only 3-hydroxyanthran- ilic acid, 3-hydroxykynurenine and o-aminophenol decreased enzyme activity. The inhibition was greater if the buffered solutions (pH 7.4) of these three compounds were kept overnight before use, but the effect was prevented if these compounds were prepared in solutions of L-ascorbic acid and/or L-cysteine HCl. This observation indicates that the autoxidation products were probably responsible for inhibition of the enzyme. Further study of the oxidation products including the phenylquinoneimine formed from the oxidation of 3-hydroxyanthranilic acid in air, cinnabarinic acid, xanthommatin, 2-amino-3H-isophenoxazin-3-one, 1,9-dimethyl-2-amino-3H-phenoxazin-3-one and actinomycin D showed that all these compounds inhibited enzyme activity. A non-competitive type of inhibition was observed in the presence of cinnabarinic acid and xanthommatin. Cinnabarinic acid, xanthommatin, 2-amino-3H-isophenoxazin-3-one, 1,9-dimethyl-2-amino-3H-phenoxazin-3-one, a nd actinomycin D all have the same phenoxazinone ring system, suggesting that the driving factor in the inhibition of the azoreductase is the presence of the phenoxazinone chromophore. The chemical resemblance of these phenoxazinones to the coenzyme riboflavine further supports this supposition.     

Application of orthogonal functions to the determination of prednisolone and hydrocortisone in some pharmaceutical preparations

Glenn's method of orthogonal functions has been successfully applied to the direct spectrophotometric determination of the title compounds in presence of phenylephrine and/or neomycin sulphate without preliminary separation. The proposed methods when applied to the analysis of market preparations are in good agreement with those of the triphenyltetrazolium colour reaction recommended as the official method.     

Studies with tryptophan metabolites in vitro. effect of zinc,manganese, copper and cobalt ions on kynurenine hydrolase and kynurenine aminotransferase in normal mouse liver

The possible mechanisms by which increasing concentrations of Zn²⁺, Mn²⁺, Cu²⁺, or Co²⁺ may affect the vitamin B₆-dependent enzymes kynurenine hydrolase and kynurenine aminotransferase. were studied in normal mouse liver homogenates. It was found that Zn²⁺ inhibited kynurenine hydrolase. whereas Mn²⁺ activated this enzyme, but both Zn²⁺ and Mn²⁺ activated kynurenine aminotransferase. Co²⁺ and Cu²⁺ inhibited both enzymes. This inhibition is attributed to the blocking and inactivation of the -SH groups of these enzymes and may be due to the adequate sequence of the -SH groups in both enzymes for Cu²⁺ or Co²⁺ action. This is in contrast to the inadequate sequence of these groups in kynurenine aminotransferase for Zn²⁺ action. The decreasing order by which these metal ions inhibit (a) kynurenine hydrolase is Cu²⁺ > Co²⁺ > Zn²⁺, and (b) kynurenine aminotransferase is Cu²⁺ > Co²⁺. The decreasing order of the per cent activation of the aminotransferase enzyme is Mn²⁺ > Zn²⁺. These decreasing orders fall into a more reasonable order approximating the order of complex stability of these metal ions.     

Capillarkompression als Ischämiefolge

Zusammenfassung Bei normotherm inkubierten menschlichen Papillarmuskeln entwickelten sich im Verlauf der Ischämie zusätzlich zu hypoxischen Mitochondrienveränderungen Zeichen einer zunehmenden Gewebsspannung, die offensichtlich durch ein Gewebsödem sowie durch physiologische und pathologische Verkürzungen des kontraktilen Apparats bedingt ist. Wichtigste Folge der Spannungszunahme scheint eine Kompression der Capillaren zu sein. Gestützt durch ergänzende Untersuchungen an Meerschweinschenpapillarmuskeln, wird dieser Mechanismus als das morphologische Substrat des unter anoxischen und ischämischen Bedingungen ansteigende Coronarwiderstandes angesehen. Zur Erklärung der physiologischen Verkürzungserscheinungen wird die Hypothese einer Insuffizienz des relaxierenden Systems mit nachfolgender terminaler Kontraktion diskutiert.

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Compression of capillaries as a result of ischemiaElectronmicroscopic investigations on papillary myocardium of man and guinea-pigs

Summary Along with hypoxic alterations of mitochondria, ultrastructural signs of tension were seen to develop within 45 to 90 minutes in papillary myocardium of man in the course of ischemia under normothermic conditions. The tension seems to be caused by oedema and by contractions of an increasing number of cells, some of which no longer show a normal filament pattern. Apart from leading to stretching of cells which are otherwise intact and to filament tearing, the most important effect of the tension appears to be the compression of capillary vessels. Compression is mainly observed adjacent to contracted cells. This mechanism is considered to be the cause of the rise in coronary resistance observed after myocardial hypoxia and ischemia. Additional studies on papillary muscles of guinea pigs support this view. Ischemic contraction may partly be explained by a loss of function of the relaxing system, due to a lowering of the ATP concentration under a critical level, followed by terminal shortening, using up the residual ATP.

     

Study of lung function changes among different grades of byssinosis

El-Sadik, Y. M., Moselhi, M., El-Hinady, A. R., and Mostafa, M. N. (1972).Brit. J. industr. Med.,29, 184-187. Study of lung function changes among different grades of byssinosis. This study comprised 80 workers of whom 50 are byssinotics, 15 are chronic asthmatic bronchitics, and 15 are free of chest symptoms.

A comparison of the changes in forced expiratory volume in one second due to exposure in the first working day in the week among them (80 workers) showed a greater reduction in byssinotics than among the others. Reduced maximum expiratory flow rates were found only in byssinotics. Independent of exposure, only third-grade byssinotic cases (22 out of 50) showed changes in predicted vital capacity, residual volume, total lung capacity, three seconds per cent vital capacity, total vital capacity timed in seconds, and air velocity index.

The pattern of changes in these lung functions is mostly obstructive; only two cases showed the pattern of restrictive disease.

This study denotes that two types of changes in pulmonary functions occur due to byssinosis. The first type is a temporary change in pulmonary functions which occurs only on exposure to the aetiological factor (cotton or flax dust). This type occurs among all grades of the disease. The nature of this type is obstructive. The second type of change is permanent. This type occurs only among the third grade of the disease and is not dependent on immediate exposure. This type of change is mostly obstructive but may show some restriction.

     

The activities of urinary α-esterases in bilharziasis and their possible role in the diagnosis of bilharzial bladder cancer in Egypt

The activities of serum and urinary α-esterases were studied in 49 bilharzial bladder cancer patients, 92 bilharzial patients with other, different, urologic diseases and 22 normal healthy controls.Among the groups studied, the bilharzial bladder cancer patients showed the highest level of urinary-α-esterases and the lowest ratio of serum/urine activity. These patients showed a significant increase in the activity of urinary α-esterases as compared with the normal controls or with the other different bilharzial groups. Although a small but significant increase in serum activity was observed in all the bilharzial groups studied compared with the normal healthy controls, no significant difference was found between the bilharzial bladder cancer patients and the other different bilharzial groups.Biochemical determination of urinary α-esterases for bilharzial patients revealed a high degree of accuracy for the diagnosis of bilharzial bladder cancer (95 · 9%), with low falsely positive (3 · 26%) and falsely negative (4 · 08%) results. The activity of urinary α-esterases is recommended as a screening test for bilharzial bladder cancer.     

In vitro studies of the effect of metal ions, EDTA and their mixtures on kynurenine aminotransferase and kynurenine hydrolase.

In the present study use was made of the chelating ability of EDTA and the activating property of some metal ions Ca(II), Mg(II) or Mn(II) to counteract the inhibitory effect of Cu(II), Co(II), Pb(II) or Zn(II) ions on the B6-dependent kynurenine hydrolase and on kynurenine aminotransferase. These may be of help in studying the therapeutic trials in the treatment of metal poisoning. EDTA was able to counteract the inhibitory effect of Cu(II) or Co(II) on kynurenine aminotransferase and partially counteract the inhibitory effect of Cu(II), Co(II) on kynurenine aminotransferase and partially counteract the inhibitory effect of Cu(II), Co(II), Pb(II) or Zn(II) ions on kynurenine hydrolase. The difference in the response of the two B6-dependent enzymes to EDTA is attributed to the difference in the functional groups involved in the active site(s) of the two apoenzymes. Moreover, Mn(II), Ca(II) and Mg(II) ions have the ability to counteract some of the inhibitory effect of these metal ions.     

Coated bedpans: their cleaning and disinfection.

This paper reports on tests of cleaning and disinfection of stainless steel bedpans which have been coated with either a silicone grease or polytetrafluoroethylene (PTFE). The coatings were applied manually using an aerosol spray (silicone grease and PTFE), and by an industrial process (PTFE). Soils used comprised (i) British Standard Soil (B.S., 1966), (ii) human serum albumin labelled with technetium-99m (HSA-Tc), and (iii) a suspension of Streptococcus faecalis in broth. Tests of cleaning and disinfection were carried out in automatic washing and steam disinfector machines. Results show that aerosol spraying impairs the cleaning process but that bedpans coated by the industrial process with PTFE are superior to uncoated bedpans.     

Dimethylnitrosamine demethylase activity of rat liver microsomes after partial hepatectomy

It is known that partial hepatectomy increases the hepatocarcinogenicity of dimethylnitrosamine (DMN). To investigate why this procedure increases the hepatocarcinogenicity of DMN, the activity of liver DMN demethylase was determined on Wistar male rats at different time intervals after partial hepatectomy. The ld₅₀ for DMN administered 1 day after partial hepatectomy was also compared to that for the control animals. The enzyme activity reached its lowest point (47 per cent) 1 day after operation, and at 3 days had recovered to about 90 per cent of the control values. The ld₅₀ for partially hepatectomized rats 44 hr after i.p. injection of DMN was 114 mg/kg body weight as compared to 82 mg/kg for control animals. The reduction rather than increase of enzyme activity after hepatectomy shows that increased DMN carcinogenicity after hepatectomy is not caused by a compensatory increase of demethylase activity associated with liver regeneration.