[Disseminated Mycobacterium genavense infection in patients with HIV infection. Description of 5 cases and review of the literature]. / Infección diseminada por Mycobacterium genavense en pacientes con infección por HIV. Descripción de 5 casos y revisión de la literatura.

BACKGROUND: Five cases of disseminated infection by Mycobacterium genavense in patients with HIV infection are reported with a review of the literature. MATERIAL AND METHODS: A description of the clinical, epidemiologic and therapeutic characteristics of five cases are presented. The initial isolation of the microorganism was performed in Bactec 13A from blood and bone marrow aspirates. Subcultures were made in different media and the growth characteristics evaluated. Sensitivity to NAP was determined by radiometric techniques and gas chromatography allowed a possible identification. Definitive identification was based on PCR amplification of the gene which codifies the 65kDa protein and the posterior restriction of the amplified fragments by using BstEII and HaeIII. RESULTS: All five patients were males with HIV infection and a lymphocyte count of less than 25 cells/mm3 with an non-specific clinical picture similar to that produced by M. avium complex (MAC). Empiric antiMAC treatment was administered in four of the patients with good clinical response. All five strains were sensitive to NAP. The greatest growth rate was obtained in the subcultures with acid pH in liquid medium. Gas chromatography was very similar to that of M. simiae. Amplification of the gene which codifies the 65 kDa protein and posterior restriction with BstEII resulted in 2 fragments of 325 and 125 bp, while restriction with HaeIII resulted in two fragments of 140 and 105 bp. CONCLUSIONS: Mycobacterium genavense represents 9% of the disseminated infections by mycobacteria in AIDS patients. The clinical manifestations, empiric treatment and response is similar to that of infection by M. avium complex. Growth is favored by acid pH in liquid medium. Susceptibility to NAP leads to possible identification which should be confirmed by molecular techniques.

[Anti-calcium effects of 4-hydroxypropiophenone derivatives--potential beta-adrenoreceptor blockers]. / Antikalciový efekt derivátov 4-hydroxypropiofenónu--potenciálnych blokátorov beta-adrenoreceptorov.

The present paper carries out the pharmacological evaluation of 4-(2-hydroxy-3-isopropylaminopropoxy)-3-(alkoxymethyl) propiophenones with an ethoxy, propoxy and butoxy-group, whose structures are typical of the blockers of beta-adrenergic receptors. In the above-mentioned compounds the anticalcium effect on the frequency and the amplitude and the negative chronotropic and the negative inotropic effects were evaluated by means of the method of spontaneously pulsing guinea-pig atria within a concentration range of 4-16 microgram.cm-3. The obtained results confirmed a significant anticalcium effect on the heart rate in the compounds with a propoxy and a butoxy group, and in the standard verapamil. In all three compounds as well as in the standard verapamil, no anticalcium effect on the amplitude was found. The results of this membrane efficacy are in agreement with the preceding evaluation of the antidysrhythmic and anti-isoprenaline activity with the most marked effect in the compound with a propoxy group. On the basis of these results it is possible to conclude that in these derivatives of 4-hydroxypropiophenone also the anticalcium effect can participate, besides the beta-adrenolytic and the membranostabilizing effects, in the antidysrhythmic activity.

[Changes in basic nitrogen in a group of potential new beta- adrenolytics--derivatives of p-hydroxyacetophenone and p-hydroxypropiofenone]. / Obmeny na bázickom dusíku v skupine nových potenciálnych betaadrenolytík--derivátov p-hydroxyacetofenónu a p-hydroxypropiofenónu.

Within the relationship of the structure and effect of new beta-adrenolytic agents derivatived from p-hydroxyacetophenone and p-hydroxypropiophenone with a propoxymethyl group in the lipophilic part of the molecule and with a propanamine, a butanamine and a pyrrolidine in the side-chain were studied. In order to prepare these substances, a procedure was selected from several tested ones, in which 4-hydroxy-3propoxymethylphenylketone were treated with chloromethyloxirane and subsequent reaction a hydrobromic acid were prepared 4-(3-brom-2-hydroxypropoxy)-3-propoxymethylalkylketone. Final substances were prepared reaction with amine. The structure of prepared compounds was confirmed on the basic interpretation of the IR, UV and 1H NMR spectra. The results of pharmacological evaluation of selected compounds showed a significant beta 1-blocking activity lower than acebutolol. Their local anesthetic activity is low according with their partition coefficients. The characteristic of the prepared compounds was supplemented by the determination of their partition coefficients, surface tension, dissociation constants and acute toxicity.

Rapid preliminary differentiation of species within the Mycobacterium tuberculosis complex: proposition of a radiometric method.

A radiometric method using the "Bactec 460-TB" apparatus now enables rapid obtaining of drug-susceptibility data and differentiation of clinical mycobacterial specimens into those belonging to the Mycobacterium tuberculosis complex (comprised of M. tuberculosis, M. bovis, M. bovis BCG and M. africanum) and non-tuberculous mycobacteria, using a specific inhibitor (p-nitro-alpha-acetyl-amino-beta-hydroxypropiophenone). In the present work, further differentiation of the M. tuberculosis complex into 4 individual species was achieved using the susceptibility of strains to 1.25 micrograms/ml of thiophene-2-carboxylic acid hydrazide, 40 micrograms/ml of D-cycloserine, and 100 micrograms/ml of pyrazinamide.

[Derivatives of para-hydroxyacetophenone and para-hydroxypropiophenone as a potential new beta-adrenolytic agent]. / Deriváty para-hydroxyacetofenónu a para-hydroxypropiofenónu ako nové potenciálne beta-adrenolytiká.

Within the framework of the study of the structure-effect relationship, a series of novel potential beta-adrenolytic agents derived from p-hydroxyacetophenone and p-hydroxypropiophenone with an alyloxymethyl and a cycloalkyloxymethyl group in the lipophilic part of the molecule and an isopropyl and a tert-butyl group in the hydrophilic part on the basic nitrogen were prepared by means of a well-tried method. The structure of the prepared drugs was confirmed on the basis of interpretation of the IR, UV, 1H-NMR and mass spectra. The results of pharmacological evaluation of selected drugs show that the agents poses beta-adrenolytic and antiarrhythmic activity. From the viewpoint of comparison of the individual drugs subjected to testing the presence of an alyl seems more advantageous than that of a cyclohexyl. The characteristic of the prepared drugs was supplemented by the determination of their partition coefficients, surface tension and acute toxicity.

Radiometric studies on the use of selective inhibitors in the identification of Mycobacterium spp.

Radiometric selective inhibition tests were developed and evaluated for the rapid differentiation of Mycobacterium spp. Both a p-nitrobenzoic acid (PNB) test and a commercially-prepared p-nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP) test successfully differentiated M. tuberculosis and M. bovis from "atypical" mycobacteria or mycobacteria other than tubercle bacilli (MOTT). Thiophene-2-carboxylic acid hydrazide (TCH) readily distinguished human M. tuberculosis strains from M. bovis, irrespective of resistance to isoniazid. Both PNB and TCH tests were utilised in a routine radiometric susceptibility testing scheme over a period of 1 year in which 110 isolates of M. tuberculosis, 10 of M. bovis and one isolate of BCG were correctly differentiated from 10 isolates of MOTT. The rapidity, sensitivity and specificity of these radiometric tests can play a useful role in mycobacterial identification.

Selective inhibition of the Mycobacterium tuberculosis complex by p-nitro-alpha-acetylamino-beta-hydroxypropio phenone (NAP) and p-nitrobenzoic acid (PNB) used in 7H11 agar medium.

The potential of p-nitrobenzoic acid (PNB) and p-nitro-alpha-acetylamino-beta-hydroxypropiophenone (NAP) for discriminating the Mycobacterium tuberculosis (M.tb) complex from other mycobacteria was evaluated in cases of clinical isolates. For this purpose, 500 micrograms/ml of PNB and 5 or 10 micrograms/ml of NAP were incorporated in 7H11 agar medium, and appropriate dilutions corresponding to about 10(6) viable units were then plated on PNB- or NAP-containing media. Results were reported as growth or no growth as compared to a parallel control. Our data reconfirmed the potential of PNB to discriminate M.tb complex bacteria. This study also showed for the first time that the NAP test (used until now in 7H12a broth only) can also be successfully applied using 7H11 agar. Also, preliminary data with 5 micrograms/ml of NAP on a limited number of strains suggested that it may discriminate the M.tb complex bacilli from M. xenopi and M. gastri better than PNB in 7H11 agar.

A series of inhibitors of azo dye hepatocarcinogenesis partially reverse the azo dye-induced decrease in liver RNA/DNA ratio.

The DNA and RNA content and the mitotic index were determined in the livers of rats pair-fed for 10 days on a control diet, and diets containing 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'MeDAB), either alone or in combination with the inhibitors of azo dye carcinogenesis acetanilide (0.08%), p-hydroxypropiophenone (PHP, 1%), urea (5%), dehydroacetic acid (DHAA, 0.25%), butylated hydroxytoluene (BHT, 0.3%) and 3-methylcholanthrene (3MC, 0.067%). The liver RNA/DNA ratio was increased in rats fed the 3'MeDAB diet following ingestion of each of the inhibitor plus carcinogen-containing diets. The increases were significant except in the instance of urea. The increase was mainly due to increased RNA content in rats fed 3'MeDAB plus acetanilide, DHAA, BHT and 3MC when compared with rats fed 3'MeDAB alone. In rats fed PHP and 3'MeDAB, an increase in total liver DNA that was noted in rats fed 3'MeDAB alone did not take place, while total liver RNA content was similar in both groups; the RNA/DNA ratio was therefore greater in rats protected from 3'MeDAB carcinogenesis by PHP. The results are discussed in relationship to the effects of carcinogens on RNA forming genes and the role of the nucleolus in cell differentiation.

Structure-activity relationship of 5-hydroxykynurenamine analogues in isolated dog cerebral arteries.

In helically-cut strips of cerebral arteries isolated from dogs, analogues of 5-hydroxykynurenamine (5-HK), including 2-(3'-aminopropyl)-aniline (Cpd. I), 2'-amino-3-dimethylamino-3'-hydroxypropiophenone(CPD. II), 2'-amino-3-dimethylamino-5'-hydroxypropiophenone (Cpd. III) and 2',3-diamino-propiophenone (kynurenamine), caused a dose-related contraction which was antagonized by treatment with methysergide. The potency for inducing contractions was in the order of 5-hydroxytryptamine greater than 5-HK greater than Cpd. III greater than kynurenamine, Cpd. I and Cpd. II. Treatment with the 5-HK analogues antagonized the contractile response to 5-hydroxytryptamine in a dose-dependent manner, the antagonistic potency being in the order of 5-HK greater than Cpd. III greater than kynurenamine, Cpd. II greater than Cpd. I. Alterations in the hydroxy group on the benzene ring and/or radicals of long side chain of 5-HK attenuated the agonistic and antagonistic actions of 5-HK; however, the attenuation of these actions differed. Thus, the radicals appear to be involved in the agonistic and antagonistic actions to a different extent.

Effect of various factors on the induction of liver tumors in animals by quinoline.

Tumorigenic effect of a diet containing quinoline on the liver of various animals and the synergistic or antagonistic effect by other chemicals on quinoline hepatocarcinogenesis in rats were examined. It was concluded that 4,4'-diaminodiphenylmethane (0.1%) and 3-methylcholanthrene (0.0067%) had a significant inhibitory effect on liver carcinogenesis due to quinoline in rats, but 1-naphthyl isothiocyanate (0.06%) and p-hydroxypropiophenone (1.0%) had no inhibitory effect in the present observations. Transmission electron-microscopic study demonstrated the fine structure of vascular tumors induced by quinoline. On the other hand, it was found that quinoline induced liver tumors in both sexes of mice and rats but not in hamsters or guinea pigs. Male rats were more susceptible than females to the tumorigenic action of quinoline, and mice showed the least susceptibility. Histological changes in the liver of rats or mice induced by quinoline were clasified as hemangioendotheliomas or hemangiosarcomas and hepatocellular carcinomas. Several rats treated with quinoline had hemangiosarcomatous metastatic foci in the lung.

Effect of various factors on induction of liver tumors in animals by the alpha-isomer of benzene hexachloride.

The tumorigenic effect of a diet containing the alpha-isomer of benzene hexachloride (alpha-BHC) on the liver of various animals was examined. It was found that alpha-BHC induced liver tumors in male and female mice but not in rats or hamsters in the present observations. Histological changes in the liver of mice induced by alpha-BHC were also much greater than those induced in rats or hamsters. Male animals were more susceptible to the tumorigenic action of alpha-BHC than females. Among different strains of mice, the DDY showed greatest susceptibility and the C57BL/6 showed the least. Induction oflpha-BHC was not inhibited by concomitant feeding of 1-naphthyl isothiocyanate or p- hydroxypropiophenone. However, 3-methylcholanthrene slightly inhibited their induction by alpha-BHC.