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Biomedical subjects

M Nasr

Publications and source records attributed to M Nasr.

At least 19 recordsLinked to original sources
PubMed1995

[Allergy and professional exposure to sulfur compounds: questions posed].

We present here four cases of respiratory diseases which may be due to the exposition or to the handling of sulfur derivatives due to their professional activity. The responsibility of these compounds stands on the clinical history, biological cellular tests and for one of them on the evolution under a metabisulfite-free diet and a positive oral provocation test at 5 mg. The present economical crisis makes the patient-clinician relationship difficult, due to patients' wishing to hide their pathologies or their professional activities.

Adult↗
PubMed1992

Genistein inhibits protein histidine kinase.

Protein histidine kinase was prepared from whole cell extracts of the yeast, Saccharomyces cerevisiae. The enzyme was assayed using either histone H4 or a synthetic peptide corresponding to residues 70 to 102 of histone H4 as an in vitro substrate. With either substrate, both genistein and its solvent, dimethyl sulfoxide (Me2SO), inhibited protein histidine kinase. Me2SO alone gave a cooperative dose-response curve, with inhibition changing from almost zero below 10% Me2SO to 80% at 20% Me2SO with either substrate. Genistein gave a simple dose-response curve with 50% inhibition of protein histidine kinase at 110 microM genistein. In experiments with protein histidine kinase, genistein was a noncompetitive inhibitor with respect to ATP, histone H4 or the synthetic peptide, although, in the case of the synthetic peptide, the data were also consistent with competitive inhibition. These data gave Km values for both ATP and histone H4 of 15 microM, in satisfactory agreement with previously reported values (Huang, J., Wei, Y., Kim, Y., Osterberg, L., and Matthews, H. R. (1991) J. Biol. Chem. 266, 9023-9031). The Km for the synthetic peptide was 80 microM. The KI values were 270 or 310 microM measured with histone H4 or the synthetic peptide as substrate, respectively. While these KI values are relatively high, relative to published KI values for genistein inhibition of protein tyrosine kinases, many reported experiments use genistein at concentrations where inhibition of protein histidine kinase occurs. It is possible that some of the observed effects of genistein in vivo may be due to inhibition of protein histidine kinase.

Adenosine Triphosphate↗
PubMed1992

Actions of endothelin at the subfornical organ.

Endothelin (ET), a potent vasoconstrictor peptide, is believed to have central sites of action and potential neurohormonal effects relating to body fluid homeostasis and blood-pressure regulation. Systemic endothelin binds to receptors at circumventricular organs and has been shown to increase plasma concentrations of vasopressin and increase the firing frequency of neurohypophysial vasopressin and oxytocin neurons. In the present study we have examined the effects of ET on blood-pressure following micro-injection into the subfornical organ (SFO). Micro-injection of 0.5 and 5.0 pmol of endothelin into SFO caused significant increases (10.1 +/- 1.1 and 10.2 +/- 2.1, respectively) in blood pressure, while lower doses were without effect. In addition, we have used single unit recording techniques to evaluate the effects of systemic ET on the activity of SFO neurons. Extracellular recordings from SFO neurons, antidromically identified as projecting to PVN, showed predominantly excitatory responses to systemic ET (21/35 cells). The data demonstrate that ET has excitatory actions on SFO neurons, and further raise the possibility that one of the functional consequences of such effects is an increase in arterial blood pressure.

Animals↗
PubMed1992

Computer-assisted structure-activity correlations of halodideoxynucleoside analogs as potential anti-HIV drugs.

Analysis of the structure-anti-HIV activity correlations of halo dideoxynucleosides (ddN's) in the public domain was accomplished through computer substructure searching, retrieval and sorting of in vitro anti-HIV data. In the survey, selectivity index (ratio of cytotoxicity to the potency in inhibiting HIV replication in vitro) was used to rank compounds in congeneric groups. Factors contributing to the anti-HIV activity, e.g. the nature and location of the halogen on the sugar or the base and its stereochemical configuration, could not be generalized for all the halogenated ddN's. Conclusions were drawn for specific classes within the pyrimidine and purine series, with compounds further divided into halo substitutions at the sugar 2',3',4'-positions or in the pyrimidine or purine ring systems. At the 3'-position, only a fluoro substitution enhanced the activity of the dideoxypyrimidine nucleosides. A 2'-ara fluoro substituent increased the activity of purine ddN's but decreased activity of pyrimidine ddN's. Halogenation of the side chain in acyclic adenine and 2,6-diaminopurine nucleosides improved their anti-HIV activity. Halo substitution at the 6- or 2'-ara position of selected purine ddN's resulted in compounds with increased lipophilicity, chemical stability and retention of anti-HIV activity. The number of halodideoxynucleosides tested as anti-HIV reagents suggested that this class of compounds is well studied.

Antiviral Agents↗
PubMed1991

[Epidemiology and prevention of mental disorders].

From a bibliographic analysis and personal experiences, the authors present the advantages of the epidemiologic method in psychiatry. They point out its specificity and the methodological difficulties. Since the psychiatric practices are being deeply transformed, it becomes essential to know precisely the importance and the distribution of mental diseases in the population. It is not possible to image changing a care system trend without knowing the real needs of the population. The descriptive epidemiologic method contributes to this. The aim of analytic epidemiology is ever more important since it allows to spot the circumstances in which mental diseases appear and are developed, and to elaborate etiological hypotheses. Finally, this favors preventive approaches where evaluative epidemiology permits to measure the validity and effectiveness of programs which, like those elaborated for other social calamities (transmissible diseases, degenerative diseases), take place for studies in the field of mental health disorders.

Epidemiologic Methods↗
PubMed1990

Anthraquinones as a new class of antiviral agents against human immunodeficiency virus.

Various anthraquinones substituted with hydroxyl, amino, halogen, carboxylic acid, substituted aromatic group, and sulfonate were tested to determine their activity against human immunodeficiency virus type 1 (HIV-1) in primary human lymphocytes. Among the compounds tested, polyphenolic and/or polysulfonate substituted anthraquinones were found to possess the most potent antiviral activity. Hypericin, an anthraquinone dimer previously shown to have activity against nonhuman retroviruses also exhibited anti-HIV-1 activity in lymphocytes. the active anthraquinones inhibited HIV-1 reverse transcriptase. However, this enzyme inhibition was selective only for 1,2,5,8-tetrahydroanthraquinone and hypericin. Hypericin interacts nonspecifically with protein suggesting that this effect may dictate its inhibitory activity against the viral reverse transcriptase.

Acquired Immunodeficiency Syndrome↗
PubMed1988

7-Aminoquinolines. A novel class of agents active against herpesviruses.

A series of 7-aminoquinoline derivatives was synthesized and evaluated for their capacity to produce cytotoxicity in KB cells and to inhibit the replication of herpes simplex virus (HSV) type 1. All compounds tested inhibited the replication of HSV-1 with 50% inhibitory concentrations in the range of 2-50 micrograms/mL. The antiviral activity of many compounds, however, was separated from cytotoxicity to replicating uninfected cells by only two- to fivefold higher than those required for antiviral activity. Nonetheless, six compounds (10, 28, 29, 32, 34, and 36) were identified in which the separation was greater than fivefold. All compounds examined were more potent inhibitors of viral DNA synthesis than the cellular DNA synthesis.

Aminoquinolines↗
PubMed1986

[Pleural mesothelioma. Developmental and therapeutic aspects apropos of 37 cases].

Thirty-seven cases of pleural mesothelioma seen in our unit between 1974 and 1984 have been reviewed. In cases with limited lesions early thoracotomy with an attempt at pleurectomy/lung decortication seemed to be justified. Thereafter - or initially in patients with extensive lesions - we resort to radiotherapy and/or chemotherapy. Although the final result was mediocre, we found it difficult to abstain from any treatment. Owing to the lack of large series and to the heterogeneity of those that have been published, no fixed rule can be laid down for the treatment of mesothelioma. Nevertheless, it would appear that using multiple therapeutic methods results in a somewhat longer survival.

Adult↗
PubMed1985

Computer-assisted structure--anticancer activity correlations of carbamates and thiocarbamates.

With the aid of the computer, approximately 8000 compounds that incorporate a carbamate or thiocarbamate moiety, which have been tested as potential anticancer agents at the National Cancer Institute (NCI), were classified and their structure-activity correlations against the in vivo P-388 and L-1210 leukemias were evaluated. Aromatic carbamates and thiocarbamates have shown good activity against P-388 and poor activity against L-1210. The majority of active compounds in this series of aromatic carbamates possess a 2- or 4-heteroatom-substituted phenyl attached to the carbamate oxygen atom or the thiocarbamate sulfur atom with the carbamate nitrogen atom as NHMe. The N-phenyl carbamates were much less active against P-388 than the phenyl carbamates; only bis-N-phenyl carbamates with a methylene bridge between the two phenyl groups showed good activity against both P-388 and L-1210 leukemias. Except for the mycophenolic acid carbamates, the fused phenyl carbamates showed poor activity against both P-388 and L-1210 leukemias. Certain nitrogen-heterocyclic carbamates and carbamates with heteroatom substituents have been selected by the NCI for development toward clinical trials. The nature of the heterocyclic carrier and the position of attachment to the carbamate moiety have a major role on the mode of action of the antitumor activity of these compounds.

Animals↗
PubMed1984

Computer-assisted structure-activity correlations.

Several types of Michael acceptors, including alpha,beta-unsaturated ketones, lactones, and lactams, have been extensively studied as potential anticancer agents. A concerted effort was made to explore the relationship between the structures of these compounds and their antitumor activity against P388 and L1210 leukemias. This article describes the computer-assisted structure-activity evaluation of more than 14,000 compounds, representing different classes of Michael acceptors, in the NCI file. In this study, advantage has been taken of the computer's ability to search substructures according to precise definitions and to manipulate these substructures utilizing Boolean logic. Olefinic conjugated Michael-type acceptors, e.g., styrenes with different activating groups, cinnamic acid derivatives, and alpha,beta-unsaturated nitro, cyano, sulfone, sulfoxide, and acetylenic compounds, have shown appreciable activity against P388 lymphocytic leukemia. The analysis of lactones and lactams includes substructures representing a wide variety of exocyclic and endocyclic alpha,beta-unsaturated compounds. The analysis describes the effect of certain groups, such as an --OH, --OR, alpha,beta-unsaturated ester, or epoxide, adjacent to the alpha,beta-unsaturated center, on the antitumor activity of these compounds. A combination of one or more of these activating groups with an alpha-methylene-gamma-lactone moiety significantly enhanced the activity against P388. In general, many of the classes of compounds studied have shown poor activity against the more stringent L1210 lymphoid leukemia.

Antineoplastic Agents↗
PubMed1984

Computer assisted structure-activity correlations. Evaluation of benzo(de)isoqinoline-1,3-diones and related compounds as antitumor agents.

Computer assisted evaluations of benzo(de)isoquinoline-1,3-diones and related compounds screened for antitumor activity against P388 lymphocytic leukemia and L1210 lymphoid leukemia are presented. Two important features necessary for good anticancer activity are the nature of the imide side-chain and the type of substituent on the aromatic portion. Based on these considerations 1H-benzo(de)isoquinoline-1,3(2H)dione,5-amino-2-(2-dimethyl-aminoethyl) (NSC 308847) has been selected for preclinical toxicology studies.

Animals↗
PubMed1981

The incidence of water-related diseases in the Brak area, Libya from 1977 to 1979, before and after the installation of water treatment plants.

The incidence of nine water-related diseases in the Brak oases of the Sahara desert, before and after the installation of water treatment plants, are reported. Immediately following installation of the plants there was a drop in the incidence of most of the water related diseases. There then followed a gradual deterioration in the treatment plants and within a year the incidence of four of the diseases was again rising. Furthermore neither malaria or giardiases showed any drop in incidence over the study period. Bacillary dysentary, infectious hepatitis and bilharzia did however drop significantly over the three years. A correlation between bacillary dysentary and the mean noon-time temperature for two of the three years was noted.

Ascariasis↗
PubMed1978

Synthesis of benzo-benzothiopyranoquinolines (pyridobenzothioxanthones) as possible schistosomicidal and antitumor agents.

The synthesis of a new class of compounds structurally related to cyclohexenothiaxanthones and benzothiaxanthones including a pyridine ring is described in an attempt to find compounds that may have schistosomicidal and carcinostatic activity. Synthesis was achieved through the condensation of amino-cyclohexenothiaxanthones and amino-benzothiaxanthones with ethyl acetoacetate by the Knorr and Conrad-Limpach methods.

Animals↗
PubMed1978

Synthesis of pyrimido[5,4-c]quinolines and related quinolines as potential antimalarials.

3-Ethylaminomethyl-2-methyl-4(1H)-quinolone (1a) and its 6-CH3, 6-OCH3, and 7-Cl derivatives were prepared by means of the Mannich reaction. Conversion to the 4-chloro derivatives and condensation with 3-chloroaniline gave the corresponding 4-(3-chloroanilino) derivatives. Cyclization of 4-(3-chloroanilino)-2,6-dimethyl-3-ethyl-aminomethylquinoline (3a) and its 6-OCH3 derivative with paraformaldehyde gave 1-(3-chlorophenyl)-3,9-dimethyl-3-ethyltetrahydropyrimido[5,4-c]quinoline (4a) and the 9-OCH3 derivative 4b. Treatment of 4b with benzaldehyde gave 1-(3-chlorophenyl)-3-ethyl-9-methoxy-5-styryltetrahydropyrimido[5,4-c]quinoline (5). 3-Benzylaminomethyl-6-methoxy-2-methyl-4(1H)-quinolone (1e) and 3,3'-(1,3-benzyliminodimethylene)di[2-methyl-4(1H)-quinolone] (6b) were also synthesized. The compounds were inactive as antimalarials.

Animals↗