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Biomedical subjects

E Chenu

Publications and source records attributed to E Chenu.

At least 19 recordsLinked to original sources

[Chronic hyperventilation syndrome].

Hyperventilation syndrome is a frequent, but poorly understood clinical entity. The clinical expression is a rich combination of respiratory, cardiac and neurological signs which can simulate various organic diseases. Hypocapnia remains the primum movens for most authors although the relationship with psychiatric situations, in particular in anxious patients, is increasingly emphasized. The diagnosis is currently based on the elimination of diseases associated with hyperventilation, then on Nijmegen's questionnaire and is confirmed by the reproduction of the same clinical picture in a voluntary hyperventilation test. Respiratory function tests offer little information. Treatment is based on combining rehabilitation therapy focused on the diaphragm and on relaxation. Specialized care may be needed in psychiatric patients.

Chronic Disease

[Plastic bronchitis].

We report a case of plastic bronchitis occurring in a 58 year-old man free from underlying pulmonary disease. Relief of symptoms was observed under steroid therapy (1 mg/kg), but relapse occurred as treatment being tapered. Such evolution is in accordance with recent published data.

Bronchitis

In vivo eradication of Friend virus as an experimental HIV-model, by combination of zidovudine, acriflavine and an ellipticine analogue. Possible application to the treatment of human pre-AIDS?

Simultaneous administration of zidovudine, acriflavine and celliptium to Friend virus-injected mice eradicates the virus, as evidenced by the impossibility of the treated-mouse serum, when injected to virgin recipients, to induce spleen foci formation. An adapted preliminary protocol given to patients in whose p 24 antigen was present in the blood, lead to a considerable reduction of that marker. The cures lasted 3 weeks, and were repeated after 3-week intervals. Since p 24 antigen returns to pre-treatment levels at the end of the interval, research should concentrate on the maintenance of the effect during the interval.

AIDS-Related Complex

The in vivo effect of ellipticine analogues on the blood concentration of Friend virus: a murine model for studying anti-HIV drugs.

The viremia of a mouse carrying a murine retrovirus, the Friend virus, was taken as a model for screening drugs which could be active on the human HIV retrovirus. Ellipticine and two of its analogues injected ip at appropriate doses drastically reduced the viremia of the Friend virus-injected mice, as measured by transfer of their serum on day 8 of the treatment to secondary recipients and numeration, in the spleens of the latter, of the foci the remaining virus had induced. Since phase I and II trials have already been published (for leukemia treatment), the efficacy of those drugs on HIV-1 positive AZT-resistant patients can be tested directly.

Acquired Immunodeficiency Syndrome

Virostatic in vivo effect of elliptinium on Friend's retrovirus (a model for HIV infection).

As we had discovered the virostatic effects of some analogues of acriflavine, a non-oncostatic intercalating agent, on HIV1 and on its best murine model, Friend's virus [7], we then studied other non- or poorly oncostatic intercalating agents, in particular ellipticins (whose negligible cytostatic effect with methoxy-9-ellipticin we first published. We report in this paper the in vivo virostatic effect of 2-methyl-9-hydroxy-ellipticinium (elliptinium) on Friend's virus.

Animals

Can virostatic chemotherapy and/or adoptive allogeneic immunotherapy eradicate in vivo Friend's virus infection?

While none of the three drugs which exert an in vitro anti-HIV effect, neither AZT nor the other two, acriflavine and elliptinium, which we have shown to be more efficient than AZT, is able to eradicate Friend's virus in vivo, the combination of the 3 drugs at much smaller doses than when given alone seems able to eradicate it in almost 30% of the infected animals. This possible eradicating effect of virostatics in combination is compared with the results we had previously obtained with lymphocytes of virus-immunized allogeneic donors.

Animals

Oxalato-platinum or 1-OHP, a third-generation platinum complex: an experimental and clinical appraisal and preliminary comparison with cis-platinum and carboplatinum.

A new platinum complex, oxalatoplatin or l-OHP, which, at the same metal dose in experimental tests is as efficient as cisplatin, and is more so at a lower metal dose than carboplatin; which is as efficient in human tumors of the testis and ovary as these other analogs, and more so in melanoma and breast cancer; which is not nephrotoxic, cardiotoxic or mutagenic, and hardly hematotoxic and neurotoxic, is described and compared with the above-mentioned platinum complexes. Combined with 5Fu, it induces a high number of remissions in colorectal cancer, and has brought about cures in inoperable gastric cancers. Combined with carboplatin, it has resulted in a high proportion of cures in L1210-carrying mice, which no other two-by-two combination of these complexes has achieved.

Animals

Synthesis and evaluation of antileukemic activity of 5-thienyl- or 5-(2-furyl)-2,3-dihydro-6,7-bis(hydroxymethyl)-1H-pyrrolizine bis(alkylcarbamates) and derivatives.

Treatment of N-(2-furoyl)proline or N-thenoylprolines and N-(2-thenoyl)thiazolidine-4-carboxylic acid with acetic anhydride and dimethyl acetylenedicarboxylate gave 5-substituted derivatives of dimethyl 2,3-dihydro-1H-pyrrolizine-6,7-dicarboxylate and derivatives of dimethyl 5-(2-thienyl)pyrrolo[1,2-c]thiazole. Reduction of 2 with lithium aluminum hydride gave the diols 3a, 3b, 3c and 3d. These diols yielded the corresponding diacetates 4 by treatment with acetic anhydride. The bis(methylcarbamates) 5a, 5b, 5c, and 5d and bis(isopropylcarbamates) 6b and 6c are obtained with the appropriate isocyanates. The 1-substituted pyrrolizines were synthesized, the 1-acetoxy compounds 7b and 7c further transformed into 1-hydroxy and 1-oxo analogues. The action of hydrochloric acid on 1-acetoxy derivatives gave 3H-pyrrolizines. Evaluation of antileukemic activity was investigated on the leukemia L1210 in vivo, on several bis(alkylcarbamates). The compounds 5c and 5d show good antileukemic activity comparable with the mitomycin.

Animals

Cytostatic action of two nitrosoureas derived from cysteamine.

2-Chloroethyl nitrosocarbamoylcystamine or ICIG-1325 (CNCC) is a lipid-soluble isomeric mixture of nitrosoureas. Its dose-effect relationship on L1210 leukaemia is characterized by a large maximally efficient dose-range (MEDR), greater than that of other nitrosoureas. CNCC also demonstrated significant therapeutic activity on intracerebrally (i.c.) transplanted L1210 leukaemia and on six transplanted solid tumours, TM2 mammary carcinoma, M555 ovarian carcinoma, B16 melanoma, glioma 26, 3LL, Lewis lung carcinoma and colon 26 carcinoma. It was inactive on fibrosarcoma ICIG-Ci4. Its antitumour activity spectrum is wider than that of the related compounds 2-[3-(2-chloroethyl) 3-nitrosoureido]D-glucopyranose (CZT), (chloro-2-ethyl)-1(ribofuranosyl-isopropylidene-2'-3' paranitrobenzoate-5')-3 nitrosourea (RFCNU), and (chloro-2-ethyl)-1 (ribopyranosyl triacetate-2'-3'-4')-3 nitrosourea (RPCNU). A study of its metabolic disposition in animals has shown that CNCC undergoes extensive first-pass metabolism leading to the formation of four main plasma metabolites. These metabolites are water-soluble nitrosoureas that arose from the bioreduction of the disulphide bridge followed by the methylation and the oxidation of the thiol groups. Experimental screening was performed with these chemically synthesized metabolites. Both N'-(2-chloroethyl)-N-[2-(methylsulphinyl)ethyl]-N'-nitrosourea (CMSOEN2) and N'-(2-chloroethyl)-N-[2-(methylsulphonyl)ethyl]-N'-nitrosourea (CMSO2EN2) are very active on L1210 leukaemia grafted intraperitoneally (i.p.) and i.c., L40 leukaemia, B16 melanoma, glioma 26 and Lewis lung carcinoma. Their effectiveness is better than that of the parent compound CNCC. In addition,the percentage of mice cured after CMSOEN2 or CMSO2EN2 treatment is increased especially on B16 melanoma and glioma 26. 6 Haematological toxicity of both active metabolites is lower than that of CNCC, particularly on platelets which is the main toxicity location due to nitrosoureas.

Animals

Antitumor activity of l-OHP in mice.

The isomeric mixtures of platinum complexes of diaminocyclohexane (DACH) had been found active on several murine tumors. A recent separation of the oxalato-platinum complex of trans-l-DACH isomer allowed more precise screening studies and permitted the selection of one compound: l-OHP was submitted to our murine tumor screening system. The drug was given: (a) at doses of 1-12 mg/kg i.p. or i.v. on day 1, 5 and 9 compared to identical doses of cis-dichlorodiamine platinum II (CDDP) in L1210 bearing mice and (b) to AkR leukemia, LGC lymphoma, glioma 26, B16 melanoma, MA 16-C mammary carcinoma and Lewis lung carcinoma bearing mice at 2 dosages: 5 mg/kg (minimal effective dose on L1210), and 8 mg/kg (subtoxic dose in L1210). Acute LD10 and LD50 appeared similar to CDDP and l-OHP. l-OHP administered i.p. was more active on L1210 than CDDP. On L1210 grafted intracerebrally and on LGC lymphoma l-OHP increased significantly the lifespan while CDDP was inactive. On AkR leukemia, both drugs were active but l-OHP was less toxic. Both drugs were inactive on murine solid tumors. No renal toxicity was observed with l-OHP as compared to CDDP.

Animals

Comparison of the experimental antitumor activities of three nitrosourea derivatives chlorozotocin, RFCNU and CNCC encapsulated in liposomes with those in the free state.

L1210 leukemia was used to compare the antitumor activities of three nitrosoureas (chlorozotocin, RFCNU and CNCC) encapsulated in liposomes with those in the free state. The results obtained varied according to the chemical structure of the compound, its solubility in oil or water, the route of administration into the body, and the treatment dose. The application of liposomes in the chemotherapy of malignant disease deserves further investigations.

Animals

Effects of B16 melanoma transplantation on the respiration of grouped C57Bl female mice.

Two batches of 110 females C57Bl mice were grafted with B 16 melanoma, the first batch at the age of 67 days, the second at 82 days. The animals were divided into groups of 10, and kept under a LD 12 : 12 regimen. The growth of the tumors was more rapid in the second batch. This was accompanied in this batch, by a decrease in body growth, a diminution of heart rate and an increase in QRSII amplitude. Significant decreases in carbon dioxide emission (VCO2) level, mostly during the dark period of time, when the mice had their greatest activity, and decrease in respiratory photic variations at light transitions were obtained when the tumors were well developed. Harmonic analysis of the continuous recording of carbon dioxide shows slight changes in VCO2 ultradian (40 minutes less than tau less than 12 hours) rhythms. The effects on respiration were confirmed by different survival rates and rectal temperatures between tumor grafted and controls submitted to an acute nitrogen normobaric hypoxia.

Animals