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PubMed1987

[Addition of HPA 23 to cyclosporin in the treatment of thrombopenic purpura in HIV-positive subjects].

We associated HPA 23 (inhibitor of the reverse transcriptase) to cyclosporin A (CSA) for two homosexual patients with positive HIV serology, who had a peripheral thrombocytopenia resistant after alone CSA treatment. HPA 23 was given for 15 days at a dose of 4 mg/kg/day in a 24 hours continuous perfusion. The circulating tungsten blood concentration was about 4.4 micrograms/ml (between 3 and 8.4 micrograms/ml). Even if HPA 23 has frequently been responsible of thrombocytopenia at a dose superior than 2 mg/kg/day and in spite of any CSA activity in single treatment, this association shows a significant platelets increase. But thrombocytopenia reappeared a week after the stay of HPA 23 treatment. So, it is possible that HPA 23 might have, at this circulating blood concentration, an antiviral activity in vitro. In this hypothesis there might be a relation between antiviral replication and autoimmune disorders and, at least, CSA might oppose against the thrombocytopenia induced by HPA 23.

Adult↗
PubMed1988

Role of xanthine oxidase in the interferon-mediated depression of the hepatic cytochrome P-450 system in mice.

Interferon, interferon inducers, and a variety of other immunomodulators are known to depress the hepatic cytochrome P-450 drug-metabolizing system. Two concepts have been proposed to explain this phenomenon. (a) The steady-state of cytochrome P-450 is altered through decreased synthesis and increased degradation of cytochrome P-450 apoprotein. (b) Interferon induces xanthine oxidase; superoxide generated by interferon-induced xanthine oxidase destroys cytochrome P-450. The current study investigated the second concept. Administered polyribonucleotides [polyriboinosinic acid.polyribocytidylic acid (poly IC), polyriboinosinic acid.polycytidylic acid, polylysine and carboxymethylcellulose, mismatched poly IC], recombinant murine gamma-interferon, and a natural murine alpha/beta-interferon were shown to depress hepatic cytochrome P-450 and selected microsomal cytochrome P-450-dependent monooxygenase reactions and to induce hepatic xanthine oxidase activity. The feeding of tungstate in the drinking water largely depleted xanthine oxidase in mice; cytochrome P-450 levels and monooxygenase activities were not affected by tungstate treatment. Tungstate rendered the level of xanthine oxidase much below that in mice that had not received tungstate regardless of whether or not they had received poly IC or interferon; nevertheless, poly IC and interferon produced losses of cytochrome P-450 and monooxygenase activities in these tungstate-treated mice equivalent to those observed in mice that had not received tungstate. The administration of N-acetylcysteine did not prevent the loss of cytochrome P-450 induced by poly IC, as has been reported, nor did the incubation of microsomal cytochrome P-450 with buttermilk xanthine oxidase and hypoxanthine cause a loss of cytochrome P-450, which has also been reported. It is concluded from these studies that the induction of xanthine oxidase and the loss of cytochrome P-450 generated by interferon are coincidental rather than causally related phenomena.

Acetylcysteine↗
PubMed1988

Reverse transcriptase activity (RTA) in lymphocyte cultures of HIV-infected patients receiving short treatments of HPA 23. A biological evaluation.

Ammonium tungsto antimoniate (HPA 23) is a potent inhibitor of nucleic acid polymerases and reverse transcriptases of retroviruses. Its in vivo activity as an HIV inhibitor was previously published. However, its clinical use is limited by pharmacological parameters (short half-life and intravenous administration) and significant side effects (thrombocytopenia). In order to evaluate the place of this drug in the therapeutic strategy of HIV-infected patients, we administered 1.5 mg/kg of HPA 23 in 15 infected patients at various stages of the disease twice a day during 14 days. A significant decrease of reverse transcriptase activity (less than 15% of the initial value) was noticed in 13 patients. This activity remained low at least 6 weeks after the end of the treatment in 8 patients. Thrombocytopenia was the only significant side effect reported and was always transient. This study suggests that HPA 23 can be used as an induction treatment in patients infected by HIV. A maintenance treatment has to be defined, as well as the association to other drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Cellular and molecular mechanisms of antiretroviral effects of HPA23.

HPA23 is an antimonio-tungstate that exhibits numerous antiviral activities both in vivo and in vitro. It has been described as a competitive inhibitor of human immunodeficiency virus (HIV) reverse transcriptase (RT). Patients treated with daily injections of HPA23 show an inhibition of HIV RT activity in cell culture in 60% of the cases. Using biophysical (electronic spin resonance [ESR]), ultrastructural (microspectroscopic analysis), chemical (spectroscopy), and biological (cell culture) assays, HPA23 cellular and molecular mechanisms may be summarized as follows: 1) competitive inhibition of HIV-RT, 2) no or slight effect on cells infected with HIV in culture, 3) interactions with the cell membranes when long incubations are performed, and 4) antiviral activity possibly mediated by immune modulator effect of the drug.

Antimony↗
PubMed1989

Application of a silver-binding assay to the determination of protein in cerebrospinal fluid.

We evaluated a silver-binding assay for use in measuring total protein in cerebrospinal fluid. The advantage of this procedure over other methods is that, because of its sensitivity, it requires only a 0.5-microL sample. The procedure, which takes approximately 40 min to complete, involves dilution of 0.5-microL samples to 1 mL with distilled water containing sodium dodecyl sulfate, followed by addition of glutaraldehyde and an ammoniacal silver solution. After color development for 30 min, the reaction is terminated with sodium thiosulfate and the absorbance is measured at 420 nm. This assay displayed within-run and day-to-day precision (CV) of 3.1% to 13% over the range of 210 to 1370 mg/L. It showed substantially less protein-to-protein variation than the Coomassie Blue dye-binding procedure when tested with albumin, globulin, and transferrin. It also yielded an accurate estimation of hemoglobin. Moreover, preliminary studies suggested that it was capable of quantifying immunoglobulin light chains and glycoproteins. In a study of 54 human cerebrospinal fluid samples, results of the silver-binding assay corresponded more closely with those obtained with a rate biuret assay (intraclass correlation coefficient = 0.91) than did either the dye-binding or classical Lowry methods.

Albumins↗
PubMedDate not supplied

Honey protein as internal standard for stable carbon isotope ratio detection of adulteration of honey.

Using the difference in stable carbon isotope ratio between a honey and its protein fraction permits objective evaluation of possible adulteration of honey with small amounts (7-20%) as well as larger amounts of corn or cane sugar. The present uncertainty in interpretation of results from pure honey with delta 13C values outside the generally accepted limits for pure honey of -27.5% to -23.5% is eliminated; likewise TLC testing to resolve questionable samples with delta 13C values between -23.5 and -21.5% is not needed. Fifty certified samples of pure honey were used to establish criteria for purity, and 38 other samples with delta 13C values in the "questionable" or "adulterated" range for the AOAC official method were tested. A difference of 1.0% or more between honey and protein fractions is proposed to indicate adulteration.

Carbon Isotopes↗
PubMed1989

[Pulmonary pathology due to cobalt and hard metals].

For forty years, cases of interstitial pneumonia and bronchial asthma have been described in hard metal workers (i.e., alloys of tungsten carbide and cobalt). Recently we have reported comparable pulmonary lesions in workers in the diamond industry who were exposed to cobalt unassociated with tungsten carbide. The exposure came from the diamond cobalt discs used for polishing diamonds, which had as the hard element microdiamonds, cemented in an alloy of pure cobalt. The hard metals on the other hand consisted of cobalt and tungsten carbide. Forty-seven diamond cutters (i.e., nearly 1% of those exposed) presented with broncho-pulmonary pathology due to cobalt. Nineteen had a fibrosing alveolitis, sometimes documented by a pulmonary biopsy and more often by a broncho-alveolar lavage which revealed characteristic multinucleated giant cells. Thirteen had occupational asthma, often proved by specific inhalation provocation tests to cobalt or by lung function measurements at the place of work. Two patients had mixed forms and in thirteen a probable diagnosis was suggested. The pathogenesis of cobalt might be explained by cytotoxic action such as has been demonstrated in animal experiments. Either results suggest a sensitising or allergic action. Tungsten carbide does not produce pulmonary lesions but its association with cobalt intensifies the effects of the latter.

Alloys↗
PubMed1989

Needle holder damage to surgical needles.

Clamping surgical needles between the jaws of needle holders with teeth markedly weaken the needles, making them prone to breakage. In contrast, clamping surgical needles between either smooth needle holder jaws or jaws embedded with tungsten carbide particles did not alter the ductility of surgical needles.

Alloys↗
PubMed1987

AIDS: the virus, antivirals and vaccines.

The speed of research into the pathogenesis of AIDS is breathtaking, and it is now possible to review potential therapeutic approaches against the AIDS virus. This review concentrates upon antiviral drugs and vaccine development.

Acquired Immunodeficiency Syndrome↗
PubMed1987

The mechanism of action of molybdenum and tungsten upon collagen structures in vivo.

The effect of in vivo administration of molybdenum (as sodium molybdate) and tungsten (as sodium tungstate) was investigated in the skin of laboratory rats. It was proved that the amount of both bound molybdenum and tungsten in collagen is relatively small being 0.05 and 0.06 moles per mole respectively. Besides the fraction of firmly bound molybdenum and tungsten a much higher extractable pool of both these metals was found. It was also demonstrated that in vivo shadowing of collagen is caused by the fraction of loosely bound metals. On the other hand pronounced changes were shown in the mechanical properties of connective tissue after molybdate and tungstate administration. Surprisingly, the change in mechanical properties indicated a lower level of cross-linking after the administration of the investigated metals. It is therefore concluded that bitopical binding of molybdenum and tungsten in the collagen structure is unlikely. It also appears that the biological effect of these metals is due to the competition with copper and the interference with the physiological cross-linking reactions based on the partial blockade of lysyloxidase.

Animals↗
PubMed1988

Mystery of the separating tungsten carbide burs.

Three instances of tungsten carbide bur separation, one of which resulted in the patient swallowing the separated bur head are described. This spate of bur heads separating from the shank was associated with a cold sterilising solution used for disinfection.

Corrosion↗