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PubMed1977

[Concentration of intravenously administered gammaglobulin preparations in dog skin (author's transl)].

Chemical modification of standard gammaglobulin with enzyme treatment (pepsin) or stabilization (beta-propiolactone) is able to influence elimination, fragmentation and organ distribution of intravenously administered gammaglobulins as shown in 36 dogs after i.v. application of allogenic and xenogenic gammaglobulin preparations. Pepsin-gammaglobulin was eliminated and fragmented most rapidly. Gammaglobulin concentrations of all preparations in the skin showed as slower decrease than comparable blood concentrations. The highest skin concentrations 10 days after i.v. application were found for beta-propiolactone gammaglobulin with 6.2 +/- 1.6 microgram/g compared to a blood level of 7.9 +/- 0.9 microgram/ml.

Animals↗

PubMed1985

Evaluation of skin carcinogenicity of technical 2,2-bis-(p-glycidyloxyphenyl)-propane in CF1 mice.

The carcinogenic potential of a technical-grade epoxy resin, Araldite GY 250, of which the diglycidyl ether of bisphenol A (DGEBPA) is the main component, was investigated in CF1 mice. Groups of 50 male and 50 female mice were treated for 2 yr by repeated epidermal application of a 1 or 10% (v/v) solution in acetone. The controls, 50 mice of each sex, were treated with acetone alone. The treatment had no effect on survival and no excess incidence of skin tumours occurred. A positive control group of 50 male and 50 female CF1 mice was treated by epidermal application of 2% (v/v) beta-propiolactone in acetone. In this group there was a high incidence of malignant skin tumours at the site of application and, consequently, increased mortality. Treatment with neither DGEBPA technical nor beta-propiolactone induced systemic neoplasia.

Acetone↗

PubMed1984

The effect of some common inactivation procedures on the antigens of bovine herpesvirus 1.

Bovine embryonic kidney cells were infected with bovine herpesvirus 1 (BHV1) or were sham-inoculated. When cytopathic effect was apparent, the cells were treated with beta-propiolactone, formalin, heat (56 degrees C), or ultraviolet irradiation until the virus was inactivated. Infected-treated, infected-untreated (IU) and sham-inoculated cultures were solubilized using Triton X-100 detergent. Resulting preparations were tested by 2-dimensional- and fused rocket-immunoelectrophoresis and were evaluated for their ability to inhibit virus neutralization by BHV1 antiserum. Eleven viral antigens were detected consistently in IU preparations, which strongly inhibited virus neutralization. Eight or more IU antigens were detected in beta-propiolactone-treated, formalin-treated and heat-treated preparations; these inhibited virus neutralization less strongly than the IU preparations. No IU antigens were detected in ultraviolet-treated preparations, nor did this material inhibit virus neutralization. One of the IU antigens was reduced preferentially by all treatments. The selective destruction of antigens by the various treatments might allow antigen-specific serological testing to distinguish vaccinated from naturally-exposed cattle.

Animals↗

PubMed1976

Detection of different types of damage in alkylated DNA by means of human corrective endonuclease (correndonuclease).

Corrective endonuclease (correndunclease) activity of HeLa cells was assayed with alkylated DNA. Double-stranded, covalently closed DNA from phage PM II was treated with methyl methanesulfonate, N-methyl-N-nitrosourea, beta-propiolactone, or diepoxybutane to introduce alkylated bases and alkali-labile sites into the DNA. The damaged DNA was incubated with an extract of HeLa cells that catalyzes the formation of breaks at apurinic sites in double-stranded DNA. Methylated DNA was broken at every alkali-labile site by the HeLa correndonuclease, which indicated that these sites are similar to the apurinic sites produced by heating at acid pH. DNA alkylated with beta-propiolactone or diepoxybutane containing the same number of alkali-labile sites was broken to a far lesser extent. This indicates the presence of a second type of alkali-labile damage that is correndonuclease-insensitive.

Alkylating Agents↗

PubMed1982

Inactivation of rabies virus in reagents used for the fluorescent rabies antibody test.

Procedures for inactivating rabies virus in reagents used for the fluorescent rabies antibody test are described. Mouse brain adsorbing suspensions containing greater than or equal to 10(9) 50% lethal doses of virus per ml were rendered noninfectious by treatment with 0.1% beta-propiolactone or by heating at 56 degrees for greater than or equal to 30 min. Viable virus in tissue impression smears was inactivated by acetone fixation at 50 degrees C for greater than or equal to 30 min or by immersion in 0.1% beta-propiolactone at 37 degrees C for 2 h. Inactivated reagents gave specific and sensitive reactions in the fluorescent rabies antibody test.

Acetone↗

PubMed1976

Ethylenimine-inactivated rabies vaccine of tissue culture origin.

The replication of seven rabies virus strains (CVS, HEP, PV, ERA, WIRAB, CPZ and BOLIVAR) in BHK cells and the inactivation dynamics of these strains by beta-propiolactone, acetylethylenimine, and ethylenimine were studied to find the most immunogenic strain and the most economic and stable inactivating agent for the production of an inactivated tissue culture rabies vaccine for animal use. The seven strains reached the peak of virus production 3 to 5 days after inoculation of the cell culture; PV yielded the highest virus titer (10(9) plaque-forming units/ml). The infectivity of virus suspensions containing 10(7) to 10(8) plaque-forming units/0.1 ml was inactivated by beta-propiolactone in 0.5 h, acetylethylenimine in 3.0 h, and ethylenimine in 1.0 h. Most of the vaccine lots prepared with the different strains and inactivating agents passed a modified National Institutes of Health potency test. The vaccines prepared with the PV strain had consistently higher antigenic values (equal or better than four) than the other six strains. This difference was highly significant (F6,12=59.8), whereas there were no statistically significant differences among the antigenic values of the vaccine lots prepared with the three inactivating agents. Batches of lyophilized and liquid vaccine stored at 4 C maintained potency for over 1 year. Ten dogs vaccinated with a vaccine prepared with the PV strain and inactivated with ethylenimine developed a good antibody response and resisted challenge 60 days after vaccination, while seven of eight nonvaccinated controls died of rabies. This information indicates that an inactivated, stable, economic, and easy-to-prepare rabies vaccine can be produced in BHK cells by using the PV strain and ethylenimine as an inactivating agent.

Animals↗

PubMed1981

Early syncytium formation by bovine leukemia virus.

Bovine leukemia virus (BLV) from either persistently infected bat cells or fetal lamb kidney cells induced rapid syncytium formation in F81 indicator cells. Distinct syncytia were seen within 2 h after inoculation of cells with highly concentrated (500-fold) cell-free BLV preparations and within 4 to 8 h when unconcentrated cell-free BLV preparations were used. Indicator cell densities of 1 x 10(5) to 2 x 10(5) were optimal for rapid and maximal syncytium formation. Pretreatment of BLV with reference BLV leukemic serum and antiserum prepared against purified BLV significantly inhibited (95%) syncytium formation. Reference bovine viral diarrhea virus serum, foamy-like bovine syncytial virus serum, and control serum had little effect (17% inhibition). Antiserum to BLV gp51 inhibited syncytium formation by greater than 96%, whereas antiserum to BLV p24 reduced syncytium activity to a much lesser extent (38% inhibition). Treatment of BLV with beta-propiolactone (0.005 to 0.05%) had little or no effect upon syncytium-forming activity, whereas UV irradiation (15 ergs/mm(2) per s for 30 min) reduced, but did not completely destroy, the fusion activity. However, both beta-propiolactone and UV irradiation drastically reduced the replication potential of BLV, as demonstrated by the lack of p24 expression in the inoculated cells. Concentrations of cycloheximide, cytosine arabinoside, tunicamycin, and 2-deoxy-D-glucose which effectively blocked cellular macromolecular synthesis did not significantly inhibit syncytium formation. These latter results suggested that de novo protein and DNA synthesis as well as protein glycosylation were not required for early syncytium formation. Thus, these experiments demonstrated that replication of BLV by the indicator cells was not essential for cell fusion.

Animals↗

PubMed1989

Oncogene activation in experimental carcinogenesis: the role of carcinogen and tissue specificity.

Techniques of molecular biology have been used to determine the relationship of cellular oncogenes to mechanisms of experimental carcinogenesis. Model systems involving three direct-acting alkylating carcinogens, two organ sites, and two species have been employed to elucidate the relationships between carcinogenic etiology, tissue specificity, and activation of known and novel oncogenes. Dimethylcarbamyl chloride, a reactive acylating agent, induces tumors of both the rat nasal mucosa and mouse skin whose DNA is devoid of NIH 3T3 transforming activity. Beta-propiolactone-induced rat nasal carcinomas contain a novel oncogene, 6 to 9 kb in size, whereas a mouse skin carcinoma induced by this agent possesses an H-ras oncogene activated by a 61st codon A to T transversion mutation. The novel oncogene activated in rat nasal tumors induced by beta-propiolactone is distinct from one found in methylmethane sulfonate-induced tumors. The implications of these findings for understanding how oncogenes fit into general mechanism of carcinogenesis are discussed.

Animals↗

PubMed1978

[Detoxification of tetanus toxin].

Reported in this paper are experiments conducted to compare formaldehyde, glyoxal, malondialdehyde, succindialdehyde, glutardialdehyde, adipindialdehyde, beta-propiolacton, and pyrocarbonic acid diethylester for their toxifying properties. Tetanus toxin, 1.5 million dlm/ml or 120 binding units, was used. Glutardialdehyde proved to be the most favourable compound and was followed by formaldehyde against the background of the experimental arrangement used, that is determination of concentrations for inactivation and antigenic properties of the toxoids. Glyoxal, malondialdehyde, succindialdehyde, and beta-propiolactone followed in some distance, whereas no inactivation at all was obtained from adipindialdehyde and pyrocarbonic acid diethylester.

Adipates↗

PubMed1976

Restriction of carcinogen-induced error incorporation during in vitro DNA synthesis.

The in vitro accuracy of DNA replication has been investigated through the measurement of the frequency with which noncomplementary nucleotides were incorporated during polynucleotide replication. The effect of beta-propiolactone treatment of deoxynucleotide templates, ribopolynucleotide templates, and the DNA polymerase from avian myeloblastosis virus was determined. Treatment of the deoxynucleotide template, poly(dA) (see article) oligo(dT) 12-18, by beta-propiolactone resulted in an increased frequency of noncomplementary nucleotide incorporation during DNA polymerization. Carcinogen treatment of the ribonucleotide templates, poly(rA) (see article) oligo(dT) 12-18, and poly(rC) (see article) oligo(dG) 12-18, and carcinogen treatment of avian myeloblastosis virus DNA polymerase did not alter the frequency of noncomplementary nucleotide incorporation. This suggested that carcinogen-induced error incorporation during DNA synthesis was restricted solely to the treatment of a deoxynucleotide template.

Avian Myeloblastosis Virus↗

PubMed1985

[Experimental reconstruction of flexor tendon injuries with a free transplant tendon-tendon sheath unit].

The authors, in their experiments on chickens, imitate human "no man's land" flexor tendon injuries of bad prognosis. For reconstruction of gliding surfaces they transplanted composite flexor tendon grafts containing flexor tendons with their sheath, pulleys, and vincula. Autologous grafts were compared with homologous composite tendon grafts preserved in beta-propiolacton. Summarizing the results of macroscopic and light microscopic examinations they state that the tendon sheath of the autologous composite tendon grafts revitalize in two weeks, and their tissue structure remains practically intact. The composite tendon allografts conserved in beta-propiolacton on the contrary rebuild much more slowly, on the average over three months. Regeneration is accompanied by round-cell infiltration. In the case of the autogenous graft generally smaller, and in the case of homologous composite flexor tendon graft more multitudinous adhesions occurred between flexor tendon and tendon sheath. The authors conclude from the literature and their own results that the reconstruction of flexor tendons with autologous composite flexor tendon grafts is a proper method for the restoration of severe flexor tendon injuries. Before clinical use, homologous composite flexor tendon grafts require more experimental investigation.

Animals↗

PubMed1981

[Studies on the corrosive action of some disinfectants suitable for aerosol-disinfection (author's transl)].

Under defined conditions the corrosive effect of several disinfectants (hydrogen peroxide, peracetic acid, formaldehyde, beta-propiolactone, Wofasteril, Lysoformin and Tegodor 73) was investigated with different metals and synthetic products after repeated aerosolation. At 6 plastics no alterations of their surface quality, their tensile strength and their compression resistance were observed. The strongest corrosive effect was produced by hydrogen peroxide and peracetic acid resp. the commercial preparation Wofasteril. Two aldehyde-containing disinfectants caused little changes of the colour coat of silver, brass, titanium and zinc, steel showed strong alterations; the effect of formaldehyde was very similar. The repeated disinfection with beta-propiolactone produced little colour changes on the surface of brass, titanium and zinc, on steel a strong corrosion was observed. In a control test without disinfectants colour changes of metal surfaces and strong damage of steel was produced by a high humidity. These results and the practical applicability are discussed.

Corrosion↗

PubMed1981

Circadian variation in the susceptibility of mouse epidermis to chemical carcinogens.

Groups of hairless nice were given a single topical application of each of two highly-reactive carcinogens (methylnitrosourea and beta-propiolactone) at 12(00) and 00(00). The tumor yield was as follows: for methylnitrosourea there was a slightly higher yield of skin tumours in the animals painted at 12(00); for animals painted with beta-propiolactone, there was a significantly higher skin tumour yield in those painted at 12(00). When the groups painted with the two carcinogens are considered together, there was a significantly higher number of animals with all types of tumours in the group painted at 12(00). Hence, there seems to be a circadian variation in the sensitivity of a tissue to a single contact with a chemical carcinogen. This may be related to the proliferative state of the tissue involved: at 12(00), DNA and cell division takes place at a more rapid rate than at 00(00).

Adenoma↗

PubMed1979

[Longterm therapy with i.v.-gamma-globulin in children (author's transl)].

gamma-Globulin for treatment should be injected by the intravenous route whenever possible. An unsplit molecule would be of great advantage in this context but there is the problem of antigenicity. One possibility to attain a good tolerance for i.v.-gamma-globin is to treat the molecule with beta-propiolactone. The acute tolerance and the efficacy of this preparation are proven. We wanted to find out if the modification of the immunoglobulin by beta-propiolactone would induce new antigene properties, which could lead to antibody production after repeated injections. There were no antibodies to be found neither in vivo nor in vitro in 6 children, which received 8--166 injections of this preparation.

Adolescent↗

PubMed1978

Chemical carcinogen alteration of SV40 virus induced transformation of normal human cell populations in vitro.

The frequency of simian papovirus 40 (SV40) induced transformation of human cells was enhanced after pretreatment with either napthylamine-2,N-methyl-N'-nitrosoguanidine (MNNG), N-acetyl-2-fluorenylacetamide (N-Ac-AAF), benzo[a]pyrene (BP), aflatoxin B1, propane sultone (PS), beta-propiolactone, 4-nitroquinoline oxide (4-NQO), methylmethane sulfonate (MMS) or diethyl nitrosamine (DEN). Posttreatment with 4-NQO, MMS, MNNG or DEN inhibited transformation; while posttreatment with either aflatoxin B1, beta-propiolactone or napthylamine-2 did not alter transformation similar to the action of N-Ac-AAF and BP. All carcinogens that altered transformation after pretreatment damaged cellular DNA. Pretreatment or posttreatment with carcinogens 3-methylcholanthrene (3-MCA) or 7,12-dimethylbenzanthrene (7,12-DMBA), that did not damage cellular DNA also did not enhance transformation. Moreover, pre- or posttreatment with other weak or non-carcinogens that did not damage cellular DNA did not alter virus induced transformation. All foci formed in the co-carcinogen treated cultures whether the carcinogen inhibited or enhanced transformation were virus directed. While a similar pattern of response existed for carcinogens that either enhance or inhibit transformation, each of the carcinogens that enhanced or inhibited foci formation damaged cellular DNA. Moreover, those carcinogens that enhanced focus formation, compared to the carcinogens that inhibited focus formation, exhibited similar DNA damage profiles.

Carcinogens↗

PubMed1970

Inactivated smallpox vaccine. A comparison of inactivation methods.

Vaccines were prepared from a single pool of high-titred vaccinia virus and inactivated by six methods, namely heat, formalin, hydroxylamine, beta-propiolactone, ultraviolet irradiation, and visible light and methylene blue. Large doses of the vaccines were required to protect mice against intracerebral challenge. Differences in protection were not attributable to the method of their inactivation. The vaccines also induced similar degrees of skin immunity in rabbits which showed no severe dermal reactions when challenged with either homologous killed vaccine or live virus. The virus-neutralizing, haemagglutinin-inhibiting and complement fixing antibody responses to the vaccines differed; heat-inactivation preserved these antigens least well and beta-propiolactone apparently the best. In both rabbits and mice there was little association between the different antibody responses to each vaccine or between the degrees of antibody response and the protection they induced. The relation of these findings to pox-virus immunity and the use of inactivated smallpox vaccine in man is discussed.

Animals↗

PubMed2004

Catalytic carbonylation of beta-lactones to succinic anhydrides.

A well-defined, highly active and selective catalyst for the synthesis of succinic anhydrides from CO and beta-lactones is reported. At 200 psi of CO, the catalyst [(N,N'-bis(3,5-di-tert-butylsalicylidene)phenylenediamino)Al(THF)2][Co(CO)4] carbonylates beta-propiolactones to succinic anhydrides in high yield. (R)-beta-Butyrolactone is carbonylated to (S)-methylsuccinic anhydride with clean inversion of stereochemistry, while cis-2,3-dimethyl-beta-propiolactone yields exclusively trans-2,3-dimethylsuccinic anhydride. These data are consistent with a mechanism involving nucleophilic attack by [Co(CO)4]- on the beta carbon of the lactone, followed by CO insertion and anhydride formation.

Journal Article↗

PubMed1997

Multicenter crossover comparison of the safety and efficacy of Intraglobin-F with Gamimune-N, Sandoglobulin, and Gammagard in patients with primary immunodeficiency diseases.

The safety and clinical efficacy of a liquid, beta-propiolactone-stabilized intravenous gamma-globulin, Intraglobin-F, was evaluated in a multicenter, double-blind study comparing Intraglobin-F to Gamimune-N, Sandoglobulin, or Gammagard. beta-Propiolactone stabilizes the IgG molecule to decrease aggregate formation and is a potent virucidal agent that reduces the risk of viral transmission by intravenous gamma-globulin (IVIG) preparations. Twenty-seven patients with primary immunodeficiency diseases were enrolled at three centers. Each patient received 6 months of therapy with either Intraglobin-F or the IVIG preparation that they had received during the preceding 3 months, then crossed over to the other preparation. Twenty-three patients completed the study. One patient withdrew because of an adverse event, generalized urticaria. A second patient withdrew because of fatigue and perceived decreased efficacy. Adverse reactions were comparable and occurred in 8.7% of the infusions of Intraglobin-F and 6% of the infusions with Sandoglobulin. None were severe or life-threatening. There was no discernible difference in efficacy between any of the products. The number of days when patients noted symptoms in their diaries was similar for Intraglobin-F and the comparison preparations, 4158 vs 4143. Similarly, there were no differences in the number of physician visits (33 vs 22), days missed from work or school (405 vs 404), days with fever (41 vs 47), or days of prophylactic antibiotics (675 vs 642). There was an increase in the number of days when antibiotics were given therapeutically (578 vs 451); most of the difference was attributable to one patient. There also was a difference in the number of days of hospitalization (21 vs 0), but 19 of the days were accounted for by two patients. When the patients were asked to score their feeling of well-being on a scale of 1 to 5, with 1 being entirely well, the mean score for the patients on Intraglobin-F was 1.86 (range, 1.0 to 3.0), compared to 1.85 (range, 1.0 to 3.2) for patients while on the comparison preparations. Trough IgG levels were slightly lower during the period when patients were treated with Intraglobin-F compared to the other products. There were no abnormalities in blood chemistries or hematologic parameters. Thus, Intraglobin-F is comparable to three of the marketed IVIG preparations in efficacy and safety, as well as patient acceptability, and offers the additional benefit of an extra virucidal step to reduce further the risk of transmitting viral infections.

Adolescent↗