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PubMed1992

Radiation protection of male fertility in mouse and rat by a combination of 5-hydroxy-L-tryptophan and a thiol compound (AET).

Sperm abnormalities and fall in total sperm count following different doses (4 Gy, 5 Gy and 6 Gy) of whole body gamma irradiation (WBGR) were studied in adult male Swiss strain A mice. The protecting ability of a combination of 5-hydroxy-L-tryptophan (5-HTP, 100 mg/kg) and 2-aminoethyl isothiuronium bromide hydrobromide (AET, 20 mg/kg) was also investigated. Pretreatment with a 5-HTP+AET formulation i.p., 30 min before irradiation modified the fall in sperm counts significantly. Exposures to 4 Gy, 5 Gy and 6 Gy WBGR caused marked increase of sperm abnormalities which could be significantly reduced by pretreatment with 5-HTP-AET. WBGR with 4 Gy, 5 Gy and 6 Gy produced a short period of sterility associated with oligospermia but these abnormalities were corrected by pretreatment with 5-HTP+AET. This finding was supported by breeding experiments in pretreated adult male Sprague-Dawley rats which showed delivery of normal offsprings in drug-protected irradiated groups in contrast to irradiated controls.

5-Hydroxytryptophan↗
PubMed1985

Embryonic survival in mice treated with AET, MEA or 5-HT on the first day of pregnancy.

The embryotoxicity of AET, MEA, and 5-HT was investigated in Porton mice. Female mice on the first day of gestation were injected intraperitoneally with 2-amino-ethylisothiouronium bromide hydrobromide (AET), cysteamine hydrochloride (MEA) or serotonin-creatinine sulphate (5-HT) in a dose of 40 mg/kg body weight. Uterine contents were examined on the nineteenth day of pregnancy. As compared with controls, in mice treated with AET, MEA or 5-HT, a smaller number of live fetuses and a greater number of non-implanted embryos, resorptions, and dead fetuses were found. Not all females which were injected with these compounds had live fetuses. Among the compounds, MEA appeared to be more toxic than AET and 5-HT.

Animals↗
PubMed1984

Effects of AET and MEA treatment prior to X-irradiation of mice on the first day of pregnancy.

Porton mice were whole-body X-irradiated with a dose of 500 R or, 15 minutes before X-irradiation, injected with AET or MEA, in a dose of 40 mg/kg of body weight, on the first day of pregnancy. On the nineteenth day of gestation, taking into consideration females in whose uteri live foetuses were observed, the increase in their body weight throughout pregnancy, the number of foetuses in the uterus, the body weight of foetuses, and the placenta weight were determined. As compared with controls, in X-irradiated mice and in those prior to exposure to X-rays, injected with AET or MEA, both statistically non-significantly greater placenta weight and statistically significantly lower increase in the female body weight during gestation, number of foetuses in the uterus, and body weight of foetuses, with the exception of statistically non-significantly lower number of female foetuses in only X-irradiated mice, number of male foetuses and body weight of female foetuses in those treated with AET, as well as total, female and male body weight in those injected with MEA were found. In females before X-irradiation injected with AET or MEA, in relation to those only X-irradiated, statistically significantly greater body weight of foetuses was observed.

Animals↗
PubMed1995

Radioprotection against biological effects of internal radionuclides in vivo by S-(2-aminoethyl)isothiouronium bromide hydrobromide (AET).

UNLABELLED: Radionuclides employed in diagnostic and therapeutic nuclear medicine impart radiation energy to tissue over an extended period of time, which depends on the physical half-life and the biological properties of the radiochemical employed. It is therefore important to examine the capacity of chemical radioprotectors to mitigate damage caused by chronic irradiation by incorporated radionuclides. METHODS: Spermatogenesis in mouse testis is used as the experimental model, and spermatogonial cell survival as measured by testicular spermhead count is the biological end point. The capacity of S-(2-aminoethyl)isothiouronium bromide hydrobromide (AET) to mitigate radiation damage caused by chronic irradiation by the radiochemicals 125IUdR, H125IPDM and 210Po-citrate, is investigated. RESULTS: The radioprotection provided by AET is substantial and similar for both of the radioiodinated compounds with dose modification factors (DMF) of 4.0 +/- 1.2 for 125IUdR and 3.4 +/- 0.4 for H125IPDM. In contrast, the damage caused by 210Po alpha particles is protected against to a lesser degree (DMF = 2.4 +/- 0.5). CONCLUSION: The present radioprotection data for AET, in conjunction with our earlier findings for the chemical protectors cysteamine and vitamin C in the same experimental model, suggest that such compounds may be clinically useful as mitigating agents against biological damage caused by incorporated radionuclides. The observed DMFs for AET also support our earlier premise that the mechanism by which DNA-incorporated Auger emitters impart biological damage is primarily radical mediated, and hence indirect in nature.

Animals↗
PubMed1977

Radioprotective effectiveness and toxicity of ATP, AET and serotonin applied individually or simultaneously to mice. III. Radioprotective effects of pair combinations.

The work reported was done as part of an intensive investigation on toxic and radioprotective properties of three substances, ATP, AET and serotonin, administered singly or in combination to mice, with a view to identifying optimal dose ratios for cocktails. Male C57BL mice were exposed to 850 R X-rays (LD100/11) following pretreatment with drug pairs at various dose ratios. Thirty-day survival was scored. For ATP-AET, protection increased with the amount of ATP in the combination; this pair was found to be most effective at an ATP-to-AET ratio of 11:1. A similar trend was observed with ATP-Serotonin, though only up to a certain ATP level beyond which no further increase in protective effect were produced; the most favorable ratio was of 24:1. A maximum synergistic action was displayed by the AET-Serotonin pair as compared to the other two pairs; its best ratio was of 4:1. Using probit analysis, a number of PD50 (protectant dose affording 50% survival in lethal irradiation) values were estimated for the three pairs of protective agents.

Adenosine Triphosphate↗
PubMed1979

A methodological study of E-rosette formation using AET-treated sheep red blood cells.

The influence of some of the well knwon technical variables on the E-rosette technique was examined using sheep red blood cells (SRBC) treated with 2-aminoethylisothiouronium bromide (AET). With AET treatment, E-rosette formation becomes less dependent on time and temperature and on the presence of serum. The mechanical stability of the rosettes is enhanced, and the number of SRBC attached to each rosette-forming lymphocyte (RFC) is markedly increased, leading to a sharper distinction between RFC and non-RFC. Ultimately, significantly more E-receptor carrying lymphocytes become detectable. Evidence is provided that the specificity of the E-rosette technique is unchanged after AET treatment of SRBC, in spite of the enhanced binding. A simple and reliable method for E-RFC identification is documented.

Animals↗
PubMed1984

The action of anticlastogens in human lymphocyte cultures and its modification by rat liver S9 mix. I. Studies with AET and sodium fluoride.

The action of beta-aminoethylisothiouronium bromide hydrobromide (AET) and sodium fluoride (NaF) on the clastogenic activity of Trenimon, cyclophosphamide, and bleomycin was tested on cultures of human peripheral lymphocytes with and without the addition of rat liver S9 mix. In addition, the influence of both anticlastogens on the SCE-inducing activity of Trenimon and cyclophosphamide was examined under the same conditions. In the absence of S9 mix both substances displayed the known anticlastogenic action when TR was the standard clastogen but acted coclastogenically in the experiments with BM. Under the influence of rat-liver S9 mix this action on TR-induced chromosome damage was decreased and only a slight anticlastogenic effect was observed in the experiments with activated cyclophosphamide. S9-activated BM lost some of its strong chromosome-damaging effect and AET proved clearly anticlastogenic under these test conditions. AET displayed a slight decreasing effect on SCE induced by TR, but had no effect on CP-induced SCE. No anti-SCE effect at all was found in the experiments with NaF. Detailed analyses revealed different actions of both anticlastogens on the different types of structural chromosome damage.

Animals↗
PubMed2005

Anatomic Endodontic Technology (AET)--a crown-down root canal preparation technique: basic concepts, operative procedure and instruments.

AIM: To illustrate the conceptual basis and the operative procedure of the Anatomic Endodontic Technology (AET) technique and to illustrate the specific instruments used in each phase. SUMMARY: The basic characteristics of the AET technique are reported. The instruments and procedure are described in three phases: coronal access, coronal-middle preparation and apical preparation. In the first phase, correct cavity design is described. In the coronal-middle phase, the use of four stainless steel shaping instruments, powered by a reciprocating handpiece is described, incorporating a brushing-milling action against canal walls. During the apical phase, dedicated apical stainless steel and NiTi hand instruments are used to complete the preparation. The stainless steel apical files are used with a 1/4 turn and withdrawal movement whilst the NiTi are used in 360 degrees rotary motion. KEY LEARNING POINTS: Most current canal shaping techniques do not prepare all the canal walls and can result in over-enlargement in some areas. AET defines three regions of the canal: coronal (from the cavo-surface of the access cavity), coronal-middle, and apical. Coronal-middle instrumentation is undertaken with four mechanically driven stainless steel shaping instrument used in brushing-milling action against canal walls. Apical preparation is completed by hand and with the formation of a stop.

Dental Alloys↗
PubMed1990

Atypical endocrine granules in atypical endocrine tumor (AET) of the lung. An immunoelectron microscopic study.

Highly dense granules are a hallmark for recognizing atypical endocrine tumor (AET) of the lung. We report a case of AET with many atypical neurosecretory-type granules: moderately dense granules (mean size 373.7 nm) and "target" granules with a central dense core (425.1 nm), both apparently larger than the highly dense granules (223.3 nm). Immunoelectron microscopical studies demonstrated that all three types of granule were positive for gastrin-releasing peptide (GRP), human chorionic gonadotropin alpha-subunit (hCG alpha), calcitonin or serotonin. Although the size profiles of positive granules were similar for calcitonin and hCG alpha, they were different from those of GRP or serotonin granules. The presence of atypical granules and the different size profiles of hormonal products in AET indicate that caution is required in ultrastructural evaluation of granules in lung carcinomas.

Adenocarcinoma↗
PubMed1975

Radioprotection of whole-body gamma irradiation induced alterations in lipid metabolism of liver and plasma by AET (S-2, aminoethyl isothiuronium Br. H. Br.) and serotonin in rats.

Radioprotective effect of AET, serotonin and their mixture has been studied on liver and plasma lipid metabolism 24 hrs and 48 hrs after irradiation in fasted male rats. AET and serotonin both gave significant radioprotection to certain liver and plasma lipid components, but the mixture of the two afforded a better protection. The non-radioprotection of plasma NEFA, phospholipids and phosphatidyl choline levels by serotonin observed in irradiated rats was because serotonin itself raised the levels of these lipids in control rats. Serotonin alone or in mixture effectively protected the radiation-induced increased incorporation of NaH2(32)PO4 into liver phospholipids. Mixture of AET and serotonin failed to protect the increased incorporation of aceae-1-14-C into liver total fatty acids and cholesterol, but it prevented this increased incorporation into liver triglycerides and phospholipids.

Acetates↗
PubMed1991

Acid phosphatase and arylsulphatase activities in testes after AET or MEA treatment of adult mice.

Temporal changes of acid phosphatase (E.C. 3.1.3.2) and arylsulphatase (E.C. 3.1.6.1) activities in testes of adult Swiss mice after AET (2-amino-ethylisothiouronium Br. HBr) or MEA (cysteamine HCl) treatment, were studied. The animals were injected intraperitoneally with the S-containing substances in a single dose of 400 mg/kg body weight. The enzyme activities in crude organ homogenates were assessed every four hours during a 24-hour period. Administration of the aminothiol agents to mouse organism caused greater changes in the acid phosphatase activity than in the arylsulphatase activity, and the two chemical compounds AET and MEA given, influenced the enzyme activities in testes in a different way. Treatment of mice with AET resulted in a decrease of the acid phosphatase activity related to 1 g of fresh tissue at 16.00 and the whole organ weight at 24.00 and 16.00 as well as in a decrease of the arylsulphatase activity expressed per the whole weight of testes at 08.00. After MEA injection, the acid phosphatase activity related to 1 mg of protein, 1 g of fresh tissue and the whole organ weight was decreased at 20.00(1), and the enzyme activity expresse per 1 mg of protein and 1 g of fresh tissue was increased at 24.00, but the arylsulphatase activity related to both 1 mg of protein at 08.00, 12.00 and to the whole weight of testes at 08.00, was reduced.

Acid Phosphatase↗
PubMed1990

Temporary changes of arylsulphatase activity in liver after exposure of AET or MEA pre-treated mice to 60Co gamma-irradiation.

The adult male Swiss mice were either whole-body 60Co gamma-irradiated with a single dose of 10 Gy at 1900, or treated intraperitoneally with AET (2-aminoethylisothiouronium bromide hydrobromide) or MEA (cysteamine hydrochloride), in a dose of 400 mg/kg body weight, 15 minutes before irradiation. The measurements of the arylsulphatase (E.C. 3.1.6.1) activity in crude homogenate of liver were done every four hours during 24-hour period, starting at 2000. The enzyme activity towards the artificial substrate p-nitrocatechol sulphate was related to 1 mg of protein, 1 g of fresh tissue and to the whole organ weight. No fluctuations in the activity of arylsulphatase in the control mice were found. There were temporary changes in the enzyme activity expressed in nkat per 1 mg of protein and 1 g of fresh tissue in the irradiated only males, in that related to 1 g of fresh tissue and the whole organ weight in mice injected with AET before irradiation, as well as that calculated in nkat per 1 mg of protein in animals pre-treated with MEA to exposure of gamma rays. Between the particular groups of males, differences in the arylsulphatase activity related to 1 g of fresh tissue and the whole liver weight at 0400 were only observed. 60Co gamma-irradiation influenced the activity of arylsulphatase in liver. AET and MEA modified the effect of exposure of mice to gamma rays on the enzyme activity in a different way.

Animals↗
PubMed1985

Effects of AET, MEA, or 5-HT treatment before X-irradiation of pregnant C57BL mice.

C57BL++ mice were either whole body X-irradiated with a dose of 200 R or, 15 minutes before X-irradiation injected with AET, MEA, or 5-HT, in a dose of 40 mg/kg of body weight, on the first day of gestation. Uterine contents were examined on the nineteenth day of pregnancy. The number of corpora lutea was assumed as 100% and the percentage values of live and dead foetuses, resorptions, and non-implanted embryos were calculated. The percentage ratio of females with live foetuses in the uterus, in relation to the total number of those with a vaginal plug was also determined. X-irradiation of pregnant mice influenced the embryonic survival. As compared with controls, in only X-irradiated mice a lower percentage value of live foetuses and higher percentage values of non-implanted embryos and resorptions were found. One dead foetus was only observed in X-irradiated females. Percentage value of X-irradiated females with live foetuses was lower than that of control ones. High mortality of embryos occurred more often before than after the implantation of blastocysts. The percentage value of non-implanted embryos was higher than that of resorptions. AET, MEA, and 5-HT when injected to mice before their X-irradiation acted as radioprotectors. The strongest radioprotective effect was obtained following AET administration, intermediate after 5-HT treatment and the weakest one when MEA was injected.

Animals↗
PubMedDate not supplied

[Determination of the optimal proportions as regards toxicity of AET, ATP and serotonin used in combination].

In experiments on mice, a study was made of the quantitative dependence of toxicity of AET, ATP and serotonin applied in combinations. The toxicity decreased when ATP was combined with AET and increased when ATP of AET were combined with serotonin. The toxicity of a combination of all three substances was reduced by introducing high doses of ATP.

Adenosine Diphosphate↗
PubMed1985

Effects of AET and MEA treatment of mice on the first day of pregnancy.

Porton female mice were injected intraperitoneally with 2-aminoethylisothiouronium bromide hydrobromide (AET) or cysteamine hydrochloride (MEA) in a dose of 40 mg/kg of body weight on the first day of pregnancy. On the last, nineteenth, day of gestation, taking into consideration females in whose uterus live fetuses were observed, the increase in their body weight throughout pregnancy, the number of fetuses in the uterus, the body weight of fetuses, and placental weight were found smaller in mice treated with AET or MEA, than in control ones. Among the injected compounds, AET appeared to be less toxic than MEA.

Animals↗
PubMed1983

The E-rosette test: variations in results using E from different sheep. Effect of FCS and of AET treatment.

Sheep erythrocyte (E) rosette tests were performed with E from 3 different sheep. The E rosette test for "active" T lymphocytes was performed with untreated E. E tests for the quantitation of the total number of T lymphocytes were performed with untreated as well as AET-treated E, in assays with and without fetal calf serum (FCS). Lymphocytes from patients with active and stable multiple sclerosis (MS) and with infectious mononucleosis (IM) as well as from healthy individuals were examined. The "total" E test performed with untreated E from one sheep and lymphocytes from patients with active MS gave lower percentages of rosette-forming cells (RFC) than when E from the other two sheep were used. FCS in the medium, or AET treatment of E partly but not wholly abrogated this difference. The origin of the E is thus of importance for the results of the rosette tests in patients with active MS, even if FCS or AET treatment is used.

Animals↗
PubMed1996

Radioprotective efficacy of HT + AET in encapsulated form.

Entrapment of 5-hydroxyl-L-tryptophan (HT) in erythrocyte ghost prepared by hypotonic method and high voltage electric discharge method are nearly same. Release of HT with beta-aminoethylisothiuronium bromide hydrobromide (HT + AET) in in vitro system is rapid but only a portion of the entrapped amount is released. Release of HT + AET in serum marginally increases at 2 hr. Compared to release in in vitro medium the release in serum is less. Survival studies with Swiss albino mice indicates that compared to HT alone, the combination of HT + AET shows about 9 times percentage survival. The same combination in the encapsulated form show comparable percentage survival though the amount needed is 1/200th times compared to free form.

Animals↗
PubMed1992

Effects of STS-557 and 20 Aet-1 on sperm functions and serum level of testosterone in bonnet monkey (Macaca radiata).

Treatment of adult male bonnet monkeys with STS-557 (17 alpha-cyanomethyl 17 beta-hydroxy estra-4, 9(10)-dien-3-one; 12 mg/monkey daily for 15 weeks; i.m.) reduced the sperm count from the 9th week, leading close to azoospermia on the 2nd post-treatment week which persisted until the 10th post-treatment week and normalcy was restored on the 13th post-treatment week. The sperm motility was reduced from the 9th week of treatment to 8th post-treatment week. The fertilizing ability of spermatozoa (formation of swollen sperm head or pronuclei in zona-free hamster eggs) was abolished from the 8th week of treatment to the 7th post-treatment week. The serum level of testosterone was reduced from the 2nd to 12th week of treatment (data on subsequent weeks were not collected). When 20 Aet-1 (testosterone-trans-4-n butyl cyclohexyl carboxylate; 40 mg/monkey, single; i.m.) was administered on the first day of STS-557 treatment, the sperm count was reduced from the 10th week, with near azoospermia ensuing on the 13th week which continued until the 8th post-treatment week; recovery was observed on the 12th post-treatment week. The motility was low from the 8th week of treatment to 6th week after withdrawal of treatment. The fertilizing ability of spermatozoa was abolished from the 8th week to the 12th week of treatment (data on last week of treatment were not collected). The serum level of testosterone was maintained within normal range except on the 2nd, 6th and 12th week of treatment. 20 Aet-1 alone had no significant effect on these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗