Decreased Essential Antioxidants and Increased Lipid Hydroperoxides Following High-Dose Radiochemotherapy

The blood from 19 patients having bone marrow transplantation was examined for the essential antiox-idants alpha-tocopherol and beta-carotene as well as lipid hydroperoxides before, at and after bone marrow transplantation (BMT). Conditioning therapy, preceding BMT in order to achieve marrow ablation and immunosuppression, consists of high-dose chemotherapy which is mostly combined with total body irradiation (TBI). In order to see a possible difference between patients with and without additional TBI, we divided the patients up into two groups; patients receiving TBI (RT⁺) and patients without TBI (RT-). All patients required total parenteral nutrition beginning one week prior to BMT.

After conditioning therapy plasma levels of absolute and lipid-standardized alpha-tocopherol and beta-carotene decreased in both groups, presumably as a result of an enhanced breakdown of these antioxidants. The loss of these lipid-soluble antioxidants has to be considered as a possible cause for early post-transplant toxicity. Lipid hydroperoxides increase significantly in the group of patients with additional TBI, whereas the other group, receiving no additional TBI, showed no significant change.

We suggest high-dose supplementation of essential antioxidants for patients undergoing BMT.     

Influence of allogeneic bone marrow transplantation on the endocrine system in children

With increasing survival rates of children grafted for different malignancies concerns about the longterm side effects of this treatment are growing. Therefore, investigations on the function of endocrine systems were conducted in a total 28 patients grafted for various reasons: ALL (N = 18), AML (N = 1), SAA (N = 3), CML(N = 4), neuroblastoma (N = 2). The results can be summarized as follows: 1. The extent of hormonal derangements is primarily dependent on the extent of irradiation prior to BMT. Integrity of hormonal systems was found in cases without irradiation (SAA) or if TBI did not exceed 3 Gy. 2. Primary hypogonadism was present in 18 patients. 3. Primary hypothyroidism was present in 2 patients. 4. Growth impairment was observed in 8 patients. In four of these cases growth hormone deficiency was the cause. In four other cases with graft-versus-host-disease and hepatic involvement SmC/IGF I levels were severely diminished. The data suggest that in most cases BMT itself has relatively few negative effects on the endocrine regulatory system. However, more detailed investigations before and after BMT will be needed to further validate these observations.     

Acute and late effects in the course of and after total body irradiation with following bone marrow transplantation in patients with different forms of leukaemia

The acute reaction in the course of a total body irradiation (TBI) appears in an organ-specific damage of the stem cells. Moreover, there are unspecified central-nervous stress reactions. Clinical reactions are obtained by the study and symptomatic therapy is proposed. 90 patients with different forms of leukaemia were observed. We documented the course in a specific "protocol system". Reactions like an increase of body temperature, changes of pulse and blood pressure were registered. The occurrence of gastro-intestinal reactions is a typical symptom of the acute radiation syndrome e.g. vomiting and diarrhoea are demonstrated in dependence of the applicated dose of irradiation. Further symptoms of TBI appeared in the later period. Mucositis, parotitis, a decreased function of the salivary glands and diarrhoea as well as vomiting are characterized by different intensity and temporary termination. A difference between allogeneic and autologous transplantation is caused by a medicamental additional treatment. During the late period these symptoms will disappear completely. Moreover, after TBI and BMT late effects are a cataract and some changes in the hormonal system demanding a specific correction or substitution respectively.     

Growth and growth hormone in children after bone marrow transplantation

Growth and growth hormone (GH) were investigated every year in 24 children after allogeneic bone marrow transplantation (BMT) for severe aplastic anemia (SAA) or leukemia. Conditioning included total body irradiation (TBI) in all cases of leukemia. The young leukemic children grew poorly. At 4 years after BMT, the mean standard deviation score for attained height had decreased from 0 to -1.73. GH deficiency was diagnosed with provocation tests. Three years after BMT, 10/18 children had a subnormal response. Ten children were further investigated with 24-hour GH profiles. Children with SAA had normal growth and GH levels. TBI seemed to be the major factor responsible for impaired growth.     

The antioxidant status of patients subjected to total body irradiation.

BACKGROUND AND PURPOSE: Total body irradiation (TBI) is a routine preconditioning procedure for the treatment of leukemia and aplastic anemia, prior to bone marrow transplantation (BMT). Ionizing radiation generates reactive oxygen derived species (ROS) that can be removed by antioxidants. Our purpose is to determine the antioxidant status of patients undergoing TBI by evaluating the oxidant stress and their antioxidant capacity. MATERIAL AND METHODS: We evaluated by cyclic voltammetry (CV) the total antioxidant capacity (TAC) in plasma of 14 patients undergoing TBI prior to BMT. The levels of the antioxidants, ascorbic acid (AA) and uric acid (UA) were determined by HPLC-ECD. The oxidant stress level was calculated by the ratio [dehydro ascorbic acid]/total ascorbic acid]. RESULTS: TAC was reduced by 36% (p < 0.02) but after 4 months recovered to a level 22% higher than before the treatment (p < 0.05). Both, AA and UA, decreased following irradiation by 84% (p < 0.02) and 24% (p < 0.05) respectively, but returned to a level of 21% and 320% after 4 months compared to baseline values. The changes in [UA] were affected by Allopurinol (xanthine oxidase inhibitor), given as a routine pretransplant therapy until day -1. The [dehydroascorcbic acid]/[total ascorbic acid] (%) was 45% (range of normal controls = 13.2 +/- 1.5%) and increased by 69% following TBI. In order to obtain a decrease in the TAC of plasma in vitro, comparable to that in vivo, a 1000 fold higher dose of irradiation was required. CONCLUSIONS: TBI caused a pronounced decrease in antioxidant capacity and an excessive increase in oxidant stress. We assume that TBI alters antioxidant homeostasis greatly enhancing the stress damage. CV measurements may lead to a better understanding of the balance between oxidant stress and antioxidant utilization, and to a reconsideration of the routine use of Allopurinol as pretreatment for TBI, and antioxidant support before and/or after TBI.     

Human osteoblasts exhibit sexual dimorphism in their response to estrogen on microstructured titanium surfaces

Disruption of axonal transport plays a pivotal role in diabetic neuropathy. A sex-dimorphism exists in the incidence and symptomatology of diabetic neuropathy; however, no studies so far have addressed sex differences in axonal motor proteins expression in early diabetes as well as the possible involvement of neuroactive steroids. Interestingly, recent data point to a role for mitochondria in the sexual dimorphism of neurodegenerative diseases. Mitochondria have a fundamental role in axonal transport by producing the motors’ energy source, ATP. Moreover, neuroactive steroids can also regulate mitochondrial function. Here, we investigated the impact of short-term diabetes in the peripheral nervous system of male and female rats on key motor proteins important for axonal transport, mitochondrial function, and neuroactive steroids levels. We show that short-term diabetes alters mRNA levels and axoplasm protein contents of kinesin family member KIF1A, KIF5B, KIF5A and Myosin Va in male but not in female rats. Similarly, the expression of peroxisome proliferator-activated receptor γ co-activator-1α, a subunit of the respiratory chain complex IV, ATP levels and the key regulators of mitochondrial dynamics were affected in males but not in females. Concomitant analysis of neuroactive steroid levels in sciatic nerve showed an alteration of testosterone, dihydrotestosterone, and allopregnanolone in diabetic males, whereas no changes were observed in female rats. These findings suggest that sex-specific decrease in neuroactive steroid levels in male diabetic animals may cause an alteration in their mitochondrial function that in turn might impact in axonal transport, contributing to the sex difference observed in diabetic neuropathy.     

Breath ethane generation during clinical total body irradiation as a marker of oxygen-free-radical-mediated lipid peroxidation: A case study

Total body irradiation (TBI) is used therapeutically for treatment of leukemias and other malignancies of the hemopoietic system. Ionizing radiation produces oxygen free radicals that contribute to cytotoxicity. Breath collected from one patient undergoing therapeutic TBI showed measurable changes in levels of ethane during treatment. Breath ethane is a marker of lipid peroxidation of n-3 fatty acids. The TBI treatment involved 4 days of irradiation. The largest changes in breath ethane occured on Day 2. The increased levels of breath ethane on Day 2 were correlated to clinical manifestations of toxicity. The correlation of the onset of gastrointestinal side effects with higher levels of breath ethane suggests that breath ethane may be a clinically useful measure of the toxicity of various TBI fractionation treatment protocols currently in use at different medical centers. The levels of breath ehtane on the other days of treatment were lower, suggesting that the oxidative-antioxidative balance of the patient may be important in protection against free radical mediated injury. These results for a single patient suggest that breath ethane may be a promising approach to elucidate the role of antioxidants in clinical TBI and should be extended for verification to a larger volunteer patient population.     

Male orangutan subadulthood: a new twist on the relationship between chronic stress and developmental arrest

Both in the wild and in captivity, a marked and enduring arrest of secondary sexual developmental occurs in some male orangutans (Pongo pygmaeus) (Kingsley [1982] The Orang-Utan: Its Biology and Conservation, The Hague: Junk; Utami [2000]). Researchers have hypothesized that chronic stress, perhaps related to aggression from mature males, causes endocrine changes altering growth and maturation rates in these males (Maple [1980] Orangutan Behavior, New York: Van Nostrand Reinhold; Graham [1988] Orangutan Biology, Oxford: Oxford University Press). In this study, urine samples were collected over a 3-year period from 23 captive male orangutans to test the hypothesis that developmentally arrested male orangutans have an endocrine profile consistent with chronic stress. Three study males were juveniles, seven were arrested adolescents, six were developing adolescents, and seven were mature adults. Morning samples were analyzed by radioimmunoassay for levels of the stress hormones cortisol and prolactin, and group hormone profiles were compared by analysis of variance. Results indicate that developing adolescent male orangutans have a significantly higher stress hormone profile than juvenile, developmentally arrested adolescent, or adult males. These results imply that the arrest of secondary sexual development in some male orangutans is not stress-induced, but instead perhaps an adaptation for stress avoidance during the adolescent or "subadult" period. These data, together with previously reported data on levels of gonadotropins, testicular steroids, and growth-related hormones, define endocrine profiles associated with alternative reproductive strategies for males with and males without secondary sexual features (Maggioncalda et al. [1999], [2000].     

Pneumocystis carinii infection sensitizes lung to radiation-induced injury after syngeneic marrow transplantation: role of CD4+ T cells

A murine model of bone marrow transplant (BMT)-related lung injury was developed to study how infection sensitizes lung to the damaging effects of total body irradiation (TBI) at infectious and TBI doses that individually do not cause injury. Mice infected with Pneumocystis carinii exhibited an asymptomatic, rapid, and transient influx of eosinophils and T cells in bronchoalveolar lavage fluid (BALF). In contrast, mice infected with P. carinii 7 days before receiving TBI and syngeneic BMT (P. carinii/TBI mice) exhibited severe pulmonary dysfunction, surfactant aggregate depletion, and surfactant activity reductions at 17 days post-BMT. BALF from P. carinii/TBI mice contained a disproportionate initial influx of CD4(+) T cells (CD4(+):CD8(+) ratio of 2.7) that correlated with progressive lung injury (from 8 to 17 days post-BMT). Levels of TNF-alpha in BALF were significantly increased in P. carinii/TBI mice compared with mice given either insult alone, with peak values found at 11 days post-BMT. In vivo depletion of CD4(+) T cells in P. carinii/TBI mice abrogated pulmonary dysfunction and reduced TNF-alpha levels in BALF, whereas depletion of CD8(+) T cells did not affect lung compliance or TNF-alpha. Lung injury was not attributable to direct P. carinii damage, since CD4-depleted P. carinii/TBI mice that exhibited no injury had higher average lung P. carinii burdens than either mice given P. carinii alone or undepleted P. carinii/TBI mice. Together, these results indicate that P. carinii infection can sensitize the lung to subsequent TBI-mediated lung injury via a process dependent on non-alloreactive CD4(+) T cells.     

Allogeneic bone marrow transplantation for hepatocellular carcinoma: hepatocyte growth factor suppresses graft-vs.-host disease

Allogeneic bone-marrow transplantation (BMT) can induce a powerful graft-vs.-tumor (GVT) effect not only on hematological malignancies but also on solid tumors. However, graft-vs.-host disease (GVHD) is a major complication of allogeneic BMT. We assessed GVT effect on hepatocellular carcinoma (HCC) and the effects of hepatocyte growth factor (HGF) gene transduction on GVHD in HCC transplanted mice. (C57BL/6 x C3H/HeJ)F(1)(B6C3F1, H-2(bxk)) mice were used as recipients and C3H/HeJ(H-2(k)) mice were used as donors. Hepa1-a (a C57L mouse-derived hepatoma cell, H-2(b)) was subcutaneously injected into the recipient mice. Tumor bearing mice were treated in the following ways: group 1, no treatment; group 2, total body irradiation (TBI); group 3, TBI and BMT; group 4, TBI and BMT with empty vector; group 5, TBI and BMT with HGF gene transduction; group 6, TBI and BMT with administration of FK506, a representative immunosuppressive agent. Acute GVHD was assessed by histological examination of the liver, small intestines, and large intestines. Tumor growth was markedly suppressed in mice that received an allogeneic BMT. Donor-derived CD8(+) T cells had infiltrated into the tumor, and cytotoxic CD8(+) T cells against HCC were present. However, among the four groups that received a BMT, this suppressive effect was weaker in group 6 compared with the other three groups (groups 3, 4, and 5). HGF gene transduction improved GVHD while preserving the GVT effects. Allogeneic BMT markedly suppresses the growth of HCC. Simultaneous HGF gene transfer can suppress GVHD while preserving the GVT effect.     

Prenatal diagnosis in a familial form of male pseudohermaphroditism due to 17-keto reductase deficiency

In an infant considered at birth as a female but with easily palpable gonads in the labia major, the XY karyotype and the endocrine studies (determination of plasma levels of steroid hormones under basal conditions and during hCG stimulation) were consistent with the diagnosis of male pseudohermaphroditism due to 17-keto reductase deficiency. During the second pregnancy an amniocentesis revealed a 46 XY karyotype. Endocrine studies performed on the amniotic fluid at midgestation suggested that the fetus was affected by the same enzyme defect. After birth, the diagnosis was demonstrated with anatomical an endocrine studies.     

Faecal sexual steroids in sex typing and endocrine status of great bustards

Faecal sexual steroids have been used in field studies evaluating the relationships between gender and the multiple factors influencing endocrine status of individuals. The determination of faecal steroids has been also proposed as an alternative, non-invasive sexing method when other methods were deemed impractical or risky for the health of birds. In this study, we quantified sexual steroid hormones in faeces of the great bustard (Otis tarda), a large and sexually dimorphic polyginic bird species that it is threatened and subjected to intense wildlife management. We evaluated differences between captivity and wild conditions, flocks and sexes, and used faecal steroids to develop sex determination procedures. We found similar steroid levels in captive and wild bustards, no differences between unisexual wild flocks and clear between-sexes differences in testosterone but not estradiol. Faecal steroids accurately discriminated gender in both captive and wild known-sex great bustards. Total testosterone concentration was always higher than estradiol concentration in faecal samples from males, but estradiol was not always higher than testosterone in females. Faecal steroids failed to reveal the presence of young males in female flocks during winter, despite faecal testosterone levels increased with age in a small sample of captive males. Our results show that faecal steroid measurement for both sexing and characterizing the endocrine status of great bustards is feasible, and therefore it should be valuable in wildlife management, especially in combination with additional information obtained from faeces as diet.     

Sexual behaviour and LH secretion in spayed androgenized ewes after a s?ngle injection of testosterone or oestradiol-17beta

The behavioural and endocrine responses to single injections of 50 or 500 microgram oestradiol-17beta or 5 mg testosterone were recorded in spayed (control) ewes and in spayed ewes exposed to testosterone between Days 30 and 80 or Days 50 and 100 of prenatal life, The control ewes showed oestrus after injections on 17/18 occasions. The androgenized ewes showed poorer oestrous responses to each hormone although rams showed interest in the ewes. Masculine sexual and aggressive behaviour was shown by the androgenized ewes given either steroid. Both steroids caused a reduction in the plasma LH levels of all the ewes (negative feedback), followed by a preovulatory-type surge (positive feedback). The peak LH values were significantly lower (P is less than 0.05) in the Day 50-100 androgenized ewes than in the controls. It is concluded that prenatal androgenization causes a qualitative shift in the sexual behaviour of ewes from the female type to the male type and affects the sensitivity of the brain to "positive feedback" by steroids.     

Different onsets of oxidative damage to DNA and lipids in bone marrow and liver in rats given total body irradiation.

We examined time-dependent changes in antioxidant vitamins and oxidative damage to DNA and lipids in the bone marrow, liver, and plasma of rats given total body irradiation (TBI) with X-rays at 3 Gy. The oxidative damage to DNA and lipids was evaluated by measuring increases of 8-hydroxydeoxyguanosine (8OHdG) in DNA and 4-hydroxy-2-nonenal (HNE), respectively. After the TBI, marked increases in 8OHdG and HNE were detected at 3 to 5 h in the bone marrow, while gradual increases in these parameters were detected after a few days in the liver. These changes in 8OHdG and HNE were well correlated within each tissue. In the bone marrow, levels of both vitamin C and vitamin E were decreased by the TBI; however, the changes in vitamin C were earlier and greater than those in vitamin E. In the liver, the level of vitamin C did not decrease, but that of vitamin E decreased due to the TBI. Changes in HNE, vitamin C, and vitamin E in the plasma were similar to those in the liver. Within each tissue, the time of decrease in antioxidants was almost the same as that of the increase in oxidative damage. An increase in total iron due to the TBI was also detected in these tissues. In particular, the total iron in the bone marrow was markedly increased at a few hours after the TBI, with a slight increase in transferrin and no increase in ferritin. Exposure studies performed on cells or isolated DNA showed that an increase in 8OHdG was detected immediately after irradiation at more than 100 Gy in bone marrow cells and at less than 10 Gy in isolated DNA, suggesting that an increase in 8OHdG is undetectable even in bone marrow immediately after the TBI at 3 Gy. These results indicate that the onset of oxidative damage to DNA and lipids was delayed after TBI at 3 Gy, that it was quite different in the bone marrow and the liver, and that an increase in iron and decrease in antioxidant vitamins were involved in the mechanism of oxidative damage.     

Parental Investment and Territorial/Sexual Behavior in Male and Female Reed Warblers: Are they Mutually Exclusive?

The behavioral and endocrine changes from prenesting to feeding phases of reproduction were examined in free-living reed warblers. Apart from the onset of feeding behavior, these changes in males are particularly evident in song, territorial behavior and circulating levels of testosterone. The interactions between an individual's physiology and behavior during these behavioral transitions were tested first by correlating song and feeding rates with circulating levels of testosterone and secondly by implanting feeding males with steroids and documenting the resulting effects on song, territoriality and parental behavior. The physiological mechanisms associated with the transition from the sexual phase (nest-building and egg-laying) to the parental (incubation and feeding) in females were also examined. In this case, estrogens were implanted during the parental phase to enhance sexual behavior. The results demonstrate an antagonistic relationship between sexual/territorial behavior and parental care in males which is mediated by changes in circulating androgens and no such antagonism in females. The effects of parental manipulation on the feeding rates of the partners and the growth rates of offspring have been examined to shed light on the necessity for male parental input.     

Reproductive hormone profiles in captive male orangutans: Implications for understanding developmental arrest

For many years researchers have described some male orangutans as “subadult.” These males are of adolescent to adult age and are reproductive, but have little to no secondary sexual trait development. Until now the only endocrine study of this arrest of secondary sexual trait development was performed by Kingsley (1982, 1988). She found that “subadult” or arrested males have lower testosterone levels than similar age developing adolescents or adult males. In this study, urine samples were collected over a two-year period from 23 captive male orangutans in order to more fully define male endocrine profiles. Three study males were juveniles, seven were arrested adolescents, six were developing adolescents, and seven were mature adults. Morning samples were analyzed by radioimmunoassay for levels of testicular steroids and gonadotropins and group hormone profiles were compared by analysis of variance. Results illustrate that arrested adolescent orangutans have significantly lower testosterone and dihydrotestosterone (DHT) levels than developing adolescents, but significantly higher levels than juveniles. Luteinizing hormone (LH) levels also differed between arrested and developing adolescents, with arrested males having lower levels. However, follicle stimulating hormone (FSH) levels were similar in both morphs of adolescent male. The overall hormone profiles for arrested and developing adolescent male orangutans suggest that arrested males lack levels of LH, testosterone, and DHT necessary for development of secondary sexual traits. However, they have sufficient testicular steroids, LH, and FSH to fully develop primary sexual function and fertility. These endocrine data help define alternative developmental pathways in male orangutans. The authors discuss the relationship between these developmental pathways and male orangutan reproductive strategies, and hypothesize about their prepubertal socioendocrine determination. Am J Phys Anthropol 109:19–32, 1999. © 1999 Wiley-Liss, Inc.     

重组人血小板生成素早期干预救治重症急性放射病猴的实验研究

重组人血小板生成素（rhTPO）是一种能促进巨核系祖细胞增殖、分化生成血小板的造血因子,研究表明它能促进射线照射小鼠造血功能恢复,前期工作证明rhTPO早期干预可显著提高致死剂量照射小鼠的活存率.本文以7.0Gy照射恒河猴为重度骨髓型急性放射病（ARS）模型,研究了rhTPO早期干预对重症ARS的治疗作用,并与WR2721和＂500＂的辐射防护作用进行了比较,结果发现rhTPO早期干预可明显促进ARS猴造血功能恢复,改善ARS猴症状,简化对症治疗措施,提高重度骨髓型ARS猴活存率,其对重度骨髓型ARS的防治作用优于现有的辐射防护药WR2721和＂500＂,有望开发成安全有效的新型辐射防治药物.     

Clinical and endocrine spectrum in patients with the 45,X/46,XY karyotype

Summary Cytogenetic and endocrine studies were performed in five unrelated 45,X/46,XY individuals in an attempt to correlate them with their clinical expression and gonadal morphology. A lack of a consistent pattern between cytogenetic findings and phenotype was observed.Endocrine studies revealed a wide spectrum of hypothalamic, pituitary, and gonadal hormone production as assessed by the base line levels of LH, FSH, T, and ⁴-A and their responses to appropriate exogenous stimulation (LH-RH and HCG). An adequate correlation between endocrine findings with gonadal morphology and phenotype could be established; thus demonstrating that patients with this particular chromosome complement have a functional integrity of the gonadotropin hypothalamic pituitary activity modulated accordingly with the gonadal function of each particular case.     

L-arginine mitigates radiation-induced early changes in cardiac dysfunction: the role of inflammatory pathways

Our earlier studies demonstrated the ability of L-arginine (L-Arg) to reverse radiation-induced immune dysfunction. The aim of the present study was to investigate cardiac dysfunction up to 24 h after 2 Gy of total-body irradiation (TBI) and its mitigation by L-Arg. The current studies also explore the association of radiation-induced inflammation and electrocardiographic (ECG) abnormalities. TBI-induced cardiac iNOS and kinin B1 R, changes in the ECG profile like bradycardia, increased RR interval, ST elevation and increased QRS duration at 4 h and 24 h after TBI. TBI with 2 Gy induced inflammatory responses in spleen and cardiac tissue. L-Arg administered 2 h after TBI (TBI+L-Arg) mitigated the entire inflammatory response and ECG profile toward normalcy. L-Arg administered just before TBI (L-Arg +TBI) could not reverse the above-mentioned changes. Radiation-induced inflammatory responses at +4 h and +24 h after TBI in spleen and cardiac tissue correlated with the changes in ECG profile at the corresponding time. The results suggest the ability of L-Arg administered at the correct therapeutic window to mitigate radiation-induced cardiac dysfunction at 4 and 24 h after TBI.     

Modulation of short term and long term memory by steroid sexual hormones

Many studies have evidenced a functional interrelation between the nervous and endocrine systems in the modulation of mnemonic processes, and others have established the role played by certain hormones in these processes; however, few studies have dealt with the effects of sexual steroids on learning and memory. The aim of this work was to determine whether shortterm and long-term memory is subject to hormonal modulation. Male Wistar rats, randomly assigned to 13 groups, 1 control and 12 experimental groups, were trained on a one-trial passive avoidance conditioning. The control group received saline solution, and each of the 12 experimental groups received a treatment consisted in one of following pharmacological doses of: 5, 10, 20, 30 mg of testosterone enanthate, 0.2, 0.4, 0.8, 1.2 mg estradiol valeriate, or 1, 2, 4, 6 mg norandrostenolone decanoate, respectively. All substances were applied 45 min before the training session. Retention of the learned response was tested 10 min (short-term memory) and 24 h (longterm memory) after the training session. Results indicate that under these experimental conditions the short-term memory is facilitated with testosterone enanthate at doses of 20 and 30 mg, the estradiol valeriate at doses of 0.4 mg and the nor-androstenolone decanoate at doses of 4 mg, whereas the long-term memory is facilitated with testosterone enanthate at doses of 30 mg, estradiol valeriate at doses of 1.2 mg and the nor-androstenolone decanoate at doses of 4 mg. The other studied doses were no effective.