Microstructure and selected mechanical properties of aged Ti-15Zr-based alloys for biomedical applications.

In this study, Ti-15Zr-xMo (5, 10, 15, and 20 wt%) alloys were submitted to solution and aging treatments and their effects evaluated in terms of phase composition and selected mechanical properties (Vickers microhardness and Young's modulus) for use as biomedical implants. The solution treatment was performed at 1123 K for 2 h, while aging treatments were carried out at 698 K for 4, 8, and 12 h, followed by water quenching. Phase composition and microstructure were dependent of the heat treatments, with Ti-15Zr-5Mo (α +â€¯ß type) and Ti-15Zr-10Mo (metastable ß type) alloys exhibiting intense α phase precipitation. The α-phase precipitates were related to α″ → α and ß → α phase decompositions. The Ti-15Zr-10Mo alloy exhibited an intermediary isothermal ω-phase precipitation after aging for 4 h. Vickers microhardness and Young's modulus values changed gradually with the amount of α phase. Aged Ti-15Zr-15Mo and Ti-15Zr-20Mo alloys presented better combinations of hardness and Young's modulus than CP-Ti and Ti-64 ELI for biomedical applications.

Carbofuran degraded by iron-doped anatase: Weakening the cholinesterase inhibitory activity in the photoproducts mixture.

Carbofuran is a toxic carbamate pesticide, and its use has increased in recent years. While marketing information indicates stability in different chemical media, carbofuran exhibits relative photolability. The aim of this research was to decompose carbofuran and to identify the photoproducts achieved when two different doped titania photocatalysts were employed under UV irradiation. The iron-doped TiO2 materials were obtained (a) via a hydrothermal method and (b) by an ultrasound-assisted sol-gel method. The precursors were TiOSO4⋅xH2O and Fe3(NO3)·9H2O. X-ray studies confirmed that the anatase phase of the iron-doped TiO2 resulted from the two preparation methods. The photocatalytic performance of the prepared materials was monitored by LC/ESI-QTOF-MS, enabling the identification of photoproducts: oxo-carbamates, hydroxylated benzofuranes, a carboxamide, and one amine. By using the iron-doped TiO2 materials, 2,2-dimethyl-2,3-dihydrobenzofuran-3,7-diol was the most abundant photoproduct, and N,2,2-trimethyl-2,3-dihydrobenzofuran-7-amine was the only compound that had not been previously reported in the photolysis and photocatalysis of carbofuran. The product 3-hydroxy carbofuran, a cholinesterase inhibitor, was quantified and was found to be transformed into compounds that lack this inhibitive property.

Randomized controlled trial of the Valencia model of waking hypnosis plus CBT for pain, fatigue, and sleep management in patients with cancer and cancer survivors.

BACKGROUND: This study evaluated the efficacy of an intervention combining the Valencia model of waking hypnosis with cognitive-behavioral therapy (VMWH-CBT) in managing cancer-related pain, fatigue, and sleep problems in individuals with active cancer or who were post-treatment survivors. We hypothesized that four sessions of VMWH-CBT would result in greater improvement in participants' symptoms than four sessions of an education control intervention. Additionally, we examined the effects on several secondary outcome domains that are associated with increases in these symptoms (depression, pain interference, pain catastrophizing, and cancer treatment distress). METHODS: The study design was a randomized controlled crossover clinical trial comparing the VMWH-CBT intervention with education control. Participants (N = 44) received four sessions of both treatments, in a counterbalanced order (n = 22 per order condition). RESULTS: Participants were 89% female (N = 39) with mean age of 61 years (SD = 12.2). They reported significantly greater improvement after receiving the active treatment relative to the control condition in all the outcome measures. Treatment gains were maintained at 3-month follow-up. CONCLUSIONS: This study supports the beneficial effects of the VMWH-CBT intervention relative to a control condition and that treatment gains remain stable. VMWH-CBT-trained clinicians should be accessible for managing symptoms both during and after cancer treatment, though the findings need to be replicated in larger samples of cancer survivors.

Metamagnetism and weak ferromagnetism in nickel (II) oxalate crystals.

Microcrystals of orthorhombic nickel (II) oxalate dihydrate were synthesized through a precipitation reaction of aqueous solutions of nickel chloride and oxalic acid. Magnetic susceptibility exhibits a sharp peak at 3.3 K and a broad rounded maximum near 43 K. We associated the lower maximum with a metamagnetic transition that occurs when the magnetic field is about ≥3.5 T. The maximum at 43 K is typical of 1D antiferromagnets, whereas weak ferromagnetism behavior was observed in the range of 3.3­43 K.

Fractal patterns, cluster dynamics, and elastic properties of magnetorheological suspensions.

We study pattern formation and the aggregation processes in magnetorheological suspensions in the presence of a static magnetic field, and some of their associated physical properties. In particular, we analyze the elastic modes as a function of the intensity of the applied field and for several particle concentrations. We observe that the clusters formed in these systems have multifractal characteristics, which are the result of three well defined stages of the aggregation process. In these stages three generations of clusters are produced sequentially. The structure of the suspension can be well characterized by its mass fractal dimensions and the mass radial distribution. The size distribution of the second-generation clusters written in terms of their mass fractal dimension allows us to calculate the sound speed of the longitudinal modes in the large wavelength regime. This multifractal analysis applied to several kinds of aggregates reveals that the occurrence of at least three stages of aggregation is a common feature to several physical aggregation processes.

Changes in the pattern of bile acids in the nuclei of rat liver cells during hepatocarcinogenesis.

Bile acids reach the nuclei of hepatocytes, where they may play an important role in controlling gene expression by binding to nuclear receptors. In previous studies, changes in the amounts of the different molecular species of bile acids in the hepatocyte nucleus during rat liver regeneration have been reported. The aim of the present work was to investigate whether this also occurs during rat hepatocarcinogenesis. Liver cell nuclei were isolated after homogenization of livers from healthy adult rats (controls) and from rats at different time points during chemically induced hepatocarcinogenesis, corresponding to the stages of foci (12 weeks), hepatoma (20 weeks) and carcinoma (32 weeks). Bile samples from the cannulated common bile duct were collected for 1h from different sets of animals undergoing hepatocarcinogenesis. Bile acids in bile, liver homogenates and isolated nuclei were measured by GC-MS. Because the yield of nuclei isolated changed during the course of hepatocarcinogenesis (control, 20.1%; 12 weeks, 23.6%; 20 weeks, 7.8%; 32 weeks, 5.1%), amounts of bile acids in nuclei were corrected for the amount of DNA in each preparation. During hepatocarcinogenesis, bile acid concentrations in liver homogenates were reduced to approximately half the values obtained in control livers, while the levels of bile acids in both isolated nuclei and bile were not decreased. Hepatocarcinogenesis induced changes in the composition of bile acid pools. These were manifest as an increase in the proportion of cholic acid and a decrease in that of ursodeoxycholic acid in both bile and liver. These modifications differed from the changes seen in the nuclear bile acid pool, where a decrease in the proportion of cholic acid together with an increase in that of ursodeoxycholic acid were the major changes observed during hepatocarcinogenesis. With regard to the 'flat' bile acids (allo-cholic acid plus Delta(5)- or Delta(4)-unsaturated bile acids), a marked hepatocarcinogenesis-induced increase in the output of these species in bile was found. However, these bile acids were only found in liver homogenates at the hepatoma stage, whereas they were not detected in isolated nuclei at any stage of hepatocarcinogenesis. In summary, these results support the existence of a bile acid pool in hepatocyte nuclei whose composition differs from that of the extranuclear bile acid pool. Moreover, they indicate that, during hepatocarcinogenesis, the composition of the nuclear pool undergoes important alterations.

[Assessment of a preconception preventive program in a community]. / Evaluación de un programa preventivo pregestacional en una comunidad.

Primary Health Care (PHC) is the basic health support that includes health promotion and disease prevention, considering social and developmental factors. It is the main axis to pregestational health programs with the basic elements for the women's self-care. This study evaluated the impact on health behavior and adherence to a community based pregestational preventive program in 224 women of reproductive age from Mexico City. The women were exposed to a health education intervention for twelve months, with free clinical examination every six months in a mobile screening unit close to their homes. Food and hygiene one to one orientation was offered, together with anthropometric, blood pressure and biochemical evaluations. Program adherence was 55%. Most of the women were less than 25 years of age, education above nine years, non-single, housework occupation as housewives, from an extended family, with social security and two or less live children and desire for more. No differences were found in the evaluated factors between those who continued and those who left the program. When comparing initial and final data, a significant larger proportion did breast self-examination, while this was not the case for the Pap smear test, no differences were found in prevalence of anemia or overweight. Drop-out was mainly due to a lack of interest, school or work problems and change of address. While breast self examination showed a positive effect, the negative or no effect on the other factors requires the intervention of other health professionals and implies more effort from the women. If one of the objectives of the PHC is health promotion, nurse intervention is a prominent role in the community.

Changes in the lipophilicity of the surfaces of Meloidogyne incognita and Haemonchus contortus during exposure to host signals.

The surfaces of plant and animal parasitic nematodes share certain lipids, which seem to be important in the infection process. The surfaces of 2 parasitic nematodes, Meloidogyne incognita and Haemonchus contortus, were activated by different pH buffers to allow the insertion of different fluorescent probes. The lipid analogue PKH26 and the surface charge indicator, cationized ferritin, were used as probes with these nematodes but labelled only the retaining 2nd-stage moulted cuticle of H. contortus 3rd-stage larvae (L3). Shedding of the second moult of H. contortus L3 was also visualized with PKH26 and cationized ferritin. The fluorescent anionic lipid probe 5-N-(octadecanoyl)-aminofluorescein (AF18) was inserted into the epicuticle layer of M. incognita 2nd-stage juveniles (J2) and H. contortus L3, and also of the second moult of H. contortus L3. Incubation with tomato root diffusate caused modifications of the M. incognita surface allowing the insertion of AF18. Fluorescence with AF18 was significantly decreased after treating M. incognita J2 with amiloride, a potent blocker of hydrogen and sodium (H+/Na+) antiporter. No surface fluidity was observed in M. incognita J2 and H. contortus L3 pre-treated with alkaline buffer when the lipid analogue AF18 was used in fluorescence recovery after photobleaching experiments. The significance of these findings to host infection processes is discussed.

Identification and characterization of excreted-secreted products and surface coat antigens of animal and plant-parasitic nematodes.

Nematode surface coat (SC) proteins and excreted-secreted products (E-S) are likely to play important roles in the host-parasite interaction and considerable similarities can be found in SC proteins and E-S products from certain plant and animal parasitic nematodes. Monoclonal antibodies raised to E-S products of plant-parasitic nematodes were shown to cross-react with E-S products and the surface coats of the animal parasites Trichinella spiralis and Haemonchus contortus. Most of the antibodies recognized carbohydrate epitopes but the activity of 2 MAbs (IACR-CCNj.2a.15 and IACR-Misec.8D.3) which recognized proteic epitopes in these nematodes were further characterized. Antibody 2a.15 recognized the SC and oral exudate of Meloidogyne incognita, T. spiralis and H. contortus. This antigen was also immunolocalized in the lining of the oesophagus and gut and in the exudate present during ecdysis of H. contortus L3. Antibody 8D.3 reacted with the SC of these nematodes on cryosections but on live nematodes the immunofluorescence was very patchy and was shed from the nematode SC.

Developmental changes in LH secretion by male pituitaries in vitro: from the infantile to adult period.

The secretion of LH from the anterior pituitary of male rats was studied at different periods of postnatal development. According to an established classification we used rats 14 (infantile), 23 (juvenile), 45 (pubertal) and 90 (adult) days old. By using an in vitro incubation system, both basal and stimulated LH secretion were studied in the same gland. Age-related differences were observed in basal LH secretion, with juvenile and pubertal pituitaries showing higher secretion compared with infantile and adult pituitaries. However, the GnRH-induced secretory response was significantly higher in the infantile rats than in other ages. LH secretion was also studied in primary cultures from infantile or adult pituitaries. In 24 and 48 h cultures, infantile cells showed a significantly larger response to GnRH than that of adult cells. In the infantile pituitary LH-immunopositive cells showed differences in size at different locations in the gland. At the periphery of the lobes the predominant cells were smaller and angular shaped, whereas in the center of the gland the majority of the cells were ovoid shaped. In the adult pituitary, the predominant LH-positive cells were ovoid in shape and larger in size. Furthermore, 10% more LH-positive cells were observed in infantile pituitaries. On the basis of these data we propose that at the infantile period the male rat pituitary has two populations of LH-secreting cells, one with adult secretory function and shape and a second with increased sensitivity to GnRH and with a morphology atypical of the adult cell. The results presented support the hypothesis that the infantile period is a transitional stage in the rat pituitary development.

Human cementum tumor cells have different features from human osteoblastic cells in vitro.

Cells obtained from human cementoblastoma and alveolar bone were isolated and cultured. Initial and late stages of mineralization were assessed by using atomic force microscopy, scanning electron microscopy and X-ray microanalysis. In cultures of cementoblastoma-derived cells the initial stages of mineralization showed well-defined spherical-shaped structures, while the osteoblastic cells showed plaque-like deposits. These morphological patterns of mineral deposition could serve as nucleation centers for hydroxyapatite crystals. Late stages of mineralization at 28 and 35 d maintained those morphological differences established in initial cultures. The material deposited by cementoblastoma and osteoblastic cells, analyzed by EDX spectra, revealed similar Ca/P ratios for both cell types. These values were similar to those reported for hydroxyapatite in enamel and bone. Alkaline phosphatase specific activity (AlP), of osteoblastic cells at 3, 7 and 11 d, showed an increase of 27.9, 50.9 and 37.0% (p < 0.001), respectively. However, at 15 and 19 d there was an increase of AlP activity of cementoblastoma cells by 39.4 and 34.5% over osteoblastic cells (p < 0.001). Immunostaining of cementoblastoma and osteoblastic cells using a specific mAb against a cementum-derived attachment protein revealed strong immunostaining of cementoblastoma cells which was localized to the cell membrane and fibril-like structures (96.2 +/- 1.3). A few osteoblastic cells also stained weakly with the anti-CAP mAb (6.4 +/- 0.6). Sections of decalcified paraffin embedded cementoblastoma specimens, when immunostained with anti-CAP mAb, showed strong immunostaining of the cells surrounding the regular and irregularly-shaped calcified masses of the tumor. Putative cementocytes also stained positively. Immunostaining with a polyclonal antibody against osteopontin strongly stained the osteoblastic cells (89.0 +/- 3.6). Cementoblastoma cells showed weaker staining (54.2 +/- 2.4). The results suggest that cementoblastoma cells could be a major source of specific cementum proteins. These cells could provide the opportunity to elucidate the regulation of the cementogenesis process.

Effect of human and murine interferon-alpha on steroid production by rat ovarian cells.

The effect of interferon on the rat ovarian cell function was investigated. Cells from the ovary of juvenile rats were used as a model to investigate the effect of IFN-alpha on the secretion of estradiol and testosterone. In addition the effect of human IFN-alpha (hIFN-alpha) on the secretion of testosterone by the rat adult testis was studied. Present results show that leukocyte hIFN-alpha decreased the human chorionic gonadotropin (hCG) stimulated secretion of estradiol and testosterone by ovarian cells, and the production of testosterone by testis cells. Basal secretion of steroids was affected later and in less proportion than the hCG-dependent production. The IFN-alpha obtained from murine leukocytes, also inhibited the response of ovarian cells to the hCG stimulus.The nature of this effect in the secretion of the steroids is dose and time-dependent. The incubation of hIFN-alpha with an specific antibody completely blocked the effect of the cytokine on ovarian cells.

Bovine cementum extract influences murine dental follicle cells in vitro.

This study evaluated the attachment, chemoattractive, proliferative and mineralization inductive potential of a bovine cementum extract (CPE) on newborn murine dental follicle cells (MDFC) in vitro. Cementum extract was partially purified by DEAE-cellulose chromatography. A band representing an M(r) of 55,000 was excised from the gel and the protein(s) were electroeluted. Attachment assays revealed that CPE (1.0 microgram/ml) promoted MDFC attachment by 96% in comparison with collagen type I (5 micrograms/ml), and was five-fold greater compared with serum-free media (SFM), (P < 0.05). Between 1 and 5 days CPE at 1.0 microgram/ml and collagen type I at 5 micrograms/ml sustained more than 75% attachment and spreading of MDFC when compared to SFM (P < 0.05). Contrary to other reports, fibronectin (0.5 microgram/ml) was more potent than CPE in promoting MDFC chemoattraction (P < 0.05). MDFC proliferation was stimulated by CPE (0.125 microgram/ml), but this response was elicited only when CPE was used together with 10% FBS (37.3%) or 0.2% FBS (76%) (P < 0.05). Alkaline phosphatase expression by MDFC was increased by CPE (1.0 microgram/ml), in comparison to the control. Calcium deposits were detected by von Kossa staining in 14-day MDFC cultures treated with CPE. Nodule formation and its mineralization in long-term MDFC cultures were induced by CPE (1.0 microgram/ml). Molecule(s) contained in CPE appear to regulate various biological activities in MDFC, indicating that CPE could play a key role in selecting progenitor cells required for the process of cementogenesis during development.

Effect of bile acids on hepatobiliary transport of cisplatin by perfused rat liver.

The liver and kidney collaborate in the excretion of the cytostatic drug, cis-diamminedichloroplatinum(II) (cisplatin) from the body. Enhancement of this process is envisaged as a way of reducing cisplatin toxicity, thus allowing increases in the doses administered. In this sense, using different compounds, several attempts have been made to enhance cisplatin biliary excretion. In this study, the ability of endogenous compounds belonging to the bile acid family to improve cisplatin excretion by the isolated perfused rat liver was investigated. A highly choleretic bile acid (ursodexoycholic acid) and two others bile acids with marked micelle-forming properties (glycocholic acid and chenodeoxycholic acid) were chosen for study. When these drugs were given at concentrations (1 microM) that did not affect the viability of liver preparations, a correlation between the biliary excretion of platinum and bile acid output was found. This was not due to the incorporation of cisplatin into mixed micelles because no correlation between the biliary output of lecithin or cholesterol and platinum was observed. Moreover, a wash-out effect of bile acids was probably not the cause of bile acid-induced platinum output into bile because no correlation between this and bile flow was found. An enhancement in cisplatin transport processes by the hepatocyte or by direct binding of cisplatin to bile acid monomers or aggregates cannot be ruled out. In spite of the biliary induction of cisplatin output, the net excretion of platinum was reduced under bile acid administration. This was related to lower platinum contents in the liver tissue, probably due to an inhibition of the ability of the hepatocyte to take up and/or retain cisplatin while subject to bile acid infusion. In summary, our results indicate that bile acids reduce the net excretion of cisplatin by the liver even though they induce an enhancement in the transport of this compound from the hepatocyte into bile.

Prone positioning decreases episodes of hypoxemia in extremely low birth weight infants (1000 grams or less) with chronic lung disease.

Extremely low birth weight infants with chronic lung disease (CLD) have frequent episodes of desaturation (hypoxemia). We quantified oxygenation and episodes of hypoxemia in 55 infants (birth weight < or = 1000 gm) with CLD in the supine versus prone position, for 1-hour time intervals. Oxygen saturation was measured with the Nellcor N-200 pulse oximeter and a computer program. Prone positioning increased oxygen saturation from 92.0% to 94.1% (p < 0.001) and significantly decreased episodes of hypoxemia to oxygen saturation levels of less than 90%, 85%, and 80% (p < 0.001). Our findings support prone positioning for the extremely low birth weight infant with CLD in an intensive care setting.

Recombination of epithelial root sheath and dental papilla cells in vitro.

Hertwig's epithelial root sheath (HERS) cells were isolated and recombined with ectomesenchymal cells in vitro utilizing extracellular matrix components as substrate. After 14 days in culture, HERS cells were differentiated and exhibited a stratified organization. These features resembled those observed in vivo as epithelial rests of Malassez. A mineralization process was also present in HERS cells, in which calcium salts were deposited. This mineralization was correlated with the strong immunoexpression of osteopontin by HERS. The results obtained add support to the possible role of HERS in the secretion of hypocalcified material on the root during early cementogenesis.

Evidence that secretory products of the reticuloepithelial cells of the rat thymus modulate the secretion of gonadotrophins by rat pituitary cells in culture.

It is now well accepted that the endocrine system can be strongly influenced by the immunological status of the body. This laboratory has provided documented evidence that the rat thymus produces a biologically active secretion, with a molecular weight of approximately 30 kDa, that augments the gonadotrophin-releasing hormone (GnRH) stimulated secretion of gonadotrophins by isolated pituitary cells in culture. To determine the cells of origin of the factor involved, the reticulo-epithelial cells from the thymus were incubated in vitro to provide media for the examination of possible effects on the secretion of gonadotrophins by the rat pituitary. The enrichment of the culture with reticulo-epithelial cells was confirmed using anticytokeratins antibodies. It was found that the addition of such conditioned medium increased the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), with a greater effect on the former. The increment in gonadotrophin secretion was time- and dose-dependent. This same conditioned medium also potentiated the effect of GnRH on the cultured pituitary cells. The fractionation of thymic-conditioned medium using selective molecular membrane filters, provided evidence that the active factor or factors involved in the enhanced secretion of gonadotrophins are larger than 10 kDa MW. Present findings show that thymic reticulo-epithelial cells are responsible for this activity.

Participation of the kidney in the kinetics of arginine vasopressin in the water-loaded rat.

The kidney is a target organ for antidiuretic hormone (ADH) and it is also the main organ involved in the clearance of this hormone. There is controversy on the mechanisms involved in the renal handling of ADH, mainly in regard to whether it is secreted or reabsorbed. Kinetic and renal clearance studies of ADH were performed in water-loaded rats and were compared with inulin (glomerular filtration marker) and tetraethylammonium (TEA, marker of organic cation secretion). The kinetics of the three molecules fitted a bicompartmental model. Distribution constants of [125I]-ADH were twofold higher than those of inulin. Elimination constant was higher for inulin than for ADH (0.049 +/- 0.001 vs. 0.020 +/- 0.003 min-1, respectively), suggesting reabsorption of the hormone. The ratios of Clearance ADH/Clearanceinulin and ClearanceTEA/Clearanceinulin were 0.14 and 4.86, respectively. In summary, data from kinetic studies and from renal clearances suggested that ADH is reabsorbed.

SR13/PMP-22 expression in rat nervous system, in PC12 cells, and C6 glial cell lines.

SR13/PMP-22 is a protein that was identified after screening a sciatic nerve cDNA library. Our study focused on comparing the level and pattern of expression of SR13/PMP-22 protein and RNA. Northern blot analysis revealed that although SR13/PMP-22 mRNA was present in all nervous tissues and cells studied, levels were at least seven fold higher in the sciatic nerve and the spinal cord. During sciatic nerve postnatal development and maturation, the SR13/PMP-22 mRNA was detected at 2 days after birth, reached a maximal level at day 24, and decreased to 1/3 of the maximum in adult animals. Nerve transection reduced the level of SR13/PMP-22 mRNA to less than 5% in the segment distal to the nerve injury. Experiments using in situ hybridization localized the SR13/PMP-22 mRNA in Schwann cells. Schwann cells present in the vicinity or distal to the nerve cut repressed the signal for the message. In situ hybridization experiments also demonstrated that dorsal root ganglia satellite cells contained the message for SR13/PMP-22. The SR13/PMP-22 antisera used in our study showed a complex pattern of staining. As expected, the SR13/PMP-22 antibody peptide 1 immunoreacted with the sciatic nerve sheath. However, immunocytochemistry of the dorsal root ganglia revealed that the staining was contained in the neuron's cell body and processes and also in satellite cells. We also identified immunoreactive cell bodies and fibers in the spinal cord dorsal horn. Tissue culture studies demonstrated that SR13/PMP-22 mRNA is induced in NGF treated PC12 but not in C6 glioma cell lines grown under experimental conditions that stimulated cell growth arrest. Our experiments suggest that SR13/PMP-22 may have some other function(s) in addition to its hypothesized role in peripheral myelination.

Comparative effects of short term treatment with norethisterone and sex steroids on gonadotropin secretion in rat pituitary cell cultures.

The short term effects of norethisterone (NET), progesterone (P), estradiol (E2) and dihydrotestosterone (DHT) on the gonadotropin secretion of pituitary cells, from both male and female rats, in primary culture primed with E2 were studied. In female cells, NET only increased the GnRH-induced secretion of LH, while P increased both LH and FSH. Male pituitary cells showed an increased response to GnRH after P pretreatment only if the E2 concentration was augmented. However with the same E2 conditions pretreatment with NET decreased the stimulated LH, but not FSH secretion. Pretreatment with E2 inhibited LH stimulated secretion from pituitary cells of male but not female rats. Furthermore DHT treatment diminished the GnRH response for both LH and FSH in pituitary cells from both sexes. Androgen pretreatment increased basal gonadotropin secretion in male but not in female cells. Basal FSH secretion was increased by NET pretreatment in male cells. This suggests that NET is metabolized by cultured pituitary cells to A-ring reduced compounds during the 4 h incubation period. The formation of NET metabolites, particularly the 3 beta, 5 alpha and 5 alpha-NET might be responsible for the estrogenic and androgenic effects observed when NET was administered to the cultured pituitary cells.