Nucleation and growth of TiAl3 intermetallic phase in diffusion bonded Ti/Al Metal Intermetallic Laminate.

A novel nucleation and growth phenomenon for TiAl3 intermetallic phase in Ti/Al diffusion couple is proposed based on diffusion kinetics. The interdiffusion and intrinsic diffusion co-efficients are calculated to make evident of dominant diffusion of Al towards Ti in Ti/Al diffusion couple obtained by solid state diffusion bonding. It was surprising to observe that the diffusion rate of Al was around 20 times higher than Ti with the formation of Kirkendall pores near the Al/TiAl3 interface. With such dominant diffusion of Al towards Ti, the nucleation and growth of TiAl3 intermetallic phase in Ti/Al couple happens mainly at the Ti/TiAl3 interface rather than Al/TiAl3 interface which is evident by the presence of very fine nearly nano-sized TiAl3 nuclei/grains near the Ti/TiAl3 interface. Even though the intermetallic phase is expected to nucleate at Al/TiAl3 interface, the relatively larger TiAl3 grains near that interface depicts grain growth with minimal nucleation. The theoretical calculations on diffusion parameters are in accordance with experimental observations of TiAl3 intermetallic growth phenomenon in Ti/Al system.

Effect of lycopene on insulin-like growth factor-I, IGF binding protein-3 and IGF type-I receptor in prostate cancer cells.

PURPOSE: Prostate cancer is the second most common cancer that leads to death in elderly men. The risk of prostate cancer prevalence is often associated with the elevated level of insulin-like growth factor-I (IGF-I) and decreased level of IGF-binding protein 3 (IGFBP-3). Lycopene, a carotenoid, reduces the proliferation of cancer cells and induces apoptosis. Hence, higher intake of lycopene can be associated with the lower risk of prostate cancer. However, the mechanism of action of lycopene in the prevention of prostate cancer is still unclear. The present study was carried out to study the effects of lycopene on the components of IGF system and apoptosis in androgen-independent prostate cancer cells (PC-3 cells). METHODS: PC-3 cells were treated with various concentrations of lycopene, (20, 40 and 60 microM) for 24, 48, 72 and 96 h. IGF-I, IGFBP-3 and IGF-I receptor (IGF-IR) levels in lycopene-treated cells were evaluated. Annexin V and propidium iodide (PI) binding studies were done to assess apoptosis. RESULTS: PC-3 cells treated with lycopene showed a significant decrease in cell proliferation. Lycopene, at a dose of 40 microM, significantly increased the level of IGFBP-3. Lycopene-induced apoptosis was confirmed by annexin V and PI binding. Lycopene-induced DNA fragmentation was absent after 24 h treatment whereas the same was observed after 48 h treatment. There was a significant decrease in the IGF-IR expression after the cells were treated with lycopene and IGF-I. CONCLUSION: The data obtained suggest that the components of the IGF system may act as a positive regulator of lycopene-induced apoptosis in PC-3 cells. Thus, the observed lycopene-induced biological effects and their associated mechanisms are encouraging and may lead to the development of a highly successful drug for the treatment of prostate cancer.

Impact of foetal-onset hypothyroidism on the epididymis of mature rats.

It is well established that congenital hypothyroidism leads to male infertility. However, there is a dearth of information on foetal-onset hypothyroidism-induced changes in the epididymis. With regard to transient hypothyroidism, the existing literature deals mainly with the testis. However, it is not known whether there is any corresponding alteration in epididymal morphology and physiology under such a condition. The present study is therefore aimed at understanding the impact of persistent and transient hypothyroidism on the concentration of epididymal sex steroids, as they play a vital role in maintaining the normal structure and function of the epididymis. Normal rats of 90 days of age served as controls (Group I). Hypothyroidism was induced by using pregnant/lactating mothers and post-weaning rats to 0.05% (w/v) methimazole (MMI) in the drinking water. Group II were subjected to persistent hypothyroidism from day 9 of post-coitum (pc) to 90 days. Group III rats were subjected to transient hypothyroidism from day 9 day pc to day 1 post-partum (pp), 21 pp or 35 pp (IIIa, b and c, respectively) and group IV rats were given simultaneous T3 supplementation (3 microg/100 g body wt./day i.m.) with MMI from day 9 pc to day 1 pp; 21 pp and 35 pp (Group IVa, b and c). Animals from all groups were killed on day 90 pp. Serum thyroid stimulating hormone (TSH) and thyroid hormones confirmed euthyroidism in group I, IIIa, b and c and IVa, b and c rats and hypothyroidism in group II rats. Caput and cauda epididymal concentration of testosterone, dihydrotestosterone (DHT), estradiol (E2) and androgen binding protein (ABP) markedly decreased in group II rats. While the concentration of testosterone, E2 and ABP increased in group III rats, that of DHT remained unaltered. However, group IV rats maintained normal concentration of the sex steroid and ABP. The activity of 5-alpha-reductase in the epididymis of all the groups followed the same trend as that of the concentration of epididymal DHT. From the present data it is evident that persistent hypothyroidism diminishes the bioavailability of androgens and oestrogens, while transient hypothyroidism enhances the same, indicating the importance of euthyroidism during foetal and neonatal period towards the maintenance of optimal hormonal status in the epididymis required for its maturation.

Transient neonatal hypothyroidism alters plasma and testicular sex steroid concentration in puberal rats.

The stimulatory and inhibitory effects on testicular steroidogenesis of transient neonatal hypothyroidism from day 1 postpartum through different postnatal developmental events on testis at puberal age (60 days old) were studied in vivo. Hypothyroidism was induced in neonates by feeding the lactating mother or directly with 0.05% methimazole (MMI) through drinking water from the day of parturition to 10, 15, 30, 40 and 60 days, and were killed at day 60 postpartum. Plasma and testicular interstitial fluid (TIF) progesterone, testosterone, dihydrotestosterone (DHT) and estradiol concentrations were assessed. Testis weight and volume significantly increased in rats subjected to 10 and 15 days of hypothyroidism, decreased in rats subjected to 30, 40 and 60 days of hypothyroidism. A consistent increase in Leydig cell number was seen in puberal rats subjected to transient neonatal hypothyroidism but decreased in 60 days hypothyroid rats. Peritubular myoid cell number was consistently decreased in all experimental rats. Leydig cell diameter decreased consistently in all experimental groups. Persistent hypothyroidism (60 days hypothyroid) consistently decreased both plasma and TIF sex steroids. In transient hypothyroid rats, progesterone concentration decreased in both plasma and TIF. Transient hypothyroidism from birth to day 10 postnatal age maintained normal titre of plasma testosterone, whereas a significant increase in TIF testosterone concentration was evident when compared with controls. All other groups of rats subjected to transient neonatal hypothyroidism had consistently low titres of plasma and TIF testosterone. Plasma DHT concentrations in rats subjected to transient neonatal hypothyroidism remained unaltered. However, TIF DHT increased in 10 days

Growth hormone directly stimulates testosterone and oestradiol secretion by rat Leydig cells in vitro and modulates the effects of LH and T3.

The modulatory effect of GH on basal, LH and T3 mediated secretion of testosterone and oestradiol by purified rat (60 day old) Leydig cells was studied in vitro. Percoll gradient purified Leydig cells (1 x 10(3)) were cultured for 48 hours at 34 degrees C in a medium containing different concentrations of rat GH (5-400 ng/mL), after an initial culture for 24 hours at 37 degrees C. GH increased testosterone and oestradiol secretions in a dose dependent manner. While testosterone secretion reached the saturation point with 50 ng GH, oestradiol secretion reached the saturation point with 150 ng GH, followed by diminished secretions. Co-administration of minimum (10 ng) effective does of GH with minimum (25 ng) or maximum (100 ng) effective doses of oLH significantly decreased the testosterone secretion. However, an increased secretion of testosterone was observed when maximum effective doses of rGH (50 ng) and oLH (100 ng) were co-administered. Minimum effective (25 ng) or maximum effective (50 ng) doses of T3 inhibited GH mediated secretion of testosterone in vitro. Oestradiol concentration in the culture medium increased when either dose of rGH was co-administered with the minimum or maximum effective doses of oLH. T3 50 ng augmented the secretion of oestradiol by Leydig cells in the presence of GH. These results indicate that GH acts as a gonadotrophin to stimulate testosterone and oestradiol secretions by Leydig cells, and that it modulates LH or T3 induced secretion of these steroids, depending on the intensity of their stimulation.

Impact of neonatal onset hypothyroidism on Sertoli cell number, plasma and testicular interstitial fluid androgen binding protein concentration.

The impact of neonatal onset hypothyroidism from day 1 postpartum through different postnatal developmental events on rat testis was studied in vivo. Hypothyroidism was induced in neonates by feeding the lactating mother or directly with 0.05% methimazole (MMI) through drinking water from the day of birth and were killed at day 10, 15, 30, 40 and 60 postpartum. Hypothyroidism was confirmed by radioimmunoassay of thyroid hormones and TSH. Sertoli cell number, plasma and testicular interstitial fluid (TIF) androgen binding protein (ABP) concentration was quantified. Sertoli cell number was consistently decreased in all hypothyroid rats. Plasma ABP was also decreased irrespective of the duration of hypothyroidism. Unlike plasma ABP, TIF ABP concentration in hypothyroid rats increased at day 10, and 15 postpartum and decreased in other age groups. Plasma FSH level was increased significantly in all hypothyroid groups. The present investigation points out that suppression of T3 during the critical period of Sertoli cell proliferation affects their number and functional activity.

Duration-dependent effect of transient neonatal hypothyroidism on sertoli and germ cell number, and plasma and testicular interstitial fluid androgen binding protein concentration.

The impact of transient neonatal hypothyroidism on growth and function of puberal testis during different milestones of postnatal testicular development was studied in Wistar rats. Rat pups were made hypothyroid for 10, 15, 30, 40 and 60 days of postnatal age from birth by providing 0.05% (W/V) methimazole (MMI) in the drinking water of the mother, from day 1 postpartum till weaning (25 days postpartum) and thereafter in the drinking water. Control rats were raised without MMI treatment. Sertoli cell number and its function was assessed on day 60 postpartum. Sertoli cell number increased consistently in 10, 15, 30 and 40 days transient hypothyroid rats but decreased in rats subjected to continuous hypothyroidism from birth to 60 days postpartum. Rats subjected to continuous hypothyroidism from birth showed spermatogenic arrest at puberty and had only a single layer of spermatogonia. Transient neonatal hypothyroidism for 10 (or) 15 days from birth increased spermatocytes (pachytene and zygotene), spermatids (elongated and round) whereas, that of 30 and 40 days decreases the number of germ cells. Plasma androgen binding protein (ABP) concentration decreased in puberal rats belonging to all groups, whereas the testicular interstitial fluid (TIF) concentration of ABP increased significantly in 10 and 15 days hypothyroid rats while it decreased in all other groups. These findings indicate that the mitogenic activity of Sertoli cell is increased irrespective of the duration of transient neonatal hypothyroidism. However, the functional activity of Sertoli cells (ABP production) in these puberal rats varies depending upon the postnatal period at which the animals were in hypothyroid state.