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D Bulian

Publications and source records attributed to D Bulian.

15 recordsLinked to original sources
PubMed2001

Effects of melatonin in perimenopausal and menopausal women: a randomized and placebo controlled study.

In aging humans, night levels of melatonin (MEL) decline progressively. Also thyroid and gonadal functions decline during aging while gonadotropins (luteotropic hormone (LH) and follicle stimulating hormone (FSH)) steadily increase. A desynchronization of pineal circadian cyclicity as expressed by the progressive decrease of the MEL night peak may be permissively linked to the onset and progression of menopause. We studied the effects of exogenous, evening administration of MEL on the level of hormones which are known to be involved in the genesis and progression of menopause. Perimenopausal and menopausal women from 42 to 62years of age with no pathology or medication were selected. MEL was measured in saliva to divide them into low, medium and high-MEL patients. Half of them took 3mg MEL and half of them Placebo at bedtime (10-12p.m.) in a fully randomized and double-blind fashion. Three and six months later blood was taken for determination of pituitary (LH, FSH), ovarian, and thyroid hormones I(T3 and T4). All women taking MEL with low basal level of MEL and/or Placebo for three and six months showed a significant increase in levels of thyroid hormones. Before initiation of the study, a negative correlation was found in all women between LH, FSH and basal MEL levels. Within six months of treatment, MEL produced a significant diminution of LH in the younger women (43 to 49year-old), while no effect was seen in the older women (50-62years old). A decrement of FSH was observed in MEL-treated women with low basal MEL levels. In addition, most MEL-treated women reported a general improvement of mood and a significant mitigation of depression. MEL decline during aging may thus signal the derangement of pineal and pituitary-controlled ovarian cyclicity and the progressive quenching of fertility in women. These findings seem to show a recovery of pituitary and thyroid functions in MEL-treated women, towards a more juvenile pattern of regulation.

Adult↗
PubMed2000

The pineal gland and cancer. I. Pinealectomy corrects congenital hormonal dysfunctions and prolongs life of cancer-prone C3H/He mice.

Hormonal derangements almost invariably anticipate and signal the onset of tumors. Chronic, nocturnal melatonin administration delays aging in normal strains of mice. On the contrary it promotes and accelerates the onset of tumors in the cancer-prone strain of C3H/He mice. Grafting of a young pineal gland into aging mice prolongs their longevity and maintains juvenile circadian hormonal functions while pinealectomy (Px) does the opposite. We investigated if Px in C3H/He mice would modify their congenitally deranged pituitary function and affect their longevity. It was found that contrarily to Px in normal mice, Px in C3H/He mice remarkably maintains juvenile night levels of thyroid hormones and lipids, preserves a cell-mediated immune response and significantly prolongs their life. The pineal gland and its pathology may be the key for understanding, not only the causes of metabolic aging, but also the origin of those congenital or progressive aging-related hormonal alterations preceding onset of all tumors and thus allow preventive corrective interventions with pineal-derived agents.

Aging↗
PubMed2000

Transferrin treatment corrects aging-related immunologic and hormonal decay in old mice.

Experiments were conducted to study the effect of heterologous plasma transferrins separated and purified from human plasma pools on endocrine and immune functions of old, aging mice. Two similar experiments have shown that parenteral treatment with iron and zinc-free human transferrins produces a significant improvement of immunological and endocrine functions in the aging mice toward more juvenile values. Those changes occur in the thymus and its cell subsets, in peripheral blood lymphocytes, in the restoration of juvenile levels of thyroxine, in the increase of testis weight, and in the normalization of plasma zinc levels. These totally unsuspected effects of transferrin in aging mice suggest a most important role of endogenous transferrins in the maintenance of neuroendocrine and immune functions. The mechanism remains unexplained although the basic immunoenhancing and anti-apoptotic effect of transferrin-vehiculated zinc may be relevant.

Adrenal Glands↗
PubMed1999

Melatonin administration in tumor-bearing mice (intact and pinealectomized) in relation to stress, zinc, thymulin and IL-2.

Melatonin (MEL) may counteract tumors through a direct oncostatic role. MEL is also an antistress agent with immunoenhancing properties against tumors due to a suppressive role of MEL on corticosterone release. Rotational stress (RS) (spatial disorientation) facilitates metastasis progression in mice. Also, MEL counteracts tumors because of its influence on immune responses via the metabolic zinc pool, which, is reduced in tumors and stress. Zinc is required for normal thymic endocrine activity (i.e. thymulin) and interleukin-2 (IL-2) production. Because in vivo data is still controversial, exogenous MEL treatment (22 days in drinking water) in both intact and pinealectomized (px) mice bearing Lewis lung carcinoma leads to significant decrements of metastasis volume, restoration of the negative crude zinc balance, recovery of thymulin activity and increment of IL-2 exclusively in intact and px tumor bearing mice subjected to RS. Significant inverse correlations are found in both stressed intact and px tumor bearing mice after MEL treatment between zinc and corticosterone (r = 0.78, P < 0.01; r = 0.80, P < 0.01, respectively). Positive correlations between zinc and IL-2 (r = 0.75, P < 0.01; r = 0.73, P < 0.01, respectively) or thymulin (r = 0.75, P < 0.01; r = 0.82, P < 0.01, respectively) are observed in same models of mice. These findings suggest a MEL action to decrease metastasis mediated by a possible interplay between zinc and MEL, via corticosterone, with consequent restoration of thymic efficiency and IL-2 production. MEL as an antistress agent with immunoenhancing properties in cancer deserves further consideration.nuclear factor-kb; POMC, proopiomelanocortin; Px, pinealectomized mice; RIA, radioimmunoassay; RS, rotational stress; SDI, stressed intact mice; SDPx, stressed pinealectomized mice; TNF-alpha, tumor necrosis factor-alpha; ZnFTS, active zinc-bound thymulin; ZnFTS + FTS, total thymulin.

Animal Feed↗
PubMed1998

Presence of links between zinc and melatonin during the circadian cycle in old mice: effects on thymic endocrine activity and on the survival.

Links between zinc and melatonin in old melatonin treated mice with a reconstitution of thymic functions have been recently documented. Concomitant increments of the nocturnal peaks of zinc and melatonin, with a synchronization of their circadian patterns, are achieved in old mice after melatonin treatment. A recovery of the nocturnal peaks of thymulin plasma levels and of the number of thymulin-secreting cells with a synchronization of their circadian patterns are also achieved. The existence of significant positive correlations between melatonin and zinc and between melatonin and thymulin or the number of thymulin-secreting cells supports the presence of links between zinc and melatonin also during the circadian cycle with a beneficial effect on thymic functions. The altered circadian pattern of corticosteron in old mice is normalized by melatonin. The existence of inverse correlations between corticosteron and melatonin, between corticosteron and zinc and between corticosteron and thymulin or the number of thymulin-secreting cells during the whole circadian cycle, suggests the involvement of glucocorticoids pathway in the melatonin thymic reconstitution, via zinc. The presence of an interplay among zinc, melatonin, glucocorticoids and thymulin may be, therefore, supported during the circadian cycle. 'In vitro' experiments from old thymic explants show a direct action of zinc, rather than melatonin, on thymulin production, further suggesting that the action of melatonin on the thymic efficiency is mediated by the zinc bioavailability. The beneficial effect of the links between zinc and melatonin on thymic functions during the circadian cycle, may be extended to a prolonged survival in aging, where, however, zinc may be more involved.

Aging↗
PubMed1997

Long-term melatonin supplementation does not recover the impairment of natural killer cell activity and lymphocyte proliferation in aging mice.

In this study we evaluated the effect of long-term melatonin (MEL) treatment on the cytotoxic activity and number of natural killer (NK) cells and the proliferative response of spleen lymphocytes to phytohemagglutinin (PHA) or interleukin-2 (IL-2) in old mice. Seventeen-eighteen month-old Balb/c mice were supplemented with MEL (40-50 microg/day/mouse) and sacrificed after eight months. The MEL supplementation was unable to recover the low levels of both endogenous and IL-2-induced NK cell activity found in old untreated mice. Also the NK cell number was unaffected by MEL treatment. The spleen lymphocyte proliferative response to both PHA and IL-2 was not different in old MEL-treated compared to old untreated mice. These results indicate that long-term MEL supplementation does not recover the age-related deterioration of NK cell activity and lymphocyte proliferative capacity.

Adjuvants, Immunologic↗
PubMed1996

Effect of melatonin and pineal grafting on thymocyte apoptosis in aging mice.

We have evaluated the effect of chronic melatonin (MEL) treatment or pineal grafting (PG) in old mice on the apoptosis of both thymocytes and spleen lymphocytes under conditions of either serum deprivation or glucocorticoid or zinc administration. The apoptosis was correlated with the modulation of thymus and adrenal weight and corticosterone and zinc plasma levels induced by MEL treatment or PG in old mice. Balb/c mice (17-18 months old) were given supplements of MEL (40-50 micrograms/day/mouse) or grafted with a young pineal gland and then sacrificed after 8 months. Both the MEL treatment and PG partially prevented thymic involution in very old mice. Both treatments protected the thymic and spleen lymphocytes in old mice from the apoptosis induced by serum deprivation and recovered the reduced thymocyte sensitivity to the apoptosis induced by dexamethasone (DEX), present in old untreated animals, to the values found in young mice. DEX caused a bigger loss of G D /G 1 phase cells in MEL treated mice than in old untreated mice. The protective action of MEL treatment or PG on serum deprivation induced apoptosis was correlated with increased thymus weight, reduced adrenal weight and corticosterone levels and increased zinc plasma levels. The greater DEX-induced apoptosis found in MEL treated and PG mice was correlated with reduced adrenal weight and function. In vitro MEL did not affect thymocyte apoptosis in young or old mice. These results suggest that MEL treatment or PG prevent age-related thymus involution through regulation of thymocyte apoptosis which, in turn, occurs through modulation of the pituitary-adrenal axis and zinc turnover determined by the pineal hormone.

Aging↗
PubMed1996

Intraarterial hepatic chemotherapy with fluorouracil, fluorodeoxyuridine, mitomycin C, cisplatin or methotrexate as single-agent anticancer drugs for a transplanted experimental liver tumor in rats.

A prospective, controlled and standardized animal experiment was performed to study the influence of various anticancer drugs. The Novikoff hepatoma transplanted into male Sprague-Dawley rats was treated with fluorouracil (FUra), mitomycin C, methotrexate, cisplatin and fluorodeoxyuridine (FdUrd) at equi-effective dosage, in terms of side effects (weight loss), in comparison to a control group (0.9% saline solution) by locoregional application via the hepatic artery. The tumor multiplication factor (TMF = tumor volume day 12/tumor volume day 5) served as the parameter to compare the tumor growth of the various groups. All drugs showed a significant (P < 0.05) effect on the tumor growth. In comparison to the control group (mean TMF 9.66), FdUrd (3.78) and FUra (3.03) only limited the tumor growth, mitomycin C (0.96) produced stable tumor, cisplatin (0.64) and methotrexate (0.15) significantly reduced (P < 0.01) the tumor size. We suggest that, in addition to the established (FUra, FdUrd, mitomycin C) drugs, methotrexate and cisplatin should be considered in further studies of the treatment of primary and secondary liver malignancies.

Angiography↗
PubMed1996

The zinc pool is involved in the immune-reconstituting effect of melatonin in pinealectomized mice.

Melatonin (MEL) affects the immune system by direct or indirect mechanisms. An involvement of the zinc pool in the immune-reconstituting effect of MEL in old mice has recently been documented. An altered zinc turnover and impaired immune functions are also evident in pinealectomized (px) mice. The present work investigates further the effect of "physiological" doses of MEL on the zinc pool and on thymic and peripheral immune functions in px mice. Daily injections of MEL (100 micrograms/mouse) for 1 month in px mice restored the crude zinc balance from negative to positive values. Thymic and peripheral immune functions, including plasma levels of interleukin-2, also recovered. The nontoxic effect of MEL on immune functions was observed in sham-operated mice. Because the half-life of MEL is very short (12 min), interruption of MEL treatment in px mice resulted, after 1 month, in a renewed negative crude zinc balance and a regression of immune functions. Both the zinc pool and immunological parameters were restored by 30 further days of MEL treatment. The existence of a significant correlation between zinc and thymic hormone after both cycles of MEL treatment clearly shows an involvement of the zinc pool in the immunoenhancing effects of MEL and thus suggests an inter-relationship between zinc and MEL in px mice. Moreover, the existence of significant positive correlations between zinc or thymulin and interleukin-2 suggests that interleukin-2 may participate in the action of MEL, via zinc, on thymic functions in px MEL-treated mice.

Analysis of Variance↗
PubMed1994

Immune enhancement by conditioning of senescent mice. Comparison of old and young mice in learning ability and in ability to increase natural killer cell activity and other host defense reactions in response to a conditioned stimulus.

It has been clearly demonstrated that immune responses may be conditioned in a manner similar to that of the classical Pavlovian experiments. Evidence of impaired immune function in aging has raised the question of whether psychological conditioning of an immune response can also be effective in old age. The knowledge that aged mice have decreased spleen cell natural killer (NK) activity and that NK cytotoxicity, at least in young mice, can be psychologically conditioned led us to explore in old mice the possibility of conditioning the response of NK cell activity using the odor of camphor as the conditioned stimulus (CS) and the injection of Poly I:C as the unconditioned stimulus (US). Young and old male mice were divided into five and six groups, respectively. They received the CS and/or the US in association (conditioning) trials (sessions 1-9). Mice were exposed to the camphor odor alone at 72 hours after the final association trial to observe the conditioning phenomenon (session 10). The group conditioned with Poly I:C and camphor and receiving the CS at session 10 showed statistically significant increases in spleen cell NK activity over those of the control groups that did not receive the CS treatment at session 10 (2.6- and 4.0-fold increase in young and old, respectively). Treatment with camphor odor alone had no effect on boosting NK cell activity. These findings demonstrate the possibility of conditioning immune responses in old age, offering a valuable tool for attenuating age-related immune deterioration in various species, including the human. In addition, these results again confirm highly significant immune enhancement by classical conditioning and extend previous findings from female mice to males as well.

Aging↗
PubMed1994

The immuno-reconstituting effect of melatonin or pineal grafting and its relation to zinc pool in aging mice.

It has been demonstrated that melatonin, the main neuro-hormone of the pineal gland, affects thymic functions and the regulation of the immune system. In addition, experimental evidences indicate that melatonin can modulate zinc turnover. The knowledge that with advancing age both melatonin and zinc plasma levels decline, and that zinc supplementation in old mice is able to restore the reduced immunological functions, has prompted investigations on the effect of chronic melatonin treatment or pineal graft in old mice on the age-related decline of thymic endocrine activity, peripheral immune functions and zinc turnover. Both melatonin treatment in old mice and pineal graft into the thymus of old mice correct the reduced thymic endocrine activity and increase the weight of the thymus and its cellularity. A restoration of cortical thymic volume, as detected by the percentage of tissue in active proliferation, is also observed in old mice after both treatments. Thymocyte CD phenotype expression is also restored to young values. At peripheral level, recovery of peripheral blood lymphocyte number and of spleen cell subsets, with increased mitogen responsiveness also occurs. Melatonin treatment or pineal graft induce also a restoration of the altered zinc turnover in aged mice with an increment of the crude zinc balance from negative (-1.6 microgram/day/mouse) to positive value (+1.2 microgram/day/mouse), similar to that one of young mice (+1.4 microgram/day/mouse). The reduced zinc plasma level is restored to normal values. These findings support the idea that the effect of melatonin on thymic endocrine activity and peripheral immune functions may be mediated by the zinc pool.

Aging↗
PubMedDate not supplied

Circadian melatonin and young-to-old pineal grafting postpone aging and maintain juvenile conditions of reproductive functions in mice and rats.

Chronic, night administration of melatonin to aging mice and transplantation of a young pineal gland into the thymic rudiment of older mice and rats have been studied with the aim of evaluating their effects on aging of gonadal, sexual, and reproductive functions. Both melatonin administration and young-to-old pineal grafting positively affect size and function of testes and maintenance of juvenile hippocampal and testicular LHRH-receptors and beta-adrenergic receptors in the tests of old rats and mice. These results demonstrate that a pineal-directed circadian function and cyclicity is fundamental for the regulation of sexual, reproductive physiology, and that proper intervention with melatonin may potentially postpone aging of both neural and gonadal sexual function.

Aging↗