FLUORIDE ACTION NETWORK PESTICIDE PROJECT

Return to FAN's Pesticide Homepage

Return to Abstracts Page


Pineal Gland Abstracts: 1999

Note: the following is a limited selection of abstracts available at PubMed, Science Direct, and Toxnet.

Abstracts on the Pineal Gland by Year
-
2005
(Jan-June)
2004
2003
2002
2001
2000
1999
1998
1997
1996
1995
1994
1993
1992
1991
1990
Up to 1989

From Dart Special at Toxnet http://toxnet.nlm.nih.gov/

Neuroendocrinol Lett 1999;20:69-76

Maternal melatonin influences rates of somatic and reproductive organs postnatal development of male rat offspring.

Däiaz B, Däiaz E, Colmenero M, Arce A, Esquifino A, Maräin B

Dpto. de Biologäia Funcional, Universidad de Oviedo, Oviedo, Spain.
Source:

Female rat dams, housed in 12L:12D photoperiod, were pinealectomized or injected daily 1 1/2 h before onset of darkness with 250 ug melatonin/100 g BW, during pregnancy; control and pinealectomized dams received a placebo. Somatic, reproductive organs and gonadotropins levels luteinizing hormone (LH) and follicle stimulating hormone (FSH) of male offspring were examined at the following phases of their sexual development: neonate, infantile, juvenile or prepubertal and pubertal periods. Pinealectomy of the mother produced an altered developmental pattern in the offspring (PIN-X offspring). During the infantile period when pups are lacking maternal melatonin and their own melatonin rhythm is not yet established, a delayed growth of body and testis weights was observed. After the second week of life, from 15 to 25 days of age, coinciding with the initiation of the melatonin rhythm, a speed-up growth of body and testes was observed, followed by a delayed growth from 25 to 30 days, in the juvenile period; this also coinciding with reduced LH levels observed at 30 days of age. Indeed, in PIN-X offspring significantly greater growth rate was observed during the pubertal period than in control offspring, which could be due to the increase in LH secretion up to normal values observed in the PIN-X offspring. Seminal vesicles of the PIN-X offspring also showed delayed growth, which was overcome at the pubertal period. Melatonin (MEL) treatment during pregnancy produced minor alterations in postnatal development of the reproductive tract. Only increased pituitary gland weight was observed at 15 and decreased at 25 days of age. At 25 days of age, MEL offspring reached the highest LH values, and at 30 days of age, PIN-X offspring still show low values. Which suggests that other factors than the endocrine activity of the gland are affecting the somatic growth of the pituitary gland. Seminal vesicles weight was delayed at 25 days of age in the MEL offspring. These results indicate that maternal melatonin is necessary for a normal somatic growth and postnatal development of reproductive organs of the offspring.


From Dart Special at Toxnet http://toxnet.nlm.nih.gov/

Teratology 1997 Dec;56(6):388

Effects of melatonin on methylmercury-induced teratogenesis in mice.

Esparza JL, Colomina MT, Domingo JL, Llobet JM, Corbella J

Laboratory of Toxicology and Environmental Health, "Rovira i Virgili" University, Reus, Spain.

Methylmercury is a widely distributed environmental pollutant whose embryotoxic and teratogenic effects in mammals are well known. In the present study, we assessed whether melatonin (MLT), a pineal hormone with a well established antioxidant activity, could act as a defense against methylmercury chloride (MMC)-induced maternal and developmental toxicity in mice. On gestational days 10-13, a series of four doses of MLT were given by gavage to pregnant mice following a single oral exposure to 25 mg/kg of MMC on day 10 of gestation. MLT was administered at 0, 40, and 100 mg/kg/day. Three additional groups of MMC-untreated pregnant mice received the same MLT doses on the same gestational days. Embryo/fetal toxicity in the MMC-treated groups was clearly evidenced by a significant increase in the number of non-viable implants, an increase in the incidence of cleft palate, as well as a decrease in fetal body weight and a delay in fetal ossification of some skeletal districts. Although some beneficial effects of MLT on MMC-induced maternal and fetal toxicity could be observed, those effects did not reach the level of statistical significance. Moreover, MLT treatment did not exert any significant reduction on the number of litters with fetuses affected by cleft palate or other morphological defects. Consequently, under the current experimental conditions MLT would not be an effective agent in protecting against MMC-induced developmental toxicity.

 

J Pineal Res 1999 Nov;27(4):226-9

Alzheimer beta protein mediated oxidative damage of mitochondrial DNA: prevention by melatonin.

Pappolla MA, Chyan YJ, Poeggeler B, Bozner P, Ghiso J, LeDoux SP, Wilson GL

University of South Alabama Medical Center, Department of Pathology and Neurology, Mobile 36617, USA. mpappoll@usamail.usouthal.edu

Abstract: Most contemporary progress in Alzheimer's disease (AD) stems from the study of a 42 43 amino acid peptide. called the amyloid beta protein (Abeta), as the main neuropathologic marker of the disorder. It has been demonstrated that Abeta has neurotoxic properties and that such effects are mediated by free-radicals. Exposure of neuronal cells to Abeta results in a spectrum of oxidative lesions that are profoundly harmful to neuronal homeostasis. We had previously shown that Abeta25-35 induces oxidative damage to mitochondrial DNA (mtDNA) and that this modality of injury is prevented by melatonin. Because Abeta25 35 does not occur in AD and because the mode of toxicity by Abeta25-35 may be different from that of Abeta1-42 (the physiologically relevant form of Abeta), we extended our initial observations to determine whether oxidative damage to mtDNA could also be induced by Abeta1-42 and whether this type of injury is prevented by melatonin. Exposure of human neuroblastoma cells to Abeta1-42 resulted in marked oxidative damage to mtDNA as determined by a quantitative polymerase chain reaction method. Addition of melatonin to cell cultures along with Abeta completely prevented the damage. This study supports previous findings with Abeta25-35, including a causative role for Abeta in the mitochondrial oxidative lesions present in AD brains. Most important, the data confirms the neuroprotective role of melatonin in Abeta-mediated oxidative injury. Because melatonin also inhibits amyloid aggregation, lacks toxicity, and efficiently crosses the blood-brain barrier, this hormone appears superior to other available antioxidants as a candidate for pharmacologic intervention in AD.


Full free article available at http://jcem.endojournals.org/cgi/content/full/84/1/323

J Clin Endocrinol Metab. 1999 Jan;84(1):323-7.

Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer's disease, and apolipoprotein E-epsilon4/4 genotype.

Liu RY, Zhou JN, van Heerikhuize J, Hofman MA, Swaab DF.

Netherlands Institute for Brain Research, Amsterdam.

Sleep disruption, nightly restlessness, sundowning, and other circadian disturbances are frequently seen in Alzheimer's disease (AD) patients. Changes in the suprachiasmatic nucleus and pineal gland are thought to be the biological basis for these behavioral disturbances. Melatonin is the main endocrine message for circadian rhythmicity from the pineal. To determine whether melatonin production was affected in AD, melatonin levels were determined in the cerebrospinal fluid (CSF) of 85 patients with AD (mean age, 75 +/- 1.1 yr) and in 82 age-matched controls (mean age, 76 +/- 1.4 yr). Ventricular postmortem CSF was collected from clinically and neuropathologically well defined AD patients and from control subjects without primary neurological or psychiatric disease. In old control subjects (>80 yr of age), CSF melatonin levels were half of those in control subjects of 41-80 yr of age [176 +/- 58 (n = 29) and 330 +/- 66 (n = 53) pg/mL, respectively; P = 0.016]. We did not find a diurnal rhythm in CSF melatonin levels in control subjects. In AD patients the CSF melatonin levels were only one fifth (55 +/- 7 pg/mL) of those in control subjects (273 +/- 47 pg/mL; P = 0.0001). There was no difference in the CSF melatonin levels between the presenile (42 +/- 11 pg/mL; n = 21) and the senile (59 +/- 8 pg/mL; n = 64; P = 0.35) AD patients. The melatonin level in AD patients expressing apolipoprotein E-epsilon3/4 (71 +/- 11 pg/mL) was significantly higher than that in patients expressing apolipoprotein E-epsilon4/4 (32 +/- 8 pg/ml; P = 0.02). In the AD patients no significant correlation was observed between age of onset or duration of AD and CSF melatonin levels. In the present study, a dramatic decrease in the CSF melatonin levels was found in old control subjects and even more so in AD patients. Whether supplementation of melatonin may indeed improve behavioral disturbances in AD patients should be investigated.

PMID: 9920102 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10821215&dopt=Abstract

J Pediatr Endocrinol Metab 1999 May-Jun;12(3):355-62

Melatonin and sex hormone interrelationships--a review.

Luboshitzky R, Lavie P.

Endocrine Institute, Haemek Medical Center, Afula, Israel.

Melatonin, the main hormone secreted by the pineal gland at night, plays a major role in regulating reproductive physiology in seasonal breeders and influences the age of sexual maturation in laboratory rodents. In humans these relationships are less clear. Evidence supporting a melatonin-reproductive hormone relationship relies on findings of abnormal melatonin secretion in disorders of the reproductive system and on pathologies of the pineal gland which are associated with clinical abnormalities of the reproductive hormones. Normal melatonin rhythms are closely related to those of the reproductive hormones during infancy and reciprocally correlated during puberty. The demonstration of melatonin receptors in the brain and in reproductive organs, together with the localization of sex hormone receptors in the pineal gland, further strengthen these relationships. However, it is not yet clear that these correlations are functionally related, as data on the antigonadal effects of exogenous melatonin on the reproductive hormones are not conclusively established.

Publication Types:

PMID: 10821215 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10572942&dopt=Abstract

Biochim Biophys Acta 1999 Oct 18;1472(1-2):206-14

Identification of highly elevated levels of melatonin in bone marrow: its origin and significance.

Tan DX, Manchester LC, Reiter RJ, Qi WB, Zhang M, Weintraub ST, Cabrera J, Sainz RM, Mayo JC.

Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio 78284-7762, USA.

Bone marrow is an important tissue in generation of immunocompetent and peripheral blood cells. The progenitors of hematopoietic cells in bone marrow exhibit continuous proliferation and differentiation and they are highly vulnerable to acute or chronic oxidative stress. In this investigation, highly elevated levels of the antioxidant melatonin were identified in rat bone marrow using immunocytochemistry, radioimmunoassay, high performance liquid chromatography with electrochemical detection and mass spectrometry. Night-time melatonin concentrations (expressed as pg melatonin/mg protein) in the bone marrow of rats were roughly two orders of magnitude higher than those in peripheral blood. Measurement of the activities of the two enzymes (N-acetyltransferase (NAT) and hydroxyindole-O-methoxyltransferase (HIOMT)) which synthesize melatonin from serotonin showed that bone marrow cells have measurable NAT activity, but they have very low levels of HIOMT activity (at the one time they were measured). From these studies we could not definitively determine whether melatonin was produced in bone marrow cells or elsewhere. To investigate the potential pineal origin of bone marrow melatonin, long-term (8-month) pinealectomized rats were used to ascertain if the pineal gland is the primary source of this antioxidant. The bone marrow of pinealectomized rats, however, still exhibited high levels of melatonin. These results indicate that a major portion of the bone marrow's melatonin is of extrapineal origin. Immunocytochemistry clearly showed a positive melatonin reaction intracellularly in bone marrow cells. A melatonin concentrating mechanism in these cells is suggested by these findings and this may involve a specific melatonin binding protein. Since melatonin is an endogenous free radical scavenger and an immune-enhancing agent, the high levels of melatonin in bone marrow cells may provide on-site protection to reduce oxidative damage to these highly vulnerable hematopoietic cells and may enhance the immune capacity of cells such as lymphocytes.

PMID: 10572942 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10599869&dopt=Abstract

J Neural Transm 1999;106(9-10):869-81

Maternal photoperiodic exposures alter the neonatal growth, pineal functions and sexual development of the Indian palm squirrel F. pennanti. Short communication.

Bishnupuri KS, Haldar C.

Department of Zoology, Banaras Hindu University, Varanasi, India.

The phenomenon of maternal transfer of photic information to their young ones is still an enigma. Existing reports in some rodents of temperate zone suggest that photoperiodic condition experienced by mother during their gestation period influences the pineal physiology of fetus, but nothing has been reported about the growth and sexual development of pups. Present experiment for the first time explains the effect of gestational photoperiod on the growth and sexual development of pups from a seasonally breeding tropical rodent F. pennanti. The results suggest that, constant light (LL; 24L: OD) and long day length (LDL; 14L: 10D) experiencing mother conveyed the photic information to young ones to inhibit the pineal function, while short day length (SDL; 10L: 14D) stimulated the pineal function in pups. Altered pineal functions of pups ultimately interfered with their growth and sexual maturation. Most interestingly, the pups delivered by DD experiencing mothers and then reared under same condition, at the age of 40 days attained a level of growth and sexual maturity equivalent to the growth and sexual maturation of 60 days old pups under natural day length (NDL) condition. Therefore, we may suggest that the photic information perceived by the mother alter her normal melatonin level, hence, passing through placenta melatonin influences the growth and sexual maturation of the young ones.

PMID: 10599869 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10561222&dopt=Abstract

J Clin Oncol 1999 Jun;17(6):1829-37

Comment in:

Trilateral retinoblastoma: a meta-analysis of hereditary retinoblastoma associated with primary ectopic intracranial retinoblastoma.

Kivela T.

Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. tero.kivela@helsinki.fi

PURPOSE: To obtain refined knowledge regarding trilateral retinoblastoma (TRb), which is a syndrome that consists of hereditary retinoblastoma associated with an intracranial neuroblastic tumor.
MATERIALS AND METHODS: Using a systematic literature review, we contacted authors to obtain missing information. Data from 106 children were used in a meta-analysis including frequency distributions and Kaplan-Meier survival curves.
RESULTS: TRb showed no sex predilection. Median age at diagnosis of retinoblastoma was 5 months (range, 0 to 29 months); age at diagnosis was younger among 47 children (47%) with familial retinoblastoma compared with age at diagnosis among 52 children (53%) with sporadic retinoblastoma (2 v 6.5 months, P <.0001). TRb usually affected the second or third generation with retinoblastoma. Median time from retinoblastoma to TRb was 21 months (range, 6 months before to 141 months after); time to TRb was longer for 78 (77%) pineal tumors compared with 23 (23%) suprasellar tumors (32 v 6.5 months, P <.0001). The size (27 v 32 mm, P =.57) and prognosis (survival of 9 v 8 months, P =.91) of pineal and suprasellar tumors were similar. TRb was detected earlier (1 v 22 months, P =.0007) and the child survived longer if neuroimaging was routinely performed (16 v 8 months, P =.001), but age at death was similar (36 v 37 months, P =.98). Cumulative 5-year survival (which was likely to indicate cure) was 27% (v 0%) if screening was undertaken. All children whose TRb exceeded 15 mm in size died.
CONCLUSION: The family history, age at diagnosis, and laterality of retinoblastoma in children with TRb resembled that of ordinary hereditary retinoblastoma. Suprasellar TRb were diagnosed earlier, and may arise earlier, than pineal TRb. Screening by neuroimaging could improve the cure rate if cases of TRb were detected when tumors were 15 mm or smaller in size.

Publication Types:

PMID: 10561222 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10810540&dopt=Abstract

Adv Exp Med Biol 1999;460:395-405

MLT and the immune-hematopoietic system.

Maestroni GJ.

Istituto Cantonale di Patologia, Center for Experimental Pathology, Locarno, Switzerland.

It is now well recognized that a main actor in the continuous interaction between the nervous and immune systems is the pineal hormone MLT. T-helper cells bear G-protein coupled MLT cell membrane receptors and, perhaps, MLT nuclear receptors. Activation of MLT receptors enhances the release of T-helper cell type 1 (Th1) cytokines, such as gamma-interferon and interleukin-2 (IL-2), as well as of novel opioid cytokines which crossreact immunologically with both interleukin-4 (IL-4) and dynorphin B. MLT has been reported also to enhance the production of interleukin-1 (IL-1), interleukin-6 (IL-6) and interleukin-12 (IL-12) in human monocytes. These mediators may counteract stress-induced immunodepression and other secondary immunodeficiencies, protect mice against lethal viral and bacterial diseases, synergize with IL-2 in cancer patients and influence hematopoiesis. In cancer patients, MLT seems to be required for the effectiveness of low dose IL-2 in those neoplasias that are generally resistant to IL-2 alone. Hematopoiesis is apparently influenced by the action of the MLT-induced-opioids (MIO) on kappa-opioid receptors present on stromal bone marrow macrophages. Most interestingly, gamma-interferon and colony stimulating factors (CSFs) may modulate the production of MLT in the pineal gland. A hypothetical pineal-immune-hematopoietic network is, therefore, taking shape. From the immunopharmacological and ethical point of view, clinical studies on the effect of MLT in combination with IL-2 or other cytokines in viral disease including human immunodeficiency virus-infected patients and cancer patients are needed. In conclusion, MLT seems to play a crucial role in the homeostatic interactions between the brain and the immune-hematopoietic system and deserves to be further studied to identify its therapeutic indications and its adverse effects.

Publication Types:

PMID: 10810540 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10231732&dopt=Abstract

J Pineal Res 1999 Apr;26(3):178-83

Mechanisms underlying the effects of estrogen on nocturnal melatonin synthesis in peripubertal female rats: relation to norepinephrine and adenylate cyclase.

Hayashi K, Okatani Y.

Department of Obstetrics and Gynecology, Kochi Medical School, Japan.

We previously reported that estrogen modulates the nocturnal synthesis of melatonin in the pineal gland of peripubertal female rats. These effects appeared to be mediated by the modulation of N-acetyltransferase (NAT) activity. The present study assessed the mechanism underlying the effects of estrogen deficiency and stimulation on pineal melatonin synthesis in peripubertal female rats. We measured the norepinephrine levels and adenylate cyclase activity in pineal gland homogenates obtained from 4-10-wk-of-age female Sprague Dawley rats at mid-dark during the daily light/dark cycle. The animals were ovariectomized and daily s.c. administration of estradiol benzoate (E2B, 1.0 microgram/d) was initiated at 4 wk of age. Pineal norepinephrine levels increased significantly from Week 3 to 4 (P < 0.0001), and remained unchanged thereafter. Neither ovariectomy nor E2B administration significantly affected norepinephrine levels. Adenylate cyclase activity in the pineal gland peaked at 4 wk in untreated (control) rats. Ovariectomy at Week 4 led to a significant increase in adenylate cyclase activity at Week 8. At Week 10, adenylate cyclase activity returned to control levels. S.c. injection of E2B suppressed the ovariectomy-induced increase in adenylate cyclase activity to the level seen in control rats. These changes in mid-dark adenylate cyclase activity resembled those previously observed with NAT activity. The results suggest that estrogen modulates adenylate cyclase activity in the pineal gland of peripubertal female rats. The inhibitory effect of estrogen on melatonin synthesis appeared to be mediated in part, by changes in the norepinephrine-induced stimulation of pineal adenylate cyclase activity.

PMID: 10231732 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11462112&dopt=Abstract

Neuroendocrinol Lett 1999;20(3-4):179-188

Melatonin in humans-where we are 40 years after its discovery.

Karasek M.

Laboratory of Electron Microscopy, Chair of Pathomorphology, Medical University of Lodz, Czechoslowacka 8/10, 92-216 Lodz, Poland. karasek@psk2.am.lodz.pl

Although the pineal gland was well known for more than 2000 years and has been documented since Galen (130-200 AD), for many centuries different theories concerning its function were presented. The organ was believed to be a sphincter (ancient Greeks), the point at which the soul preeminently controls the body (Descartes, 1596-1650), a rudimentary organ (up to the 19th century), and a gland having endocrine function. Endocrine function of the pineal was postulated already at the end of 19th century and the beginning of the 20th century with the notion of antigonadotropic pineal influence, and the functional cooperation between the pineal and hypothalamo-hypophysial axis, but no secretory substance responsible for the gland function was known. In 1958 Lerner and coworkers succeeded in isolating from bovine pineal glands the compound termed melatonin because of its blanching effect on melanophores. This discovery constituted the milestone for further pineal research. Since then the knowledge of the structure and function of the pineal gland has tremendously increased, especially during the last two decades. However, it should be stressed that many problems in pineal research still must be solved. In this paper, the recent knowledge on the role of melatonin in humans is briefly presented.

PMID: 11462112 [PubMed - as supplied by publisher]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11458197&dopt=Abstract

Neuroendocrinol Lett 1999;20(6):343-349

The pineal gland as a central regulator of cytokine network.

Lissoni P.

Divisione di Radioterapia Oncologica, Ospedale San Gerardo, 20052 Monza (Milano), Italy.

Even though cytokines may fundamentally act as local factors, the recent advances in the knowledge of neuroimmunomodulation (NIM) would suggest the existence of a central regulation of their secretion and activity. Several neuroactive substances have appeared to influence cytokine secretion, and on the other hand cytokines may modulate the neuroendocrine functions. However, at present only for the pineal gland, whose fundamental NIM role is well known, it is possible to recognize reciprocal influences between cytokine action and pineal endocrine activity, suggesting the existence of feedback mechanisms responsible for a central regulation of cytokine network. Melatonin (MLT), which is the most investigated pineal immunomodulating hormone, may stimulate IL-2 release by T helper-1 (TH-1) lymphocytes and that of IL-12 by dendritic cells (DC), whereas both IL-2 and IL-12 would inhibit MLT release. The physiological significance of IL-2-IL-12-MLT interactions would be the maintenance of an effective TH-1-dependent cellular immunity, including the anticancer immune response. A third possible pineal-cytokine feedback mechanism involves tumor necrosis factor-alpha (TNF-alpha) secretion, with a stimulatory effect of TNF-alpha on MLT release and an inhibitory one of MLT on TNF-alpha production. This finding would explain the anti-cachectic property of MLT itself. A further knowledge of pineal-cytokine interactions, as well as of other endocrine-immune circuits, will allow a better definition of the physiopathology of human chronic immunoinflammatory diseases, whose clinical course has appeared to be influenced by psychoemotional factors.

PMID: 11458197 [PubMed - as supplied by publisher]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11462104&dopt=Abstract

Neuroendocrinol Lett 1999;20(3-4):139-144

Pineal gland, melatonin and cancer. NEL Review.

Karasek M, Pawlikowski M.

Laboratory of Electron Microscopy, Chair of Pathomorphology, Medical University of Lodz, Czechoslowacka 8/10, 92-216 Lodz, Poland. karasek@psk2.am.lodz.pl

Studies on the relationship between the pineal gland, melatonin and neoplastic disease have recently become one of the most fascinating aspects of pineal research. The first data suggesting a link between the pineal and cancer were published 70 years ago. However, the real progress in this area of research has been made in the last two decades. The bulk of the experimental evidence indicates the influence of the pineal gland on the malignant tumor formation and/or growth. The majority of reports point toward the oncostatic action of the pineal, exerted most probably by its hormone, melatonin, via different mechanisms, including modulation of endocrine and immune systems and direct antiproliferative action. The mechanisms of the oncostatic action of the pineal seem to be, however, very complex. There is some indication that the pineal gland may also play a role in human malignancy. Alterations in melatonin concentrations have been demonstrated in various tumor types including breast cancer, prostate cancer, colorectal carcinoma, and uterine cancer. Moreover, melatonin has been reported to be helpful in therapy of advanced cancer of various types. However, detailed 24h melatonin profiles must be studied in large numbers of patients with different types of tumors before determining whether melatonin concentrations have any diagnostic and/or prognostic values in cancer patients. Moreover, well designed clinical trials should be performed on the possible therapeutic significance of melatonin in neoplastic disease.

PMID: 11462104 [PubMed - as supplied by publisher]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11554386&dopt=Abstract

Neuro-oncol 1999 Jan;1(1):14-25

Descriptive epidemiology of primary brain and CNS tumors: results from the Central Brain Tumor Registry of the United States, 1990-1994.

Surawicz TS, McCarthy BJ, Kupelian V, Jukich PJ, Bruner JM, Davis FG.


Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, 2121 West Taylor Street, Chicago, IL 60612-7260, USA.

The Central Brain Tumor Registry of the United States (CBTRUS) obtained 5 years of incidence data (1990-1994)--including reports on all primary brain and CNS tumors--from 11 collaborating state cancer registries. Data were available for 20,765 tumors located in the brain, meninges, and other CNS sites, including the pituitary and pineal glands. The average annual incidence was estimated at 11.5 cases per 100,000 person-years. The higher incidence of tumors in male patients (12.1 per 100,000 person-years) than in female patients (11.0 per 100,000 person-years) was statistically significant (P < 0.05); the higher incidence in whites (11.6 per 100,000 person-years) compared with blacks (7.8 per 100,000 person-years) was statistically significant (P < 0.05). The most frequently reported histologies were meningiomas (24.0%) and glioblastomas (22.6%). Higher rates for glioblastomas, anaplastic astrocytomas, oligodendrogliomas, anaplastic oligodendrogliomas, ependymomas, mixed gliomas, astrocytomas not otherwise specified, medulloblastomas, lymphomas, and germ cell tumors in male than in female patients were statistically significant (P < 0.05), with relative risks (RR) ranging from 1.3 to 3.4. Meningiomas were the only tumors with a significant excess in females (RR = 0.5). We noted higher occurrence rates in whites than in blacks for the following histologies: diffuse astrocytomas, anaplastic astrocytomas, glioblastomas, oligodendrogliomas, ependymomas, mixed gliomas, astrocytomas NOS, medulloblastomas, nerve sheath tumors, hemangioblastomas, and germ cell tumors, with RRs ranging from 1.5 to 3.4. Racial differences in occurrence rates were not observed for predominately benign meningiomas or pituitary tumors. This study represents the largest compilation of data on primary brain and CNS tumors in the United States. Standard reporting definitions and practices must be universally adopted to improve the quality and use of cancer registry data.

PMID: 11554386 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10551769&dopt=Abstract

J Pineal Res 1999 Nov;27(4):221-5

Melatonin and protection from genetic damage in blood and bone marrow: whole-body irradiation studies in mice.

Vijayalaxmi, Meltz ML, Reiter RJ, Herman TS.

Department of Radiology, The University of Texas Health Science Center, San Antonio 78284, USA. vijay@uthscsa.edu

The objective of this study was to examine the potential radioprotective properties of pharmacological doses of melatonin in whole-body irradiated mice. CD2-F1 male mice were treated with melatonin, a secretory product of the pineal gland, and then whole-body irradiated with an acute dose (150 cGy) of 137Cs gamma rays. Peripheral blood and bone marrow cells were examined for genetic damage, which was determined by comparing the incidence of micronuclei (MN) in both melatonin pre-treated and non-treated irradiated animals (and control mice). The percentages of polychromatic erythrocytes (PCEs) in unirradiated mice ranged between 3.1 +/- 0.23 and 3.2 +/- 0.19 in the peripheral blood and between 51.0 +/- 2.03 and 52.8 +/- 2.00 in the bone marrow. Whole-body irradiation resulted in a significant decrease in the percentages of PCEs in the peripheral blood and bone marrow cells. In both tissues, irradiated mice that were pre-treated with melatonin (5 or 10 mg/kg) exhibited a dose-dependent increase in the observed incidence of PCEs relative to the expected incidence. The incidence of MN in unirradiated mice ranged between 4.2 +/- 0.92 and 4.6 +/- 0.97 in the peripheral blood and between 5.0 +/- 1.05 and 5.5 +/- 1.08 in the bone marrow. Whole-body irradiation resulted in a significant increase in the incidence of MN in both tissues. In both tissues, irradiated mice that were pre-treated with melatonin exhibited a significant and dose-dependent reduction in the observed incidence of MN (relative to the expected incidence). Under the experimental conditions tested, the data indicate that melatonin has the ability to protect the genetic material of hematopoietic cells of mice from the damaging effects of acute whole-body irradiation.

PMID: 10551769 [PubMed - indexed for MEDLINE]


Full free report available at: http://www.jbc.org/cgi/content/full/274/31/22041

J Biol Chem 1999 Jul 30;274(31):22041-7

Melatonin promotes osteoblast differentiation and bone formation.

Roth JA, Kim BG, Lin WL, Cho MI.

Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, New York 14214, USA.

Prior studies have demonstrated that the pineal hormone, melatonin, can stimulate chloramphenicol acetyltransferase activity in Drosophila SL-3 cells transfected with a chloramphenicol acetyltransferase reporter construct containing the response element of rat bone sialoprotein (BSP). Based on these findings, studies were performed to determine whether melatonin could similarly modulate the expression of BSP in two cell lines, the MC3T3-E1(MC3T3) pre-osteoblast and rat osteoblast-like osteosarcoma 17/2.8 cell. Initial studies demonstrated that MC3T3 cells grown in the presence of 50 nM melatonin underwent cell differentiation and mineralization by day 12 instead of the 21-day period normally required for cells grown in untreated media. Melatonin increased gene expression of BSP and the other bone marker proteins, including alkaline phosphatase (ALP); osteopontin; secreted protein, acidic and rich in cysteine; and osteocalcin in MC3T3 cells in a concentration-dependent manner. Levels of melatonin as low as 10 nM were capable of stimulating transcription of these genes when cells were grown in the presence of beta-glycerophosphate and ascorbic acid. Under these conditions, melatonin induced gene expression of the bone marker proteins; however, this does not occur until the 5th day after seeding the culture dishes. Thereafter, MC3T3 cells responded to melatonin within 2 h of treatment. The fully differentiated rat osteoblast-like osteosarcoma 17/2.8 cells responded rapidly to melatonin and displayed an increase in the expression of BSP, ALP, and osteocalcin genes within 1 h of exposure to the hormone. To determine whether melatonin-induced osteoblast differentiation and bone formation are mediated via the transmembrane receptor, MC3T3 cells were treated in the presence and absence of melatonin with either luzindole, a competitive inhibitor of the binding of melatonin to the transmembrane receptors, or pertussis toxin, an uncoupler of G(i) from adenylate cyclase. Both luzindole and pertussis toxin were shown to reduce melatonin-induced expression of BSP and ALP. These results demonstrate, for the first time, that the pineal hormone, melatonin, is capable of promoting osteoblast differentiation and mineralization of matrix in culture and suggest that this hormone may play an essential role in regulating bone growth.

PMID: 10419530 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10379416&dopt=Abstract

Appl Neuropsychol 1999;6(2):108-14

Longitudinal neuropsychological evaluation of a case of pineal tumor occurring in an adolescent girl.

Crews WD Jr, Jefferson AL, Barth JT.

University of Virginia Health Sciences Center, Charlottesville 22908, USA.

There has been a relative absence of studies that have longitudinally examined the neuropsychological profiles of patients suffering from pineal tumors. A case is reported of an adolescent girl with a pineoblastoma and spinal metastases who received extensive chemotherapy and cranio-spinal irradiation. Neuropsychological assessments conducted approximately 5 months and 2.5 years posttumor diagnosis revealed a diversity of impairments indicative of mild to moderate neuropsychological dysfunction. By the 2nd evaluation (2 years postbaseline) there was evidence of increased neurocognitive impairment suggestive of greater dysfunction of the patient's right, versus left, cerebral hemisphere. Overall, the patient's neuropsychological profile coincided with the Syndrome of Nonverbal Learning Disabilities as proposed by Rourke and his colleagues (Rourke, 1987, 1988, 1995; Rourke & Tsatsanis, 1996). These findings are discussed in light of the Syndrome of Nonverbal Learning Disabilities (and the related white matter model) and the possible negative impact of the patient's pineal tumor and subsequent chemotherapy and cranio-spinal irradiation on her neuropsychological functioning.

PMID: 10379416 [PubMed - indexed for MEDLINE]