Epiphysis Sixth sense

Pineal Gland Activation Course

World renowned expert on the pineal gland, Shaktipat Seer has helped thousands around the planet activate their pineal gland safely. Through pineal gland activation you can have a thorough cleansing of your aura, bringing into full effect the latent kundalini powers of your body. Over the years he has perfected his ability to give direct transmission of Spiritual Energy to the Third Eye Chakra, setting alight the glowing powers of the Philosophers Stone of the Neo Cortex region. Discover A Simple System That Anyone Can Do, Regardless Of Age Or Ability And From The Comfort Of Their Own Home. Through Pineal Gland Activation You Can Have A Cleansing Of Your Aura, Bringing Into Full Effect The Latent Kundalini Powers Of The Body Leading To. Shaktipat Seer is not trying to give you some cooky pseudo-science that many snake oil salesman push that has no real transcendental benefit. Instead he is merely presenting the natural way that this process has been effected (through transmission of Shakti to the Third Eye) in the East (India,Tibet,China etc.) for thousands and thousands of years.

Pineal Gland Activation Course Summary


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The Pineal Gland A Melatonin Factory On A 24hour Schedule

At the time I started working in this field around 1968, Aaron Lerner's discoveries of melatonin and the high concentrations of melatonin in the pineal gland were well known (17,18), as was the high amount of serotonin in the pineal gland (19). Julie Axelrod and his coworkers were generally interested in biogenic amine metabolizing enzymes, so it was not long before Lerner's findings led to their demonstration that the pineal gland had the enzymatic machinery required to convert serotonin to N-acetylserotonin and N-acetylserotonin to melatonin (20,21). This established the pineal gland as a melatonin factory. Interest in the regulation of melatonin levels first focused on the last enzyme in melatonin synthesis, hydroxyindole-O-methyltransferase (HIOMT). Axelrod and his coworkers characterized the protein and found that high levels were found only in the pineal gland, based on studies in mammals (12,24-27). In contrast, serotonin acetyla-tion was thought to be mediated by a widely...

The Role Of Nacetyltransferase In Regulating Rhythms In Pineal Indole Metabolism

My entre into the pineal field came after hearing Russell Reiter give a seminar entitled The Truth About the Pineal Gland , which I attended while both of us were at the University of Rochester. I came there in 1967 from Rice University after receiving my Ph.D. on the recently discovered thyroid hormone calcitonin. My goal in Rochester was to use in vitro techniques to study the hormonal control of bone metabolism as a fellow with Larry Raisz. After about a year of bone work, I realized that if I was going to make a contribution to science and establish a productive independent research program, the chances were slim that this could be done in the bone field. This area was filled with many well established, large and intensely competitive groups. I started to look around for new fields to conquer. I liked endocrinology and a look at my endocrinology text gave me my some indication of where I should go the pineal gland or thymus. The reason Not too much seemed to have been known about...

Types Of Pinealocytes

According to structural and ultrastructural criteria vertebrate pinealocytes have been subdivided into three major categories true pineal photoreceptors, modified pineal photoreceptors and pinealocytes sensu stricto (11,59 cf. 43). True pineal pho-toreceptors are restricted to anamniotes, modified pineal photoreceptors are predominantly found in lacertilian and avian species and pinealocytes sensu stricto form the parenchyma of the mammalian and also the ophidian pineal gland.

The Blood Brain Barrier

A second barrier exists at the circumventricular organs (CVOs). The CVOs are located close to the ventricles of the brain and they include the chorioid plexuses, the median eminence, the organum vasculosum of the lamina terminalis, the subfornical organ, the subcommissural organ, the area postrema, the neuro-hypophysis and the pineal gland.

Resultsand Discussion

Acute exposure of dark-adapted chicks to UV-A light produced a marked suppression of nighttime NAT activity of the pineal gland. The magnitude of the observed decline in the enzyme activity was dependent on the duration of the light pulse and age of chicks, with two weeks old birds being more sensitive than seven weeks old animals (Figure 1). In another set of experiments, after a 5 min pulse of UV-A light chicks were transferred to darkness and a time course of NAT reactivation was determined for the pineal gland. When the exposure took place at the beginning of the fourth hour of the dark phase, i.e., when levels of both NAT-mRNA and NAT activity are increasing (5), the small UV-A light-evoked decline in the enzyme activity gradually deepened during the first 40min treatments of the birds with darkness, from 9 (at 0min) to 43 (at 40min). After 40min of darkness, NAT activity of the chick pineal gland began to rise, reaching complete restoration within 2 hours (Figure 2A). When the...

Pediatric Brain Tumors

When any brain tumor is discovered on an imaging study, an appropriate differential diagnosis can be offered by answering several questions. Is the tumor extra- or intra-axial Is the tumor infratentorial (i.e., posterior fossa), or supratentorial Is it hemispheric, sellar, suprasellar, or in the vicinity of the pineal gland What additional distinguishing imaging characteristics does the mass display Various imaging features of pediatric brain tumors are listed in Tables 8-12.

Associated With Open Procedures

In varied examples, arthroscopy has been described either in conjunction with open procedures or as a prelude to a subsequent open procedure. Futami et al.91 described the role of arthroscopy in coordination with pinning for slipped capital femoral epiphysis, and Ruch has described arthroscopic guidance in positioning for core decompression in the presence of AVN.91,92 Hawkins described arthroscopically assisted debridement of the hip via a miniarthrotomy, and Sekiya et al. have reported a similar method of arthroscopy via a limited anterior approach.93,94 Osteotomy is occasionally performed for a variety of hip disorders.95 Arthroscopy may be a useful adjunct in the planning process for selecting candidates for oste-otomy.5 Its role in staging of AVN and addressing coexistent intraarticular pathology has also been described.71

Differential Diagnosis

The diagnosis of osteosarcoma is usually uncomplicated when typical histology is complimented by clinical and radiographic information. The histologic variants when examined without benefit of the aforementioned information may give rise to other diagnostic possibilities. Osteoblastoma and fracture callus may bear some resemblance to conventional intramedullary osteosarcoma, if dealing with minimal tissue samples. The findings of cellular anaplasia, atypical mitotic figures, and an infiltrative border will help rule out osteoblastoma, whereas non-neoplastic cartilage and reactive bony trabeculae lined by osteoblasts are typically seen in a fracture callus. Chondroblastic osteosarcoma can be distinguished from chondrosarcoma by detecting definitive osteoid formation. Distinguishing between giant cell tumor of bone and giant cell osteosarcoma can be difficult. The finding of pleomorphism in the mononuclear cells and atypical mitotic figures help argue against giant cell tumor of bone....

Determination of Gs and ADRmRNA by In Situ Hybridization

To analyze expression of the PKA subunit transcripts, RNA extraction was performed according to a modification of a previously described procedure (42,16) or by use of the Qiagen Mini-RNA kit. A single pineal gland or 100,000 cells were extracted in 300 l Qiagen lysis buffer, processed according to the supplier's protocol and finally eluted into 50 l DEPC water. Northern blots of total RNA samples obtained from rat pineal glands six hours after light on (midday 12 00) and six hours after light off (midnight 24 00) were hybridized with cDNA probes against human RIa, RIP, RIIa and RII . The use of human cDNA probes for the detection of rat mRNA is possible since the interspecies homology for PKA subunit isoforms is more than 90 at the nucleotide level (26). Thus, human probes were expected to detect rat mRNA as has also been shown for bovine mRNAs (42). One to 3 l of the above described RNA preparations were used for a single reverse-transcriptase reaction performed with

Adrenergic Receptors in the Membrane ofthe Rodent Pinealocyte

In rodents, norepinephrine (NE) is released nocturnally from the intrapineal nerve endings of sympathetic neurons originating from the superior cervical ganglion (21) and binds to a- and P -adrenergic receptors on the pinealocyte membrane (32). The - and -adrenergic receptors are the predominant neurotransmitter receptors in the rodent pineal organ. Of all rat tissues tested the pineal organ exerts the highest expression of 1-adrenergic receptor mRNA (40). Beside these adrenergic receptors, which are in the focus of this contribution, many other, e.g. peptidergic-, monoaminergic-, and cholinergic receptors are present in the rodent pineal gland as well (61,39). However, the P 1 -adrenergic receptor appears to be most important for AANAT mRNA upregu-lation and stimulation of melatonin biosynthesis (32,61,35). persists in constant darkness, is ablated in ganglionectomized animals and is therefore truly circadian (51 Figure 1). Interestingly the expression of the a 1 B-adrenergic...

Melatonin As A Seasonal Time

Melatonin transduces the effect of changes in daylength in photoperiodic mammals and thus times seasonal cycles in reproduction, moulting, somatic growth, fattening and other seasonal characteristics. This is the best characterised biological role(s) of melatonin (1,60,61). The photoperiodic transduction mechanism involves light perception by the retina, entrainment of the circadian rhythm generating system in the SCN and the inhibitory effect of light on the secretion of melatonin by the pineal gland (see other chapters). The result is that melatonin is secreted only at night, and the duration of secretion varies with the annual cycle in nightlength and thus daylength. The duration of melatonin secretion appears to be the critical parameter affecting the melatonin target tissues since daily infusions of melatonin of appropriate duration and maintained for many weeks, mimics the effect of long day (short period infusion) and short days (long period infusion) on seasonal physiology...

Circadian Regulation Of

As discussed above, early studies of mammalian photoperiodism led to two major types of findings (a) evidence that the circadian system is employed in the measurement of day length and (b) support for the involvement of the PMR, and more specifically the duration of the nocturnal increase in pineal MEL secretion, as an endocrine signal related to the photoperiod. The relation between these two types of conclusions can be understood by examining the influence of the circadian system on the PMR. It was clear from early studies that the circadian oscillator(s) of the suprachias-matic nuclei (SCN) is essential for regulating the PMR in mammals this contrasts with the situation for birds and reptiles, where the pineal gland has both photoreceptors and an intrinsic circadian rhythmicity (46). Later results in laboratory rats were interpreted as suggestive that circadian regulation of the PMR was best explained by a dual-oscillator model. Furthermore, these observations indicated that both...

Developmental Aspects Of Photoperiodism

The ability of the dam to influence the photoperiod responses of her offspring is dependent on some action of her pineal gland pups born to pinealectomized dams failed to exhibit differential responses to a postpartum 14 L photoperiod in relation to the day length in effect during gestation. Further, when pinealectomized dams were administered daily MEL infusions during late pregnancy, the photoperiodic responses of their male pups were related to the duration of the MEL infusions Mothers receiving long duration MEL infusions (to simulate a short day gestational photoperiod) gave birth to pups that showed relatively rapid testis growth in 14 L testis growth was slower in males born to mothers that had received long duration MEL infusions (simulating a long day gestational photoperiod). These results may indicate that the fetuses are able

Intraventricular Tumors

Ependymoma and glioblastoma multiforme. Although juvenile pilocytic astrocytomas most often originate from the floor of the third ventricle, they may arise from the posterior pituitary or optic system and extend into the ventricle. Low-grade astrocytomas, as well as anaplastic astrocytoma and glioblastoma multiforme, typically originate from the thalamic region. Ependymomas, and less frequently subependymomas, originate from the ventricular wall. These lesions are more common in the lateral ventricles. Subependymal giant cell astrocytoma, which may be associated with tuberous sclerosis, often originates at the foramen of Monro and is more frequently seen in the lateral ventricle. Colloid cysts are the most common lesions located in the third ventricle 3 . Although rare, epidermoid and dermoid tumors may occur in the third ventricle, and usually are solid rather than cystic at this location. Meningiomas originating from the velum inter-positum and choroid plexus papillomas are also...

Clear Cell Chondrosarcoma

This uncommon histologic variant contains tumor cells with abundant clear cytoplasm and little matrix. Involvement of the epiphysis is common. Although the cells have abundant clear cytoplasm with sharply defined cell borders, the growth pattern is still lobular. Nuclei are large and may be binucleated. The limited matrix production is chondroid and calcifications may be present (55,56).

The bloodCNS barriers

With the exception of the subcommisural organ, the fenestration of blood vessels makes the CVOs part of the blood-CSF barrier. CVOs are recognized as important sites for blood-brain communication as neurosecreto-ry products gain access to the bloodstream and blood-borne substances can be detected by neuronal structures. The term CVOs comprises the following organs pineal gland, median eminence, neurohypophysis, subfornical organ, area postrema, subcommissural organ, organum vasculosum of the lamina terminalis (Fig. 4). Sometimes the CP is also included as well as the intermediate and neural lobes of the pituitary 26 .

Scn Cells Expressing mt1 Receptor mRna Coexpress Avp mRna In Syrian And Siberian Hamsters

Many animals, especially mammals living in temperate zones, confine life history events to specific times of the year. For example, species of hamsters and voles bred in the long days of spring summer, whereas species of sheep and deer breed in the short days (SDs) of fall winter (1). The most noise-free seasonal cue in their environment is the photoperiod (10). The photoperiod triggers, seasonal responses, including changes in reproductive status mentioned above, as well as cycles of body mass and fat and pelage (1). This photic information is transmitted to the pineal gland via a multi-synaptic circuit beginning with the retina and concluding with the pinealocytes (5). Among the central nervous system structures included in this circuit is the suprachiasmatic nucleus (SCN) of the hypothalamus, the predominant biological clock. The pineal gland, through its primary hormone melatonin (MEL), triggers these and many other seasonal responses (1). MEL is synthesized and released only...

Health Impact of Obesity

Obesity can negatively impact a young person's health in many ways besides the neurological, cardiovascular, and metabolic effects. The patient is at risk for developing hepatic steatosis, polycystic ovary disease, and orthopedic problems like slipped capital femoral epiphysis, pseudotumor cerebri, and sleep apnea 45 . Finally, the psychosocial trauma of low self-esteem and social isolation can significantly impact the quality of the child's life. Having a chronic disease like obesity, with or without comorbidities, can be traumatic for a pre-adolescent or an adolescent. In one cross-sectional study by Schwimmer et al., 106 severely obese children and adolescents aged 5 to 18 years ranked their health-related quality of life the same as did children and adolescents with cancer 46 .

Lateral Uncovering Of The Femoral Head

Hip Femoral Head Gauge

The relationship of congenital hip dysplasia and labral pathology has been well defined.9,10 Severe dys-plasia carries a significant incidence of an inverted ac-etabular labrum (Figure 3.28). Milder degrees of dys-plasia, characterized by slight lateral uncovering of the femoral head, or slight valgus position of the femoral neck may be associated with milder degrees of labral disease (Figure 3.29). Additionally, subtle congenital or developmental changes such as those associated with mild Legg-Calve-Perthes disease or mild untreated slipped capital femoral epiphysis may be associated with symptomatic labral or chondral lesions in adulthood (Figure 3.30).

Osteochondritis Dissecans

Osteochondritis dissecans should be distinguished from osteochondrosis of the capitellum, which is known as Panner's disease. Panner's disease is characterized by fragmentation and abnormally decreased signal intensity within the ossifying capitellar epiphysis on the T1-weighted images similar in appearance to Legg-Calve-Perthes disease in the hip. Panner's disease is believed to represent avascular necrosis of the capitellar ossification center that occurs secondary to trauma. Subsequent scans reveal normalization of these changes with little or no residual deformity of the capitellar articular surface. The articular surface typically remains intact and does not undergo fragmentation or loose-body formation.

Richard N Villar and Nicola Santori

Femoral head to the medial border of the acetabular fossa behind the transverse ligament. It provides stability and restraint during the early phases of hip development. Furthermore, it gives mechanical support to the artery of the ligamentum teres or foveolar artery. This vessel is an important nutritional source during certain periods of growth. The anatomy of the circulation to the head is not constant during development, but differs significantly at different ages. During fetal life, three groups of vessels supply the hip joint the lateral epiphyseal, the anterior metaphyseal, and the foveolar artery. From 4 months of infancy onward, the vessels of the ligamentum teres regress. At this stage they play no part in the nutrition of the ossification center the main supply until the age of 7 years is the lateral epiphyseal vessels. The contribution from the artery of the ligamentum teres increases again in early adolescence (7 to 11 years). It penetrates the ossification center and...

Circadian sleepwake rhythms

Melatonin is related to the light-dark cycle rather than the sleep- wake cycle. It is secreted by the pineal gland during darkness and suppressed by exposure to bright light. It influences circadian rhythms via the suprachiasmatic nucleus pacemaker which, in turn, regulates melatonin secretion by relaying light information to the pineal gland. Its widespread popularity as a sleep-promoting agent is not justified by what little is known about its action and clinical effectiveness. (1.1)

Lifespan and the Circadian Insomnias

In assessing clock amplitude in the elderly, it is advantageous to measure more than one variable, e.g. core temperature nadir and circulating MLT levels. Impaired thermoregulation on the one hand, and potential pathology to the pineal gland and the circuitous pathway from the suprachiasmatic nuclei (SCN) (including autonomic innervation) on the other, makes hazardous single variable amplitude estimation in the aged.

Obstructive Hydrocephalus Due to Tumors

Midline tumors - particularly those of the pineal gland and posterior fossa - commonly result in obstructive hydrocephalus and, indeed, this is one of the principal ways in which these conditions present, especially in children. Although preliminary shunting of the hydro-cephalus has been advocated, in the majority of cases, the hydrocephalus will resolve following removal of the obstructive pathology. In their series of posterior fossa tumors with hydrocephalus, Kumar et al. reported that a shunt was required in 18.9 of cases 7 . Young age at presentation, incomplete tumor removal and malignant midline tumors were factors increasing the likelihood of shunt requirement.

Melatonin Duringaging

The pineal gland, through its hormone melatonin is involved in animal and human reproduction. It has been suggested that melatonin may be involved in the aging process (8). Melatonin is produced and secreted into the blood in a circadian rhythm with maximal production always during the dark phase of the day. The 24h rhythm of melatonin production is very robust in young animals, but this circa-dian rhythm deteriorates with age. Thus, in old animals the amounts of melatonin secreted are lower than that of young individuals and the supplemental administration of melatonin may be beneficial in delaying age-related degenerative conditions (7). Long-term melatonin treatment in rats can postpone the age related decrease in survival rates, circulating sex steroids and 125I-melatonin binding sites in the brain (5).

In Vivo Effects ofMLT on Mammary Cancer

Melatonin, the major hormonal product of the pineal gland, has repeatedly been shown to exert a negative influence on the development and growth of hormone-responsive breast cancer (10,11). Most of the work to date on the onco-static effects of MLT in vivo has been conducted in the 7,12-dimethylbenzanthracene (DMBA)- and N-nitroso-N-methylurea (NMU)-induced hormone-responsive rat mammary tumor models. The DMBA model has been studied with respect to the effects of pinealectomy, photoperiod, and MLT administration on the growth and regression of mammary tumors. Blask et al. (10) found that DMBA-induced mammary tumorigenesis is inhibited in light-deprived female rats, and that pinealec-tomy not only prevents this growth inhibition but actually enhances tumor growth. The advantage of the NMU model over the DMBA model is that the growth characteristics of the NMU-induced tumors more closely resemble those of human breast cancer cells. The tumor cells of this model are primarily responsive...


Maintenance of health depends to a significant extent on the ability of the exposed host to respond appropriately and, eventually, to adapt to environmental stressors. It is now well established that inappropriate or maladaptative response to such stressors weaken the body's resistance to other stimuli from the environment such as pathogenic organisms or cancer cells. It is fair to consider the social environment as part of the general environment which has an impact on the body via redundant and reciprocal interactions between the body and the brain. These are linked by the nervous, endocrine, and immune systems and utilize a large array of chemical messengers including hormones, cytokines and neurotransmitters (72). There is abundant evidence that there are functional afferent nerve endings in the tissue of the immune and hematopoietic systems arising from both the sympathetic and parasympathetic systems (1,2). It is also clear that many neurotransmitters, neuroendocrine factors and...

Other Endocrine Glands

There are several other glands in the endocrine system, including the thymus gland, the pineal gland, and the parathyroid glands. There are also specialized endocrine cells in the brain, stomach, small intestine, liver, and other organs. The major endocrine glands and their functions are listed in Table 50-2. Pineal Gland

Melatonin Role and Circadian Rhythms in Children with OSAS

Melatonin is produced by pineal gland. Light inhibits its secretion. Hence, a rhythmical secretion pattern is seen in all species, including humans. In humans, the highest melatonin levels are found in 2- to 5-year-old children from that age, secretion decrease progressively (Waldhauser, Weiszenbacher, and Tatzer 1988). It has long been known that melatonin has sleep-promoting properties and regulates the sleep-wake cycle. Melatonin has a strong circadian rhythm with high values during the nighttime and low values in the afternoon. Sleep disorders impair the quality of life for children with neurodevelopmental disabilities and their families. Melatonin, a natural regulator of sleep, may be an effective therapy in this area (Wassmer and Whitehouse 2006).

Gateways into the brain

Vascular Organ Lamina Terminalis

Sagittal view of the anatomical relationship among the circumventricular organs (CVOs), which are located on the midline of the brain (AP, Area postrema SFO, subfornical organ ME, median eminence PI, pineal gland OVLT, organum vasculosum of the lamina terminalis) 24 . Figure 4. Sagittal view of the anatomical relationship among the circumventricular organs (CVOs), which are located on the midline of the brain (AP, Area postrema SFO, subfornical organ ME, median eminence PI, pineal gland OVLT, organum vasculosum of the lamina terminalis) 24 .

Parasitic Retinal Disorders Definition


Findings and diagnostic considerations A grayish white, vascularized retinal tumor will be observed on ophthalmoscopy. In its advanced stages, this tumor was formerly referred to as an amaurotic cat's eye. Infiltration of the vitreous body, anterior chamber (pseudohypopyon), and orbit may occur. A retinoblastoma that also involves the fellow eye and pineal body is referred to as a trilateral retinoblastoma. U A trilateral retinoblastoma is defined as additional manifestation of the tumor in the pineal body.

Melatoninand Reproduction

A major physiological role of melatonin in adult mammals is the regulation of seasonal reproduction (for reviews see 3,21,33,68 and this volume). The pineal gland is necessary for appropriate perception of seasonal changes in day length and thus for the proper timing of reproduction in species which breed seasonally. The duration of the nocturnal melatonin elevation is regulated by the photoperiod. Melatonin ultimately affects reproductive activity by modulating the activity of hypothalamic neuroendocrine circuits whose activity is necessary for gonadal function. In the broadest Figure 2. The maternal pineal gland is the source of melatonin rhythms in fetal sheep. Top panel Melatonin rhythms in the mother and fetus are similar in phase and amplitude. Lower panel Removal of the maternal pineal abolishes maternal and fetal melatonin rhythms. Modified from Ref. 87. Figure 2. The maternal pineal gland is the source of melatonin rhythms in fetal sheep. Top panel Melatonin rhythms in the...

Sources Of Melatonin During Development

The primary source of circulating melatonin in adult mammals is the pineal gland (38). Melatonin levels are elevated at night. As reviewed in detail elsewhere in this volume, melatonin production from the pineal is regulated by the circadian clock in the suprachiasmatic nuclei. Other tissues appear capable of producing melatonin. Melatonin is produced rhythmically in the retina, but the retina does not appear to contribute significantly to circulating melatonin levels in rodents. N-acetyltransferase activity and NAT gene expression occur in other tissues, including brainstem and pituitary (12). With precursor loading it is possible to detect significant production of melatonin in the gastrointestinal tract, although melatonin synthesized in the gastrointestinal tract does not appear to contribute to circulating levels of the hormone (24). It is nevertheless possible the local production of melatonin within the abdomen may provide a pool capable of reaching the fetus. The primary...

Proposed Autonomic Regulation Of Melatonin Syntheis By Glutaminergic Systems

Based on these observations, we concluded that rat pinealocytes are equipped with machineries for input, output and termination of the glutamate signals (Fig. 1). Since the same pinealocytes express all these glutaminergic elements, the glutamate may be used as autocrine- or paracrine-like signals in the endocrine organ upon stimulation, pinealocytes secrete L-glutamate so as to inhibit NE-stimulated melatonin synthesis. Excess amount of glutamate is rapidly taken up by the reuptake system(s). Thus, melatonin synthesis in pinealocytes is negatively regulated by the glutaminergic systems. The glutamate-evoked regulation of melatonin synthesis seems to be a novel type of hormonal regulation, because a classical neurotransmitter is involved in the hormonal synthesis. Now, we are trying to reveal the elements of the pineal gluta-minergic systems at the molecular level. The glutamate-evoked inhibition of melatonin synthesis is observed even in the presence of NE, indicating that the...

Hypersomnia associated with neurological conditions

Brain tumours Brain tumours of specific location may result in excessive sleepiness in the absence of raised intracranial pressure. Excessive sleepiness is typically permanent. This is the case with some tumours affecting the posterolateral hypothalamus (gliomas, hamartomas, suprasellar craniopharyngiomas more than metastases or malignant lymphomas), the pineal gland (pinealomas, teratomas, astrocytomas), and the upper brainstem.

Melatonin Aging And The Circadian System

Aging is associated with a number of changes in the morphology, physiology and biochemistry of the pineal gland resulting in a significant reduction of the nocturnal melatonin levels in rodents and humans alike (12,20,27). It has been hypothesized that the age-related disruption of this robust signal affects the integrity of circadian time structures and is a precursor of disease states (2,21). Recent studies indicate that decreased binding of melatonin to the SCN of old rats is correlated with disruption in overt circadian rhythmicity (43), whereas treatment with the melatonin agonist, S-20242, can partially reverse the age-related decrease in the amplitude of the circa-dian temperature rhythm (13). We have recently found that in some hamsters treatment with melatonin in the food increases the amplitude and cohesiveness of the rhythm of locomotor activity which often becomes fragmented and disorganized in old animals (Van Reeth, unpublished results). Further support for some linkage...

Disruption Of The Ligamentum Teres

The exact function of the ligamentum teres remains an enigma. Although its accompanying artery contributes to the vascularity of the epiphysis in childhood, its importance in the adult is less clear. The vessel remains patent in a variable percentage of adults and likely does little to contribute to the vascularity of the femoral head.38,39 The ligament contributes little to the stability of the joint, but it has been proposed that it has a windshield wiper effect that may facilitate lubrication and nutrition of the joint sur-faces.40 It may well have proprioceptive and nocio-ceptive importance as well.

Conclusion And Perspectives

Melatonin Macrophage

MLT may be considered as a potential immunotherapeutic agent and an important endogenous neuroimmunomodulator. An hypothetical pineal gland-immune system physiological network might, therefore, take shape (Figure 1). The proper functioning of such network might be crucial in the adaptative response of the organism to environmental demands and, thus, in the maintenance of health. However, we are still far from a complete understanding of the mechanism underlying the immunological and hematopoietic action of MLT. For example, it is not clear whether MLT acts on Th1 or Th2 cells or on both. In addition, it is not known whether MLT may induce cytokine gene expression or whether its action is posttranslational only. These seem important questions as the Th1 Th2 balance and the resulting cytokines production are crucial for a successful immune response and may be relevant in immune-based pathologies (23). The stimulatory effect of MLT on IL-2 and gamma-IFN and the lack of influence on IL-4...

Siberian Hamster As Model For Study Of Photoperiodism

The Siberian hamster (Phodopus sungorus) has served as a useful subject for investigation into the neuroendocrine basis of photoperiodism. Observations made in this species have contributed very significantly to current concepts regarding the importance of the circadian system and the pineal gland in the photoperiodic mechanism. Siberian hamsters exhibit several robust seasonal variations that are regulated primarily by day length. These include seasonal changes in reproduction, body weight and fat stores, thermoregulation, and pelage. During the summer, most Siberian hamsters exhibit reproductive activity, maximum body lipid stores, and a gray pelage. In winter, most individuals have regressed gonads and low circulating concentrations Early work clearly established the importance of the pineal gland for photoperiodic responses in Siberian hamsters (22), and continuous release implants of melatonin (MEL) were shown to exert marked effects on the reproductive system, resembling the...

Second Messengers II Cyclic AMP cAMP

Rat pinealocytes were shown to contain the alpha-subunits of the G-proteins Gs, Go and Gi (5,6). Their amount did not vary between day and night, but was upregu-lated under stimulus-deprivation, suggesting that these G-proteins may be involved in denervation supersensitivity (5,6). Also the mRNA levels of Gs in the rat pineal gland remain constant at day and night (39 Figure 3). Gs links the activation of the -adrenergic receptors to the activation of adenylate cyclase which causes a drastic increase in intracellular CAMP-concentrations mirrored by a solid increase in extracellular cAMP levels (Co mean 73 6 fMol ml NE for 1 h mean 1429 226 fMol ml SEM N 4). Information about the types of adenylate cyclase (AC) expressed in the rodent pineal gland is sparse (70).

Upward cerebellar herniation

This occurs with large or superior cerebellar masses and produces a clinical picture which is indistinguishable from the central herniation syndrome. With progressive crowding of the tentorial notch, the pineal gland and suprapineal recess are displaced superiorly and the superior cerebellar and posterior cerebral arteries may be compressed against the free margins of the tentorium. This can lead to ischemic infarction of the superior cerebellum and occipital lobes which further complicates matters. If the precipitating lesion has not already obstructed the flow of cerebrospinal fluid, upward herniation of the cerebellum will often do so at the level of the aqueduct of Sylvius. This produces a counterbalancing effect in which the tentorial notch is invaded from below by the herniating cerebellum and from above by the

Vasoactive Intestinal Polypeptide VIP

Inhibited VIP mRNA expression in the SCN of hamsters for at least several hours, and this effect does not require the pineal gland. Thus, the pineal gland may chronically and differentially modulate the expression of VIP mRNA in the SCN where the activity of VIP neurons is decreased after the short photoperiod. Evidence suggest that VIP neurons of the SCN project to the paraventricular nuclei, which is a necessary component of the neural pathway generating the circadian pacemaker, and also modulates the endocrine functions with which these neurons have been associated (Duncan 1998).

Posterior Extension Injuries

Complications from these lesions are the result of the operative treatment itself. As with any other surgery requiring hardware placement around the elbow, pain from hardware is the most common complication. This is treated by removal after the fracture has healed, as determined on radiographs. Spur formation secondary to overgrowth of the olecranon epiphysis can occur.19 In some patients, it becomes symptomatic and may have to be excised. Apophyseal arrest rarely occurs and does not have a significant effect on elbow function.

Glutamate Signal Input

To test this hypothesis, we investigated whether class II mGluRs are expressed in pineal glands. There are two known isoforms of class II mGluRs, mGluR2 and mGluR3 (19,23-25). RT-PCR analysis and Northern blotting of pineal RNA demonstrated the expression of mRNA for mGluR3. No expression of the mRNAs for mGluR3 was observed in other tissues tested. There was no detectable hybridization of the mGluR2 probe to pineal gland RNA, indicating that the level of mGluR2 transcript was below detection limit of our Northern analysis. Furthermore, immunohistochemistry with antibodies specific for class II mGluRs demonstrated that the antigen was expressed in synaptophysin-positive cells, an indicator of pinealocytes (10,5,14). No antigen was present innon-pinealocyte cells. Gila , the major subunit of the Gi protein that is linked to mGluR3, was also detected immunologically in pinealocytes but not in other cells types (16). These results confirmed that both mGluR3 and Gi proteins are present in...

In the theory of mind an intelligent supervisor in the brain that reads information and commands action

Rephrasing Eliot on cats (Eliot 1939), the naming of homunculi is a difficult matter. In psychology they become variants of 'central executives' (see working memory). In physiology they resurface disguised as 'grandmother cells', 'command neurons', and more (see below). In philosophy, homunculi have been discussed many years before they were so named. Descartes' proposal that the pineal gland is the site of the soul (Descartes 1649) is a version of the homunculus with

Melatonin Biosynthesis

Scheme of some currently known signal transduction pathways in the rodent pineal gland. ER, endoplasmatic reticulum HIOMT, hydroxyindole-O-methyl-transferase. The other abbreviations are explained in the text. Modified after 61,39). Figure 10. Scheme of some currently known signal transduction pathways in the rodent pineal gland. ER, endoplasmatic reticulum HIOMT, hydroxyindole-O-methyl-transferase. The other abbreviations are explained in the text. Modified after 61,39).

The Future Of Aanat

In what directions will AANAT research go It is reasonable to predict that continued investigations of AANAT will lead to a better understanding of clock control of gene expression in vertebrates this should come form studies on the chicken and pike. Studies on rat AANAT promoters will shed light on the molecular basis of control of tissue specific expression of genes in the pineal gland and retina. Analysis of AANAT degradation should lead to a detailed understanding of this process in the pineal gland and will also reveal how proteolysis is regulated in the nervous system. Pharmacology studies are expected to lead to the identification of agents that modify AANAT activity in the pineal gland and elsewhere, with the possible evolution of such agents into AANAT-directed drugs that influence sleep and behavior. I expect that studies on the structure of AANAT will enhance our understanding of fundamental elements of enzyme action and will also provide a description of three dimensional...


The more abnormal the tissue, the more difficult it may be to identify the origin of the tissue. Frequently, however, some clues can be found at the edge of the specimen. One may see gray matter, recognizable with neurons, but bits of cerebral cortex cannot easily be differentiated from basal ganglia or spinal cord gray unless one sees leptomeninges on the surface. One may see white matter or myelinated fibers, which should differ in CNS or peripheral nervous system (PNS), but bits of CNS white matter in the cerebrum cannot be distinguished from those in the spinal cord or cerebellum unless one sees other landmarks - again, leptomeninges being helpful in non-cortical locations. White matter bundles separated by thin connective tissue septa are a relatively specific architecture of the optic nerve. Other structures, such as the pituitary gland, pineal gland, peripheral nerve, choroid plexus and leptomeninges can usually be identified with little difficulty.


Melatonin is synthesized from the amino acid tryptophan (tryptophan 5-hydroxytryptopha serotonin N-acetylserotoni melatonin). In the chick retina, mRNA levels and activities of two enzymes in this pathway, tryptophan hydroxylase (TPH) and arylalkylamine N-acetyltranferase (AA-NAT), display circadian rhythms. The dramatic nocturnal increase in melatonin production in this tissue in part reflects circadian clock-driven increases in mRNA encoding both enzymes. This appears to be translated into increases in both TPH and AA-NAT protein. In the case of AA-NAT, however, this translation is strongly dependent upon environmental lighting. Light acts through post-transcriptional mechanisms to regulate AA-NAT activity a hypothetical mechanism is proteasomal proteolysis that is otherwise inhibited in the dark by second messengers. Accordingly, melatonin production in the retina, as in the chicken pineal gland, is thought to be regulated by two mechanisms. One is clock-driven changes in TPH and...


Both the inhibitory effects of ceramide on cyclic nucleotides and the L-type Ca2+ channel current appear specific because 1) C2- and C6-ceramide produce similar effects on the nucleotides and the current 2) C2-dihydroceramide, an inactive analogue of ceramide, is without effect and 3) PPMP, an inhibitor of ceramide metabolism which elevates ceramide levels in other cell types, produces the same effect as exogenous ceramide. Indeed, our data on PPMP indicate that there may be a high rate of turnover of sphingomyelin in the rat pineal gland since 15 min of treatment with PPMP is sufficient to generate enough ceramide endogenously to produce a similar inhibitory effect to that observed after exogenous ceramide. Our results, together with the known involvement of ceramide in the inhibitory effect of cytokines on the L-type Ca2+ channel current in rat ventricular myocytes (29), suggest that the sphingomyelin cycle likely plays an important role in the regulation of L-type Ca2+ channels in...


The first demonstration in sheep that melatonin secretion from the pineal gland relays effects of photoperiod to time seasonal characteristics was achieved by housing Soay rams under a driving 32-week lighting regimen (28). Under these conditions, sheep without a functional pineal gland (pinealectomised or superior cervical ganglionec-tomised) were shown to be unable to adjust their long-term physiological rhythms to the changing photoperiod, although the intrinsic cyclicity persisted (44). Definitive evidence that the daily rhythm in melatonin secretion from the pineal gland mediates effects of photoperiod was provided from studies in which pinealectomised ewes were treated with programmed infusions of melatonin designed to mimic the normal daily patterns of melatonin secretion (4,6). Short-duration infusions (8-h daily) were found to suppress gonadotrophin (LH) secretion, as normally occurs in pineal intact ewes under long days, while conversely long-duration infusions promoted...


MRI is the preferred modality to diagnose osteochondromas as it clearly demonstrates this cartilage cap. Growth is by enchondral ossification, and it ceases at the time of epiphyseal closure. Osteochondromas commonly present as a painless mass in patients between 10 and 20 years of age, or are found incidentally at all ages. In children, these tumors show an avid concentration of radiophosphate due to the ongoing enchondral ossification. Uptake wanes with fusion of the adjacent epiphysis. Reactivation or persistence of high abnormal uptake by the exostosis after skeletal maturation should be viewed as suspicious for malignant transformation. The frequency of transformation to chondrosarcoma is low in solitary exostosis ( less than 1 ) but is higher in hereditary multiple exostosis, exceeding 10 in some reports. Absent uptake of radiophosphate virtually excludes malignant change.


The most common location of extragonadal germ cell tumors occurs in two midline sites the mediastinum (thymus) and the diencephalop-ineal (pineal and infundibulum) region. The origin of these non-neuroectodermal tumors remains unknown but may be related to the persistence of primordial germ cells which disseminate widely throughout many tissues and organs in the early embryo. These extra-gonadal germ cells typically have an ephemeral existence and undergo an apoptotic death. It is possible that some of these cells may survive and, over time, transform into a neoplasm. This is in contrast to the theory that the presence of these cells is related to a migrational defect. The pineal gland is the most common site of intracranial germ cell tumors (37-45 ), followed by the suprasellar region (27-35 ), with 10 of tumors involving both regions at presentation

Relevant Anatomy

The pineal gland has a central location in the brain, such that the distance between it and the surface of any portion of the scalp is almost the same, regardless of which surgical approach is taken to this region. The anatomy of the parenchymal tissue and, more importantly, the vascular structures are critically important in considering the most appropriate approach to these tumors. Pineal tumors occupy the posterior aspect of the third ventricle and the quadrigeminal cistern. They may involve the quadrigeminal plate inferiorly, the posterior commissure and thalamus anterolat-erally and the roof of the third ventricle and splenium superiorly. The arterial supply to the pineal gland is from the medial posterior choroidal artery. The draining veins from the pineal body and habenular trigone are the superior and inferior pineal veins that flow into the vein of Galen or the internal cerebral veins. The veins for the superior and inferior colliculi, the superior and inferior quadrigeminal...


Salter-Harris type IV fracture of the lateral humeral condyle. A T2*-weighted gradient-echo coronal image of a partially flexed elbow reveals the thin metaphyseal fracture fragment (small arrows) and extension of the fracture through the unossified trochlear epiphysis (large arrow). These fractures may require open reduction and internal fixation. C, capitellum. (Courtesy of Phoebe Kaplan, MD) FIGURE 4.8. Salter-Harris type IV fracture of the lateral humeral condyle. A T2*-weighted gradient-echo coronal image of a partially flexed elbow reveals the thin metaphyseal fracture fragment (small arrows) and extension of the fracture through the unossified trochlear epiphysis (large arrow). These fractures may require open reduction and internal fixation. C, capitellum. (Courtesy of Phoebe Kaplan, MD)


Stable fixation of a bone segment requires mounting with levels of fixation close to the nonunion site or to the area of corticotomy, and levels of fixation close to the proximal or distal epiphysis of the long bone. These represent the cause of major tolerability problems, and one recently established solution is to use mountings that move away from the joints. This possibility must be used within careful limits because even here the main rule is to maintain the stability of the device. This must never be reduced by oversimplified constructions.

Thomas G Sampson

Coxa saltans interna is a hip syndrome resulting in the iliopsoas tendon snapping pathologically over structures beneath it, causing a loud audible click or clunk, which may be associated with pain. It is thought the most common involved structure it courses over is the iliopectineal eminence (Figure 12.1) however, other intraarticular structures may be large loose bodies and exostoses. The differential diagnosis must rule out labral tears, synovial chon-dromatosis, and abnormal shapes of the femoral head from an old slipped capital femoral epiphysis or hip dysplasia and acetabular retroversion.

Mechanism Of Action

This would explain why in LLC-bearing mice, MIO rescue hematopoiesis against the toxic action of cancer chemotherapy. LLC is, in fact, known to release GM-CSF (77). Activated Th cells may produce also GM-CSF. This might account for the therapeutic and positive hematopoietic effects of MLT when administered together with IL-2 in cancer patients (19).The cytokines involved in the immune-hematopoietic action of MLT may exert an influence on the production of MLT by the pineal gland. The pineal gland is, in fact, located outside the blood-brain barrier and some reports show that gamma-IFN may directly affect the synthesis of MLT in the pineal gland (76). MLT whose synthesis is regulated by the photoperiod, activates its specific membrane receptor (mt1) in T-helper type 1 cells (Th1) or the nuclear receptor RZR ROR (NR) in macrophages (M). This stimulates the secretion of cytokines such as gamma-IFN, IL-2, MIO and IL-1, IL-6 respectively. In turn, these cytokines may...


Musculoskeletal effects include scoliosis, kyphosis, hypoplasia, and fibrosis of bone and soft tissues, as well as slipped capital femoral epiphysis (Mayfield et al. 1981 Pastore et al. 1982 Kajanti 1983). Most of the patients who develop scoliosis have been treated with moderate to high doses of orthovoltage radiation therapy (1500-5000 cGy) and received asymmetric irradiation of the spine. Some patients were also irradiated under 6 months of age, while others underwent laminectomy for epidural disease (Mayfield et al. 1981 Pastore et al. 1982 Kajanti 1983).


Of the other two members of this orphan receptor group, RZR ROR gamma is highly expressed in skeletal muscle72 while RZR ROR beta is specific to the brain. RZR ROR beta is present in a number of regions generally known to be involved in receiving and processing sensory input, such as the dorsal horn of the spinal cord, layers IV and V of the sensory cortex, and the thalamus.190 RZR ROR beta is also expressed in several regions involved in the regulation of circadian rhythms, including the retina, suprachiasmatic nuclei, and the pineal gland. It had been suggested that melatonin was a ligand for RZR ROR beta 15 however, this now seems to be in doubt.14 Nevertheless, the light dark cyclic changes in RZR ROR beta in the pineal gland and the retina suggest that this gene plays some role in circadian timing.3 That RZR ROR beta has an essential role in development is demonstrated by the phentoype of the null mutants which exhibit ataxia, retinal degeneration, and male infertility.3


Demonstration of 17 HSD activity in the brain of rats and monkeys (81,82) indicated that 17 HSD protein and mRNA would also be present. Recent analysis of both rat and frog brains has demonstrated that 17 HSD type I was expressed in the brain (83,84). In adult rat brains, 17 HSD protein was detected in non-neuronal cells (GFAP-positive cells) in the hypothalamus, hippocampus, thalamus, cortex, cerebellum, caudate putamen, and pineal gland (83). In the hypothalamus, 17 HSD immunoreactivity was detected in astrocytes in the paraventricular, arcuate, and supraoptic nuclei. Immunoreactivity was detected in all pyramidal layers of the hippocampus, paraventricular nucleus in the thalamus, all layers of the cortex, and all layers of the cerebellum. II mRNA, but not type I mRNA, was found in the brain, kidney, liver, lung, placenta, and testis, and type I mRNA was found only in the liver (116). Extensive biochemical studies by Karavolas and colleagues demonstrated rat 3aHSD activity in...

Endogenous Hormones

Melatonin (N-acetyl-5-methoxy-tryptamine) is proposed to be a factor in the etiology of breast cancer.54 This hormone is secreted by the pineal gland and synthesized during darkness.55 There are a number of proposed mechanisms by which melatonin could effect breast cancer development induction of apoptosis,56 inhibition of cell proliferation,5758 scavenging of reactive oxygen species, and immunomodulation.55 59 Consistent with this theory, observational studies have shown evidence that women who work at night have an elevated risk of breast cancer, while residence in the Arctic, blindness, and visual impairment are all associated with decreased breast cancer risk.60-65 However, a recent large prospective study found no evidence that the level of melatonin was associated with risk of breast cancer.66


Our data confirm the existence of a reciprocal modulation between the hypo-thalamic-pituitary-gonadal axis and pineal gland. Also, they show that the timing of studied points within the light dark cycle is critical for the evidence of melatonin action in adult male rats and also suggest an interaction between the light dark cycle, melatonin secretion and responsiveness to MLT.