Neuroprotective effects of ginseng total saponin and ginsenosides Rb1 and Rg1 on spinal cord neurons in vitro

Spinal cord injury is a major cause of disability and results in many serious physical, psychological, and social difficulties. Numerous studies have shown that traumatic spinal cord injuries (SCI) lead to neuronal loss and axonal degeneration in and around the injury site that cause partial disability or complete paralysis. An important strategy in the treatment of SCI is to promote neuron survival and axon outgrowth, making possible the recovery of neural connections. Using an in vitro survival assay, we have identified ginsenosides Rb1 and Rg1, extracted from ginseng root (Panax ginseng C. A. Meyer), as efficient neuroprotective agents for spinal cord neurons. These compounds protect spinal neurons from excitotoxicity induced by glutamate and kainic acid, as well as oxidative stress induced by H(2)O(2). The neuroprotective effects are dose-dependent. The optimal doses are 20-40 microM for ginsenosides Rb1 and Rg1. The effects are specific for Rb1 and Rg1, since a third ginsenoside, Re, did not exhibit any activity. Ginseng has been used for thousands of years in the treatment of neurological disorders and other diseases in Asia. Ginsenosides Rb1 and Rg1 represent potentially effective therapeutic agents for spinal cord injuries.     

Tumor suppressor genes: new pathways in gynecological cancer

The Retinoblastoma (Rb-1) and p53 genes appear to play an important role in controlling cell division, and mutations in Rb-1 and p53 have been reported widely in non-gynecological cancers. Unlike other cancer-related genes, which become activated during carcinogenesis, it is the loss of wild type p53 and Retinoblastoma protein (RB) function that is thought to contribute to cancer development. These genes therefore, have been called tumor suppressor genes since normal function appears to be necessary for negative control of cell growth. Several viral oncoproteins have been shown to interact with RB and p53. It seems likely that the formation of these complexes inactivates the cellular protein resulting in an overall effect similar to somatic mutation of the Rb-1 or p53 genes. The HPV16 transforming proteins E7 and E6 complex with protein products of Rb-1 and p53, respectively. In HPV positive anal and cervical tumors the normal function of RB and p53 may be inhibited by these viral proteins and so mutation within the RB-1 and p53 gene coding sequences would not appear to be a necessary step in the genesis of these tumors. However, in HPV negative tumors from the same tissues, loss of wild type Rb-1 and p53 activity may only be achieved by somatic mutation of these genes.     

Expression of Rb2/p130 protein correlates with the degree of malignancy in gliomas

It has been reported that there is an inverse correlation between the immunohistochemical expression of Rb2/p130, a member of the retinoblastoma gene family, and the degree of malignancy in at least some histological types. In order to investigate the expression of this protein in gliomas, we evaluated 58 samples from patients with resected gliomas. We focused on the relationship between the degree of malignancy of the glioma and the immunohistochemical detection of Rb2/p130. Expression of Rb2/p130 was observed in 38 glioma specimens (65.5%), including a high expression level in low-grade glioma specimens (>30% positive cells in 84% of tumors) and a low expression level in high-grade glioma specimens (>30% positive cells in 12% of tumors). The most aggressive of the gliomas exhibited very low to undetectable levels of Rb2/p130. Moreover, we observed an inverse correlation between Rb2/p130 expression and the degree of malignancy. These findings suggest that the differentiation of gliomas might be partially mediated by the Rb2/p130 gene, and that Rb2/p130 expression can additionally be an indicator of a better prognosis in patients with gliomas.     

Selective changes in the shapes of parasagittal bands of Aldoc (Zebrin) mRNA in the rat vermis of the cerebellum after repeated methamphetamine injections

In the cerebellum the mossy and climbing projections, which excite Purkinje cells, display a parasagittal and striped organization. These projections also excite Zebrin (aldolase C: Aldoc) parasagittally. To evaluate the possibility that external stimuli can change the organization of the bands of Aldoc mRNA, we compared the effects of repeated methamphetamine administration on the Aldoc mRNA stripes in the four transverse (anterior, central, posterior and nodular) regions of the vermis with the effects on the glutamate transporter EAAT4 (SCL1A 6) mRNA stripes. In the posterior region the injections four times daily increased the fragmentation of the Aldoc mRNA stripes. The presence of a large amount of fragmentation (forty/cerebellum slice), was accompanied with large lateral dislocations of the Aldoc mRNA stripes. In the central and nodular regions, where the size of the stripe areas decreased significantly the stripes were dislocated laterally. The dislocations of the Aldoc mRNA bands did not occur after a single methamphetamine injection and thus repeated injections were necessary to change the distributions of the lateral bands. In contrast, the distributions of the SCL1A 6 mRNA stripes did not change, even though there was mild fragmentation (six/slice) of the SLC1A 6 mRNA stripes in the anterior region and decreases in the numbers (twelve/slice) in the nodular region. We concluded that excess dopamine selectively changes the location of the Aldoc mRNA compartments in the vermis while the SLC1A 6 mRNA stripes could be changed by other inputs and thus the specific transmitter system might change the specific compartment of the cerebellum.     

Role of leptin in the control of feeding of goldfish Carassius auratus: interactions with cholecystokinin,neuropeptide Y and orexin A,and modulation by fasting

To assess the role of leptin on food intake regulation in goldfish, we examined the effects of central (intracerebroventricular, ICV) and peripheral (intraperitoneal, IP) injections of recombinant murine leptin on feeding behavior. Centrally (100 ng/g) and peripherally (300 ng/g) injected leptin both caused a significant decrease in food intake, compared to the saline-treated controls. To test the hypothesis that leptin influenced orexigenic neuropeptide systems in goldfish, fish were co-injected with neuropeptide Y (NPY) or orexin A and leptin. Both NPY (5 ng/g) and orexin A (10 ng/g) significantly increased food intake. Fish co-injected ICV with NPY (5 ng/g) or orexin A (10 ng/g) and leptin (1 or 10 ng/g) had a food intake lower than that of fish treated with NPY or orexin A alone. NPY mRNA expression in goldfish brain was reduced 2 and 6 h following central injection of leptin. To test the hypothesis that the cholecystokinin (CCK) mediates the effects of leptin in goldfish, fish were simultaneously injected ICV with an ineffective dose of leptin (10 ng/g) and either ICV or IP with an ineffective doses of CCK (1 ng/g ICV or 25 ng/g IP). These fish had a food intake lower than vehicle-treated fish, suggesting that leptin potentiates the satiety actions of CCK. CCK hypothalamic mRNA expression was increased 2 h following central treatment with leptin. The CCK receptor antagonist proglumide blocked both central and peripheral CCK satiety effects. Blockade of CCK brain receptors by proglumide resulted in an inhibition of the leptin-induced decrease in food intake and an attenuation of the inhibiting action of leptin on both NPY- and orexin A-induced feeding. These data suggests that CCK has a role in mediating the effects of leptin on food intake. Fasting potentiated the actions of leptin and attenuated the effects of CCK. Whereas fasting had no effects on the brain mRNA expression of CCK, it increased the brain mRNA expression of NPY and decreased the expression of CART. These changes in neuropeptide expression were partially reversed when fish were treated ICV with leptin. These results provide strong evidence that, in goldfish, leptin influences food intake, in part by modulating the orexigenic effects of NPY and orexin and that its actions are mediated, at least in part, by CCK.     

Aldosteronism revisited: perspectives on less well-recognized actions of aldosterone

Aldosterone is a mineralocorticoid with protean actions in both epithelial and nonepithelial cells. These include endocrine properties of circulating aldosterone that promote Na(+) resorption at the expense of well-recognized K(+) excretion and less well-recognized Mg(2+) excretion in classic target tissues: kidneys, colon, and sweat and salivary glands. The regulation of adrenal aldosterone secretion by [Mg(2+)](o) is also less well appreciated. More recently recognized endocrine actions of aldosterone include induction of Mg(2+) efflux in exchange for Na(+) in such nonepithelial cells as peripheral-blood mononuclear cells and influence on epithelial cells of the choroid plexus, where aldosterone alters the composition of cerebrospinal fluid that contributes to blood-pressure regulation. An association between primary aldosteronism and idiopathic intracranial hypertension has recently been reported. Extraadrenal steroidogenesis with de novo aldosterone production by the cardiovasculature, where its auto-/paracrine properties may contribute to tissue repair at sites of injury, has been observed. These less well-recognized actions of aldosterone have led to a revival of interest in how this steroid molecule contributes to the pathophysiology of various clinical disorders.