Questions about FTY720

A board to discuss future MS therapies in early stage (Phase I or II) trials.

Postby sh8un » Fri Jun 23, 2006 8:10 pm

Good luck carole. Wish you all the best and thank you for having the courage to participate in the trial. I am sure that you have done your homework on it but it still takes courage. Please keep us updated.
NN
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Postby carolew » Sat Jun 24, 2006 6:07 am

I shall. Flipflopper is also waiting for this study.
have a great day all. Carole
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Postby bromley » Sat Jun 24, 2006 8:33 am

Carolew,

Good luck with the trial.

macular edema
- I've always thought the devil himself must have dream't up this disease on a bad day. It now looks like his brother is involved in coming up with therapies. I can't believe that this disease can cause vision problems / loss and one of the promising therapies offers the risk of something similar!

I wish you all the best and hope you see good results.

Ian
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isaria sinclairii

Postby jimmylegs » Sat Jun 24, 2006 9:45 am

hi all i was doing a bit of reading about fty today

if anyone gets super impatient waiting for trials of it, perhaps you could try out the original chinese traditional medicine version? isaria sinclairii? perhaps with less side effects. i can't find a study looking at treatment with the traditional version and side effects. i wonder what chinese practitioners call it...

i have seen cordyceps mentioned as the same as isaria. i am not at all sure about this, although they do both seem to be a fungus that grows on a caterpillar! cordyceps sinensis seems to have similar immunoregulatory properties. and (apparently) you can take it in huge amounts with no adverse effects. (i have yet to find the study)

i found it quite interesting that its action is linked to adenosine, because i was recently looking into ms and uric acid/inosine (http://en.wikipedia.org/wiki/Inosine), and found that it is an adenosine precursor.

here are some links on the mushroom stuff...

http://www.alive.com/1433a4a2.php

http://www.nutritiondome.com/71030.html

i also found a cordyceps literature review (not at all specific to ms but interesting nonetheless):

INPR Cordyceps sinensis Monograph
Institute for Natural Products Research

Immune Functions: Numerous animal and in vitro studies have shown that Cordyceps sinensis fruit body and mycelial extracts are potent immunopotentiators. Cultured fruit bodies of
Cordyceps sinensis prepared as a water extract produced a significant increase in the phagocytic activity of Kupffer cells after oral administration in rats for 25 days, but not after two days. The increase compared to control rats was seen in a 36% greater colloidal carbon clearance value from a dosage of 200 mg/kg p.o., whereas half the amount was ineffective (Nakamura et al., 1999). A water extract of cultured Cordyceps sinensis (100 µg/mL) was shown to dose-dependently reverse murine renal cell neoplasm-induced suppression of murine macrophage (J774A.1 cell line) oxidative burst (chemoluminescent), following co-incubation of the Cordyceps sinensis extract with the tumor cells. At 8 hours co-incubation, the activity of the macrophages was significantly enhanced (Jiao and Lau, 1998).

Am J Clin Nutr 2000 Aug; 72(2 Part 2):624S-636S
Selected herbals and human exercise performance.
Bucci LR [Record supplied by publisher], Weider Nutrition International, Salt Lake City.

Herbs have been used throughout history to enhance physical performance, but scientific scrutiny with controlled clinical trials has only recently been used to study such effects. The following herbs are currently used to enhance physical performance regardless of scientific evidence of effect: Chinese, Korean, and American ginsengs; Siberian ginseng, mahuang or Chinese ephedra; ashwagandha; rhodiola; yohimbe; CORDYCEPS: fungus, shilajit or mummio; smilax; wild oats; Muira puama; suma (ecdysterone); Tribulus terrestris; saw palmetto berries; beta-sitosterol and other related sterols; and wild yams (diosgenin). Controlled studies of Asian ginsengs found improvements in exercise performance when most of the following conditions were true: use of standardized root extracts, study duration (>8 wk, daily dose >1 g dried root or equivalent, large number of subjects, and older subjects. Improvements in muscular strength, maximal oxygen uptake, work capacity, fuel homeostasis, serum lactate, heart rate, visual and auditory reaction times, alertness, and psychomotor skills have also been repeatedly documented. Siberian ginseng has shown mixed results. Mahuang, ephedrine, and related alkaloids have not benefited physical performance except when combined with caffeine. Other herbs remain virtually untested. Future research on ergogenic effects of herbs should consider identity and amount of substance or presumed active ingredients administered, dose response, duration of test period, proper experimental controls, measurement of psychological and physiologic parameters (including antioxidant actions), and measurements of performance pertinent to intended uses. PMID: 10919969

Cell Biochem Funct 2000 Jun;18(2):93-7
Inhibitory effect of cordyceps sinensis and cordyceps militaris on human glomerular mesangial cell proliferation induced by native LDL.
Zhao-Long W, Xiao-Xia W, Wei-Ying C, Department of Internal Medicine, Zhong Shan Hospital, Shanghai Medical University, Shanghai, P.R. China.

Native LDL, in low concentrations, promotes proliferation of cultured human glomerular mesangial cells. LDL stimulated [(3)H]-thymidine incorporation into DNA of human glomerular mesangial cells. Increased concentrations of LDL led to increased [(3)H]-thymidine incorporation. When LDL concentrations were 5, 10 and 50 &mgr;g ml(-1), [(3)H]-thymidine incorporation was 919.5+/-216, 1106+/-132, and 1200+/-210, respectively. When Cordyceps sinensis 100, 200, 300, 400 &mgr;g ml(-1) plus LDL 10 &mgr;g ml(-1) were added, [(3)H]-thymidine incorporation was 99+/-19 and 53+/-8, respectively, P<0.01 compared with controls. With Cordyceps militaris at similar concentrations plus LDL 10 &mgr;g ml(-1), [(3)H]-thymidine incorporation was respectively 192+/-75, 168+/-66, 145+/-53 and 72+/-16, P<0.01 compared with controls. The data suggest that LDL may play a critical role in mediating mesangial cell hypertrophy or proliferation involved in the development of glomerulosclerosis. Cordyceps sinensis and Cordyceps militaris inhibited, to a certain degree, proliferation of cultured human glomerular mesangial cell induced by LDL. Copyright 2000 John Wiley & Sons, Ltd. PMID: 10814966, UI: 20275640

Life Sci 2000 Feb 25; 66(14):1369-76
Protein constituent contributes to the hypotensive and vasorelaxant activities of Cordyceps sinensis.
Chiou WF, Chang PC, Chou CJ, Chen CF, National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC.

Cordyceps sinensis is a herb medicine in China for the treatment of general debility after sickness and for persons of advanced age. In the present study, cordyceps sinensis was extract by phosphate buffer saline (PBS) and dialyzed overnight against PBS using a membrane cut off at 3,500 dalton molecular weight. The resulting macromolecule Cordyceps sinensis fraction was assayed in anesthetized rats for hypotensive effects and in isolated aorta for vasorelaxant effects. Intravenous injection of Cordyceps sinensis (8,16, 24 and 32 mg/kg, respectively) suppressed significantly the mean arterial pressure (MAP) in a dose-dependent manner. 32 mg/kg of Cordyceps sinensis induces the maximal hypotensive response with a 58 +/- 4 mm Hg (from 107 +/- 6 to 49 +/- 3 mm Hg) change in MAP and a over 45 min action duration. In aortic rings precontracted with phenylephrine treatment with Cordyceps sinensis between 0.5 and 500 microg/ml induced dose dependent relaxation. Maximal vasorelaxant response evoked by 150 microg/ml Cordyceps sinensis was 68.9 +/- 7.3%. Furthermore, Cordyceps sinensis -induced vasorelaxation is mediated by the endothelium possibly by stimulating the release of the nitric oxide and endothelium-derived hyperpolarizing factor. In conclusion, the present study revealed that presence of a constituent in Cordyceps sinensis which reduces MAP by relaxing the vascular beds directly. However, the effect may be caused by a single active ingredient or by the combined action of many active agents found in the Cordyceps sinensis extract. PMID: 10755473, UI: 20216249

Br J Nutr 2000 Feb; 83(2):197-204
Effects of the mycelial extract of cultured Cordyceps sinensis on in vivo hepatic energy metabolism and blood flow in dietary hypoferric anaemic mice.
Manabe N, Azuma Y, Sugimoto M, Uchio K, Miyamoto M, Taketomo N, Tsuchita H, Miyamoto H, Department of Animal Sciences, Kyoto University, Japan.

The beneficial effects of a traditional Chinese medicine, Cordyceps sinensis, on mice with hypoferric anaemia were evaluated by NMR spectroscopy. Experimental hypoferric anaemia was induced in mice by feeding with an Fe-free diet for 6 weeks. They were then given extract from cultured Cordyceps sinensis (200 mg/kg body weight daily, orally) and were placed on an Fe-containing recovery diet (35 mg Fe/kg diet) for 4 weeks. In vivo 31P and 2H NMR spectra acquired noninvasively and quantitatively at weekly intervals were used to evaluate hepatic energy metabolism and blood flow in the mice. During the 4-week Cordyceps sinensis-extract treatment, consistent increases were observed in liver beta-ATP: inorganic phosphate value by liver 31P NMR spectroscopy, representing the high energy state, and in blood-flow rate as determined by 2H NMR spectroscopy of deuterated water (D2O) uptake after intravenous injection of D2O. The haematological variables (the packed cell volume and the haemoglobin level) and the hepatic intracellular pH, which was determined from the NMR chemical shift difference between the inorganic phosphate peak and the alpha-phosphate peak of ATP, were not significantly different between Cordyceps sinensis-extract-treated and control mice. As blood flow and energy metabolism are thought to be linked, the Cordyceps sinensis-extract-increased hepatic energy metabolism in the dietary hypoferric anaemic mice was concluded to be due to increased hepatic blood flow. PMID: 10743500, UI: 20207903

Chung Kuo Chung Yao Tsa Chih 1997 Feb; 22(2):111-3, inside back cover
[Anticarcinogenic effect and hormonal effect of Cordyceps militaris Link].
[Article in Chinese], Liu J, Yang S, Yang X, Chen Z, Li J, Norman Bethune University of Medical Sciences, Changchun.

Cordyceps militaris (CML) has been found good for inhibiting the growth of tumor, prolonging the survival period of mice implanted with S180, inhibiting the growth and metastasis of Lewis pneumonic cancer in the implanted mice, increasing the plasm content of cortisol and testosterone in normal rats, and elevating the weight of sexual organs in normal and castrated rats. CML exerts a malehormone-like effect. PMID: 10743207, UI: 20207610

Mol Biol Evol 2000 Apr; 17(4):629-38
Interkingdom host jumping underground: phylogenetic analysis of entomoparasitic fungi of the genus cordyceps.
Nikoh N, Fukatsu T, National Institute of Bioscience and Human-Technology, Agency of Industrial Science and Technology, Tsukuba, Japan.
Most members of the ascomycetous genus Cordyceps are endoparasitic fungi of insects and other arthropods, but about 20 of the 300 described species are parasitic to hart's truffles, Elaphomyces spp. In order to understand the evolution of host specificity and the process of interkingdom host jumping in Cordyceps, we investigated the phylogenetic relationships of 22 representatives, including 4 truffle parasites and 18 insect parasites, based on nuclear and mitochondrial rDNA sequences. Five monophyletic groups were identified in both nuclear and mitochondrial phylogenies. In three of the five clades, the members utilized hosts from the same insect group, suggesting that the endoparasite-host connections have been conserved to some extent. On the other hand, it was also shown that major host shifts between distantly related insects must have occurred repeatedly. Notably, phylogenetic analyses strongly suggested that parasites of hart's truffles originated from parasites of cicada nymphs during the evolution of the CORDYCEPS: The common habitats of cicada nymphs and hart's truffles, deep underground and associated with tree roots, suggest that the interkingdom host jumping from Animalia to Fungi might have been promoted by the overlapping ecological niche of the unrelated hosts. This finding provides an impressive case of a drastic host shift in favor of the host habitat hypothesis. PMID: 10742053, UI: 20206862

Methods Enzymol 2000; 311:348-61
Fermentation, partial purification, and use of serine palmitoyltransferase inhibitors from Isaria (= Cordyceps) sinclairii.
Riley RT, Plattner RD, Toxicology and Mycotoxin Research Unit, Russell Agricultural Research Center, United States Department of Agriculture/ARS, Athens, Georgia 30604-5677, USA.

J Lab Clin Med 1999 Nov; 134(5):492-500
Efficacy of a pure compound H1-A extracted from Cordyceps sinensis on autoimmune disease of MRL lpr/lpr mice.
Yang LY, Chen A, Kuo YC, Lin CY, Department of Pediatrics, Veterans General Hospital, Taipei, Taiwan, Republic of China.

Cordyceps sinensis (CS) is a traditional Chinese medicine with immunomodulatory effect and is effective in improving the survival of lupus mice. In the present study we isolated a pure compound (H1-A) from Cordyceps sinensis and investigated its effect on inhibiting autoimmune disease progression in MRL Ipr/Ipr mice. Our results demonstrated that MRL Ipr/Ipr mice treated daily with H1-A (40 microg/kg/d orally) for 8 weeks had a progressive reduction in anti-ds-DNA production (optical density value decreased from 0.172 +/- 0.009 to 0.112 +/- 0.015) when compared with the control group (optical density value increased from 0.141 +/- 0.036 to 0.198 +/- 0.047). In clinical presentation, the treated group had a reduction in lymphadenopathy, a delayed progression of proteinuria, and an improvement in kidney function. Histologic analysis of kidney tissue indicated that H 1-A could inhibit the mesangial proliferation that was evident in lupus nephritis. However, there was no significant change in immune complex deposition. The studies reveal that the pure Cordyceps sinensis compound (H1-A) may be potentially useful for treating systemic lupus erythematosus in human patients, and they provide some questions for further investigation of the pathogenesis of systemic lupus erythematosus and lupus nephritis.
PMID: 10560943, UI: 20023599

Biochem Genet 1999 Jun;37(5-6):201-13
Genetic diversity and taxonomic implication of Cordyceps sinensis as revealed by RAPD markers.
Chen Y, Zhang YP, Yang Y, Yang D, Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Yunnan, China.

Random amplified polymorphic DNA (RAPD) markers are used to investigate genetic variation and evolutionary relationships of 29 samples of Cordyceps sinensis from different geographical populations on the Qinghai-Tibet plateau. Out of 137 RAPD bands scored, 100 are polymorphic. A correlation is revealed between geographical distance and genetic distance. The molecular phylogenetic tree suggests that the 29 samples are divided into three notable clusters, corresponding to the geographical populations, i.e., the north population (NP), middle population (MP), and south population (SP). The NP consists of 7 northern samples from Menyuan, Maqu, and Luqu, the MP consists of 8 samples from Yushu and Chengduo, and the SP consists of 14 samples from Byma Snow Mountain, Renzhi Snow Mountain, Chongcaoxiwa, and Dacaodi. It is demonstrated that extensive genetic diversity is found among different geographical populations of C. sinensis. The genetic diversity pattern of Cordyceps sinensis may be caused by the founder effects. The taxonomic status of NP, MP, and SP populations should be that they are different subspecies rather than different species. PMID: 10544805, UI: 20012048

Biol Pharm Bull 1999 Sep; 22(9):966-70
Structural features and hypoglycemic activity of a polysaccharide (CS-F10) from the cultured mycelium of Cordyceps sinensis.
Kiho T, Ookubo K, Usui S, Ukai S, Hirano K, Department of Pharmaceutics, Gifu Pharmaceutical University, Japan.

A polysaccharide (CS-F10) purified from a hot water extract of the cultured mycelium of Cordyceps sinensis was composed of galactose, glucose and mannose in a molar ratio of 43:33:24; its molecular weight was estimated to be about 15000. The results of chemical and spectroscopic investigations suggest that CS-F10 has a comb-type structure, and has alpha-D-glucopyranosyl residues on the terminal of the side-chains and characteristic sugar residues of C. sinensis i.e., 1,5-linked beta-D-galactofuranosyl residues. CS-F10 significantly lowered the plasma glucose level in normal, streptozotocin (STZ)-induced diabetic and epinephrine-induced hyperglycemic mice after intraperitoneal administration (50 mg/kg). Administration of CS-F10 to STZ-induced diabetic mice significantly increased the activity of hepatic glucokinase. A significant reduction in the hepatic glucose output was observed following the infusion of CS-F10 using the perfused rat liver. CS-F10 also significantly decreased protein content of facilitative glucose transporter isoform 2 (GLUT2) from rat liver following i.p. administration. These effects presumably contribute to the hypoglycemic activity. PMID: 10513622, UI: 99441780

Phytochemistry 1999 Aug; 51(7):891-8
Antitumor sterols from the mycelia of Cordyceps sinensis.
Bok JW, Lermer L, Chilton J, Klingeman HG, Towers GH, Department of Botany, University of British Columbia, Vancouver, Canada.

Activity guided fractionations led to the isolation of two antitumor compounds 5 alpha,8 alpha-epidioxy-24(R)-methylcholesta-6,22-dien-3 beta-D-glucopyranoside and 5,6-epoxy-24(R)-methylcholesta-7,22-dien-3 beta-ol from the methanol extract of Cordyceps sinensis. Two previously known compounds, ergosteryl-3-O-beta-D-glucopyranoside and 22-dihydroergosteryl-3-O-beta-D-glucopyranoside were also isolated. The structures of hitherto unknown sterols were established by 1D and 2D NMR spectroscopic techniques with the former synthesized in order to confirm the identity of the sugar moiety by chemical correlation. The glycosylated form of ergosterol peroxide was found to be a greater inhibitor to the proliferation of K562, Jurkat, WM-1341, HL-60 and RPMI-8226 tumor cell lines by 10 to 40% at 10 micrograms/ml than its previously identified aglycone, 5 alpha,8 alpha-epidioxy-24(R)-methylcholesta-6,22-dien-3 beta-ol. PMID: 10423860, UI: 99352659

J Lab Clin Med 1999 Jan; 133(1):55-63
Inhibition of activated human mesangial cell proliferation by the natural product of Cordyceps sinensis (H1-A): an implication for treatment of IgA mesangial nephropathy.
Lin CY, Ku FM, Kuo YC, Chen CF, Chen WP, Chen A, Shiao MS, Department of Pediatrics and Medical Research, Veterans General Hospital-Taipei, Taiwan, Republic of China.

Cordyceps sinensis (CS) is a parasitic fungus that has been used as a Chinese medicine for a long time in the treatment of nephritis. Today, the hypothesis about the pathogenesis of immunoglobulin A nephropathy (IgAN) is that nephritogenic IgA immune complexes (IgAIC) go to the kidney to stimulate resting mesangial cells to release cytokines and growth factors. These cytokines and growth factors cause mesangial cell proliferation and release matrix, chemical mediators that lead to the glomerular injury. However, nephritogenic IgAIC in humans is still unknown. To solve this problem previously, we established an in vitro model that showed that cultured human mesangial cells (HMC) stimulated with interleukin-1 (IL-1) plus IL-6 can cause mesangial cell proliferation, increasing production of chemical mediators and superoxide anion. An in vivo model also proved that this culture medium may lead to renal injury with hematuria and proteinuria. Therefore, to fractionate the crude components that can be used in the treatment of patients with IgAN, we cultured HMC, and then an HMC activating model with HMC incubated with IL-1 and IL-6 was established. We fractionated the crude methanolic extracts from fruiting bodies of CS with the use of this in vitro inhibition of HMC activation model as our assay method. In brief, the fruiting bodies were extracted by silica gel column chromatography. One out of 6 column fractions, F-2, significantly inhibited the HMC activation by IL-1 plus IL-6. The acute toxicity test with male Institute of Cancer Research mice showed no liver toxicity or mutagenicity. Then we established an IgAN animal model with R36A (Pneumococcal C-polysaccharide purified from Streptococcus pneumoniae) as antigen and anti-R36A IgA monoclonal antibody to form nephritogenic IgA-IC, which can induce hematuria and proteinuria in mice with IgA deposition in the mesangial area. The mice in the IgAN model fed with 1% F-2 in diet had significant reduction of hematuria and proteinuria together with histopathologic improvement. Therefore this fraction was then purified by silica gel column chromatography and high-performance liquid chromatography, which got a purified compound H1-A, which can suppress the activated HMC and alleviate IgAN (Berger's disease) with clinical and histologic improvement. These results give us a new regimen for the treatment of patients with IgAN in the future. PMID: 10385482, UI: 99312208

Jpn J Pharmacol 1999 Apr; 79(4):505-8
Activation of in vivo Kupffer cell function by oral administration of Cordyceps sinensis in rats.
Nakamura K, Yamaguchi Y, Kagota S, Shinozuka K, Kunitomo M, Department of Pharmacology, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.

We investigated the effect of water extracts of Cordyceps sinensis (WECS) on Kupffer cell function in rats. Rats were received a single i.v. injection of a colloidal carbon solution and then the clearance rate from the blood were measured. The rats had been daily administered with WECS, p.o. at a dose of 200 mg/kg for 25 days until the day before the injection of colloidal carbon. The half-life of the colloidal carbon in the blood of rats administered WECS 200 mg/kg was significantly shorter than that of the control rats. This suggests that accelerated function of Kupffer cells is partially involved in the anti-metastatic action of WECS. PMID: 10361894, UI: 99288740

Jpn J Pharmacol 1999 Mar; 79(3):335-41
Inhibitory effect of Cordyceps sinensis on spontaneous liver metastasis of Lewis lung carcinoma and B16 melanoma cells in syngeneic mice.
Nakamura K, Yamaguchi Y, Kagota S, Kwon YM, Shinozuka K, Kunitomo M, Department of Pharmacology, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.

We investigated the effect of the water extract of Cordyceps sinensis (WECS) on liver metastasis of Lewis lung carcinoma (LLC) and B16 melanoma (B16) cells in mice. C57BL/6 mice were given a s.c. injection of LLC and B16 cells and sacrificed 20 and 26 days after tumor inoculation, respectively. WECS was daily administered p.o. to the mice in a dose of 100 mg/kg body weight (wt.) in the experiment of LLC and in a dose of 100 or 200 mg/kg body wt. in the experiment of B16 from one week before tumor inoculation to one day before the date of sacrifice. The tumor cells increased in the thigh in LLC-inoculated mice and in the footpad in B16-inoculated mice. The relative liver wt. of the tumor-inoculated mice significantly increased as compared to that of the normal mice due to the tumor metastasis, as verified by the hematoxylin-eosin staining pathological study in the LLC experiment. The relative liver wt. of the WECS-administered mice significantly decreased relative to that of the control mice in both the LLC and B16 experiments. WECS showed a strong cytotoxicity against LLC and B16 cells, while cordycepin (3'-deoxyadenosine), an active component of WECS, was not cytotoxic against these cells. These findings suggest that WECS has an anti-metastatic activity that is probably due to components other than cordycepin. PMID: 10230862, UI: 99245893

J Altern Complement Med 1998 Fall; 4(3):289-303
The scientific rediscovery of an ancient Chinese herbal medicine: Cordyceps sinensis: part I.
Zhu JS, Halpern GM, Jones K, Department of Pediatrics, Stanford University School of Medicine, California, USA.

Cordyceps sinensis (Berk.) Sacc. is a time-honored tonic food and herbal medicine in China, where recent research has shown that many of its traditional uses may be viewed from the basis of pharmacological activities. The ongoing exploration of C. sinensis in its wild form and cultured, fermented mycelial products derived from it, are reviewed from English and Chinese literature. Part II concludes the series with a review of C. sinensis in preclinical in vitro and in vivo studies, and open-label and double-blinded clinical trials on the respiratory, renal, hepatic, cardiovascular, immunologic, and nervous systems, and its effects on cancer, glucose metabolism, inflammatory conditions, and toxicological studies. In Part I, which appeared in the Fall 1998 issue of this journal (4(3):289-303), we discussed the effects of C. sinensis on antisenescence, endocrine and sexual functions, atherosclerosis, hyperlipidemia, and free radicals.
Publication Types: Review, tutorial, PMID: 9884180, UI: 99098649

J Altern Complement Med 1998 Winter; 4(4):429-57
The scientific rediscovery of a precious ancient Chinese herbal regimen: Cordyceps sinensis: part II.
Zhu JS, Halpern GM, Jones K, Department of Pediatrics, Stanford University School of Medicine, California, USA.

This review presents Cordyceps sinensis (Berk.) Sacc., a fungus highly valued in China as a tonic food and herbal medicine. The extant records show the continued use of C. sinensis is now centuries old. The major chemical, pharmacological, and toxicological studies on C. sinensis and the various derived, cultured, fermented mycelial products currently in use are reviewed from the English and Chinese literature. Preclinical in vitro and in vivo studies and clinical blinded or open-label trials in to date over 2000 patients are reviewed. These studies show the main activities of the fungus in oxygen-free radical scavenging, antisenescence, endocrine, hypolipidemic, antiatherosclerotic, and sexual function-restorative activities. The safety of the fungus, its effects on the nervous system, glucose metabolism, the respiratory, hepatic, cardiovascular, and immune systems, immunologic disease, inflammatory conditions, cancer, and diseases of the kidney will be reviewed in the second part of this article to be published in the winter issue of this journal. PMID: 9764768, UI: 98435797

Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1997 Jan; 17(1):35-8
[Clinical and experimental studies on elimination of oxygen free radical of jinshuibao capsule in treating senile deficiency syndrome and its deoxyribonucleic acid damage repairing effects].
[Article in Chinese] Zhang ZJ, Luo HL, Li JS, Second Affiliated Hospital of Jiangxi Medical College, Nanchang.

OBJECTIVE: To observe the efficacy of Jinshuibao capsule. METHODS: Senile patients of Deficiency Syndrome treated with Jinshuibao capsule (JSBC) as treated group and with starch capsule as control group. JSBC is a preparation of Cordyceps sinensis. RESULTS: (1) The superoxide dismutase (SOD) activity in senile patient were markedly lower than that in youth, while the malonyldialdehyde (MDA) level of the former was higher than that of the latter, P < 0.01; (2) The SOD activity increased and the MDA level decreased in the treated group after treatment, P < 0.01. JSBC also revealed satisfactory effect on relieving symptoms such as chilling, dizziness, lassitude in loin and legs, frequent nocturia and tinnitus, etc. Results of animal experiment wese in accordance with that of clinical observation. The unscheduled deoxyribonucleic synthesis (UDS) level of aged group before treatment was obviously lower than that of youth; after treatment, the change was very significant, and the difference between treated group and control group was also very significant (P < 0.01). Animal experiment showed that the sister chromatid exchange (SCE) of splenic cell in young mice group was markedly lower than that in aged mouse group. CONCLUSION: JSBC has not showed the SCE inducting effect, but could accelerate the repairing of damaged deoxyribonucleic acid (DNA). PMID: 9812650, UI: 99029193

Am J Chin Med 1998; 26(2):159-70
Cordyceps sinensis increases the expression of major histocompatibility complex class II antigens on human hepatoma cell line HA22T/VGH cells.
Chiu JH, Ju CH, Wu LH, Lui WY, Wu CW, Shiao MS, Hong CY, Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Previous studies suggest that down-regulation of the major histocompatibility complex (MHC) antigens on the cell surface of certain tumors results in an escape of immune surveillance. Cordyceps sinensis is well known for its modulatory effect on host immune system. To investigate the modulatory effect of Cordyceps sinensis on MHC class II antigen expression on hepatoma cells, immunostaining with monoclonal antibody (MAb) L243, against the HLA DR region of MHC class II antigens on human hepatoma cell line HA22T/VGH was analyzed by using flow cytofluorimetry. The degree of fluorescence intensity on L243(+) cells was expressed as relative mean fluorescence intensity (RMFI). The extract of Cordyceps sinensis (VGH-CS-ME-82, 40 micrograms/ml) was found to increase the MHC class II antigen expression on HA22T/VGH cells with the percentage of L243(+) cells 40.2 +/- 2.5 and RMFI 6.6 +/- 0.4; whereas cells without treatment disclosed the percentage of L243(+) cells 17.2 +/- 1.4 and RMFI 5.4 +/- 0.3, respectively (p < 0.05). There was a dose-related increase in the degree of fluorescence intensity in terms of RMFI on VGH-CS-ME-82 induced cells. The RMFI in cells treated with IFN-gamma 0, 0.2 and 5 ng/ml were 5.4 +/- 0.3, 8.2 +/- 0.4, and 24.9 +/- 1.5, respectively; whereas the RMFI in cells co-incubated with VGH-CS-ME-82 (40 micrograms/ml) and IFN-gamma 0, 0.2 ng/ml and 5 ng/ml were 6.7 +/- 0.2 (p < 0.05), 9.2 +/- 0.9 (p < 0.1) and 29.5 +/- 1.2 (p < 0.005), respectively. We conclude that VGH-CS-ME-82, either alone or with IFN-gamma induction, increases the MHC class II antigen expression on hepatoma cell line HA22T/VGH, which will shed light into the present immunotherapy, and make the host immune surveillance more effective against tumor cells with down-regulated MHC class II antigen expression. PMID: 9799968, UI: 99016350

Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1996 Dec; 16(12):733-7
[Experimental study on effect of Cordyceps sinensis in ameliorating aminoglycoside induced nephrotoxicity].
[Article in Chinese]
Li LS, Zheng F, Liu ZH, Research Institute of Nephrology, Jinling Hospital, Nanjing.

In order to evaluate the effect of Cordyceps sinensis (CS) on aminoglycoside (AG) induced nephrotoxicity, gentamycin was imposed on the young and old rats with CS administration. The renal tubular injury was ameliorated as evidenced by less prominent increment of BUN, SCr, sodium excretion, urinary NAGase and less severity of histopathological changes as compared with control. In addition, the use of CS could promote an earlier recovery of renal oxygen consumption insulin clearance, and sodium absorption in isolated perfused kidney from CS treated intoxicated rat than that from control. Possible mechanisms of CS on drug-induced nephrotoxicity include: (1) Accelerating the regeneration of tubular cells; (2) Protecting the sodium pump activity of tubular cells; (3) Attenuating the tubular cell lysosome hyperfunction stimulated by phagocytosis of AG as well as decreasing the tubular cell lipoperoxidation in response to toxic injury; (4) Reducing the tissue Ca++ content. PMID: 9772591, UI: 98445768

J Cell Biochem 1998 Jun 15; 69(4):483-9
Effects of a water-soluble extract of Cordyceps sinensis on steroidogenesis and capsular morphology of lipid droplets in cultured rat adrenocortical cells.
Wang SM, Lee LJ, Lin WW, Chang CM, Department of Anatomy, College of Medicine, National Taiwan University, Taipei, Republic of China.

Journal of Food and Drug Analysis, Vol. 8, No. 4, 2000, Pages
Pharmacological Functions of Chinese Medicinal Fungus Cordyceps sinensis and Related Species
SHENG-YUAN WANG1, 2 AND MING-SHI SHIAO1*
1. Department of Medical Research and Education, Veterans General Hospital-Taipei, 201, Shih-Pai Rd., Section 2, Taipei, Taiwan 112, R.O.C.
2. Institute of Traditional Medicine, National Yang-Ming University, 155, Li Nung St., Section 2, Taipei, Taiwan 112, R.O.C.

ABSTRACT
Cordyceps sinensis, an entomogenous fungus used in traditional Chinese medicine, exhibits very broad biological and pharmacological actions in hepatic, renal, cardiovascular, and immunologic systems as well as anticancer activity. Pharmacological functions of Cordyceps are primarily due to the bioactive polysaccharides, modified nucleosides, and cyclosporin-like metabolites produced by this fungus and related species. The beneficial effects on renal and hepatic function and immunomodulation-related antitumor activities are most promising and deserve great attention. Many previous studies used fruiting bodies, but recently an increasing number of studies have used cultured mycelia in investigations. It is difficult to determine if the same bioactive ingredients exist in fruiting bodies and cultured mycelia and contribute to the pharmacological actions reported in the literature. More mechanism-based, disease-oriented pharmacological studies are required to ensure clinical efficacy for particular diseases. Adjuvant therapy using C. sinensis for immune function disturbances, cancer, and renal failure is possible if double-blind, randomized placebo-control clinical studies show the efficacy of this herb.
Key words: Cordyceps sinensis, anticancer activities, hepatic function, renal function, immunomodulation, polysaccharides, modified nucleosides
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Postby flipflopper » Sat Jun 24, 2006 7:00 pm

How come nobody is wishing me good luck with the clinical trial? :wink:


On a more serious note, I just wanted to thank you Carole for posting the new info you found out about the clinical trial! I already had read about bradycardia when I was doing some research on the medication last December (thinking that perhaps the clinical trial might begin in the not too distant future). With macular edema, bradycardia and dyspnea, this drug does have unique potential side effects.

I have my regular appointment with my ms specialist at the very end of July. I will probably get some more info on when recruitment will begin and answers to some other questions I have about this trial and about FTY720. I will post again then.



bromley wrote: I've always thought the devil himself must have dream't up this disease on a bad day. It now looks like his brother is involved in coming up with therapies. I can't believe that this disease can cause vision problems / loss and one of the promising therapies offers the risk of something similar!


Something like that crossed my mind when I first found out about macular edema being a potential side-effect of FTY720
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Postby sh8un » Sun Jun 25, 2006 5:05 pm

Hi Flipflopper
So many things to read. I am sorry, I had not realized that you will be in the trial too. Of course I wish you good luck as well. Not just you but all those who go through trials. I know you are not seriously hurt but it made me feel bad I did not wish you good luck. :oops: All the best.
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Postby flipflopper » Sun Jun 25, 2006 7:39 pm

sh8un wrote:So many things to read. I am sorry, I had not realized that you will be in the trial too. Of course I wish you good luck as well. Not just you but all those who go through trials. I know you are not seriously hurt but it made me feel bad I did not wish you good luck. :oops: All the best. NN



Sh8un, thanks but I was 100% kidding around when I pointed out that nobody was wishing me good luck with the trial. There’s no need to feel bad at all!
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Postby CureOrBust » Wed Jun 28, 2006 2:19 am

From what I have read, this product has a VERY strong anti-inflamatory effect. Now, from what i understand, steroids are effective for their immune modulation as well as their anti-inflamatory effect. and they have generally been found to be ineffective over the long term (ie 10+years).

Is this product and all others that aim for anti-inflamatory, headed for the same outcome long term? or is it the immune modulation that fails long term with steroids?
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Postby CureOrBust » Tue Jul 04, 2006 5:54 am

well, i just got my bottle of Cordyceps.

http://www.drbvitamins.com/nutritionalproducts_details.asp?id=49

I am sure it is no-where near as effective as FTY720, but i'll see.
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Postby gibbledygook » Fri Jul 14, 2006 5:58 am

Hi Cureorbust! I've been taking my cordyceps sinensis for a few days now. However I don't know how much I'm taking as the script's in Mandarin. I haven't noticed any adverse events or any magic improvements. Yet. !!
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Postby ljm » Fri Jul 14, 2006 9:03 am

Just FYI. Cordyceps sinesis is available at my corner store (but then, this is California) with label claiming an average 250% increase in killer cell activity with regular use (but then, this is marketing). Its part of a range of supplements that involve organic culturing of the fungi rather than ravaging them from native environments.
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Postby gibbledygook » Mon Jul 17, 2006 2:58 am

Interesting. All my blood tests even before starting avonex (beta interferon 1a) showed that I have LOW white blood cell counts. A herbal remedy to increase my white blood cell count sounds a good idea to me.
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Postby Arron » Mon Jul 17, 2006 10:21 am

for those in the clinical trial: good luck!
for those doing a home-version of the clinical trial: be careful, let your doctor know what you're doing-- and thank you for sharing your results!
Disclaimer: Any information you find on this site should not be considered medical advice. All decisions should be made with the consent of your doctor, otherwise you are at your own risk.
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Postby gibbledygook » Thu Aug 03, 2006 7:09 am

I finished my first pack of cordyceps sinensis and I can't say I've noticed any changes at all!! Still I'm very prepared to believe that medicines can take years before their effect is more obvious so I'm going to stick with taking it for the forseeable future. Or until something better comes out! 8)
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Re: Questions about FTY720

Postby NHE » Sat Aug 05, 2006 1:52 am

gibbledygook wrote:Hi Cureorbust! I've been taking my cordyceps sinensis for a few days now. However I don't know how much I'm taking as the script's in Mandarin. I haven't noticed any adverse events or any magic improvements. Yet. !!

You are much braver than I 8O as I prefer to err on the side of caution. Just watch out for a few known bad ingredients in those herbal supplements. This article from Consumer Reports is a worthwhile read in my opinion. Don't miss the other pages of the article linked to in the left hand column.

NHE
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