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23 avril 2011 6 23 /04 /avril /2011 10:38
Neurobiol Aging. 2011 Jan;32(1):42-53. Epub 2009 Feb 23.

Thiamine deficiency increases β-secretase activity and accumulation of β-amyloid peptides.

Source

Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, PR China.

Thiamine pyrophosphate (TPP) and the activities of thiamine-dependent enzymes are reduced in Alzheimer's disease (AD) patients.

 

In this study, we analyzed the relationship between thiamine deficiency (TD) and amyloid precursor protein (APP) processing in both cellular and animal models of TD.

 

In SH-SY5Y neuroblastoma cells overexpressing APP, TD promoted maturation of β-site APP cleaving enzyme 1 (BACE1) and increased β-secretase activity which resulted in elevated levels of β-amyloid (Aβ) as well as β-secretase cleaved C-terminal fragment (β-CTF).

An inhibitor of β-secretase efficiently reduced TD-induced up-regulation of Aβ and β-CTF. Importantly, thiamine supplementation reversed the TD-induced alterations.

Furthermore, TD treatment caused a significant accumulation of reactive oxygen species (ROS); antioxidants suppressed ROS production and maturation of BACE1, as well as TD-induced Aβ accumulation.

On the other hand, exogenous Aβ(1-40) enhanced TD-induced production of ROS. A study on mice indicated that TD also caused Aβ accumulation in the brain, which was reversed by thiamine supplementation.

 

Taken together, our study suggests that TD could enhance Aβ generation by promoting β-secretase activity, and the accumulation of Aβ subsequently exacerbated TD-induced oxidative stress.

 

PMID:
 
19233513
 
[PubMed - indexed for MEDLINE]
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23 avril 2011 6 23 /04 /avril /2011 10:32
Med Hypotheses. 2011 May;76(5):629-31. Epub 2011 Feb 1.

Could thiamine pyrophosphate be a regulator of the nitric oxide synthesis in the endothelial cell of diabetic patients?

Source

Institute of Scientific Research, "Hans Selye", Querétaro, Qro., Mexico.

Thiamine (Vitamin B1) is considered an essential micronutrient for humans; its deficient intake brings about the Wernicke-Korsakoff syndrome (encephalopathy and psychosis) or beriberi (a neurological and cardiovascular disease).

 

Once thiamine enters the cells it is phosphorylated by thiamine pyrophosphokinase (TPPK), and converted into the coenzyme thiamine pyrophosphate (TPP), the active form of thiamine.

 

TPP is a relevant cofactor for transketolase (TK), α-ketoglutarate dehydrogenase (αKDH), and pyruvate dehydrogenase (PDH), all these enzymes are fundamental for glucose metabolism.

 

Diabetes mellitus (DM), however, is considered both a deficient thiamine and deficient energy state, as a consequence of the limited TPP synthesis. Recent evidences have shown that the administration of thiamine or lipid-soluble derivatives, such as benfotiamine (developed to improve the bioavailability of thiamine), has positive effects in the diabetic patient (after thiamine is transformed into TPP).

 

For this reason, administration of supplements with TPP in the diabetic patients is recommended to avoid complications, like neuropathy and nephropathy. It has been suggested that these beneficial effects are a consequence of the activation of TK (pentose pathway) or the PDH complex in mitochondria.

 

Nitric oxide (NO) is synthesized by the endothelial cell and is also an important element for the viability and functionality of this cell type. However, in the DM patient, a deficient synthesis of NO has been reported. It is relevant to mention that recent evidences have led to propose mitochondrial activity as an important regulator of nitric oxide synthesis (ON).

 

We consider that the exogenous administration of TPP facilitates the utilization of this molecule, regulating some metabolic processes such as phosphorylation of thiamine by TPPK, energy consumption (ATP), as well as mitochondrial activity, inducing eventually NO synthesis.

 

If this is confirmed, the administration of TPP to the diabetic patient would provide additional protection to endothelial cells, reducing the risk of vascular damage, to which the diabetic patient is highly susceptible.

 

PMID:
 
21288652
 
[PubMed - in process]
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23 avril 2011 6 23 /04 /avril /2011 10:30
Diabetes Obes Metab. 2011 Feb 22. doi: 10.1111/j.1463-1326.2011.01384.x. [Epub ahead of print]

Emerging role of thiamine therapy for prevention and treatment of early stage diabetic nephropathy.

Source

Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, University Hospital, Coventry CV2 2DX, U.K.

Thiamine supplementation may prevent and reverse early stage diabetic nephropathy.

This likely occurs by correcting diabetes-linked increased clearance of thiamine, maintaining activity and expression of thiamine pyrophosphate dependent enzymes that help counter the adverse effects of high glucose concentrations - particularly transketolase.

Evidence from experimental and clinical studies suggest that metabolism and clearance of thiamine is disturbed in diabetes leading to tissue-specific thiamine deficiency in the kidney and other sites of development of vascular complications.

Thiamine supplementation prevented the development of early-stage nephropathy in diabetic rats and reversed increased urinary albumin excretion in patients with type 2 diabetes and microalbuminuria in two recent clinical trials.

The thiamine monophosphate prodrug, Benfotiamine, whilst preventing early stage development of diabetic nephropathy experimentally, has failed to produce similar clinical effect.

The likely explanations for this are discussed. Further definitive trials for prevention of progression of early-stage diabetic nephropathy by thiamine are now required.


© 2011 Blackwell Publishing Ltd.

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23 avril 2011 6 23 /04 /avril /2011 10:17
Int J Neurosci. 1992 Feb;62(3-4):215-25.

Is postmenopausal osteoporosis related to pineal gland functions?

Source

Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10461.

There is currently considerable interest in the pathogenesis of postmenopausal osteoporosis, which is the most common metabolic bone disease.

Osteoporosis affects approximately 20 million persons in the United States, 90% of whom are postmenopausal women.

Although there is evidence that estrogen deficiency is an important contributory factor, the pathogenesis of osteoporosis is multifactorial and presently poorly understood.

There is evidence that pineal melatonin is an anti-aging hormone and that the menopause is associated with a substantial decline in melatonin secretion and an increased rate of pineal calcification.

Animal data indicate that pineal melatonin is involved in the regulation of calcium and phosphorus metabolism by stimulating the activity of the parathyroid glands and by inhibiting calcitonin release and inhibiting prostaglandin synthesis.

Hence, the pineal gland may function as a "fine tuner" of calcium homeostasis.

In the following communication, we propose that the fall of melatonin plasma levels during the early stage of menopause may be an important contributory factor in the development of postmenopausal osteoporosis.

Consequently, plasma melatonin levels taken in the early menopause could be used as an indicator or perhaps as a marker for susceptibility to postmenopausal osteoporosis.

Moreover, light therapy, administration of oral melatonin (2.5 mg at night) or agents which induce a sustained release of melatonin secretion such as 5-methoxypsoralen, could be useful agents in the prophylaxis and treatment of postmenopausal osteoporosis.

 

Finally, since application of external artificial magnetic fields has been shown to synchronize melatonin secretion in experimental animals and humans, we propose that treatment with artificial magnetic fields may be beneficial for postmenopausal osteoporosis.

PMID:
 
1305608
 
[PubMed - indexed for MEDLINE]
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23 avril 2011 6 23 /04 /avril /2011 10:10
Ann Med Psychol (Paris). 1994 Aug-Sep;152(7):444-56.

Chronobiology and depression: the seasonal depressions. Clinical aspects, physiopathology and specific treatments.

[Article in French]

Source

Service de Psychologie Médicale, CHRU, Hôpital Jeanne-d' Arc, Toul.

 

Seasonal Affective Disorder, described in 1984 by Rosenthal in the United States of America, was individualized in France since this concept entered the DSM III-R in 1989.

 

Firstly, the purpose of the authors was an attempt to draw the historical evolution of the concept, his clinical and epidemiological aspects.

 

Secondly, they considered the physiological hypothesises, which followed two ways of research: on the one hand the impairment of endogenous chronobiological rhythms, especially melatonin and serotonin rhythms; on the other hand the photoperiodical hypothesis.

 

Thildly, the authors proposed the main specific prospects of treatments: chimiotherapeutic methods--particularly 5-methoxypsoralen--and non chimiotherapeutic such as phototherapy.

 

 

PMID:
 
7978776
 
[PubMed - indexed for MEDLINE]
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23 avril 2011 6 23 /04 /avril /2011 10:08
Eur Psychiatry. 1995;10(3):142-54.

Antidepressant effect of 5-methoxypsoralen: The melatonin synchronizer hypothesis.

Source

Clinique de Psychiatrie et de Psychologie Médicale, Faculté de Médecine, Hôpital Pasteur, 130, avenue de la Voie Romaine, BP 69, 06002 Nice Cedex 01, France.

5-methoxypsoralen (5-MOP) stimulates pineal melatonin secretion, and a decrease in dark phase melatonin levels has been described in major depression.

As exogenous melatonin has shown synchronizer properties, authors hypothesized that giving 5-MOP would have antidepressant properties. Twenty-six inpatients meeting the criteria of major depressive disorders were enrolled in a four-week, double blind trial of 5-MOP versus amitriptyline.

 

Clinical improvement was identical in both treatment groups but biological changes were different in each group: 5-MOP patients showed an early nocturnal surge of melatonin levels that was maintained at the fourth treatment week, while melatonin levels remained unchanged in patients treated with amitriptyline.

PMID:
 
19698328
 
[PubMed - in process]
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23 avril 2011 6 23 /04 /avril /2011 10:04
Planta Med. 1995 Feb;61(1):2-8.

Anti-inflammatory and analgesic activities from roots of Angelica pubescens.

Source

Department of Pharmacology, China Medical College, Taiwan.

In the present study, we extracted Angelica pubescens (AP) with various solvents in order to find the bioactive constituents that demonstrated analgesic and anti-inflammatory effects.

 

The results were obtained as follows:

(1) Methanol-, chloroform-, and ethyl acetate-extracts effectively reduced the pain that was induced by 1% acetic acid and a hot plate.

(2) Methanol-, chloroform-, and ethyl acetate-extracts reduced the edema that was induced by 3% formalin or 1.5% carrageenan.

(3) Sixteen compounds have been isolated and identified from the roots of AP. Among these compounds, columbianadin, columbianetin acetate, bergapten, umbelliferone, and caffeic acid significantly demonstrated anti-inflammatory and analgesic activities at 10 mg/kg.

 

However, only osthole and xanthotoxin revealed anti-inflammatory activity. Isoimperatorin only demonstrated an analgesic effect.

These results revealed that the anti-inflammatory and analgesic constituents from roots of AP were related to peripheral inhibition of inflammatory substances and to the influence on the central nervous system.


PMID:
 
7700984
 
[PubMed - indexed for MEDLINE]
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23 avril 2011 6 23 /04 /avril /2011 09:57
Med Hypotheses. 1998 Jun;50(6):481-2.

Psoralens in association with seasonal affective disorder.

Source

Department of Psychiatry, University of Helsinki, Finland.

The pathogenesis of seasonal affective disorder (SAD) has been attributed to abnormal melatonin metabolism.

Perorally administered psoralens increase the daytime levels of melatonin via the competitive inhibition of hepatic melatonin metabolism.

Some findings among SAD patients are parallel to those observed after the administration of a psoralen in healthy subjects.

It is hypothesized that there may be a circulating psoralen-like substance which affects SAD patients under a low level of illumination.

Exposure to bright light during the daylight period would normalize the abnormal effect independently of the season.

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23 avril 2011 6 23 /04 /avril /2011 09:54
Drugs. 1998 Oct;56(4):667-90.

5-Methoxypsoralen. A review of its effects in psoriasis and vitiligo.

Source

Adis International Limited, Auckland, New Zealand. demail@adis.co.nz

5-Methoxypsoralen, a naturally occurring linear furocoumarin, has been successfully used in combination with ultraviolet (UV) A irradiation [psoralen plus UV (PUVA)] to manage psoriasis and vitiligo.

 

In patients and volunteers, PUVA 5-methoxypsoralen causes a dose-related increase in cutaneous photosensitivity.

 

However, mean minimum phototoxic doses (MPD) were 30 to 50% greater with 5-methoxypsoralen than with 8-methoxypsoralen within individuals; this suggests lower photoactivity with 5-methoxypsoralen.

 

In comparative clinical trials of parallel design, psoriasis clearance rates of > 90% or > 97% were observed in similar numbers of patients (60 to 77%) receiving oral PUVA 5-methoxypsoralen (typically 1.2 mg/kg) or oral PUVA 8-methoxypsoralen (0.6 mg/kg) treatment.

 

Generally, 5-methoxypsoralen recipients required a greater total UVA exposure than 8-methoxypsoralen recipients to achieve end-point. However, study end-point was achieved sooner with oral or topical PUVA 5-methoxypsoralen in a small number of patients with psoriasis who received both treatments simultaneously and contralaterally.

 

Up to 56% of patients with vitiligo achieved > 75% repigmentation with 5-methoxypsoralen (oral or topical) combined with UV irradiation (lamp or sun); the face and trunk were the most responsive areas.

 

Lack of response to PUVA 5-methoxypsoralen treatment was observed in up to 16% of patients with psoriasis and, in 1 trial, in 22% of those with vitiligo. Lesion spreading during treatment of vitiligo was also observed in 7 (19%) patients in 1 study.

 

The incidence and severity of adverse events was generally lower in PUVA 5-methoxypsoralen 1.2 mg/kg than in PUVA 8-methoxypsoralen 0.6 mg/kg recipients. Nausea and/or vomiting, pruritus and erythema were the most commonly reported adverse events in the short term; they occurred about 2 to 11 times more frequently in 8-methoxypsoralen than 5-methoxypsoralen recipients within clinical trials.

 

Adverse hepatic events after oral administration of the drug were uncommon.

Long term tolerability data for PUVA 5-methoxypsoralen are scarce; however, carcinogenicity was not reported during a 14-year observation period of 413 patients with psoriasis.

 

CONCLUSION: Similar lesion clearance rates were observed with oral 5- or 8-methoxypsoralen plus UVA exposure in patients with vitiligo or psoriasis, although patients given 5-methoxypsoralen often required a greater total UV exposure than 8-methoxypsoralen recipients.

The incidence of short term cutaneous and gastrointestinal adverse effects is markedly less with 5-methoxypsoralen than with 8-methoxypsoralen, which is an advantage, although the long term tolerability of 5-methoxypsoralen has yet to be fully established.

Nevertheless, in appropriately selected patients, PUVA 5-methoxypsoralen therapy may be recommended as an alternative first-line systemic treatment option for the management of vitiligo or psoriasis.


PMID:
 
9806110
 
[PubMed - indexed for MEDLINE]
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23 avril 2011 6 23 /04 /avril /2011 09:49
Arch Pharm Res. 1999 Jun;22(3):324-6.

Inhibitory activity of monoamine oxidase by coumarins from Peucedanum japonicum.

Source

College of Pharmacy, Chungnam National University, Taejon, Korea.

 

Four coumarins were isolated from chloroform extract of the root of Peucedanum japonicum and identified as praeruptorin A(1), xanthotoxin (2), psoralen (3) and bergapten (4) on the basis of spectroscopic methods.

 

The inhibitory activities of these coumarins on monoamine oxidase prepared by mouse brain were tested. The IC50 values of them were shown to be 27.4 microM (1), 40.7 microM (2), 35.8 microM (3), and 13.8 microM (4), in vitro.



PMID:
 
10403141
 
[PubMed - indexed for MEDLINE]
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