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Pain. 1999 Mar;80(1-2):45-55.
Peripheral antinociceptive action of amitriptyline in the rat formalin test: involvement of adenosine.

Sawynok J, Reid AR, Esser MJ.

Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada. sawydals.dal.ca

The present study determined (1) whether amitriptyline could produce a local antinociceptive action in the formalin test, (2) whether endogenous adenosine was involved in this action, and (3) which other systems might contribute to such an action. Coadministration of amitriptyline 10-100 nmol with 2.5% formalin produced a dose-related reduction in phase 1 (0-12 min) and phase 2 (16-60 min) flinching behaviours, as well as in phase 2 biting/licking time (no phase 1 expression). This action was not seen or only partially expressed at low concentrations of formalin (0.5%, 0.75%). Coadministration of caffeine with amitriptyline partially reversed the antinociceptive action of amitriptyline against both behaviours at 2.5% formalin. At 1.5% formalin, caffeine still produced only a partial reversal of effect; this appeared to be due to a block of adenosine A1 receptors, as it was also seen with the selective adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine. Using antagonists for a number of other systems, no evidence for an involvement of alpha-adrenergic, histamine, excitatory amino acid or opioid receptors in the action of amitriptyline was observed or inferred. A local anaesthetic action for amitriptyline remains a possibility for the residual action. These results indicate that amitriptyline can produce a local peripheral antinociceptive action which is mediated, in part, by an interaction with endogenous adenosine, most likely an inhibition of the cellular uptake of adenosine with a consequent activation of adenosine A1 receptors on sensory nerve terminals. Local application of amitriptyline by cream or gel might prove to be a useful method of drug delivery in inflammatory pain states.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10204717&dopt=Abstract



J Nutr Sci Vitaminol (Tokyo). 2003 Feb;49(1):56-63.
Anti-obesity effects of a mixture of thiamin, arginine, caffeine, and citric acid in non-insulin dependent diabetic KK mice.

Muroyama K, Murosaki S, Yamamoto Y, Odaka H, Chung HC, Miyoshi M.

Research and Development Section, Takeda Food Products Ltd., 3-20 Imoji, Itami 664-0011, Japan. k_muroyamti.biglobe.ne.jp

Anti-obesity effects of a mixture of thiamin, arginine, caffeine, and citric acid (TACC) were investigated in non-insulin dependent diabetic KK mice. Feeding of either arginine or caffeine significantly suppressed an increase in hepatic lipid contents in fasted-refed KK mice. In addition, each component admixed with a low-calorie diet effectively reduced adipose tissue weight in KK mice previously fed a high-calorie diet. The decrease in adipose tissue weight was greater with a mixture of arginine and caffeine, and much greater with TACC than with arginine or caffeine alone. Moreover, plasma insulin concentration was significantly lower in mice fed TACC than in control mice. The anti-obesity effects of TACC were also shown when it was supplemented with a tea beverage. Adipose tissue weight, hepatic triglyceride contents, and plasma insulin concentration were significantly lower in mice given TACC-supplemented tea than in control mice. These results suggest that TACC is effective in reducing adipose tissue mass as well as improving disorders in lipid metabolism.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12882397&dopt=Abstract [PubMed - in process]



J Appl Physiol. 2003 Jul 25 [Epub ahead of print].
INFLUENCE OF AGE AND RUN TRAINING ON CARDIAC Na+-Ca2+ EXCHANGE.

Mace LC, Palmer BM, Brown DA, Jew KN, Lynch JM, Glunt JM, Parsons TA, Cheung JY, Moore RL.

Department of Integrative Physiology, University of Colorado at Boulder, Boulder, CO, USA.

The effects of age and training on myocardial Na(+)-Ca(2+) exchange were examined in sedentary young (YS; 14-15 mo), aged sedentary (AS; 27-31 mo) and aged trained (AT; 8-11 wk treadmill run training) male Fischer Brown Norway rats. Both whole heart performance and isolated cardiocyte Na(+)-Ca(2+) exchange characteristics were measured. At the whole heart level, a small but significant slowing of late isovolumic left ventricular (LV) relaxation, which may be indicative of altered Na(+)-Ca(2+) exchange activity, was seen in hearts from AS rats. This subtle impairment in relaxation was not observed in hearts isolated from AT rats. At the single cardiocyte level, late action potential (AP) duration was prolonged, resting membrane potential was more positive, and overshoot potential was greater in cardiocytes isolated from AS rats relative to cardiocytes isolated from YS rats (P<0.05). Training did not influence any of these age-related AP characteristics. In electrically paced cardiocytes, neither shortening nor intracellular [Ca(2+)] ([Ca(2+)]i) dynamics were influenced by age or training. Similarly, neither age nor training influenced the rate of [Ca(2+)]i clearance via forward (Na(+)in/Ca(2+)out) Na(+)-Ca(2+) exchange following caffeine-induced Ca(2+) release from the sarcoplasmic reticulum, or in cardiac sodium-calcium exchanger protein (NCX1) expression. However, when whole-cell patch clamp techniques combined with fluorescence microscopy were used to evaluate the ability of Na(+)-Ca(2+) exchange to alter cytosolic [Ca(2+)] ([Ca(2+)]c) under conditions where Vm and internal and external [Na(+)] and [Ca(2+)] could be controlled, we observed age-associated increases in forward Na(+)-Ca(2+) exchange-mediated [Ca(2+)]c clearance (P<0.05) that were not influenced by training. The age-related increase in forward Na(+)-Ca(2+) exchange activity provides a hypothetical explanation for the late AP prolongation that we observed in this study.


online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12882992&dopt=Abstract [PubMed - as supplied by publisher]








Loss of hair changes the appearance of a person, and the identity of the person in social context to a certain extent. Hair growth is a complex biological process, which has not yet been completely understood. A multitude of therapeutic measures, including drugs, surgery, and suppelements have been made available, and used. However, due to the diversity of the problems underlying hair loss, there is no single solution for all hair loss cases. Most of chemical drugs and hair transplantation surgeries are not free from varying degrees of undesirable side effects on health.

Hair Million is an alternative solution to hair loss problems. Albeit only anecdotally, it has demonstrated efficacy in the improvement for age-related hair thinning and hair loss for a significant fraction of people who take it as recommended. We do not know the mechanisms of action as to how Hair Million works to help stop hair loss, and promote hair growth. We only know by anecdotal observations. There has been no clinical trials nor placebo controlled statistical analysis.
















DHEA is a natural hormone, and it is produced in our body by the adrenal glands. DHEA has been suggested to provide numerous potential benefits. DHEA (or dehydroepiandrosterone) is converted into androgens (male hormones) or estrogens (female hormones) in the cells.







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