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Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 991 records · Page 55Linked to original sources
PubMedDate not supplied

Antiepileptic potential of cannabidiol analogs.

In audiogenic seizure (AGS) susceptible rats, the acute (intraperitoneal and intravenous) dose-response effects of (--)-cannabidiol (CBD) for preventing AGS and for causing rototod neurotoxicity (ROT) were determined. Also, the anti-AGS and ROT effects of 10 CBD analogs, given in intravenous doses equivalent to the AGS-ED50 (15 mg/kg) and ROT-ID50 (31 mg/kg) of CBD, were ascertained. Compared to CBD, (--)-CBD diacetate and (--)-4-(2'-olivetyl)-alpha-pinene were equally effective whereas (--)-CBD monomethyl ether, (--)-CBD dimethyl ether, (--)-3'-acetyl-CBD monoacetate, (+)-4-(2'-olivetyl)-alpha-pinene, (--)-and (+)-4-(6'-olivetyl)-alpha-pinene, (+/-)-AF-11, and olivetol were less effective anticonvulsants. Except for (--)- and (+)-4-(2'-olivetyl)-alpha-pinene and olivetol, all analogs showed less ROT than CBD. Also, CBD and all analogs were not active in tetrahydrocannabinol seizure-susceptible rabbits, the latter a putative model of cannabinoid psychoactivity in humans. These data suggest anticonvulsant requirements of 2 free phenolic hydroxyl groups, exact positioning of the terpinoid moiety in the resorcinol system and correct stereochemistry. Moreover, findings of separation of anticonvulsant from neurotoxic and psychoactive activities, notably with CBD diacetate, suggest that additional structural modifications of CBD may yield novel antiepileptic drugs.

Acoustic Stimulation↗
PubMedDate not supplied

Effect of (+)-gossypol on fertility in male hamsters.

(+)-Gossypol was isolated from the bark of Thespesia populnea and tested for its ability to inhibit the fertility of male hamsters. Male hamsters of proven fertility were treated orally for 54 days with 40 mg/kg of (+)-gossypol, 40 mg/kg of racemic gossypol, or 5% gum acacia (vehicle control) and were mated with estrous female hamsters during the fourth and seventh weeks of treatment. Both the control and the (+)-gossypol-treated animals exhibited normal fertility throughout the experiment. The racemic gossypol-treated animals were infertile when evaluated during both the fourth and seventh weeks of treatment. Morphologic examination of the testicular tissue could not explain the loss of fertility. These data demonstrate the inability of (+)gossypol to decrease male fertility and suggest that the activity of racemic gossypol may be due primarily to the presence of the (-) optical isomer.

Animals↗
PubMedDate not supplied

Infrared spectroscopic characterization of the interaction of lipid bilayers with phenol, salicylic acid and o-acetylsalicylic acid.

The interaction of phenol (PHE), salicylic acid (SA) and o-acetylsalicylic acid (ASA) with bilayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was investigated by infrared spectrometry. The temperature of the main gel to liquid crystal phase transition of DPPC is markedly depressed in the presence of the three guest molecules. The temperature depression depends on the nature and concentration of the additives. The temperature of the pretransition is also affected by these guest molecules and the depression in temperature is even more pronounced than that of the main transition temperature. Possible modes of interaction of these guest molecules with the lipid bilayers are discussed.

1,2-Dipalmitoylphosphatidylcholine↗
PubMedDate not supplied

Impact of fears on quality of life in patients with a silent disease: osteoporosis.

Fears and apprehensions are often cited as contributing to decreased quality of life; however, questions relating to worry over the future are rarely included in generic quality-of-life questionnaires. We report an effort to quantify the effect of fear on quality-of-life domains as measured by using the Short-Form 36 (SF-36) Health Survey. In the course of developing an osteoporosis-targeted quality-of-life (OPTQoL) questionnaire, we asked participants to complete the SF-36 Health Survey and another questionnaire containing items that women with osteoporosis could be expected to find difficult or worrisome. Two hundred twenty-two women with established osteoporosis (loss of height, kyphosis, history of fractures); 101 women with known low bone mineral density (BMD) but without established osteoporosis; and 142 women with no known osteoporosis completed both the osteoporosis questionnaire and the SF-36 Health Survey. This test version of the OPTQoL contained two domains for fears of osteoporosis and the consequent fractures and deformities; these domains were termed fears now and fears future. After adjusting for age and selected comorbidities, we estimated the additional contribution of the two fears domains on the domain scores of the SF-36 Health Survey. For women with established osteoporosis, the fears now domain explained 4% to 8% of the variance within each domain of the survey. For women with low BMD only, fears now had a significant effect only on the physical functioning domain of the survey and explained 4% of the variance of that domain. Fears future had a significant role in explaining the SF-36 Health Survey score on all domains except physical functioning among women with established osteoporosis; however, the fears future domain explained less of the variance (2% to 5%) among these women than did the fears now domain. For women with low BMD only, fears future had a significant impact only on the mental health and the general health domains (4% and 5% of the variance, respectively). Osteoporosis-related fears appear to explain a small but significant percentage of the variation in quality of life for women in midlife.

Adult↗
PubMedDate not supplied

SHP-1 variant proteins are absent in motheaten mice despite presence of splice variant transcripts with open reading frames.

Motheaten mice have a mutation that causes abnormal splicing of the SHP-1 gene producing transcripts that are out of frame. Thus, motheaten mice cannot produce normal SHP-1 protein. However, we have found that the SHP-1 locus in normal mice is expressed as multiple in-frame splice variant transcripts. We report here that the motheaten SHP-1 gene is likewise expressed in multiple spliced forms, two of which are in frame. One of these two variants, which is also present in normal mice, lacks the exon containing the motheaten mutation and is therefore expected to encode an active phosphatase with only one of the two SH2 domains of SHP-1. We showed that both of these variants produce phosphatases with a higher specific activity than SHP-1, suggesting that motheatein mice are not SHP-1 null. The possibility that motheaten mice produce disregulated phosphatases offered a simple explanation for the puzzling observation that substrates of SHP-1 are hypo-phosphorylated in motheaten mice. We tested this by measuring for SHP-1 protein and activity in motheaten macrophages. However, we did not detect specific activity, and found that one of these variant proteins was unstable. These findings likewise suggest that little or no SHP-1 variant proteins exist in normal cells.

Alternative Splicing↗
PubMedDate not supplied

Copernicus revisited: amyloid beta in Alzheimer's disease.

The beta-amyloid hypothesis of Alzheimer's Disease (AD) has dominated the thinking and research in this area for over a decade and a half. While there has been a great deal of effort in attempting to prove its centrality in this devastating disease, and while an enormous amount has been learned about its properties (e.g., putative toxicity, processing and signaling), Abeta has not proven to be both necessary and sufficient for the development, neurotoxicity, and cognitive deficits associated with this disease. Instead, the few treatments that are available have emerged from aging research and are primarily directed toward modification of acetylcholine levels. Clearly, it is time to rethink this position and to propose instead that future approaches should focus upon altering the age-related sensitivity of the neuronal environment to insults involving such factors as inflammation and oxidative stress. In other words "solve the problems of aging and by extension those of AD will also be reduced." This review is being submitted as a rather Lutherian attempt to "nail an alternative thesis" to the gate of the Church of the Holy Amyloid to open its doors to the idea that aging is the most pervasive element in this disease and Abeta is merely one of the planets.

Age Factors↗
PubMedDate not supplied

Essential fatty acids and the brain: possible health implications.

Linoleic and alpha-linolenic acid are essential for normal cellular function, and act as precursors for the synthesis of longer chained polyunsaturated fatty acids (PUFAs) such as arachidonic (AA), eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), which have been shown to partake in numerous cellular functions affecting membrane fluidity, membrane enzyme activities and eicosanoid synthesis. The brain is particularly rich in PUFAs such as DHA, and changes in tissue membrane composition of these PUFAs reflect that of the dietary source. The decline in structural and functional integrity of this tissue appears to correlate with loss in membrane DHA concentrations. Arachidonic acid, also predominant in this tissue, is a major precursor for the synthesis of eicosanoids, that serve as intracellular or extracellular signals. With aging comes a likely increase in reactive oxygen species and hence a concomitant decline in membrane PUFA concentrations, and with it, cognitive impairment. Neurodegenerative disorders such as Parkinson's and Alzheimer's disease also appear to exhibit membrane loss of PUFAs. Thus it may be that an optimal diet with a balance of n-6 and n-3 fatty acids may help to delay their onset or reduce the insult to brain functions which these diseases elicit.

Animals↗