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Biomedical subjects

C Tang

Publications and source records attributed to C Tang.

257 records · Page 15Linked to original sources

Differences in red blood cell choline and lipid-bound choline between patients with Alzheimer disease and control subjects.

The concentrations of red blood cell choline, glycerophosphocholine, phosphocholine and lipid-bound choline were measured in patients with Alzheimer disease (AD) and in normal elderly controls. Red blood cell choline in the Alzheimer group (41.4 +/- 9.2 nmol/ml) was significantly higher (p less than 0.023) than in the elderly controls (18.7 +/- 2.3 nmol/ml). Red blood cell lipid-bound choline (1387 +/- 58 nmol/ml) in the AD group was significantly lower (p less than 0.0022) than in the age-matched controls (1667 +/- 65), while there were no significant differences in glycerophosphocholine or phosphocholine. Plasma choline and lipid-bound choline did not differ significantly between the groups. The mechanisms for these changes still need further study, although the finding of decreased lipid-bound choline supports the concept of altered phospholipid metabolism in patients with AD.

Alzheimer Disease↗

Burn area color changes after superficial burns in childhood: can they be predicted?

Pigmentation changes after superficial burn injuries are often difficult to predict. We analyzed a sample of patients with burn injuries, looking for clinical indicators of predictable color changes in burn wounds. A sample of 50 children, predominantly those with pigmented skins, who had sustained superficial partial-thickness, (second degree) thermal, scald, or friction burns, were retrospectively grouped. Chemical and electric burns, and those needing skin grafts were excluded. Forty-one patients returned for interview and examination, an average of 63 months after injury (range, 3 to 276 months). All patients had their skin color graded in terms of the Fitzpatrick scale--a numeric scale that combines innate skin color plus reported history of skin response to sun exposure, to assign a value from 1 to 6, where white skin that reddens but does not tan on sun exposure is 1 and heavily pigmented black skin is 6. The burn site, as well as unburned areas of control skin, were tested for reflectance and luminance with use of a well-validated spectrophotometric technique. As an addendum, clinical photographs of a further 50 patients were similarly analyzed. During the first 3 years after injury, burn site color changes were variable. Subsequently, there was cumulative hyperpigmentation at the burn site, provided that the melanocyte-bearing deep dermis had not been destroyed. Hyperpigmentation correlated significantly with skin color, as quantified by the Fitzpatrick scale (p < 0.01), and with time after injury (p < 0.05).

Burns↗

Metabolic chiral inversion of stiripentol in the rat. I. Mechanistic studies.

To study enantioselective aspects of the disposition of stiripentol (STP), a chiral allylic alcohol undergoing development as an antiepileptic drug, a stereoselective synthesis was developed and the configuration of the two enantiomers determined to be (R)-(+) and (S)-(-). Following a single oral dose (300 mg kg-1) of the individual enantiomers to adult male Sprague-Dawley rats, it was found that (R)-STP was transformed extensively to its antipode, whereas little inversion was detected when (S)-STP was administered. Studies on the mechanism of this apparently unidirectional chiral inversion revealed that the phenomenon was dependent on the presence of the side-chain C==C double bond, because the enantiomers of the corresponding saturated alcohol (D2602) did not interconvert in vivo. Experiments with analogs of STP labeled with deuterium or oxygen-18 at the chiral center showed that, whereas the deuterium was retained in vivo, partial loss of the 18O occurred from both enantiomers of the drug. Pretreatment of rats with pentachlorophenol (40 mumol kg-1 i.p.), an inhibitor of sulfation (and possibly other conjugation reactions), led to a marked decrease in the rate of conversion of (R)-STP to its antipode, suggesting that the chiral inversion phenomenon may be mediated, at least in part, by an enantioselective conjugation process.

Administration, Oral↗

Metabolic chiral inversion of stiripentol in the rat. II. Influence of route of administration.

As described in the accompanying study, it was found that when the S enantiomer of stiripentol [(S)-STP] was given orally to rats, blood specimens contained only (S)-STP, whereas following administration of an equivalent dose of (R)-STP, both R and S forms of the drug were detected in the systemic circulation. In the present study, we investigated the influence of route of administration on this apparently unidirectional chiral inversion of (R)-STP in the rat. When (R)-STP was given either intravenously (60 mg kg-1) or intraperitoneally (300 mg kg-1), the inversion phenomenon was not observed, indicating that the process must take place presystemically. Following oral administration of either enantiomer of STP, it was found that the drug present at various points along the gastrointestinal tract became progressively enriched in molecules of R configuration, such that the free STP in cecum, large intestine, and feces consisted largely of the R enantiomer, regardless of the configuration of the administered drug. In a parallel in vitro study, it was demonstrated that STP undergoes acid-catalyzed racemization, the rate of which is appreciable at the pH value of the rat stomach (pH approximately 4). On the basis of these observations, it is proposed that the apparent metabolic chiral inversion of (R)-STP results from the combination of at least two factors: 1) partial acid-catalyzed racemization in gastric acid (that affects both enantiomers equally), and 2) enantioselectivity in one or more of the processes involved in the absorption, first pass metabolism or biliary excretion of STP, such that the S isomer appears selectively in the systemic circulation, whereas the R enantiomer is eliminated preferentially in the feces.

Administration, Oral↗

Genetic regulation of preimplantation mouse embryo survival.

The preimplantation period of mammalian development is characterized by cleavage of a one-cell embryo to a blastocyst stage embryo. During preimplantation development, 15%-50% of the embryos die as a result of factors that are largely unknown. Two parameters of preimplantation development, a fast rate of development and a low degree of fragmentation, are indicative of good embryo quality. There is mounting evidence that genes control both rate of development and degree of fragmentation. We have discovered a gene, Ped (preimplantation embryo development), which controls the rate of preimplantation embryonic cleavage. The Ped gene is encoded by two similar genes, Q7 and Q9, in the Q region of the mouse major histocompatibility complex (MHC). The Ped gene product is an MHC class Ib protein, the Qa-2 antigen. The mechanisms by which the Ped gene controls rate of embryonic cleavage division are being explored. In order to understand genetic mechanisms underlying the second criterion of embryo quality, degree of fragmentation, we have begun to assess expression of the genes that could potentially regulate apoptosis in preimplantation embryos. We have shown that staurosporine can induce apoptosis in mouse blastocysts. By using RT-PCR, we have shown that genes encoding protein in the two major gene families that regulate apoptosis, the Bcl-2 and caspase gene families, are present in preimplantation embryos. We hypothesize that there is a homeostatic mechanism by which genes that regulate cell survival and those that regulate cell death determine the overall viability of preimplantation embryos.

Animals↗