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Biomedical subjects

P Webb

Publications and source records attributed to P Webb.

At least 91 records · Page 5Linked to original sources
PubMed1991

Aziridinyl nitropyrroles and nitropyrazoles as hypoxia-selective cytotoxins and radiosensitizers.

A series of 1- and 2-substituted 4- and 5-nitropyrroles and 3- and 4-nitropyrazoles has been prepared and evaluated in vitro as radiosensitizers of hypoxic cells and as bioreductively-activated cytotoxins. Both the nitropyrroles and the nitropyrazoles were considerably less effective, based upon the differential between hypoxic and aerobic toxicity, than were similar 2-nitroimidazoles bearing alkylating moieties. The trends in radiosensitizing efficiency observed for both classes of drugs corresponded with their one-electron reduction potentials (E1(7] as measured by pulse radiolysis, although they were generally more effective than predicted from previous correlations of E1(7] with sensitizing efficacy and reactivities. Furthermore, the enhancement of sensitizing efficiency by the incorporation of alkylating groups is considerably greater than has been observed for nitroimidazoles. alpha-[(1-Aziridinyl)methyl]-3-nitropyrazole- 1-ethanol (10, E1(7) = -456 mV) and methyl 5-nitro-1-(cyclopropylcarbonyl)pyrrole-2-carboxylate (25, E1(7) = -326 mV) were the most effective radiosensitizers in vitro. Only 3-[cis-2,3-dimethyl-1-aziridinyl) methyl)-1-oxo-3,4-dihydro-6-nitro-1-H-pyrrolo [2,1-c] oxazine (22) and methyl 5-nitro-1-(cyclopropylcarbonyl)pyrrole-2-carboxylate (25) showed significant bioreductively-activated cytotoxicity, with differentials of 3.5. Although these differential toxicities were coupled with significantly lower aerobic toxicity compared with similar 2-nitroimidazoles, this series was not deemed effective enough to warrant further evaluation. The electron affinity and radiosensitization could be manipulated by chemical design but hypoxia-selectivity was not clearly related to these properties.

Animals↗
PubMed1990

Energy exchange in downhill and uphill walking: a calorimetric study.

Energy balance can be written as 1) M = sigma Q +/- W +/- S, expressed as power (W), where M is the rate of metabolic energy transformation, sigma Q the rate of heat loss, W the work rate, and S the rate of body heat storage. When submaximal treadmill exercise continues long enough, body temperature stops changing, S becomes zero, and the heat storage term is dropped from equation 1. For uphill walking the equation becomes 2) M = sigma Q + Wvert, and for downhill walking it becomes 3) M = sigma Q - Wvert. This study tested the energy balance equations with direct measurements of heat exchange using a suit calorimeter and M from standard measurements of respiratory gas exchange. Ten healthy men walked on a motor driven treadmill at 1.5 m.s-1 at grades of 0, 5, 10, -5, and -10% for 70-90 min to ensure a thermal steady state. As expected, +Wvert was identified as a power output, whereas -Wvert was accounted for as a power input, totally transformed to heat in the downhill walking subject. There also appeared to be a quantity of non-thermal energy, Wwalk, needed to satisfy the energy balance equation. This was significant at 0, 5, and 10% grades (P less than 0.01) but not significant at -5 and -10% grades (P greater than 0.05). The data confirm previous results for level walking and extend them to include uphill walking. While it had been suggested that Wwalk represents an externalization of energy at the foot, the present data suggest an alternative explanation.(ABSTRACT TRUNCATED AT 250 WORDS)

Calorimetry↗
PubMed1989

Water referencing for spectroscopic imaging.

A water referencing algorithm for addressing the spectroscopic imaging problems of low SNR and main field inhomogeneities is proposed. Using the location of the water peak from each voxel and additional a priori information results in a parametric estimation problem. Optimum estimates of the desired metabolite concentration can then be computed and displayed in an image format. The algorithm is shown to be very stable in the presence of noise and is insensitive to Bo inhomogeneity. A detailed error analysis as well as extensions to the basic data model are also discussed. Results from both 1H and 31P experiments are presented to verify the predicted good performance even with extremely low signal-to-noise ratio data.

Algorithms↗
PubMed1989

A fast spectroscopic imaging method using a blipped phase encode gradient.

Many methods of chemical shift imaging have been described recently. In most cases, these methods couple resolution and imaging time. The most flexible methods use time-varying gradients to cover a large region of k space on each excitation. We present here a new time-varying gradient method that offers a decrease in scan time (when SNR is sufficient), simplifies the reconstruction problem by retaining an essentially rectilinear sampling grid, and makes efficient use of scan time by minimizing gradient reversals. Implementation on a standard high-field imaging system (GE Signa) is discussed, and experimental results are shown. An application of the method to the generation of water reference data sets is described.

Fourier Analysis↗
PubMed1989

Effects of dietary fish oil or pectin on blood pressure and lipid metabolism in the DOCA-salt hypertensive rat.

This study investigated the effects of diets containing fish oil or pectin on blood pressure and lipid metabolism in the deoxycorticosterone acetate (DOCA)-salt hypertensive rat. Three groups (8 rats/group) of unilaterally nephrectomized rats were fed for 21 d one of three purified diets: a) 8% fish oil + 2% safflower oil + 5% alpha cellulose (fish oil diet), b) 10% safflower oil + 5% pectin (pectin diet), or c) 10% safflower oil + 5% alpha cellulose (control diet). Each of the diets contained 6% NaCl and all rats received DOCA (30 mg/kg body wt, subcutaneously) twice weekly. Systolic blood pressure of rats fed fish oil was significantly lower (P less than 0.05) than that of rats fed the control diet; there was no significant difference between the pectin and control groups. Plasma renin activity and net sodium and potassium balances were similar among the three groups. Plasma total cholesterol, LDL cholesterol and HDL cholesterol were significantly lower (P less than 0.05) in the group fed the fish oil diet than in the group fed the control diet. Total, LDL and HDL cholesterol did not differ between rats fed the pectin and rats fed the control diet. Plasma triglyceride concentration did not differ among the three groups. Thus, dietary fish oil attenuated the development of DOCA-salt hypertension, unrelated to alterations of net sodium balance. Fish oil feeding also lowered total, LDL and HDL cholesterol, but did not alter the HDL/LDL ratio. In contrast, dietary pectin exerted no effect on blood pressure or lipid metabolism.

Animals↗
PubMed1989

Influence of inducers and inhibitors on the metabolism in vitro and neurochemical effects in vivo of MDMA.

(S)-(+)- and (R)-(-)-3,4-methylenedioxymethamphetamine (MDMA) were metabolized in vitro by rat liver microsomes via N-demethylation to 3,4-methylenedioxyamphetamine (MDA). Whereas no difference was found in the biotransformation of the two enantiomers in the male rat or in the phenobarbital (PB) treated animals of either sex, more than twice as much MDA was formed from (S)-(+)- than from (R)-(-)-MDMA in the untreated female rat. Although 3-methylcholanthrene (3MC) pretreated rat liver microsomes were less active than those from the untreated rats of the same sex, they formed more MDA from (+)- than from (-)-MDMA. The enantioselective metabolism thus appears to be associated with the relative abundance of individual cytochrome P-450 isozymes. (S)-(+)- and (R)-(-)-MDMA.HCl (20 mg/kg) were about equipotent in depleting serotonin (5-HT) levels in the frontal cortex at 3 hrs and 1 wk following oral administration to female rats. Pretreatment of rats with SKF-525A attenuated and that with PB enhanced the 5-HT depleting potential of either isomer at 3 hrs. The 5-HT depleting potency of (+)-MDMA was significantly greater than that of its (-)-antipode at 3 hr in PB pretreated, but not in SKF-525A pretreated animals. The results suggest that the neurochemical effects of MDMA are caused by the formation of an active metabolite in vivo, and since both enantiomers were N-demethylated in vitro to approximately the same extent by PB pretreated rat liver microsomes, the active metabolite may be other than MDA.

3,4-Methylenedioxyamphetamine↗
PubMed1988

Characterization of response elements for androgens, glucocorticoids and progestins in mouse mammary tumour virus.

We have characterized steroid response elements in mouse mammary tumour virus (MMTV) by transient transfection. Four partial inverted repeats of the sequence TGTTCT function as response elements for androgen, as well as for glucocorticoid and progestins, although the relative hormone inductions mediated by each oligonucleotide were different. Mutational analysis of the left half of the palindrome showed that a perfect dyad symmetry is not required for optimum activity as a steroid response element. To investigate potential interactions between steroid receptors and transcription factors we have analysed the minimum sequence requirements for a hormone response. Interestingly, a single 15 bp steroid response element and a TATA box are sufficient for steroid inductions. When the distance between the two elements was increased by up to two turns of the helix the hormone induction initially increased and then gradually declined with no obvious periodicity.

Animals↗