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N Lowe

Publications and source records attributed to N Lowe.

66 records · Page 4Linked to original sources
PubMed1987

Potentiation of ethanol-induced hepatic vitamin A depletion by phenobarbital and butylated hydroxytoluene.

Administration of ethanol, phenobarbital or butylated hydroxytoluene (BHT) each resulted in significantly lower hepatic vitamin A than in untreated controls. When ethanol was combined with either phenobarbital or BHT, a striking potentiation of the depletion was observed, resulting in hepatic vitamin A values of less than 5% of normal, whether expressed per gram of liver or per 100 g body wt. These effects were observed for both retinol and retinyl esters, measured by high pressure liquid chromatography. By contrast, lung levels of retinol and retinyl esters were significantly higher in rats treated with ethanol, but remained unchanged in rats treated with phenobarbital or butylated hydroxytoluene compared with control animals.

Animals↗
PubMed1987

Morbidity after termination of pregnancy in first trimester.

The outcome of termination of pregnancy was observed in relation to the preoperative clinical and microbiological findings in 167 women attending a day care abortion unit in Liverpool. Before termination, Chlamydia trachomatis was isolated from the cervix of 19 (11%) of the patients and high counts (greater than 10(4) colour changing units (ccu) per ml of specimen) of mycoplasmas were found in 30 (18%). Coexistent infections with chlamydiae and high counts of mycoplasmas occurred in only seven (4%) women. Trichomonas vaginalis, yeasts, or pathogenic bacteria were found in vaginal swabs from 30 (18%) women. After undergoing termination, seven (4%) women developed pelvic inflammatory disease (PID), five (71%) of whom had yielded C trachomatis before undergoing termination. A further 13 (8%) patients developed minor morbidity of the upper genital tract; high count mycoplasmal infection had been found in seven (54%) and chlamydial infection in three (23%) of these women before termination. In contrast, C trachomatis had been isolated from only 11 (8%) and high counts of mycoplasmas from 23 (16%) of the 147 women who had uneventful recoveries after undergoing termination. No correlation was apparent between the presence of vaginal pathogens before termination and the development of untoward sequelae postoperatively. Neither the history nor clinical examination before termination would have indicated that chlamydial or mycoplasmal infections were present, or that postoperative complications were likely to occur. Abnormal cervical cytology, however, was found in 86 (52%) of women overall, including 15 (79%) of the 19 women with chlamydial infection.

Abortion, Induced↗
PubMed1986

Interaction of drugs and retinol.

In liver microsomes of ethanol-fed rats, retinol competitively inhibited the hydroxylation of aniline, the demethylation of dimethylnitrosamine, and the oxidation of ethanol to acetaldehyde, whereas the inhibition of benzphetamine demethylation was of the mixed type in microsomes of phenobarbital-treated, ethanol-treated or control rats. Conversely, benzphetamine exerted a striking inhibition of the 4-hydroxylation of retinol in microsomes of phenobarbital-treated rats. At the concentration used, ethanol (100 mM) and dimethylnitrosamine (10 mM) had no such effect. In vivo administration of phenobarbital resulted in a 9-fold increase in the Vmax of the microsomal retinol 4-hydroxylase activity, with a 3-fold increase of the Km, whereas ethanol feeding resulted in a doubling of the Vmax with no significant change in the Km. The induction of this microsomal retinol-metabolizing system may contribute to the hepatic vitamin A depletion that has been reported previously after either ethanol or drug administration. Conversely, the observed inhibition, by retinol, of microsomal drug metabolism, including the demethylation of dimethylnitrosamine, may be of significance with regards to the interaction of retinol with carcinogenesis.

Animals↗
PubMed1986

Depletion of cutaneous glutathione and the induction of inflammation by 8-methoxypsoralen plus UVA radiation.

The purpose of this study was to examine the dose response and time course relationships between PUVA (psoralen + UVA) depletion of skin glutathione (GSH) and the induction of inflammation. Dorsal skin fold thickness (DSFT), an index of cutaneous edema, was used as a noninvasive measure of inflammation. Ornithine decarboxylase (ODC) was used as a measure of epidermal damage. Female hairless mice were given 8-methoxypsoralen (8-MOP) (dissolved in corn oil) by gavage at different doses, and 2 h later the mice were irradiated with 5 J/cm2 UVA. At 24 h, DSFT measurements were taken, the mice were killed, and reduced GSH, glutathione disulfide (GSSG), and glutathione-S-transferase were measured in the epidermis and dermis. Epidermal GSH was depleted 0, 11, 45, 87, and 98% from vehicle and/or UVA-treated levels (0.7 mM) after 0.1, 0.5, 5, 25, and 50 mg/kg, respectively. In the dermis GSH decreased from 0.3 mM by 47, 87, and 91% after 5, 25, and 50 mg/kg 8-MOP, respectively. Increases in DSFT of 20, 141, and 242% were observed after 5, 25, and 50 mg/kg doses, respectively. GSSG accounted for a small portion of total GSH in the skin after PUVA treatment. The maximal decreases in GSH were not observed until 24-48 h after PUVA treatment. PUVA treatment leads to dose-related increases in dermal edema, epidermal ODC, and depletion of GSH levels from both compartments in the skin. The time course of glutathione loss suggests that PUVA may interfere with its resynthesis or utilization from the circulation.

Animals↗
PubMed1985

Polyamines in clinical disorders.

An edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles. The Director of Conferences is William M. Pardridge, MD, Associate Professor of Medicine.Polyamines, necessary for cell growth, influence many cell functions. As small polyvalent cations they can change the configuration of large polyvalent anions, such as DNA, and alter their sensitivity to other molecules including chemotherapeutic agents. By altering polyamine content in a cell, we can change its growth, its susceptibility to drugs and change other cellular functions. Malignant conditions, other proliferative diseases and infections are the most apparent clinical conditions likely to improve by depleting polyamines and suppressing cell growth. Proliferative disorders of the skin respond to many agents that suppress polyamine metabolism. Hyperoxia may suppress cell growth in the lung by suppressing polyamine metabolism.

Animals↗
PubMed1984

Decreased hepatic vitamin A after drug administration in men and in rats.

Eleven patients with moderate drug-induced liver changes were found to have extremely low hepatic vitamin A levels (less than 10% of normal). Their serum vitamin A, retinol-binding protein, and transthyretin were only slightly affected. In rats, two representative drugs (phenobarbital and methylcholanthrene) produced a significant depression of hepatic vitamin A, whereas plasma vitamin A levels remained normal. The livers of drug-treated animals showed no abnormalities except for the expected proliferation of the smooth endoplasmic reticulum and induction of microsomal enzymes and cytochrome P-450 (phenobarbital) and P-448 (methylcholanthrene). These findings suggest that the decrease in hepatic vitamin A may be secondary, at least in part, to enhanced microsomal metabolism.

Animals↗
PubMed1983

Hardness of domestic water and blood lead levels.

The effect on the blood lead levels of residents in an area in which a soft plumbo-solvent water was hardened is examined. Water lead levels fell after hardening was introduced whereas there was a small rise in water lead levels in a control area monitored over the same time. The blood lead levels of residents fell after hardening and the fall was slightly greater than would have been predicted on the basis of the change in water lead levels. This suggests that lead is less well absorbed from hard water than from soft water. Following hardening there was a significant fall in mean blood lead level of subjects living in houses which had initially had negligible amounts of lead in the water. This suggests that hard water may interfere with the absorption of lead from sources other than water.

Humans↗
PubMedDate not supplied

Effects of vitamin A and ethanol on liver plasma membrane fluidity.

To study possible mechanisms whereby vitamin A and ethanol may affect liver plasma membranes, rats were fed liquid diets containing either 6 international units of vitamin A per kcal or 5 times more, with or without ethanol (36% of total energy as isocaloric substitution for carbohydrate). Vitamin A supplementation resulted in 2- to 3-fold increases of liver plasma membrane free retinol (p less than 0.005) and retinyl esters (p less than 0.001), particularly esters of palmitate and oleate, whereas cholesterol esters did not change. The fluorescent probe 1,6-diphenyl-1,3,5-hexatriene revealed decreased fluidity as measured by an increase in fluorescence polarization which correlated significantly with retinyl palmitate plus oleate content in membranes. In rats fed ethanol chronically, we first verified our previous observation of a decrease in liver plasma membrane fluorescence polarization. We now find this effect to be associated with (and possibly due to) an increase of cholesterol ester content. In linear regression analysis, the change in fluorescence polarization correlated positively with vitamin A (p less than 0.02) and negatively with cholesterol ester contents (p less than 0.001). Ethanol feeding partially offset the effect of vitamin A supplementation on fluorescence polarization. We conclude from these observations that liver plasma membranes contain a significant amount of vitamin A, that vitamin A supplementation increases membrane fluorescence polarization and that chronic ethanol administration can interfere with this effect.

Animals↗
PubMedDate not supplied

Late onset Alzheimer's disease and apolipoprotein association in the Irish population: relative risk and attributable fraction.

BACKGROUND: Familial and sporadic late onset Alzheimer's disease (LOAD) shows a consistent genetic association with APOE epsilon4. AIMS: To examine the role of APOE in the AD Irish population. METHODS: One hundred and ten Irish LOAD patients and 217 ethnically-matched controls were genotyped for APOE marker as described by Crook et al. Chi square test was used to compare allelic and genotypic frequencies between patients and controls samples. Attributable fractions were calculated as described by Levin. RESULTS: A highly significant association between AD and APOE epsilon4 was observed (chi2=37.9, p=0.0000000, RR=2.18). Further, the influence of APOEepsilon4 seems to follow a dose-dependent manner whereby individuals with the genotype APOEepsilon4/4 have a higher relative risk than those heterozygous for the epsilon4 allele (RR=4.03 and 1.76 respectively). The relative risk and the attributable fraction calculated for APOE epsilon4 are consistent with those reported for other European populations. This places the influence of this locus on AD development in the Irish population between those of the Spanish and New York white populations. CONCLUSION: These findings provide further evidence for the importance of APOE in the development of AD.

Aged↗