Low-density lipoprotein stimulated peroxide production and endocytosis in cultured human endothelial cells: mechanisms of action.

The effects of arachidonic acid metabolism and NADPH oxidase inhibitor on the hydrogen peroxide (H2O2) generation and endocytotic activity of cultured human endothelial cells (EC) exposed to atherogenic low-density lipoprotein (LDL) levels have been investigated. EC were incubated with 240 mg/dl LDL cholesterol and cellular H2O2 production and endocytotic activity measured in the presence and absence of the arachidonic acid metabolism inhibitors, indomethacin, nordihydroguaiaretic acid, and SKF525A, and NADPH oxidase inhibitor, apocynin. All inhibitors, with the exception of indomethacin, markedly reduced high LDL-induced increases in EC H2O2 generation and endocytotic activity. EC exposed to exogenously applied arachidonic acid had cellular functional changes similar to those induced by high LDL concentrations. EC incubated with 1-25 uM arachidonic acid had increased H2O2 production and heightened endocytotic activity. Likewise, EC pre-loaded with [3H]arachidonic acid when exposed to increasing LDL levels (90-330 mg/dl cholesterol) had a dose-dependent rise in cytosolic [3H]arachidonic acid. The phospholipase A2 inhibitors, 4-bromophenacyl bromide and 7,7-dimethyleicosadienoic acid, markedly inhibited H2O2 production in EC exposed to 240 mg/dl LDL cholesterol. These findings suggest that arachidonic acid contributes mechanistically to high LDL-perturbed EC H2O2 generation and heightened endocytosis. Such cellular functional changes add to our understanding of endothelial perturbation, which has been hypothesized to be a major contributing factor in the pathogenesis of atherosclerosis.

Appraising a clinical journal article in obstetrics and gynecology.

Although some physicians have the opportunity to participate in a journal club during residency, many infrequently receive formal instruction on how to critically evaluate a journal article. Systematic guidelines for appraising a clinical journal article are presented and illustrated with examples. Considering each guideline in its respective order may lead to a better understanding of what the literature may offer one's practice.

Efficacy of maternal screening and therapy in the prevention of chlamydia infection of the newborn.

Routine cervical cultures for chlamydia were obtained during the third trimester of pregnancy to identify infected mothers whose infants may also be infected. The effectiveness of maternal erythromycin therapy in preventing disease due to chlamydia among infants born to these women was also assessed. Clinical outcome of treated mothers and infants was compared to that of untreated subjects. Of 1082 women who were cultured, 85 (7.8%) were positive for chlamydia. Erythromycin therapy was prescribed for 38 of these women. Nasopharyngeal/conjunctival chlamydia cultures were obtained from 16 infants of culture-positive, treated mothers and 21 infants of culture-positive, untreated mothers. None of the infants born to culture-positive, treated mothers developed infection with chlamydia, while five of 21 infants of untreated mothers (p less than 0.04) were culture-positive and symptomatic (four with conjunctivitis, one with pneumonia). On follow-up of the infants born to chlamydia-positive mothers, there was no evidence that chlamydia-infected infants had more frequent episodes of upper respiratory infection and otitis media during the first six months of life. This study demonstrated that diagnosis and treatment of cervical chlamydia infection during the third trimester of pregnancy provides a practical approach to the prevention of infection in the newborn.

Endogenous creatinine clearance during pregnancy. II. Variations in normal standards based on methodology.

A comparison of the endogenous creatinine clearance (ECC) values by using creatinine levels measured by the autoanalyzer and the modified Jaffe reaction using Lloyd's reagent was performed in 108 normal ambulatory pregnant women at various stages of gestation. The mean ECC was found to be significantly lower when the former method was employed except between 39 and 41 weeks when the values became similar. The mean ECC when calculated from the autoanalyzer results did not vary during pregnancy since serum creatinine by this method remained fairly constant. The difference in serum creatinine level between the two methods observed during pregnancy was absent in the nonpregnant state.

Endogenous creatinine clearance during pregnancy. Part I. Methodologic considerations.

The effect of noncreatinine chromogens on the endogenous creatinine clearance (ECC) during pregnancy was investigated. It was found that these chromogens measured as plasma "creatinine" cause a significant reduction in the ECC value. This fact should be considered when the ECC value is used to evaluate renal function during pregnancy.

Massive edema of the ovary. A case report and a review of the literature.

A patient with massive ovarian edema is described. This represents the eighth such case in the literature and the largest tumor reported. The literature on massive ovarian edema is reviewed and summarized.

Letter: Study of glucose-6-phosphate and isocitrate dehydrogenases, DNA, RNA and total nitrogen in the rabbit placenta during its hypertrophic response to ovariectomy.

PIP: A review of the data presented in an article on the study of glucose-6-phosphate and isocitrate dehydrogenase, DNA, RNA ant total nitrogen in the rabbit placenta during its hypertrophic response to ovariectomy, suggest an alternative explanation than that the increase in placental weight is due to hypertrophy rather than to hyperplasia as indicated by unchanged DNA. Total nitrogen and DNA/g of tissue was simi lar in control and experimental placentas. The DNA/total nitrogen was therefore unchanged. Evidence of cellular hypertrophy was absent. The experimental group had increased placental weight, thus increased total DNA, indicating cellular hyperplasia without hypertrophy. Since there is a negative correlation between litter number and placental weight, the mean litter number should be similar in the experimental and control groups as well. Bilateral overiectomy in pregnant rabbits does lead to larger placentas and is limited to the "fetal placenta" due to hyperplasia. This response is a function of the estrogen milieu.^ieng

The regulatory effect of estrogens on fetal growth. IV. Brain development in growth accelerated fetuses in rabbits.

Brain weights and DNA, RNA, and total protein concentrations were determined on 31-day-old fetuses whose growth had been accelerated incidental to estrogen deficiency following maternal oophorectomy. Compared to controls, there were no differences in the DNA, RNA, or total protein concentrations, although the mean brain weight was increased. The higher mean brain weight in the growth accelerated fetuses was related to the increased mean fetal weight, and did not represent an independent response to the estrogen deficiency. A comparison of the influence of fetal weight versus gestational age on the weight of the fetal brain shows that gestational age exerts an effect apart from that of fetal weight.