Dipyridamole and RA-642 inhibit the production of superoxide anion and free radical damage to rat lens.

We studied the effects of dipyridamole and RA-642 on the production of superoxide anions and on oxygen radicals-induced lipid peroxidation in lens tissue homogenates from normal rats and rats given dipyridamole or RA-642 intraperitoneally. Superoxide production was evaluated by phenazine methosulphate (PMS)-induced nitroblue tetrazolium (NBT) reduction and lipid peroxidation by ferrous sulfate and ascorbic acid (FeAs)-induced malondialdehyde (MDA) production. Dipyridamole and RA-642 showed an inhibitory effect on both assays in the experiments with lens tissue homogenates from untreated or treated rats. The extent of inhibition, however, was significantly higher in pyrimidopyrimidinic-treated rats (range of inhibition at different times of incubation was 18% versus 23-57% for dipyridamole and 14% versus 73-80% for RA-642 in the assay of MDA production, and 10% versus 33-37% for dipyridamole and 2.5% versus 11-32% for RA-642 in the assay of NBT reduction). Concentrations of dipyridamole and RA-642 in lens tissue from treated animals could not be determined (less than 0.001 micrograms/mg of tissue). Although both compounds inhibited lipid peroxidation induced by oxygen free radicals, the mechanism of action might include the role of adenosine as a mediator.     

Contributions of ovarian failure and aging to blood pressure in normotensive perimenopausal women: a mixed longitudinal study

Epidemiologic studies have shown that blood pressure increases more rapidly in middle-aged women than in middle-aged men. Whether or not ovarian failure contributes to this rapid rise is still not clear. In a follow-up study begun in 1979 and to continue for 10 years, the blood pressure of 193 healthy normotensive perimenopausal women, who lived in the mixed rural/industrial community of Ede, the Netherlands and who were initially aged between 49 and 56 years, was measured annually. During the course of the study, the onset of menopause of each participant could be established. Because of the mixed longitudinal design of the study, it was possible to evaluate the effects of both chronologic aging and time pre- or postmenopause on blood pressure. After the first seven years of follow-up, it was demonstrated that blood pressure did not increase in 168 women whose body weight was relatively stable. After multivariate analyses, systolic as well as diastolic pressure showed a significant negative relation (slope, 1.34 mmHg per year and 0.63 mmHg per year, respectively) with the years since menopause. On the other hand, the observed positive relation (slope, 0.81 mmHg per year) of systolic pressure with chronologic aging was not significant. No consistent association was found between diastolic pressure and chronologic aging. It is concluded that menopause cannot be regarded as a cause of hypertension; on the contrary, ovarian failure appears to have a protective effect on the increase in blood pressure as a result of chronologic aging. on the increase in blood pressure as a result of chronologic aging.     

A population-based assessment of the disease burden of consolidated pneumonia in hospitalized children under five years of age.

BACKGROUND: Population-based studies on childhood community-acquired pneumonia are scarce in Latin America. Pneumococcal epidemiology is poorly defined, hence the World Health Organization recommended standardized chest radiograph interpretation to improve the approach to bacterial pneumonia. Therefore, our study aimed to estimate the burden of pneumonia in hospitalized children. METHODS: A three-year surveillance study was carried out in four hospitals covering a population of 229,128 inhabitants of whom 10.2% were under five years of age. Clinical records and digitization of their chest radiographs were obtained. A pediatrician and a pediatric radiologist blinded to the clinical diagnosis interpreted the digital images. RESULTS: Of 2034 patients, 826 (40.6%) had consolidated pneumonia, 941 (46.3%) had non-consolidated pneumonia, and 267 (13.1%) had no pneumonia. Children under two years of age predominated (66.9%). The average annual incidence rate for consolidated pneumonia over the three-year study period was 1175/10(5). Eighteen invasive Streptococcus pneumoniae were isolated from patients with consolidated pneumonia and two from those with non-consolidated pneumonia. Respiratory syncytial virus was evenly distributed between both X-ray groups. CONCLUSIONS: Patients younger than two years of age predominated, being the main targets for anti-pneumococcal conjugated vaccines. Incidence rates provided evidence of the burden of consolidated pneumonia for childhood, estimating the potential benefits of vaccination.     

The relevance of therapeutic drug monitoring in plasma and erythrocytes in anti-cancer drug treatment.

Therapeutic drug monitoring generally focuses on the plasma compartment only. Differentiation between the total plasma concentration and the free fraction (plasma water) has been described for a number of limited drugs. Besides the plasma compartment, blood has also a cellular fraction which has by far the largest theoretical surface and volume for drug transport. It is with anti-cancer drugs that major progress has been made in the study of partition between the largest cellular blood compartment, i.e., erythrocytes, and the plasma compartment. The aim of the present review is to detail the progress made in predicting what a drug does in the body, i.e., pharmacodynamics including toxicity and plasma and/or red blood cell concentration monitoring. Furthermore, techniques generally used in anti-cancer drug monitoring are highlighted. Data for complex Bayesian statistical approaches and population kinetics studies are beyond the scope of this review, since this is generally limited to the plasma compartment only.     

The value of MCA, CA 15-3, CEA and CA-125 for discrimination between metastatic breast cancer and adenocarcinoma of other primary sites

MCA, CA 15-3, CEA and CA 125 were determined in the serum of 49 patients with metastatic breast cancer and 38 patients with metastatic adenocarcinoma of other primary sites. By using the 99th percentile of the normal value distribution as the cut-off point, the positive predictive value (PV+) was found to be 85% (95% CI 76-94) for MCA, and 71% (95% CI 61-81) for CA 15-3. When receiver-operating-characteristic (ROC) curves were constructed, the PV+ for CA 15-3 was increased to 82% (95% CI 72-92), using 60 U ml-1 as the cut-off point. With the exception of two patients who had a slightly elevated MCA, MCA and CA 15-3 identified the same patients with breast cancer. By combining a positive MCA or CA 15-3 with a negative CEA and CA 125, further improvement of the PV+ could be achieved; 100% (95% CI 91-100). We conclude that MCA and CA 15-3 may play a useful role in discrimination between patients with metastatic breast cancer and those with adenocarcinoma of other primary sites.     

The ventral rib cage muscles in the dog: contractile properties and operating lengths

To have some insight into the mechanical interplay between the parasternal intercostal and triangularis sterni muscles during breathing, we have examined the isometric contractile properties of these two muscles in the dog. Using piezoelectric crystals, we have also measured the respiratory changes in muscle length in eight spontaneously breathing animals in the supine posture, and we have compared the in situ relaxation length (Lr) of these two muscles to their respective in vitro optimal force-producing length (Lo). The triangularis sterni and parasternal intercostals had similar isometric twitch, force-frequency, and length-tension characteristics. These two muscles, therefore, are intrinsically similar. In supine dogs, however, they operate on quite distinct segments of their length-tension curve. Whereas Lr for the parasternals corresponded to 117% Lo, Lr for the triangularis sterni was only 75% Lo. This suggests that the triangularis sterni in supine dogs operates on a poorly advantageous portion of its length-tension curve. However, shortening of the parasternals during inspiration causes considerable passive distension of the muscle. As a result, the triangularis sterni is much closer to its optimal length when it starts contracting in early expiration.     

Astroglial alterations in rat hippocampus during chronic lead exposure.

The present study was performed in order to follow the response of astroglial cells in the rat hippocampus to chronic low-level lead exposure. The experiments combined immunohistochemistry using anti-glial fibrillary acidic protein (GFAP) antibody and conventional transmission electron microscopy (EM). Chronic administration with drinking water [1 g% w/v (subclinical dose) of lead acetate dissolved in distilled water] was started through the mother's milk when pups were 7 days old. Following weaning, experimental offspring were treated for 3 months with the same concentration of adulterated water. The group of intoxicated animals and their controls were sacrificed by perfusion-fixation at 30, 60, and 90 days of exposure. After 60 days of lead treatment, staining of GFAP-positive cells demonstrated an astroglial transformation from the quiescent to the reactive state, characterized by an increase in GFAP. In control rats no changes in GFAP immunostaining were observed. The intensity of the astroglial response was enhanced after 90 days of lead intoxication, showing an increment of GFAP immunoreactivity. Quantification of these changes was made by computerized image analysis, confirming that the sectional areas of the astroglia in lead-exposed animals were larger than those in controls. These results are consistent with the ultrastructural alterations. Simultaneously with the increment in gliofilaments, intranuclear inclusions were seen in some astrocytes. The mechanisms by which lead affects astrocytes are unknown. Probably the astroglial changes induced by lead intoxication produce microenvironmental modifications that may disturb the neuronal function.