Multidrug resistance protein 1-mediated transport of saquinavir by microglia

Regulation of CNS distribution of the human immunodeficiency virus (HIV) protease inhibitor saquinavir may involve ATP-dependent membrane-bound efflux transport proteins that are expressed in several brain cellular compartments. We recently characterized molecular and functional expression of one such transporter, multidrug resistance protein-1 (MRP1) in microglia, the primary brain cellular target of HIV. In the present study, we further examine subcellular localization of MRP1 in a microglia cell line (MLS-9) using immunogold cytochemistry and directly demonstrate MRP1-mediated export of saquinavir. MRP1 localized primarily to the plasma membrane of the MLS-9 cells. [14C]Saquinavir efflux by MLS-9 monolayers was inhibited by well-established MRP1 inhibitors. These results indicate that MRP1 contributes, in part, to the overall low permeation of protease inhibitors in the brain.     

Disseminated Acanthamoeba infection in a human immunodeficiency virus-infected infant

Infection with Acanthamoeba is difficult to diagnose and treat. We present the first case of disseminated Acanthamoeba infection in an HIV-infected infant. The infant survived 2 years with treatment with several agents having anti-Acanthamoeba activity in vitro.     

The role of fetal breathing motions compared with gasping motions in pulmonary airway uptake of intra-amniotic iron dextran

OBJECTIVE: We hypothesized that normal fetal breathing, not acute asphyxial gasping, results in the movement of iron dextran from the amniotic cavity into the fetal lungs. In addition, the amount of iron dextran moving into the fetal lungs is cumulative with time. STUDY DESIGN: Twelve pregnant New Zealand White rabbits at 25 days of gestation were sedated and underwent ultrasound-guided injections of iron dextran into the amniotic cavities of the rabbit fetuses in both horns of each pregnant doe. Oxygen saturation was maintained at >90% in the pregnant does. The 12 does were then equally assigned to four groups on the basis of the duration of fetal exposure to the dextran (0, 8, 16, and 24 hours). At the end of each time point, one half of the fetuses received an intracardiac injection of potassium chloride to induce gasping just before necropsy. Gasping was confirmed by ultrasound scanning. At necropsy, the fetal lungs were evaluated grossly and underwent histomorphometry for iron distribution and quantification in the fetal airways. RESULTS: In the animals that received iron dextran, there was no significant difference in iron accumulation at any time point between those animals that did and did not receive potassium chloride, which suggests that acute gasping does not increase the accumulation of amniotic fluid substances in the lungs. The amount of iron in the fetal airways increased significantly with progressive length of exposure. CONCLUSION: We conclude that normal fetal breathing, not acute asphyxial gasping, resulted in the movement of intra-amniotic iron dextran into the fetal lungs and that the amount of substances that move into the fetal lungs accumulated with time.     

Hepatic osteodystrophy in chronic cholestasis: evidence for a multifactorial etiology

Children with cholestatic liver disease have been thought to develop hepatic osteodystrophy resulting from vitamin D and calcium malabsorption, resulting in secondary hyperparathyroidism and osteomalacia or rickets. However, treatment with vitamin D has not always proven successful in improving the bone disturbance. The aim of our study was to determine the role of vitamin D deficiency in the pathogenesis of hepatic osteodystrophy. We studied five patients, three female and two male, ages 0.9-19 yr, with biopsy-proven chronic cholestatic liver disease and previously low serum levels of vitamin D despite oral intake of vitamin D preparations. Patients were admitted to the Clinical Research Center for 8 days for sunlight deprivation and ultraviolet light substitution and for determinations of serum 25-hyroxyvitamin D(25(OH)) D2 and -D3, osteocalcin, and type I collagen telopeptide (ICTP), the last two being markers of bone formation and resorption, respectively. Samples were taken on admission, at discharge, and 1 month later. Results demonstrated low serum levels of osteocalcin and normal circulating levels of ICTP. Admission serum 25(OH)D2 levels were uniformly low or undetectable and remained so. Admission levels of circulating 25(OH)D3 were normal or low and did not rise during ultraviolet light therapy or subsequent resumption of oral vitamin D therapy and remained low 1 month later. These results indicate that in the face of low-normal to low total 25(OH)D levels, the low osteocalcin and normal ICTP levels suggest that decreased bone formation and not increased bone resorption is the main determinant of bone loss in a subset of children with chronic cholestatic liver disease.     

Longitudinal assessment of the middle cerebral artery peak systolic velocity in healthy fetuses and in fetuses at risk for anemia

OBJECTIVE: Our purpose was to assess the feasibility of longitudinal assessment of the middle cerebral artery peak systolic velocity (MCA-PSV) to predict fetuses who will have severe anemia. STUDY DESIGN: Doppler measurement of MCA-PSV was serially performed in 15 healthy fetuses (99 measurements; range: 4-9 per fetus), 8 fetuses who were mildly anemic (41 measurements; range: 3-10 per fetus), and 11 who were severely anemic (50 measurements; range: 2-7 per fetus) at their first cordocenteses. Linear models were fitted to the data from individual fetuses and the slopes were determined. The average rate of change (slope) of MCA-PSV as a function of gestational age in the 3 groups was calculated from these data. Estimated average slopes were computed using restricted maximum likelihood. F tests were used for hypothesis tests, with the degrees of freedom based on the Kenward and Roger approximation. The values of MCA-PSV and hemoglobin were expressed as multiples of the median (MoM). A P <.05 indicated statistical significance. RESULTS: Gestational age at the time of the Doppler studies ranged from 15.1 to 41 weeks in the healthy fetuses. It was between 15 and 33.4 weeks in the fetuses who became anemic. The estimated average slopes increased with the degree of anemia (P =.03). The difference in mean slope between the severely anemic sample and the healthy sample was statistically significant (estimated difference = 2.2, SE =.65, P =.01). The difference in mean slope between the mildly anemic and healthy samples was not statistically significant (estimated difference = 1.1, SE =.06; P =.08). CONCLUSIONS: We have demonstrated that the MCA-PSV slope is an excellent tool for identifying those fetuses who will become severely anemic and, therefore, need to be followed up more closely during the pregnancy. Our findings expand the clinical applications to which Doppler ultrasonography can be applied in monitoring pregnancies at risk for fetal anemia.     

Study of refractive changes inTimiş.county

The aim of the study was to assess the prevalence of common refractive errors ?n children investigated at the "Louis Turcanu" Hospital's Ambulatory from Timisoara. This was a cross-sectional study done from January to June 2002 ?n the Ophthalmologic Medical Office. The target group was those of children from Timis County. We examined 646 children with a mean age of 10.7 years (from 0 to 18 years). A cycloplegic refraction examination was performed on all the children, using a computerized Humphrey-Zeiss autorefractometer. The statistical analysis was performed using CDC's Epi Info 2002. ?n the analysis, we used the Odds Ratio, the exact Fisher test and the chi-squared test. Among the 646 children, 407--63% (CI95 = 59.1-66.7) had refraction errors, of which 1.5% (CI95 = 0.8-2.9) were myopic whereas 49.8% (CI95 = 45.9-53.8) were hyperopic. Astigmatism was found ?n 11.8% (CI95 = 9.4-14.6). The study showed higher prevalence for the 14-16 age, emphasizing the importance of these examinations.     

Solar ultraviolet radiation exposure of infants and small children

Townsville, in Queensland, Australia, experiences very high levels of ambient solar ultraviolet radiation (UVR) throughout the year and has a predominantly white population which is prone to developing skin cancer. The UVR exposure of 1-year-old and 2 1/2-year-old children raised in Townsville was measured using UVR-sensitive polysulphone film badges. In two separate exposure studies undertaken for 7 days in October 1995 and 5 days in April 1997, exposure at the chest and shoulder for each subject was determined. The chest exposures for the 1-year-olds were significantly higher at weekends than on weekdays, whereas for the 2 1/2-year-old children the shoulder exposures were significantly higher at weekends than on weekdays. The median daily total exposure for 1-year-old infants was 0.4 SED (standard erythemal dose) for the chest and 0.4 SED for the shoulder. The median daily total exposure for 2 1/2-year-olds was 0.6 SED for the chest and 0.9 SED for the shoulder. Although the median daily total exposures were comparatively low, the maximum values for the chest and shoulder were 6.5 SED and 2.4 SED, respectively, for the 1-year-old infants, and 20.6 SED and 8.4 SED, respectively, for the 2 1/2-year-olds. While the 2 1/2-year-old children spent most of their time outside between 9 am and 4 pm, the 1-year-old infants spent more time outside before 9 am and after 4 pm. Exposure increases with age in early childhood. Increased mobility and a greater tendency to play outdoors is likely to account for the higher exposure levels in 2 1/2-year-old children, compared to 1-year-old infants.