Maze learning and motor activity deficits in adult mice induced by iron exposure during a critical postnatal period

Newborn mice were administered Fe(2+) (iron succinate: 7.5 mg/kg, b. wt) on either Days 3-5, 10-12 or 19-21, or vehicle (saline) at the same times, postnatally. Spontaneous motor behaviour and radial arm maze learning were tested at the age of 3 months. It was found that mice treated with Fe(2+) during postnatal Days 10-12 were markedly hypokinetic during the 1st 20-min test period and hyperkinetic during the 3rd and final 20-min test period. These mice showed an almost complete lack of habituation of spontaneous motor activity parameters to the test chambers. In the radial arm maze, the Days 10-12 treatment group evidenced significantly both more errors in arm choices and longer latencies to acquire all eight pellets; these mice showed also a severe trial-to-trial retention deficit as indexed by retention quotients. These behavioural deficits were observed also in animals treated with Fe(2+) during postnatal Days 3-5, but the effects were less pronounced, indicating the higher susceptibility of the brain for Fe(2+)-induced damage during Days 10-12 postpartum. Treatment with Fe(2+) on Days 19-21 did not induce behavioural alterations in comparison with its respective control (vehicle) group. Analysis of total brain iron content indicated significantly more iron (microg/g) accumulation in the basal ganglia, but not frontal cortex, of mice from the Days 3-5 and 10-12 Fe(2+) (7.5 mg/kg) treatment groups. The contribution of iron overload during the immediate postnatal to later functional deficits seems to implicate symptoms of Parkinsonism but the kinetics of iron uptake to the brain and its regional distribution at this critical period of development awaits elucidation.     

The reactions of articular cartilage to experimental wounding: role of apoptosis

OBJECTIVE: To determine the cellular and matrix responses to experimental wounding of articular cartilage. METHODS: Immature and mature bovine articular cartilage was used as an in vitro model system to study the cellular responses to cartilage wounding. Explant cultures were wounded centrally with a trephine and maintained for up to 10 days. TUNEL labeling together with ultrastructural analyses were used to assess the nature of the observed cell death. In vitro labeling with 3H-thymidine was used to detect cell proliferation, and 2 antibodies (COL2-3/4M and BC-13) were used to detect changes in matrix turnover. RESULTS: Cell death was observed as a response to wounding and was considered to be a combination of necrosis and apoptosis. In immature tissue, cell death was more pronounced, particularly in the articular surface region. Within the area of cell death, many cells that did not die subsequently underwent proliferation. The collagenous network showed evidence of denaturation in the area of the wound, but "aggrecanase" activity was not detected. CONCLUSION: There are 2 contrasting, but related, responses to cartilage wounding--apoptosis and proliferation. In order to improve cartilage repair, future studies need to elucidate the regulatory mechanisms that determine these responses.     

Endometrial morphology in asymptomatic postmenopausal women

Few data are available regarding endometrial histologic features in asymptomatic perimenopausal and postmenopausal women. This study encompasses endometrial biopsy specimens obtained from 801 such women before enrollment in a multicenter study of estrogen-progestin replacement. One endometrial cancer was found (0.13%); four additional biopsy specimens showed atypia (total 0.63%). The endometrium was atrophic in 373 (46.9%), proliferative in 133 (16.7%), secretory in 54 (6.8%), and hyperplastic in 41 (5.2%). Insufficient tissue for diagnosis was obtained in 195 (24.5%). We conclude that the yield for neoplasia is so low that screening endometrial biopsy is not justified in asymptomatic perimenopausal and postmenopausal women.     

Night cough counts and diary card scores in asthma.

A tape recording system for recording night cough in asthmatics at home is described. Objective cough counts and half hour periods containing cough did not correlate with diary card scores awarded to eight children on seven nights each. Night cough diary scores may mislead in the assessment of symptom severity.     

Effects of prior administration of steroids upon recovery from lethal sepsis

The effects upon survival of large doses of steroid administered to dogs prior to challenging them with lethal sepsis was evaluated in this study. Dogs were given 30 milligrams per kilogram of body weight per day of methylprednisolone sodium succinate for one, two or eight days and then were infused with 9.72 +/- 0.35 X 10(9) Escherichia coli per kilogram of body weight. All dogs in group 1 (n equals six) not given steroid died within 25 hours. Of the dogs in group 2 (n equals 12) given one or two doses of steroid previously, 42 per cent permanently survived (more than seven days). All dogs in group 3 (n equals five) given eight daily doses of steroid prior to infusion of Escherichia coli died within 17 hours. Dogs in group 4 (n equals six) were given eight daily doses of steroid prior to infusion of Escherichia coli and treated on the day of infusion of Escherichia coli with a regimen of methylprednisolone and gentamicin sulfate which results in a 100 per cent survival rate when given to dogs that have not received prior treatment with steroid. Thirty-three per cent of the dogs in group 4 permanently survived. One or two daily large doses of steroid did not detrimentally affect survival of the dogs. Eight days of steroid administration suppressed endogenous cortisol production. When the dogs were treated with six hours of steroid-antibiotic therapy, survival benefits were limited.     

Correlation of high-resolution computed tomography and gross anatomic sections of the temporal bone: II. Vestibular apparatus

High-resolution computed tomography (CT) of isolated temporal bones was performed in the transaxial, coronal, and sagittal planes at 1.5-mm intervals. The temporal bones were then sectioned at 2.0-mm intervals in planes parallel to the CT scans. The structures making up the vestibular apparatus were identified, and the planes in which each is best visualized were selected for the illustrations. The vestibule, oval window, tympanic cavity, and tympanic portion of the facial nerve are best seen in the transaxial and coronal planes; the arch of the superior semicircular canal in the transaxial plane and its limbs in the coronal plane; the arch of the posterior semicircular canal in the coronal and sagittal planes and its limbs in the transaxial plane; and the common crus in the sagittal plane. The horseshoe-shaped lateral semicircular canal is displayed in the transaxial plane, and the relationship of its lateral limb to the tympanic segment of the facial nerve is best demonstrated in the sagittal plane. The ampullae of all three canals can be appreciated equally well in all three planes.     

SHORT COMMUNICATION: Inhibition of rat mammary tumorigenesis by dietary cholesterol

The effects of dietary cholesterol and oxidized cholesterolon mammary tumor development were examined in female Sprague-Dawleyrats exposed to the carcinogen N-methyl-N-nitrosourea (MNU).Animals were administered 50 mg/kg MNU at 50 days of age andfed either a control (AIN-76) diet or the control diet supplementedwith 0.3% cholesterol or 0.3% oxidized cholesterol for up to26 weeks. The oxidized cholesterol was prepared by heating cholesterolat 110°C for 48 h. Gas chromatographic analysis of the oxidizedcholesterol revealed a 2% yield of oxidation products in additionto a large amount of unchanged cholesterol (>96%). Tumorincidence in the cholesterol group (67%) was significantly lowerthan in the control group (96%, P <0.05), but the oxidizedcholesterol group (79%) was not significantly different fromthe control or cholesterol groups. Average number of tumorsper animal was lower in the cholesterol group (1.5) than inthe control (2.8) or oxidized cholesterol groups (2.3, P <0.005).Serum low density lipoprotein (LDL) cholesterol was greaterin the cholesterol (185± 38 mg/dl) and the oxidized cholesterolgroups (160± 34 mg/dl) than in the control (55±4 mg/ dl, P <0.05), although there was no difference betweenthe cholesterol and the oxidized cholesterol groups. These resultsshow that dietary cholesterol inhibits mammary tumor developmentin this model. Elevated serum LDL cholesterol may inhibit denovo cholesterol synthesis in preneoplastic and/or tumor cells,thereby inhibiting their proliferation.