Chronic low-level lead toxicity in the rat: III. An integrated assessment of long-term toxicity with special reference to the kidney

Male and female rats whose mothers had been exposed to Pb before and during pregnancy and lactation at exposure levels of 0, 0.5, 5, 25, 50, and 250 ppm Pb as Pb-acetate in drinking water were continued on the respective regimens for 6 or 9 months. Body weights of males and females were not significantly different from controls at 6 months of age; however, female body weights were significantly decreased at 250 ppm at 9 months of age. In males at 9 months of age, spleen weights were significantly increased at 250 ppm Pb and kidney weights were increased at 0.5 ppm Pb and above; in females the liver, pituitary, and heart weights were affected at 250 ppm Pb. No significant Pb effects were found in sperm counts or sperm morphology, hematology profiles, or serum chemistries. Blood, brain, femur, and kidney Pb levels as well as urinary ALA excretion were all significantly dose related. Histopathological lesions were noted in the spleen (250 ppm) and in the kidney as evidenced by cytomegaly/karyomegaly (beginning at 5 ppm in males; 25 ppm in females), nuclear inclusion body formation and increased numbers of iron-positive granules within renal proximal tubule cells. These effects were more marked after 9 months exposure. Ultrastructural studies revealed mitochondrial swelling and the presence of increased numbers of lysosomes within renal proximal tubule cells. Energy-dispersive X-ray microanalysis, performed on adjacent sections, showed the highest intracellular Pb concentrations in nuclear inclusion bodies within renal proximal tubule cells. Inhibition of renal mitochondrial respiration for both succinate and NAD-linked substrates was found in 50- and 250-ppm Pb exposure groups at 9 months but not at 6 months. Mitochondrial δ-aminolevulinic acid synthetase and ferrochelatase, but not δ-aminolevulinic dehydratase, were also found to be inhibited at these Pb levels at 9 months. The lowest exposure level resulting in a detectable effect of Pb (cytomegaly/karyomegaly in renal proximal tubule cells) was 5 ppm associated with a median blood Pb concentration of 11 μg/dl.     

IMPORTANCE OF ANTIDIURETIC PROPERTIES OF VASOPRESSIN IN EXPERIMENTAL RENAL HYPERTENSION

1. Homozygous Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI) developed one-kidney, one-clip (1K–1C) and two-kidney, one-clip (2K–1C) Goldblatt renal hypertension. 2. However, the systolic blood pressure (SBP) in 1K–1C Brattleboro rats was significantly lower than in non-DI hypertensive 1K–1C Long-Evans (LE) rats. 3. Treatment with the synthetic antidiuretic analogue of vasopressin, DDAVP (l-desamino-8-D-arginine vasopressin), increased the SBP in the DI rats to the same level as in 1K–1C Long-Evans. This elevation of SBP was associated with increased extracellular fluid volume in the DI rats after DDAVP. 4. The results suggest that vasopressin is not essential for the development of renal hypertension but the absolute levels of blood pressure achieved in 1K–1C hypertension are volume-dependent and thus influenced by the water-retaining properties of vasopressin.     

Mycobacterium marinum infections acquired from tropical fish tanks

Mycobacterium marinum is reported for the first time in New Zealand. Three cases of infection on the hands of tropical fish fanciers are described with details of treatment. Probable sources of the organism were investigated and possible explanations for its presence in New Zealand are discussed.     

Integrin display increases in the wounded rabbit medial collateral ligament but not the wounded anterior cruciate ligament

The differential capacities of the anterior cruciate and medial collateral ligaments to heal may be related to differences in cellular function. This study tested the hypothesis that differential expression of integrins occurs in these ligaments after injury. The integrins are a family of cell surface receptors that mediate adhesion, migration, and other cellular functions critical to the healing of a wound. A similar complement and amount of the β₁ subfamily of integrins are known to be present on the unperturbed anterior cruciate and medial collateral ligaments in humans and rabbits. A partial laceration was surgically created in these two ligaments in 12 anesthetized New Zealand White rabbits. Immunohistochemistry was performed on sections from the ligaments at 1, 3, 7, and 10 days after injury, using monoclonal antibodies directed against the integrin subunits β₁, α₅, α₆, and α_v. Between 3 and 7 days, the wounded medial collateral ligament demonstrated a striking increase in staining for the β₁, α₅, and α_v subunits on the fibroblasts, within the repair site, and on capillary endothelium. Increased staining was most marked for the β₁ subunit and less marked for the α₅ and α_v subunits. The α₆ subunit stained exclusively vascular structures within the healing medial collateral ligament. In marked contrast, the anterior cruciate ligament, which does not mount an effective repair response, demonstrated no comparable alteration of integrin expression from baseline levels. This study demonstrates that increased expression of integrins occurs coincident with wound healing in the medial collateral ligament, whereas this expression remains at baseline levels in the nonhealing wounded anterior cruciate ligament. This observation suggests that a failure to alter expression of integrins subsequent to injury may play a role in the defective healing of the anterior cruciate ligament.     

31P nuclear magnetic resonance measurement of free erythrocyte magnesium concentration in man and its relation to blood pressure

1. 31P n.m.r. spectroscopy was used to measure the dissociation constant of MgATP under simulated intracellular conditions and to measure erythrocyte free magnesium concentration. 2. In a group of 40 subjects, the relationship between erythrocyte free magnesium and blood pressure, age and sex was examined by univariate and multivariate regression analysis. 3. A weak positive association was found between erythrocyte free magnesium and mean blood pressure. This association was lost in a multivariate regression analysis including both age and sex. 4. No significant relationship was found between erythrocyte free magnesium and age, sex, family history of hypertension or use of the combined oral contraceptive pill in the sample studied.