High energy phosphate metabolism in experimental permanent focal cerebral ischemia: an in vivo 31P magnetic resonance spectroscopy study

Relative levels of phosphate metabolites in the brain were examined in vivo by 31P magnetic resonance spectroscopy (MRS) in 50 Sprague-Dawley rats before, during, and after induction of focal permanent cerebral ischemia. After acquisition of baseline spectra, rats were subjected to injury within the core of the MR spectrometer, and 31P spectra were collected for 60 min after injury: in 7 rats, permanent, acute focal cerebral ischemia was induced (ischemia group); in 6 rats, mild hypoxia (FiO2 14%) was induced at the time of the ischemic insult and was maintained for 20 min (ischemia-hypoxia group); in 6 rats, mild hypoxia (FiO2 14%) only was induced for 20 min (hypoxia group). Control studies were performed in 25 rats. Cerebral intracellular pH, calculated from the chemical shift of inorganic phosphate (Pi), decreased immediately after injury in the ischemia and ischemia-hypoxia groups. The first 31P spectrum obtained after injury was characterized by an increase in Pi and a decrease in phosphocreatine (PCr) in the ischemia and ischemia-hypoxia groups; these changes in spectra were significantly greater in the ischemia-hypoxia group. No significant changes in adenosine triphosphate (ATP) were found in either group. Within 60 min of occlusion, 31P spectra returned toward baseline spectra in both ischemia-hypoxia and ischemia groups. No significant changes were seen in spectra of rats subjected to hypoxia alone. These results confirm that 31P MRS is a sensitive measure of early changes of high energy metabolites in focal cerebral ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased bone formation in mice lacking plasminogen activators.

Plasminogen activators tPA and uPA are involved in tissue remodeling, but their role in bone growth is undefined. Mice lacking tPA and uPA show increased bone formation and bone mass. The noncollagenous components of bone matrix are also increased, probably from defective degradation. This study underlines the importance of controlled bone matrix remodeling for normal endochondral ossification. INTRODUCTION: Proteolytic pathways are suggested to play a role in endochondral ossification. To elucidate the involvement of the plasminogen activators tPA and uPA in this process, we characterized the long bone phenotype in mice deficient in both tPA and uPA (tPA-/-:uPA-/-). MATERIALS AND METHODS: Bones of 2- to 7-day-old tPA-/-:uPA-/- and wild-type (WT) mice were studied using bone histomorphometry, electron microscopy analysis, and biochemical assessment of bone matrix components. Cell-mediated degradation of metabolically labeled bone matrix, osteoblast proliferation, and osteoblast differentiation, both at the gene and protein level, were studied in vitro using cells derived from both genotypes. RESULTS: Deficiency of the plasminogen activators led to elongation of the bones and to increased bone mass (25% more trabecular bone in the proximal tibial metaphysis), without altering the morphology of the growth plate. In addition, the composition of bone matrix was modified in plasminogen activator deficient mice, because an increased amount of proteoglycans (2x), osteocalcin (+45%), and fibronectin (+36%) was detected. Matrix degradation assays showed that plasminogen activators, by generating plasmin, participate in osteoblast-mediated degradation of the noncollagenous components of bone matrix. In addition, proliferation of primary osteoblasts derived from plasminogen activator-deficient mice was increased by 35%. Finally, osteoblast differentiation and formation of a mineralized bone matrix were enhanced in osteoblast cultures derived from tPA-/-:uPA-/- mice. CONCLUSIONS: The data presented indicate the importance of the plasminogen system in degradation of the noncollagenous components of bone matrix and suggest that the accumulation of these proteins in bone matrix--as occurs during plasminogen activator deficiency--may in turn stimulate osteoblast function, resulting in increased bone formation.     

Relationship between serum prolactin, lactation and changes in maternal blood B-cell (CD19+) percents during the first 8 months post-partum

Lactation is an immunologically unique state when immune factors are produced by the mother for the protection of the infant rather than the mother. While several studies have focused on the immunological composition of human milk, much less information is available on maternal immune status during lactation. Sixty-four lactating and 43 bottlefeeding women at 1–2 weeks, 1, 2, 4 or 8 months post-partum were studied in a cross-sectional design, with 14 nulliparous women as controls. Flow cytometry analysis of peripheral blood lymphocytes showed dynamic, post-partum changes in the B-cell subpopulation. Among lactating women, the relative percents of CD19+ B-cells were significantly lower (P < 0.05) than control levels at 1–2 weeks and 1 month post-partum, but showed a significant, polynomial-linear rise (P < 0.05) over time, reaching control values by 2–4 months post-partum. Bottle-feeding women had an earlier rise in the percentage of CD 19 + cells, with relative percents always significantly higher than their lactating counterparts. The differing patterns may be due to changes in serum prolactin concentrations because, among the post-partum women, relative percents of CD19+ cells were negatively correlated with baseline serum prolactin concentrations. These results have implications for maternal immunization programs designed to enhance maternal and/or infant well-being as well as other maternal health effects related to breastfeeding.     

Suppressor-Cytotoxic T-Lymphocyte Panniculitis

Abstract: A 3½-year-old girl had fever and nonsuppurative panniculitis. Biopsies revealed lobular lymphocytic panniculitis. An extensive evaluation of the patient for infectious and other systemic diseases yielded negative results. Although the number of peripheral T lymphocytes was normal, suppressor-cytotoxic (0KT8) lymphocytes predominated in the subcutis of the lesions. Suppressor-cytotoxic T-lymphocyte panniculitis may represent a unique type of panniculitis.     

Adult nemaline myopathy with trabecular muscle fibers

The term “trabecular myopathy” has been used to designate a syndrome resembling limb‐girdle muscular dystrophy in which the predominant pathological feature is an abundance of lobulated or trabecular muscle fibers. However, the validity of this nosological entity has not been verified. Herein we describe a 63‐year‐old man with a severe, progressive myopathy who exhibited the typical pathological features of both trabecular myopathy and nemaline myopathy in association with a biclonal gammopathy. In this case, adult‐onset nemaline myopathy was probably the primary disease process. The diagnostic significance of trabecular muscle fibers remains uncertain. Muscle Nerve, 2008