Maternal-to-fetus transfer of mercury in metallothionein-null pregnant mice after exposure to mercury vapor

This study examined the role of placenta metallothionein (MT) in maternal-to-fetal mercury transfer in MT-null and wild-type mice after exposure to elemental mercury (Hg(0)) vapor. Both strains were exposed to Hg(0) vapor at 5.5-6.7 mg/m(3) for 3 h during late gestation. Twenty-four hours after exposure to Hg(0) vapor, accumulation of mercury in the major organs, except the brain, of MT-null maternal mice was significantly lower than that in organs of wild-type mice. In contrast to mercury levels in maternal organs, fetal mercury levels were significantly higher in MT-null mice than in wild-type mice. In placenta, mercury concentrations were not significantly different between the two strains. Although MT levels in major organs, except the brain, of wild type mice were markedly elevated after the exposure to Hg(0) vapor, the placental MT levels were not elevated. However, endogenous MT level in the placenta is significantly higher than that in other organs, except the liver. Gel filtration profile of the placental cytosol in the wild-type mice revealed that a large amount of placental mercury was associated with MT. In MT-null mice, mercury in placental cytosol appeared mainly in the high-molecular-weight protein fractions. Mercury in the placenta was localized mainly in the yolk sac and decidual cells in the deep layer of the decidua in both mouse strains. The similar localization of MT was found in the placenta of wild type mice. These results suggest that MT in the placenta has a defensive role in preventing maternal-to-fetal mercury transfer.     

In vitro permeation of beta-lactam antibiotics across rat jejunum and its correlation with oral bioavailability in humans

AIMS: To investigate the correlation between in vitro permeation of 11 beta-lactam antibiotics across rat jejunum and their oral bioavailability in humans. METHODS: The absorptive and secretory permeation across rat jejunum was evaluated and apparent permeability coefficients (P(app)) were determined. RESULTS: A steep, sigmoid-type curve was obtained for the relationship between P(app) in the absorptive permeation and human oral bioavailability. When the ratios of P(app) in the absorptive direction to P(app) in the secretory direction were plotted against human oral bioavailability, a much improved correlation was obtained (r = 0.98, P < 0.001). The addition of glycylglycine to both mucosal and serosal media modified the permeation of ceftibuten and cephalexin from the absorptive to the secretory direction. CONCLUSIONS: For 11 beta-lactam antibiotics rat intestinal permeation correlated well with human oral bioavailability, especially when corrected for secretory transport.     

Low dose exposure to cadmium and its health effects (1). Genotoxicity and carcinogenicity

We reviewed studies on genotoxicity and carcinogenicity of cadmium (Cd). Salmonella typhimurium and Escherichia coli exposed to Cd did not show mutagenicity, whereas cultured mammalian cells exposed to Cd showed mutation, DNA strand breaks, and chromosomal aberrations. Carcinogenicity tests showed that exposure to Cd increased the occurrence of tumors in testis, lung, prostate, hematopoietic tissues, and injection sites. On the other hand, recent epidemiologic studies are not supportive of earlier observations on the association between Cd and prostate cancer. The US NIOSH data on a possible association between Cd and lung cancer may need reevaluation. No studies which show a positive relationship between oral Cd exposure and carcinogenesis have been reported. All available data suggest that Cd should be reassigned to IARC Group 2A (probably carcinogenic to humans) from the current Group 1.     

Efficacy of active core rewarming using fluid heating system HOTLINE before and during the operation in a patient with for panperitonitis in state of shock and hypothermia

A 62-year-old man was transported to the emergency room. He was in the state of shock and hypothermia of 34.2 degrees C. Fluid therapy was started using a HOTLINE to raise the body temperature, with vasopressors, vitamin B1 and sodium bicarbonate after checking arterial blood gas. Diagnosis of panperitonitis was made and operation was started immediately. We used HOTLINE before and during the operation. Body temperature returned to normal ranges, and hemodynamic state was stabilized at the end of the operation. After the operation, he received controlled artificial ventilation and nutrition support with intravenous hyperalimentation. Though he was complicated with disseminated intravascular coagulation, he went to general ward 17 days, and was discharged at 47 days after the operation. Sepsis accompanied with hypothermia leads to poor prognosis. We used fluid therapy with rapid-heating, and obtained good outcome. HOTLINE is effective for hypothermia in an emergency patient, because its effect is sure and does not obstruct the examination and management.     

DNA damage triggers imbalance of proliferation and apoptosis during development of preneoplastic foci in the liver of Long-Evans Cinnamon rats

The mutant strain Long-Evans Cinnamon (LEC) rat accumulates copper, resulting in spontaneous hepatitis and subsequent development of hepatocellular carcinomas (HCCs) in the liver, providing a promising model for investigation of the relationship between hepatitis induced by oxidative stress and hepatocarcinogenesis. We examined DNA strand breaks in peripheral blood cells and p53 expression in livers during acute and chronic hepatitis in LEC rats, along with preneoplastic lesions, and cell proliferation and apoptosis in non-cancerous portions of livers from LEC rats aged 7-115 weeks. Immunohistochemistry using antibodies against glutathione S-transferase placental-form (GST-P), proliferating cell nuclear antigen (PCNA), and in situ DNA nick labeling (TUNEL) were used. Long-Evans Agouti (LEA) rats, a sibling line of the LEC strain, were used as controls. In the LEC rats, DNA strand breaks and expression of p53 were significantly higher than that of LEA rats at 24 weeks of age. The number of GST-P-positive (GST-P+) foci/cm2 increased and peaked at 48 weeks old, and the areas rapidly expanded thereafter. The level of cell proliferation increased with the development of hepatitis and was highest at about 48 weeks old. The induction of apoptosis in LEC rats was transiently higher than that in LEA rats during the period from 24 to 34 weeks of age. However, the ratio of PCNA-positive cells to the apoptotic index showed a growth imbalance in favor of cell proliferation, supporting sustained net growth in LEC rats. These findings suggest that DNA damage, reflected in DNA strand breaks, plays a critical role in the development of hepatocellular preneoplastic foci, with an imbalance between high proliferation and relatively low apoptosis.     

The effect of graft-tunnel diameter disparity on intraosseous healing of the flexor tendon graft in anterior cruciate ligament reconstruction

BACKGROUND: Graft-to-tunnel healing is a significant factor in anterior cruciate ligament reconstruction, but there have been few studies on the effect of graft-tunnel diameter disparity on intraosseous healing of the flexor tendon graft. HYPOTHESIS: Graft-tunnel diameter disparity of 2 mm has no effect on the pull-out strength of the graft from the bone tunnel. STUDY DESIGN: Controlled laboratory study. METHODS: Forty-two beagle dogs were divided into three groups. In each animal, reconstruction was performed in the left knee by using a 4-mm diameter autogenous flexor tendon for groups 1 and 2 and by using a 4-mm wide bone-patellar tendon-bone graft in group 3. A 4-mm diameter tunnel was drilled in the tibia of groups 1 and 3 and a 6-mm diameter tunnel, in group 2. In each group, seven animals were sacrificed at 3 and 6 weeks. RESULTS: The perpendicular fibers connecting the graft to the bone were generated in groups 1 and 2, and the number appeared to be higher in group 2, where the space was greater. There was no significant difference in the ultimate failure load between groups 1 and 2 at each period. CONCLUSION: Graft-tunnel diameter disparity of up to 2 mm may not adversely affect intraosseous healing of the flexor tendon graft. CLINICAL RELEVANCE: Surgeons need not be overly concerned about minor graft-tunnel diameter disparities.     

The effect of initial graft tension in anterior cruciate ligament reconstruction on the mechanical behaviors of the femur-graft-tibia complex during cyclic loading

BACKGROUND: Initial graft tension influences clinical results of anterior cruciate ligament reconstruction. HYPOTHESIS: Under repetitive loading conditions, the effect of initial graft tension on the biomechanical behavior of the femur-graft-tibia complex may depend on the graft and the fixation. STUDY DESIGN: Ex vivo biomechanical laboratory study. METHODS: After anterior cruciate ligament reconstruction, initial graft tension of 20, 80, or 140 N was applied to the complex for 2 minutes. Then, a cyclic force-relaxation test was performed for 5000 cycles so that the graft was stretched by 2 mm. RESULTS: In a patellar tendon graft with interference screws, the average peak load values at the 5000 th cycle were 105, 157, and 205 N for the complexes with initial tension of 20, 80, and 140 N, respectively. In a flexor tendon graft with interference screws, the values were 27, 41, and 39 N. In a flexor tendon graft with Endobutton fixation, the values were 17, 40, and 77 N. CONCLUSIONS: Considering the tension of the normal anterior cruciate ligament (16 to 87 N), an initial tension of 20 N appears to be high enough for a patellar tendon graft. For a flexor tendon graft with interference screws, an increase in initial tension above 80 N has no biomechanical advantages.     

Changes in mRNA for post-synaptic density-95 (PSD-95) and carboxy-terminal PDZ ligand of neuronal nitric oxide synthase following facial nerve transection

When the axon of motoneurons is transected, the number of synaptic boutons contacting the cell body is decreased, and the recovery of synapses depends on muscle reinnervation. Post-synaptic density-95 (PSD-95) is a protein which is located at the post-synaptic density (PSD) and it plays a pivotal role in regulating synaptic plasticity and synaptogenesis. In addition, PSD-95 binds with neuronal nitric oxide synthase (nNOS), which is competitively inhibited by carboxy-terminal PDZ ligand of nNOS (CAPON) and, thereby, nNOS activity is thought to be regulated by PSD-95 and CAPON. We investigated the changes in mRNA for PSD-95, CAPON and nNOS in the facial motor nucleus of adult rats following axotomy, by in situ hybridization, in combination with the time course of muscle reinnervation, by retrograde tracing and nNOS protein expression, by examining nicotinamide adenine nucleotide phosphate diaphorase (NADPH-d) activity. Signals of mRNA for PSD-95 and CAPON were initially expressed in the facial motoneurons, transiently decreased following axotomy and gradually recovered to the control level. When reinnervation of the axotomized nerve into muscle was observed, mRNA expression of PSD-95 and CAPON started to recover in the facial motoneurons. It was also found that mRNA and protein expression of nNOS started to increase in the axotomized facial motoneurons just prior to the recovery of mRNA expression of PSD-95 and CAPON. These results suggest that PSD-95 and CAPON are involved in synaptogenesis and/or recovery of synaptic function in motoneurons after axotomy.     

Production of Multiple Growth Factors by a Newly Established Human Thyroid Carcinoma Cell Line

A multiple growth factor-producing tumor cell line (NIM-1) was newly established from a patient with thyroid cancer and remarkable neutrophilia. NIM-1 cells also caused severe neutrophilia in nude mice bearing tumors. NIM-1-conditioned medium (NIM-1CM) contained activities that supported not only granulocyte, macrophage and eosinophil colony formation of human bone marrow cells but also the growth of colony-stimulating factor (CSF)-dependent cell lines, NFS60-KX and TF-1. Northern blot hybridization analysis revealed the constitutive expression of granulocyte-CSF (G-CSF), granulocyte/macrophage-CSF (GM-CSF) and interleukin(IL)-6 mRNAs in NIM-1 cells. Enzyme-linked immunosorbent assays (ELISA) using NIM-1CM also confirmed the production of IL-la and a small amount of IL-1β besides G-CSF, GM-CSF and IL-6 in NIM-1 cells. In addition, unexpected production of IL-11 in NIM-1 cells was detected by northern blot hybridization analysis and by bioassay using an IL-11-dependent cell line. Therefore, NIM-1 cell line is shown to produce multiple cytokines including potentially megakaryopoietic growth factors such as GM-CSF, IL-6 and IL-11.