Spontaneous hypoglycemia and insulin autoantibodies in a patient with Graves' disease

A 31-year-old woman with Graves' disease developed fasting hypoglycemia after treatment for 3 weeks with methimazole. Although the patient had not received exogenous insulin, high titers of insulin autoantibodies were found in serum and large amounts of total and free insulin (1550 and 82 microU/ml, respectively) and C-peptide reactivity (CPR, 22 ng/ml) were detected in serum. After glucose loading, blood glucose and total insulin levels increased abnormally. The immunoglobulin class of the autoantibodies was IgG and the light chains were of the kappa type. The titers of insulin autoantibodies, elevated serum total and free insulin, and CPR levels decreased gradually, but insulin autoantibodies and elevated insulin levels were still present in the serum 8 months after the episode of hypoglycemia. These findings suggest that the patient's fasting hypoglycemia was due to excess free insulin released from antibody-bound insulin, and that methimazole might play a role in the initiation of production of insulin autoantibodies.     

Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants

Objectives: To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18–22 months corrected age in extremely low birth weight infants. Method: Total plasma bilirubin and unbound bilirubin were measured in 1101 extremely low birth weight infants at 5 ± 1 days of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18–22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow‐up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. Results: Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow‐up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow‐up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. Conclusions: In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma bilirubin and death or adverse neurodevelopmental outcomes at 18–22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.     

Localized retinal nerve fiber layer defects associated with cotton wool spots

Purpose  

To introduce four cases of localized retinal nerve fiber layer (RNFL) defects after emergence of retinal cotton wool spots (CWSs).     

Dual-Scale Porosity Alumina Structures Using Ceramic/Camphene Suspensions Containing Polymer Microspheres

This study demonstrates the utility of thermo-regulated phase separable alumina/camphene suspensions containing poly(methyl methacrylate) (PMMA) microspheres as porogens for the production of multi-scale porosity structures. The homogeneous suspension prepared at 60 °C could undergo phase separation during freezing at room temperature. This process resulted in the 3D networks of camphene crystals and alumina walls containing PMMA microspheres. As a consequence, relatively large dendritic pores with several tens of microns size could be created as the replica of frozen camphene crystals. In addition, after the removal of PMMA microspheres via heat-treatment, micron-sized small spherical pores could be generated in alumina walls. As the PMMA content with respect to the alumina content increased from 0 vol% to 40 vol%, while the camphene content in the suspensions was kept constant (70 vol%), the overall porosity increased from 45.7 ± 0.5 vol% to 71.4 ± 0.5 vol%. This increase in porosity is attributed to an increase in the fraction of spherical pores in the alumina walls. Thus, compressive strength decreased from 153 ± 18.3 MPa to 33 ± 7.2 MPa. In addition, multi-scale porosity alumina objects with a honeycomb structure comprising periodic hexagonal macrochannels surrounded by dual-scale porosity walls were constructed using a 3D plotting technique.     

Breast-milk levels of polybrominated diphenyl ether flame retardants in relation to women's age and pre-pregnant body mass index

The aim of the present study was to determine associations between the occurrence of PBDEs in breast milk of women and their demographic parameters. Participants were randomly recruited from the general population in southern Taiwan. Thirty two breast milk samples were collected and subsequently 30 congeners of PBDEs were analyzed using a high resolution gas chromatograph with a high resolution mass spectrometer. The mean and median of ΣPBDEs were 3.54 and 3.31 ng/g lipid, respectively. ΣPBDE levels in breast milk were not significantly correlated with age and pre-pregnant BMI of Taiwanese mothers. We did find, however, that the higher hexaBDE level was significantly related to older age (>29 years). Higher levels of ΣPBDEs and higher brominated PBDEs, such as nonaBDEs and decaBDE, had slightly but not significantly negative correlations with lower pre-pregnant BMI (≤21 kg/m²). There were no significant differences in PBDE levels among parity and ethnic groups. ΣPBDE levels in Taiwanese breast milk were lower than those reported from the United States or Canada. ΣPBDE levels of the present study (2007-2008) are significantly lower than those found in our previous report (2000-2001). Although our results were limited by the sampling size, preliminary results suggest the exploratory relations to show positive associations of PBDE homologues (e.g. triBDEs and hexaBDEs) with maternal age. PBDEs pattern of breast milk may have changed after pentaBDEs were stopped to use in Taiwan.     

Studies of protease and protease inhibitors in familial amyloidotic polyneuropathy

Serum levels of 6 protease inhibitors, alpha 1-antitrypsin, Cl inactivator, alpha 2-macroglobulin, antithrombin-3, alpha 1-antichymotrypsin and inter-alpha-trypsin inhibitor were measured in patients with familial amyloidotic polyneuropathy (FAP) and a control group without neurologic disease. No significant differences were observed between the 2 groups. The proteolytic effect of brinase, an enzyme from Aspergillus oryzae, on amyloid tissue sections from patients with FAP was also evaluated. Amyloid fibrils were degraded by brinase, while the tissue structure remained fairly intact.     

Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay

Measurement of lactate dehydrogenase (LDH) activity released to the extracellular bathing media has been found to be a simple yet quantitative method for assessing glutamate mediated central neuronal cell injury in cortical cell culture. Extracellular LDH is both chemically and biologically stable; the magnitude of LDH efflux in the cultures correlates in a linear fashion with the number of neurons damaged by glutamate exposure.     

Chinese nutrition educational materials for renal patients.

Nutrition resources in Chinese have been developed for the patients in St. Paul's Hospital's Renal Program. The goal was to support this patient subgroup to understand and practice the complicated diet guidelines within their own language and cultural contexts.     

Reactive oxygen species regulated mitochondria-mediated apoptosis in PC12 cells exposed to chlorpyrifos

Reactive oxidative species (ROS) generated by environmental toxicants including pesticides could be one of the factors underlying the neuronal cell damage in neurodegenerative diseases. In this study we found that chlorpyrifos (CPF) induced apoptosis in dopaminergic neuronal components of PC12 cells as demonstrated by the activation of caspases and nuclear condensation. Furthermore, CPF also reduced the tyrosine hydroxylase-positive immunoreactivity in substantia nigra of the rat. In addition, CPF induced inhibition of mitochondrial complex I activity. Importantly, N-acetyl cysteine (NAC) treatment effectively blocked apoptosis via the caspase-9 and caspase-3 pathways while NAC attenuated the inhibition of mitochondrial complex I activity as well as the oxidative metabolism of dopamine (DA). These results demonstrated that CPF-induced apoptosis was involved in mitochondrial dysfunction through the production of ROS. In the response of cellular antioxidant systems to CPF, we found that CPF treatment increased HO-1 expression while the expression of CuZnSOD and MnSOD was reduced. In addition, we found that CPF treatment activated MAPK pathways, including ERK 1/2, the JNK, and the p38 MAP kinase in a time-dependent manner. NAC treatment abolished MAPK phosphorylation caused by CPF, indicating that ROS are upstream signals of MAPK. Interestingly, MAPK inhibitors abolished cytotoxicity and reduced ROS generation by CPF treatment. Our results demonstrate that CPF induced neuronal cell death in part through MAPK activation via ROS generation, suggesting its potential to generate oxidative stress via mitochondrial damage and its involvement in oxidative stress-related neurodegenerative disease.