Protein kinase Cδ mediates trimethyltin-induced neurotoxicity in mice in vivo via inhibition of glutathione defense mechanism

We investigated whether protein kinase C (PKC) is involved in trimethyltin (TMT)-induced neurotoxicity. TMT treatment (2.8 mg/kg, i.p.) significantly increased PKCδ expression out of PKC isozymes (i.e., α, βI, βII, δ, and ?) in the hippocampus of wild-type (WT) mice. Consistently, treatment with TMT resulted in significant increases in cleaved PKCδ expression. Genetic or pharmacological inhibition (PKCδ knockout or rottlerin) was less susceptible to TMT-induced seizures than WT mice. TMT treatment increased glutathione oxidation, lipid peroxidation, protein oxidation, and levels of reactive oxygen species. These effects were more pronounced in the WT mice than in PKCδ knockout mice. In addition, the ability of TMT to induce nuclear translocation of Nrf2, Nrf2 DNA-binding activity, and upregulation of γ-glutamylcysteine ligase was significantly increased in the PKCδ knockout mice and rottlerin (10 or 20 mg/kg, p.o. × 6)-treated WT mice. Furthermore, neuronal degeneration (as shown by nuclear chromatin clumping and TUNEL staining) in WT mice was most pronounced 2 days after TMT. At the same time, TMT-induced inhibition of phosphoinositol 3-kinase (PI3K)/Akt signaling was evident, thereby decreasing phospho-Bad, expression of Bcl-xL and Bcl-2, and the interaction between phospho-Bad and 14-3-3 protein, and increasing Bax expression and caspase-3 cleavage were observed. Rottlerin or PKCδ knockout significantly protected these changes in anti- and pro-apoptotic factors. Importantly, treatment of the PI3K inhibitor LY294002 (0.8 or 1.6 µg, i.c.v.) 4 h before TMT counteracted protective effects (i.e., Nrf-2-dependent glutathione induction and pro-survival phenomenon) of rottlerin. Therefore, our results suggest that down-regulation of PKCδ and up-regulations of Nrf2-dependent glutathione defense mechanism and PI3K/Akt signaling are critical for attenuating TMT neurotoxicity.     

The modified outside-in suture: vertical repair of the anterior horn of the meniscus after decompression of a large meniscal cyst

This article describes a modified suture technique designed for the vertical repair of the anterior horn of the meniscus after arthroscopic decompression of a large meniscal cyst. This procedure comprises of three steps: first, the meniscus was pierced vertically using a suture hook and a No. 0 PDS suture. Second, both ends of the No. 0 PDS on the femoral and tibial surfaces of the meniscus were pulled to the outside of the joint capsule using a spinal needle preloaded with suture material. Finally, a skin incision was made adjacent to the suture materials, and both ends were tied. We recommend this technique not only for the vertical repair of the anterior horn of the meniscus after decompression of large meniscal cyst, but also to repair a longitudinal tear of the meniscus.     

Prediction of remission in Graves' disease after thionamide therapy by technetium-99m early uptake]

In the clinical management of Graves' thyrotoxicosis, one of the most important subject is when to stop antithyroid drugs after achieving an euthyroid state. T3 suppression test and other methods have been used to forecast the outcome after drug cessation, but the results were not always satisfactory. We have attempted to predict remission of Graves' disease by single measurement of early technetium uptake without administration of triiodothyronine. Drugs were discontinued in the seventy-five patients with Graves' disease on maintenance doses of either methimazole or propylthiouracil who showed normalized uptake (4.0% or less). Of 64 patients evaluable after twelve months, 55 (86%) remained euthyroid, 8 relapsed, and 1 became hypothyroid. With its accuracy in prediction of short-term remission comparable or superior to T3 suppression test, this rapid and simple method seemed suitable for routine use in clinical practice.     

Lenticulostriate vasculopathy in twin-to-twin transfusion syndrome.

Intracranial pathology is a common and important complication in extremely low birth weight babies. Lenticulostriate vasculopathy (LSV) is an abnormal finding on cranial ultrasounds of sick babies and has been associated with congenital infection, chromosomal aberration and twin-to-twin transfusion. We describe a previously unreported situation of LSV being detected in both donor and recipient twin. This pair of monochorionic, diamniotic twins was admitted to the Neonatal Intensive Care Unit at 28 weeks of gestation. The mother underwent an emergency caesarean section because ultrasound and Doppler studies showed stage III twin-to-twin transfusion syndrome. The first twin weighed 998 g and second twin weighed 600 g. The first twin had an uneventful stay, whereas the second twin needed prolonged continuous positive airway pressure and indomethacin for patent ductus arteriosus. Both of them developed LSV. The clinical significance of this condition on the neuro-developmental outcome of a neonate has not yet been fully determined.