Does oxygen deficit to the cerebral blood flow caused by subdural hematoma and/or increased intracranial pressure affect the variations in auditory evoked potentials in white New Zealand rabbits?

The experiment entails surgically placing two subarachnoid bolts and a subdural balloon through the skull of white New Zealand rabbits. One bolt is used to raise the intracranial pressure (ICP) by continuously infusing lactated Ringer's solution (LRS) into the subarachnoid space to maintain the desired level of ICPs, and the second bolt is to monitor the ICP. A subdural balloon is inflated with a known volume of LRS to simulate a subdural hematoma condition. Using various levels of ICP and/or different sizes of balloons, auditory evoked potentials (AEPs) were recorded from a rabbit. The results indicate that a major correlation of changes in AEP peak latencies is due to mechanical forces of a mass (inflated balloon simulating a hematoma) on the brain matter rather than increased ICP. The AEP peak latencies are relatively insensitive to an increase in ICP without the simulated intracranial hematoma. This study provides evidence that oxygen deficit to the cerebral blood flow caused by deformation of certain parts of the brain could be identified using AEPs.     

In Vitro Activity of Tigecycline Against Orientia tsutsugamushi

Scrub typhus is a zoonosis caused by Orientia tsutsugamushi (O. tsutsugamushi) occurring mainly in autumn in Korea. The need of new antibiotics has arisen with a report on strains resistant to antibiotics and chronic infection. This study aims to identify susceptibility of tigecycline in-vitro as a new therapeutic option for O. tsutsugamushi. Antibacterial activity of tigecycline against the O. tsutsugamushi was compared with doxycycline using flow cytometry assay. The inhibitory concentration 50 (IC₅₀) was 3.59×10^-3 µg/mL in doxycycline-treated group. Whereas in 0.71×10^-3 µg/mL tigecycline-treated group. These findings indicate that tigecycline may be a therapeutic option for the treatment of scrub typhus.     

Use of egg yolk-derived immunoglobulin as an alternative to antibiotic treatment for control of Helicobacter pylori infection

The present study evaluated the potential use of immunoglobulin prepared from the egg yolk of hens immunized with Helicobacter pylori (immunoglobulin Y [IgY]-Hp) in the treatment of H. pylori infections. The purity of our purified IgY-Hp was 91.3%, with a yield of 9.4 mg of IgY per ml of egg yolk. The titer for IgY-Hp was 16 times higher than that for IgY in egg yolk from nonimmunized hens, and IgY-Hp significantly inhibited the growth and urease activity of H. pylori in vitro. Bacterial adhesion on AGS cells was definitely reduced by preincubation of both H. pylori (10(8) CFU/ml) and 10 mg of IgY-Hp/ml. In Mongolian gerbil models, IgY-Hp decreased H. pylori-induced gastric mucosal injury as determined by the degree of lymphocyte and neutrophil infiltration. Therefore, in this experimental model, H. pylori-associated gastritis could be successfully treated by orally administered IgY-Hp. The immunological activity of IgY-Hp stayed active at 60 degrees C for 10 min, suggesting that pasteurization can be applied to sterilize the product. Fortification of food products with this immunoglobulin would significantly decrease the H. pylori infection. In conclusion, the IgY-Hp obtained from hens immunized by H. pylori could provide a novel alternative approach to treatment of H. pylori infection.     

A pilot study of bortezomib in Korean patients with relapsed or refractory myeloma

Recent clinical trials showed that bortezomib, a novel proteasome inhibitor, had therapeutic activity in multiple myeloma. However, there was no data about the feasibility of bortezomib in Korean patients. We performed a pilot study of bortezomib in patients with relapsed or refractory myeloma (1.3 mg/m2 twice weekly for 2 week in a 3-week cycle). Seven patients were enrolled. The median age of patients was 59 yr. All patients previously received VAD (vincristine, doxorubicin and dexamethasone) and thalidomide chemotherapy. Three patients previously received alkylator-containing chemotherapy and 4 patients, autologous stem cell transplantation. Bortezomib monotherapy resulted in 3 partial remissions (43%), 3 no changes (43%) and 1 progressive disease (14%). One patient who had no response to bortezomib monotherapy experienced partial remission after addition of dexamethasone to bortezomib. The most common serious toxicity was thrombocytopenia (grade 3/4, 10 of 20 cycles (50%)) and grade 3 peripheral neuropathy was developed in 2 of 20 cycles (10%). Drug-related adverse event led to discontinuation of bortezomib in 1 patient. There was no treatment related mortality. Overall, bortezomib seems to be effective and feasible. Conduction of larger clinical studies on Korean patients is necessary to characterize clinical efficacy and safety of bortezomib more precisely.     

A novel nonsense mutation in the MPL gene in congenital amegakaryocytic thrombocytopenia

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare autosomal recessive disorder characterized by thrombocytopenia from failure of megakaryopoiesis. CAMT is one of the bone marrow failure syndromes, and the disease progression may involve other lineages leading to pancytopenia. The genetic background of CAMT is mutations in the MPL gene encoding the thrombopoietin receptor. Here, we describe a Korean male with CAMT. Molecular genetic analyses by direct sequencing revealed that he was compound heterozygous for two nonsense mutations in MPL, Tyr63X (c.189C>A), and Arg357X (c.1069C>T), the latter being a novel mutation.     

Quantum-dot-assisted fluorescence resonance energy transfer approach for intracellular trafficking of chitosan/DNA complex

Fluorescence resonance energy transfer (FRET) was employed to monitor the molecular dissociation of a chitosan/DNA complex with different molecular weights of chitosan. Chitosan with different molecular weights was complexed with plasmid DNA and the complex formation was monitored using dynamic light scattering and a gel retardation assay. As the chitosan molecular weight increased, a more condensed complex was prepared at various ratios of chitosan to DNA. Plasmid DNA and chitosan were separately labeled with quantum dots and Texas red, respectively, and the dissociation of the complex was subsequently monitored using confocal microscopy and fluorescence spectroscopy. As the chitosan molecular weight in the chitosan/DNA complex increased, the Texas red-labeled chitosan gradually lost FRET-induced fluorescence light when HEK293 cells incubated with chitosan/DNA complex were examined with confocal microscopy. This suggests that the dissociation of the chitosan/DNA complex was more significant in the high molecular weight chitosan/DNA complex. Fluorescence spectroscopy also monitored the molecular dissociation of the chitosan/DNA complex at pH 7.4 and pH 5.0 and confirmed that the dissociation occurred in acidic environments. This finding suggests that the high molecular weight chitosan/DNA complex could easily be dissociated in lysosomes compared to a low molecular weight complex. Furthermore, the high molecular weight chitosan/DNA complex showed superior transfection efficiency in relation to the low molecular weight complex. Therefore, it could be concluded that the dissociation of the chitosan/DNA complex is a critical event in obtaining the high transfection efficiency of the gene carrier/DNA complex.     

Serotonin inhibits GABA synaptic transmission in presympathetic paraventricular nucleus neurons

Activation of serotonin (5-hydroxytryptamine, 5-HT) receptors produces various autonomic and neuroendocrine responses in the hypothalamic paraventricular nucleus (PVN), including increased blood pressure and heart rate. However, the role(s) of 5-HT on the local GABA synaptic circuit have not been well understood in the PVN, where the inhibitory neurotransmitter GABA plays a key role in the modulation of sympathoexcitatory outflow. In the present study, we examined the effects of 5-HT on GABA synaptic transmission in presympathetic PVN neurons projecting to spinal cord using patch-clamp electrophysiology combined with tract-tracing techniques. Bath application of 5-HT (0.01-100 microM) reversibly decreased the frequency of spontaneous GABAergic inhibitory postsynaptic currents (sIPSC) in a concentration dependent manner (IC50, 0.07 microM), with no significant changes in the amplitudes and decay kinetics of sIPSC. The sIPSC inhibition of 5-HT was mimicked by 5-HT1A agonist, 8-OH-DPAT (8-hydroxy-2(di-n-propylamino)tetralin, 10 microM), and blocked by 5-HT1A antagonist WAY-100635 but not by 5-HT1B antagonist SB224289. 5-HT also reduced the frequency of miniature IPSC (mIPSC) (2.59+/-0.51 Hz, control vs. 1.25+/-0.31 Hz, 5-HT, n=16) in similar extent with 5-HT induced reduction of sIPSC frequency (sIPSCs, 55.8+/-6.2%, n=11 vs. mIPSCs, 52.30+/-5.85%, n=16; p>0.5). All together, our results indicate that 5-HT can inhibit presynaptic GABA release via presynaptic 5-HT1A receptors in presympathetic PVN neurons projecting to spinal cord.     

Unrelated Hematopoietic Stem Cell Transplantation for Children with Acute Leukemia: Experience at a Single Institution

We evaluate the outcomes in children with acute leukemia who received allogeneic hematopoietic stem cell transplantation (HCT) using unrelated donor. Fifty-six children in complete remission (CR) received HCT from unrelated donors between 2000 and 2007. Thirty-five had acute myeloid leukemia, and 21 had acute lymphoid leukemia. Stem cell sources included bone marrow in 38, peripheral blood in 4, and cord blood (CB) in 14. Four patients died before engraftment and 52 engrafted. Twenty patients developed grade II-IV acute graft-versus-host disease (GVHD) and 8 developed extensive chronic GVHD. With median follow-up of 39.1 months, event free survival and overall survival were 60.4% and 67.5%, respectively, at 5 yr. Events included relapse in 10 and treatment-related mortality (TRM) in 10. The causes of TRM included sepsis in 4, GVHD in 4 (1 acute GVHD and 3 chronic GVHD), veno-occlusive disease in 1 and fulminant hepatitis in 1. Patients transplanted with CB had event free survival of 57.1%, comparable to 63.2% for those transplanted with other than CB. In conclusion, HCT with unrelated donors is effective treatment modality for children with acute leukemia. In children with acute leukemia candidate for HCT but lack suitable sibling donor, unrelated HCT may be a possible treatment option at the adequate time of their disease.     

Effects of behavior modification on body image, depression and body fat in obese Korean elementary school children

This study was performed to investigate the effects of behavior modification on body image, depression and body fat in obese elementary school children. Sixty-two elementary students of the 4th to 6th grade were selected from two different Seoul schools. Thirty-four children in one school were designated as the experimental group, and 28 children from the other school as the control group. The experimental group received 60 - 70 minutes of behavior modification, once a week, for 8 weeks. The control group received neither management nor treatment. The results indicated a significant improvement of body image and a reduction in the increase rate of body fat for the experimental group. This finding strongly supports the theory that behavior modification can be used as an effective strategy in the treatment of obese children.     

Proper cut-off value of free to total PSA ratio for detection of prostate cancer in Korean men

To assess whether the free-to-total prostate specific antigen (PSA) ratio (F/T PSA ratio) would enhance prostate cancer detection in Korean men with serum total PSA levels between 4 and 20 ng/ml. Methods: A total of 240 consecutive patients whose serum PSA levels were between 4 and 20 ng/ml were enrolled in this two-year study. All patients underwent ultrasound-guided transrectal biopsies of the prostate gland. The F/T PSA ratio was measured using the Roche immunoassay. Results: Of the 240 patients, 202 (84%) had benign histologies, while 38 (16%) had prostate cancer. The two patient groups were well matched for age. The mean F/T PSA ratio showed a statistically significant difference between the two groups: in the benign histology group it was 0.14 (0.04 - 0.37), and 0.10 (0.08 - 0.20) in the prostate cancer group (p < 0.05). Out of the 183 patients with a PSA level between 4-10 ng/ml, the mean F/T PSA ratios were 0.14 and 0.11 in the benign histology (n=158) and prostate cancer groups (n=25), respectively (p < 0.05). From the 57 patients with a PSA level between 10 - 20 ng/ml, the mean F/T PSA ratios were 0.14 and 0.10 in the benign histology (n=44) and prostate cancer groups (n=13), respectively (p < 0.05). Overall, when the cut-off value of the F/T PSA ratio was 0.10, the sensitivity and specificity were 75.0% and 76.5%, while for the cut-off value of 0.15 they were 83.3% and 39.7% respectively. Conclusion: Our data demonstrated the usefulness of the free to total PSA ratio in distinguishing benign prostate disease and cancer disease, hence eliminating unnecessary biopsies. It is recommended that a cut-off value for the F/T PSA ratio of 0.10 be applied to Korean men which this is lower than the value used in Western countries.