Desensitization of GABA-induced currents in cultured rat hippocampal neurons.

The basic characteristics of desensitization of the GABAA receptor were investigated in cultured rat hippocampal neurons (three days to four weeks in vitro) using whole cell patch clamp techniques. GABA at 10-500 microM was perfused on to neurons for 30 or 60 s, with 60 s intervals of wash with control bath solution between perfusions. Desensitization, evaluated by peak-to-plateau ratio and time constants of current decay (tau), was dose-dependent and culture age-dependent. Desensitization was observed as early as three days in culture, the earliest time tested. At all ages, higher concentrations of GABA induced both larger and faster desensitization. Desensitization was markedly voltage-dependent and decreased with depolarization; peak-to-plateau ratio went from 6.3 to 1.4 and tau went from 4.6 to 26.8 s when holding potentials were changed from -80 mV to +30 mV. Low concentrations of GABA (1-2 microM) perfused for 2-60 s, which did not induce any current, had no effect on the maximal response nor desensitization produced by a subsequent application of 100 microM GABA. This finding suggests that GABA receptors were not desensitized without first being activated.     

Effects of an Interferon Inducer, Poly I:C, on Acute Ocular Infection Produced by Intracameral Inoculation of Toxoplasma gondii

A potent interferon inducer, synthetic polyinosinic acid-polycytidylic acid complex (poly I:C), was used prophylactically and therapeutically in experimental ocular Toxoplasma infections in rabbits. Daily intravenous injections of poly I:C alone or when combined with daily subconjunctival injections of the inducer delayed the appearance of conjunctivitis, corneal opacity, and iritis in Toxoplasma-infected eyes provided that the treatment was started 1 day before the infection. When the treatment was begun at the same time or 1 day after the infection, no delay in the production of the ocular lesions was noted. In no case was the treatment curative or completely suppressive.     

Spontaneous disruption of mycotic aneurysm involving innominate artery

We report a case of ruptured mycotic aneurysm involving innominate artery requiring an urgent surgical treatment. A 62-yr-old woman presented with fever and dyspnea. Previously, she was diagnosed with colon cancer and received right hemicolectomy and one cycle of adjuvant chemotherapy. On echocardiogram, pericardial effusion was noted and emergency pericardiocentesis was performed. CT scan revealed aortic aneurysm involving ascending aorta and innominate artery, and thrombi surrounding those structures. Patch repair of the defect in the ascending aorta and ringed Goretex graft to bypass the innominate and ascending aorta were performed. We believe that this is the first case of ruptured mycotic aneurysm involving innominate artery.     

Methylglyoxal induces apoptosis mediated by reactive oxygen species in bovine retinal pericytes

One of the histopathologic hallmarks of early diabetic retinopathy is the loss of pericytes. Evidences suggest that the pericyte loss in vivo is mediated by apoptosis. However, the underlying cause of pericyte apoptosis is not fully understood. This study investigated the influence of methylglyoxal (MGO), a reactive alpha-dicarbonyl compound of glucose metabolism, on apoptotic cell death in bovine retinal pericytes. Analysis of internucleosomal DNA fragmentation by ELISA showed that MGO (200 to 800 microM) induced apoptosis in a concentration-dependent manner. Intracellular reactive oxygen species were generated earlier and the antioxidant, N-acetyl cysteine, inhibited the MGO-induced apoptosis. NF-kappaB activation and increased caspase-3 activity were detected. Apoptosis was also inhibited by the caspase-3 inhibitor, Z-DEVD-fmk, or the NF-kappaB inhibitor, pyrrolidine dithiocarbamate. These data suggest that elevated MGO levels observed in diabetes may cause apoptosis in bovine retinal pericytes through an oxidative stress mechanism and suggests that the nuclear activation of NF-kappaB are involved in the apoptotic process.     

A method for photon beam Monte Carlo multileaf collimator particle transport

Monte Carlo (MC) algorithms are recognized as the most accurate methodology for patient dose assessment. For intensity-modulated radiation therapy (IMRT) delivered with dynamic multileaf collimators (DMLCs), accurate dose calculation, even with MC, is challenging. Accurate IMRT MC dose calculations require inclusion of the moving MLC in the MC simulation. Due to its complex geometry, full transport through the MLC can be time consuming. The aim of this work was to develop an MLC model for photon beam MC IMRT dose computations. The basis of the MC MLC model is that the complex MLC geometry can be separated into simple geometric regions, each of which readily lends itself to simplified radiation transport. For photons, only attenuation and first Compton scatter interactions are considered. The amount of attenuation material an individual particle encounters while traversing the entire MLC is determined by adding the individual amounts from each of the simplified geometric regions. Compton scatter is sampled based upon the total thickness traversed. Pair production and electron interactions (scattering and bremsstrahlung) within the MLC are ignored. The MLC model was tested for 6 MV and 18 MV photon beams by comparing it with measurements and MC simulations that incorporate the full physics and geometry for fields blocked by the MLC and with measurements for fields with the maximum possible tongue-and-groove and tongue-or-groove effects, for static test cases and for sliding windows of various widths. The MLC model predicts the field size dependence of the MLC leakage radiation within 0.1% of the open-field dose. The entrance dose and beam hardening behind a closed MLC are predicted within +/- 1% or 1 mm. Dose undulations due to differences in inter- and intra-leaf leakage are also correctly predicted. The MC MLC model predicts leaf-edge tongue-and-groove dose effect within +/- 1% or 1 mm for 95% of the points compared at 6 MV and 88% of the points compared at 18 MV. The dose through a static leaf tip is also predicted generally within +/- 1% or 1 mm. Tests with sliding windows of various widths confirm the accuracy of the MLC model for dynamic delivery and indicate that accounting for a slight leaf position error (0.008 cm for our MLC) will improve the accuracy of the model. The MLC model developed is applicable to both dynamic MLC and segmental MLC IMRT beam delivery and will be useful for patient IMRT dose calculations, pre-treatment verification of IMRT delivery and IMRT portal dose transmission dosimetry.     

Metastatic tumors in the sellar and parasellar regions: clinical review of four cases

Metastatic tumors in the sellar and parasellar regions are uncommon and rarely detected in clinical practice. We present four cases of sellar and parasellar metastatic tumors, which metastasized from distant organ in one case and extended directly from adjacent structures in three. Common presenting symptoms were cranial neuropathies, headache and facial pain. Invasion into the cavernous sinus was noted in all cases. We report rare cases of sellar and parasellar metastases. Also, we should consider the possibility of metastasis in these regions for patients who showed the above clinical presentations in systemic cancer patients. In extensive diseases, transient symptomatic relief could be obtained by direct surgical management, even in restricted degree.     

A rat model for radiation-induced proctitis

Radiation proctitis is a frequent acute complication encountered with pelvic irradiation. This study was aimed at establishing the optimal radiation dose for radiation-induced proctitis in rats. Female Wistar rats were used. The rectal specimens were examined morphologically at 5th and 10th day following 10-30 Gy irradiation in single fraction. With increasing dose, mucosal damage became worse, and there was a prominent reaction after > or =15 Gy. We selected 17.5 Gy as an optimal dose for radiation proctitis and examined specimens at day 1-14 and at week 4, 6, 8, and 12 after 17.5 Gy. The rectal mucosa revealed characteristic histological changes with time. An edema in lamina propria started as early as 1-2 days after irradiation and progressed into acute inflammation. On day 7 and 8, regeneration was observed with or without ulcer. Four weeks later, all regeneration processes have been completed with end result of either fibrosis or normal appearing mucosa. This study showed that the radiation injury of the rectum in rat develops in dose-dependent manner as it has reported in previous studies and suggested that 17.5 Gy in single fraction is the optimum dose to evaluate the protective effect of various medications for radiation proctitis in face of the clinical situation.     

Effect of fentanyl on TNF-alpha and IL-1beta levels during global ischemia/reperfusion in rats

To reduce surgical stress, fentanyl is frequently used for neurosurgical procedures in which focal and/or global ischemia may occur. However, the effect of fentanyl on cytokine levels during ischemia/reperfusion is still uncertain. The goal of this study was to evaluate the effect of fentanyl infusion on levels of the proinflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, during global cerebral ischemia/reperfusion in rats using the intracerebral microdialysis technique. Forty male Sprague-Dawley rats weighing 280-320 g were randomly assigned to each of four groups: group 1 (no fentanyl infusion and only ischemia/reperfusion); group 2 (1.5 ng/ml of fentanyl infusion during ischemia/reperfusion) and group 3 (3 ng/ml of fentanyl infusion during ischemia/reperfusion) (n=5 in each group). The rats were anesthetized with an intraperitoneal injection of pentobarbital (50 mg/kg). They were then intubated and ventilated with room air using an animal ventilator. A CMA-12 probe was inserted into the left hippocampal CA-1 region according to the guidelines. Artificial cerebrospinal fluid was run from the inserted microdialysis probe and infused with or without fentanyl at 3 microl/min using a microinjection syringe pump during ischemia/reperfusion. Ischemia was induced by clamping the carotid arteries. Hemorrhagic hypotension was induced for 17 min via the femoral artery, and reperfusion was accomplished by unclamping the sling and reinfusing the blood via the femoral artery. After 2 h of stabilization, the microdialysate was collected 10 times every 17 min, just before ischemia (control), after ischemia (I) and after reperfusion (R1-R8), and stored at -80 degrees C until analysis using high-performance liquid chromatography During global ischemia/reperfusion, TNF-alpha and IL-1beta significantly increased at reperfusion (R5) compared with the control value (p < 0.05). However, in both cases of fentanyl infusion, TNF-alpha and IL-1beta showed no increase compared with the control value. Fentanyl inhibited an increase of the proinflammatory cytokines, TNF-alpha and IL-1beta levels, during global cerebral ischemia/reperfusion in rats.