Importance of low-range CAG expansion and CAA interruption in SCA2 Parkinsonism

OBJECTIVES: To examine the presence of an ATXN2 mutation in patients with parkinsonism in the Korean population and to find the difference in the ATXN2 mutation between ataxic and parkinsonian phenotypes. DESIGN: Survey. SETTING: Seoul National University Hospital (a referral center). Patients Patients with Parkinson disease (PD) (n = 468) and the Parkinson variant of multiple system atrophy (MSA-P) (n = 135) who were seen at our Department of Neurology during the past 3 years. MAIN OUTCOME MEASURES: CAG expansion in spinocerebellar ataxia type 2 (SCA2) alleles was assessed by polymerase chain reaction amplification and fragment analysis, and its size and interruption were verified by cloning and sequencing. SCA2 was tested also in the family members of the probands. Striatal dopamine transporter (DAT) and D(2) receptor status were evaluated in the probands and their SCA2-positive family members using iodine I 123 [(123)I]-radiolabeled fluoropropyl (FP) 2-carbomethoxy-3-(4-iodophenyl) tropane (CIT) with single-photon emission computed tomography (SPECT) and carbon C 11 [(11)C]-radiolabeled raclopride positron emission tomography (PET). RESULTS: We found 3 patients with apparently sporadic disease with expanded CAG repeats in the ATXN2 locus. Two patients had a PD phenotype. The third patient showed an MSA-P phenotype. The CAG repeats in the ATXN2 locus of the patients were 35/22, 34/22, and 32/22, respectively (range in normal population, 19-27). The size of repeats was lower than the CAG repeats (38-51) in ataxic SCA2 in our population. The sequence of expanded CAG repeats was interrupted by CAA as (CAG)(n)(CAA)(CAG)(8) in all the patients. DNA analyses in 2 families showed 2 asymptomatic carriers in each family. In the patient with the PD phenotype, striatal DAT loss was more severe in the putamen than the caudate, and [(11)C]raclopride PET showed an increased relative putamen-caudate binding ratio. The patient with the MSA-P phenotype had severe DAT loss throughout the striatum. Two of 3 asymptomatic carriers had striatal DAT loss. CONCLUSIONS: This study demonstrates that SCA2 is one of the genetic causes of PD and MSA-P. All 3 patients had apparently sporadic disease, emphasizing the need to screen even in patients with nonfamilial disease. CAG repeats were in the low expansion range and interrupted by CAA in all patients in the low-range expansion. Therefore, accurate determination of CAG expansion and ATXN2 sequencing are warranted. [(123)I]FP-CIT SPECT and [(11)C]raclopride PET provide a useful way to evaluate the degree of nigrostriatal dopaminergic damage in SCA2-related parkinsonism and gene carriers.     

Comparison of Indomethacin, Diclofenac and Aspirin-Induced Gastric Damage according to Age in Rats

Background/Aims

Aging gastric mucosa is known to have decreased mucosal defenses and increased susceptibility to injury by nonsteroidal anti-inflammatory drugs. Depending on the type of nonsteroidal anti-inflammatory drug (NSAID), the underlying mechanisms and the extent of damage to the stomach or intestine may differ. This study was performed to evaluate the acute gastric damage caused by different doses of indomethacin, diclofenac and aspirin in rats of various ages.

Methods

For the acute models, indomethacin (10, 20 or 40 mg/kg), diclofenac (40 or 80 mg/kg) or aspirin (100 mg/kg) was given to 7- and 25-week-old and 1-year-old Sprague-Dawley rats by intragastric gavage. The gross ulcer index, damage area as assessed by imaging, histological index, myeloperoxidase (MPO) activity, and cytosolic phospholipase A₂ (cPLA₂) levels were measured after 24 hours.

Results

The gross ulcer index and damage area increased with age in the presence of three NSAIDs (p<0.05). The increases in MPO levels induced by diclofenac and aspirin were significantly higher in 1-year-old than 7-week-old rats (p<0.05). cPLA₂ expression induced by indomethacin (10 and 40 mg/kg) was greater in the 1-year-old rats, compared with 7-week-old rats (p<0.05).

Conclusions

NSAID-induced acute gastric damage increased in a dose- and age-dependent manner.     

Gastroprotective Effect of Cochinchina momordica Seed Extract in Nonsteroidal Anti-Inflammatory Drug-Induced Acute Gastric Damage in a Rat Model

Background/Aims

The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A₂ (cPLA₂), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model.

Methods

The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA₂, and 5-LOX.

Results

All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA₂ and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups.

Conclusions

SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats.     

Laboratory formulated magnetic nanoparticles for enhancement of viral gene expression in suspension cell line

One factor critical to successful gene therapy is the development of efficient delivery systems. Although advances in gene transfer technology including viral and non-viral vectors have been made, an ideal vector system has not yet been constructed. Due to the growing concerns over the toxicity and immunogenicity of viral DNA delivery systems, DNA delivery via improve viral routes has become more desirable and advantageous. The ideal improve viral DNA delivery system should be a synthetic materials plus viral vectors. The materials should also be biocompatible, efficient, and modular so that it is tunable to various applications in both research and clinical settings. The successful steps towards this improve viral DNA delivery system is demonstrated: a magnetofection system mediated by modified cationic chitosan-coated iron oxide nanoparticles. Dense colloidal cationic iron oxide nanoparticles serve as an uptake-enhancing component by physical concentration at the cell surface in presence of external magnetic fields; enhanced viral gene expression (3-100-fold) due to the particles is seen as compared to virus vector alone with little virus dose.     

A case of metastasis-induced acute pancreatitis improved by chemotherapy]

Pancreatic metastases are found in up to 40% of patients with small cell lung cancer, but metastasis-induced acute pancreatitis is rare. Treatment of metastasis-induced acute pancreatitis is initially supportive, but failure of conservative management are common. There are few reports on aggressive treatment with chemotherapy which lead to rapid clinical improvement and prolongation of survival in patients with metastasis-induced acute pancreatitis. We experienced a case of metastasis-induced acute pancreatitis in a patient with small cell lung cancer. Despite conservative treatment with dietary restriction and intravenous fluid supply, serum amylase levels increased persistently with severe abdominal pain. After chemotherapy with irinotecan and carboplatin, abdominal pain and serum amylase levels resolved dramatically.     

Local intraarterial tirofiban after formation of anterograde flow in patients with acute ischemic stroke: Preliminary experience and short term follow-up results

Objective

Despite the risk of intracranial hemorrhage, combination therapy with intravenous recombinant tissue plasminogen activator and intraarterial mechanical thrombolysis can be effective for treatment of acute ischemic stroke. We investigated the feasibility and safety of intraarterial tirofiban following formation of anterograde flow after mechanical thrombolysis in acute ischemic stroke.

Methods

We analyzed data from consecutive patients with acute ischemic stroke, who underwent treatment with intraarterial thrombolysis. All patients were evaluated immediately and 7 days later by computed tomography scanning and magnetic resonance imaging scanning with magnetic resonance angiography. For clinical outcome analysis, we followed up the NIHSS score and modified Rankin Scale score during a period of 3 months.

Results

Sixteen patients underwent treatment. The mean baseline NIHSS score was 16.1 ± 4.4 points. 75.1% of patients showed angiographic improvement; 43.8% and 31.3% had complete and partial recanalization, respectively. 53.3% and 56.3% showed clinical improvement and favorable outcome at 24 h and 3 months, respectively. One patient had symptomatic intracranial hemorrhage.

Conclusions

Our results suggest that administration of local intraarterial tirofiban after anterograde flow formation is a viable treatment strategy for patients of acute ischemic stroke for reducing the risk of reocclusion after intraarterial thrombolysis.     

Effect of Eutectic Mixture of Local Anesthetics on Pain Perception During Scaling by Ultrasonic or Hand Instruments: A Masked Randomized Controlled Trial

Background: The aims of this study are to evaluate the efficacy of a eutectic mixture of local anesthetic (EMLA) cream on pain perception during scaling and to compare the intensities of pain provoked by hand and ultrasonic instruments. Methods: Forty subjects with chronic gingivitis or periodontitis were enrolled in the study. In this randomized, split‐mouth, controlled, masked clinical trial, each of the four quadrants in subjects was randomly assigned to receive one of the following protocols: scaling with an ultrasonic scaler with or without the application of the EMLA cream or scaling with a Gracey curet with or without the application of the EMLA cream. Pain levels after each quadrant of scaling were assessed with a visual analog scale (VAS; 0 to 100 mm) and verbal rating score (VRS; 0 to 4). All subjects were recalled to detect any complications after 24 hours. Results: The mean VAS and VRS when EMLA cream was applied (18.39 ± 14.47 mm and 0.95 ± 0.69) were significantly lower (P <0.001 for VAS and VRS) compared to when EMLA cream was not used (26.54 ± 16.46 mm and 1.30 ± 0.75). The mean VAS and VRS of the ultrasonic scaler group (20.43 ± 16.40 mm and 0.98 ± 0.76) were significantly lower (P = 0.024 for VAS; P = 0.003 for VRS) than those of the Gracey curet group (24.50 ± 15.17 mm and 1.28 ± 0.69). None of the subjects showed adverse effects after EMLA‐cream application. Conclusion: Although most patients experienced limited pain during scaling, a significant reduction of pain is achieved by using EMLA cream and ultrasonic scaler.