Targeting the Progression of Parkinson’s Disease

By the time a patient first presents with symptoms of Parkinson’s disease at the clinic, a significant proportion (50-70%) of the cells in the substantia nigra (SN) has already been destroyed. This degeneration progresses until, within a few years, most of the cells have died. Except for rare cases of familial PD, the initial trigger for cell loss is unknown. However, we do have some clues as to why the damage, once initiated, progresses unabated. It would represent a major advance in therapy to arrest cell loss at the stage when the patient first presents at the clinic. Current therapies for Parkinson’s disease focus on relieving the motor symptoms of the disease, these unfortunately lose their effectiveness as the neurodegeneration and symptoms progress. Many experimental approaches are currently being investigated attempting to alter the progression of the disease. These range from replacement of the lost neurons to neuroprotective therapies; each of these will be briefly discussed in this review. The main thrust of this review is to explore the interactions between dopamine, alpha synuclein and redox-active metals. There is abundant evidence suggesting that destruction of SN cells occurs as a result of a self-propagating series of reactions involving dopamine, alpha synuclein and redox-active metals. A potent reducing agent, the neurotransmitter dopamine has a central role in this scheme, acting through redox metallo-chemistry to catalyze the formation of toxic oligomers of alpha-synuclein and neurotoxic metabolites including 6-hydroxydopamine. It has been hypothesized that these feed the cycle of neurodegeneration by generating further oxidative stress. The goal of dissecting and understanding the observed pathological changes is to identify therapeutic targets to mitigate the progression of this debilitating disease.Key Words: Parkinson’s disease, pathology, redox chemistry, metallo- chemistry, review, iron.     

Corticospinal tract location in internal capsule of human brain: diffusion tensor tractography and functional MRI study

We attempted to elucidate the corticospinal tract location at the posterior limb of the internal capsule in the human brain. Ten healthy volunteers were recruited. Probabilistic mapping was performed using the functional MRI activation resulting from a hand motor task as region of interest 1 and the corticospinal tract area of the anterior pons as region of interest 2. The average location of the highest density point of the corticospinal tract was mid-posterior portion with the standard from the most medial point to the most posterior point of the lenticular nucleus. In conclusion, we demonstrated that the corticospinal tract for the hand descended through the posterior portion of the posterior limb at the mid-thalamic level.     

Mesenteric inflammatory myofibroblastic tumors in an elder patient with early recurrence： A case report

Inflammatory myofibroblastic tumor （IMT） of the alimentary tract often occurs in children or young adults, but may occur at any age. Symptoms are nonspecific and depend on the location of the tumor. The most often involved sites are small bowel mesentery especially the distal ileum, mesotransverse colon, or great omentum. Recurrence appears to be more frequent in the extrapulmonary lesion. Herein we demonstrate a 63-year-old male patient with mesenteric INT, with an early recurrence after his first operation. We should be aware that if the tumor is larger than 8 cm, multinodular, omental, with ill-defined margin, with pathologically atypia, or ganglion-like cells, a close surveillence after primary surgery with image study might be necessary to detect the tumor recurrence early. Tumor recurrence may be asymptomatic, and it may act like a malignant tumor with a poor prognosis.     

Post-influenza pneumonia caused by the USA300 community-associated methicillin-resistant Staphylococcus aureus in Korea

Panton-Valentine leukocidin (PVL)-positive USA300 clone has been the most successful community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clone spreading in North America. In contrast, PVL-negative ST72-CA-MRSA has been predominant in Korea, and there has been no report of infections by the USA300 strain except only one case report of perianal infection. Here, we describe the first case of pneumonia caused by the USA300 strain following pandemic influenza A (H1N1) in Korea. A 50-year-old man was admitted with fever and cough and chest radiograph showed pneumonic consolidation at the right lower lung zone. He received a ventilator support because of respiratory failure. PCR for pandemic influenza A (H1N1) in nasopharyngeal swab was positive, and culture of sputum and endotracheal aspirate grew MRSA. Typing of the isolate revealed that it was PVL-positive, ST 8-MRSA-SCCmec type IV. The analysis of the PFGE patterns showed that this isolate was the same pulsotype as the USA300 strain.     

A Comparison of Factors Associated with Physical Inactivity Among East Asian College Students

Background

Little is known on the level of physical inactivity and its behavioral and cultural correlates among East Asian college students.

Purpose

The aim of this study is to examine and compare the level and behavioral and cultural correlates of physical inactivity among college students in Taiwan, Hong Kong, South Korea, Singapore, and Malaysia.

Method

Data were collected from a representative sample of college students (N?=?12,137) in five East Asian economies during the 2008?C2009 academic year. The stratified random sampling (stratum: geographic region) was used to select participating institutions. The overall response rate was 77%.

Results

The percentage of physically inactive students was 7.2% for Singapore, 8.0% for Malaysia, 13.5% for Taiwan, 16.8% for Hong Kong, and 28.5% for South Korea. When gender, age, and body mass index were controlled, fruit and vegetable consumptions were significant correlates for physical inactivity across all the five economies. In Hong Kong, Korea, and Taiwan, those who engaged in binge drinking at least once during the past 2?weeks were less likely to be physically inactive than those who did not. Religion and military experience did not independently predict physical inactivity in any of the five economies.

Conclusion

Physical inactivity varies greatly across different economies in East Asia that are usually grouped together and considered a single homogeneous entity by some researchers. However, in terms of correlates of physical inactivity, findings of the current study indicate that the transversal value of physical activity might be transformed into a universal.     

Adrenergic nerves govern circadian leukocyte recruitment to tissues

The multistep sequence leading to leukocyte migration is thought to be locally regulated at the inflammatory site. Here, we show that broad systemic programs involving long-range signals from the sympathetic nervous system (SNS) delivered by adrenergic nerves regulate rhythmic recruitment of leukocytes in tissues. Constitutive leukocyte adhesion and migration in murine bone marrow (BM) and skeletal-muscle microvasculature fluctuated with circadian peak values at night. Migratory oscillations, altered by experimental jet lag, were implemented by?perivascular SNS fibers acting on β-adrenoreceptors expressed on nonhematopoietic cells and leading to?tissue-specific, differential circadian oscillations in the expression of endothelial cell adhesion molecules and chemokines. We showed that these rhythms have physiological consequences through alteration of hematopoietic cell recruitment and overall survival in models of septic shock, sickle cell vaso-occlusion, and BM transplantation. These data provide unique insights in the leukocyte adhesion cascade and the potential for time-based therapeutics for transplantation and inflammatory diseases.     

Assessment of left and right ventricular parameters in healthy Korean volunteers using cardiac magnetic resonance imaging: change in ventricular volume and function based on age,gender and body surface area

The clinical utility of cardiac magnetic resonance imaging (CMR) is growing and is being used predominantly as a means of measuring ventricular function. The normal reference range of ventricular function may vary based on age, sex and ethnicity. At present, most CMR reference values for healthy individuals have been reported from Western countries. The intent of this study was to investigate the normal CMR reference range for left ventricular (LV) and right ventricular (RV) parameters in healthy Koreans. Healthy volunteers between the ages of 20–70 years without any history of cardiovascular disease or associated risk factors were prospectively recruited to be a part of this study. A total of 124 patients were recruited for this study. Steady-state free precession pulse sequences were used to obtain the cine images for LV and RV volume analysis. All parameters were analyzed based on age and gender, and normalized to body surface area (BSA). LV volume, mass and cardiac output were significantly greater in males than in females. However, all of these parameters which are associated with BSA and gender differences disappeared when corrected for BSA. RV volume was less in females even after the data was normalized for BSA. LV and RV volumes normalized for BSA gradually decreased with greater age, whereas the ejection fraction increased with age, thus maintaining the stroke volume index and cardiac index. LV and RV volumes, mass and function values for a healthy population largely depend on BSA and should be evaluated after normalization by BSA. LV parameters show no difference based on gender, but RV volume is less in the female. Greater age is associated with less ventricular volume, suggesting the possibility of volume sensitivity in the elderly.     

An end-to-end examination of geometric accuracy of IGRT using a new digital accelerator equipped with onboard imaging system

The Varian's new digital linear accelerator (LINAC), TrueBeam STx, is equipped with a high dose rate flattening filter free (FFF) mode (6 MV and 10 MV), a high definition multileaf collimator (2.5 mm leaf width), as well as onboard imaging capabilities. A series of end-to-end phantom tests were performed, TrueBeam-based image guided radiation therapy (IGRT), to determine the geometric accuracy of the image-guided setup and dose delivery process for all beam modalities delivered using intensity modulated radiation therapy (IMRT) and RapidArc. In these tests, an anthropomorphic phantom with a Ball Cube II insert and the analysis software (FilmQA (3cognition)) were used to evaluate the accuracy of TrueBeam image-guided setup and dose delivery. Laser cut EBT2 films with 0.15 mm accuracy were embedded into the phantom. The phantom with the film inserted was first scanned with a GE Discovery-ST CT scanner, and the images were then imported to the planning system. Plans with steep dose fall off surrounding hypothetical targets of different sizes were created using RapidArc and IMRT with FFF and WFF (with flattening filter) beams. Four RapidArc plans (6 MV and 10 MV FFF) and five IMRT plans (6 MV and 10 MV FFF; 6 MV, 10 MV and 15 MV WFF) were studied. The RapidArc plans with 6 MV FFF were planned with target diameters of 1 cm (0.52 cc), 2 cm (4.2 cc) and 3 cm (14.1 cc), and all other plans with a target diameter of 3 cm. Both onboard planar and volumetric imaging procedures were used for phantom setup and target localization. The IMRT and RapidArc plans were then delivered, and the film measurements were compared with the original treatment plans using a gamma criteria of 3%/1 mm and 3%/2 mm. The shifts required in order to align the film measured dose with the calculated dose distributions was attributed to be the targeting error. Targeting accuracy of image-guided treatment using TrueBeam was found to be within 1 mm. For irradiation of the 3 cm target, the gammas (3%, 1 mm) were found to be above 90% in all plan deliveries. For irradiations of smaller targets (2 cm and 1 cm), similar accuracy was achieved for 6 MV and 10 MV beams. Slightly degraded accuracy was observed for irradiations with higher energy beam (15 MV). In general, gammas (3%, 2 mm) were found to be above 97% for all the plans. Our end-to-end tests showed an excellent relative dosimetric agreement and sub-millimeter targeting accuracy for 6 MV and 10 MV beams, using both FFF and WFF delivery methods. However, increased deviations in spatial and dosimetric accuracy were found when treating lesions smaller than 2 cm or with 15 MV beam.