Gliomas are associated with high mortality because of their exceedingly invasive character. As these tumors acquire their invasiveness from low-grade tumors, it is very important to understand the ...detailed molecular mechanisms of invasion onset. Recent evidences suggest the significant role of microRNAs in tumor invasion. Thus, we hypothesized that deregulation of microRNAs may be important for the malignant progression of gliomas. We found that the aberrant expression of miR-21 is responsible for glioma invasion by disrupting the negative feedback circuit of Ras/MAPK signaling, which is mediated by Spry2. Upregulation of miR-21 was triggered by tumor microenvironmental factors such as hyaluronan and growth factors in glioma cells lacking functional phosphatase and tensin homolog (PTEN), but not harboring wild-type PTEN. Consistently with these in vitro results, Spry2 protein levels were significantly decreased in 79.7% of invasive WHO grade II-IV human glioma tissues, but not in non-invasive grade I and normal tissues. The Spry2 protein levels were not correlated with their mRNA levels, but inversely correlated with miR-21 levels. Taken together, these results suggest that the post-transcriptional regulation of Spry2 by miR-21 has an essential role on the malignant progression of human gliomas. Thus, Spry2 may be a novel therapeutic target for treating gliomas.
To determine the immediate and long-term therapeutic efficacies of Gufoni and head-shaking maneuvers in apogeotropic type of benign paroxysmal positional vertigo involving the horizontal semicircular ...canal (HC-BPPV), a randomized, prospective, sham-controlled study was conducted.
In 10 nationwide dizziness clinics in Korea, 157 consecutive patients (95 women, age range: 18-89 years, mean age ± SD = 59.9 ± 13.6) with apogeotropic HC-BPPV were randomized to Gufoni (n = 52), head-shaking (n = 54), or sham maneuver (n = 51). For Gufoni maneuver, patients underwent ipsilesional side-lying and upward head-turn for migration of the debris toward the vestibule. Immediate responses were determined within 1 hour after a maximum of 2 trials of each maneuver and in the following day. The patients also had weekly follow-ups for 1 month after the initial maneuver.
After a maximum of 2 maneuvers on the initial visit day, Gufoni (38/52, 73.1%) and head-shaking (33/53, 62.3%) maneuvers showed better responses than the sham maneuver (17/49, 34.7%). The cumulative therapeutic effects were also better with Gufoni (p < 0.001) and head-shaking (p = 0.026) maneuvers compared with the sham maneuver. However, therapeutic efficacies did not differ between the Gufoni and head-shaking groups in terms of both immediate (p = 0.129) and long-term (p = 0.239) outcomes.
Using a prospective randomized trial, we demonstrated that the Gufoni and head-shaking maneuvers are effective in treating apogeotropic HC-BPPV.
This study provides Class II evidence that Gufoni and head-shaking maneuvers are effective in treating apogeotropic horizontal BPPV up to 1 month after initial treatment.
NCT00810641.
Diabet. Med. 27, 1033–1040 (2010)
Aims This study compared the efficacy and safety of tramadol/acetaminophen (T/A) and gabapentin in the management of painful diabetic neuropathy.
Methods An open, ...randomized, comparative study was conducted. Subjects with painful symmetric neuropathy in the lower limbs and mean pain‐intensity score ≥ 4 on a numeric rating scale were eligible. Subjects were randomized to receive either tramadol (37.5 mg)/acetaminophen (325 mg) or gabapentin (300 mg) for 6 weeks. After 2 weeks of the titration period (1200 mg/day for gabapentin and three tablets/day for T/A), the doses were maintained if the pain was relieved. The primary efficacy outcome was a reduction in pain intensity. Secondary measures evaluated a pain relief scale, a Brief Pain Inventory, a 36‐item Short Form Health Survey, average pain intensity and sleep disturbance.
Results One hundred and sixty‐three subjects (T/A 79; gabapentin 84) were included. At the final visit, the mean doses were 1575 mg/day for gabapentin and 4.22 tablets/day for T/A. Both groups were similar in terms of baseline pain intensity (mean intensity: T/A 6.7 ± 1.6; gabapentin 6.3 ± 1.6, P = 0.168). At the final visit, the mean reductions in pain intensity were similar in both groups (T/A −3.1 ± 2.0; gabapentin −2.7 ± 2.1, P = 0.744). Both groups had similar improvements in every Short Form Health Survey category and Brief Pain Inventory subcategory, and in the mean pain relief scores.
Conclusion This study suggests that the T/A combination treatment is as effective as gabapentin in the treatment of painful diabetic neuropathy in patients with Type 2 diabetes.
Summary
In this large longitudinal study of 16,078 Korean men aged 50 years or older, we observed that baseline elevation of serum uric acid level significantly associated with a lower risk of ...incident fractures at osteoporosis-related sites during an average follow-up period of 3 years.
Introduction
Male osteoporosis and related fractures are becoming recognized as important public health concerns. Oxidative stress has detrimental effects on bone metabolism, and serum uric acid (UA) is known to be a strong endogenous antioxidant. In the present study, we performed a large longitudinal study with an average follow-up period of 3 years to clarify the role of UA on the risk of incident osteoporotic fractures (OFs).
Methods
A total of 16,078 Korean men aged 50 years or older who had undergone comprehensive routine health examinations were enrolled. Incident fractures at osteoporosis-related sites (e.g., hip, spine, distal radius, and proximal humerus) that occurred after the baseline examinations were identified from the nationwide claims database of the Health Insurance Review and Assessment Service of Korea by using selected International Classification of Diseases, 10th revision codes.
Results
In total, 158 (1.0 %) men developed incident OFs. The event rate was 33.1 per 10,000 person-years. Subjects without incident OFs had 6.0 % higher serum UA levels than subjects with OFs (
P
= 0.001). Multivariable-adjusted Cox proportional hazard analyses adjusted for age, body mass index, glomerular filtration rate, lifestyle factors, medical and drug histories, and the presence of baseline radiological vertebral fractures revealed that the hazard ratio per standard deviation increase of baseline UA levels for the development of incident OFs was 0.829 (95 % CI = 0.695–0.989,
P
= 0.038).
Conclusions
These data provide the epidemiological evidence that serum UA may act as a protective factor against the development of incident OFs in Korean men.
Summary
What is known and objective
Higher rate of statin‐related hepatotoxicity has been reported for Koreans than for Westerners. Moreover, statin‐related aminotransferase elevation for those who ...show borderline levels of aspartate transaminase (AST) and alanine transaminase (ALT) (≤×3 of UNL) at baseline has not been fully investigated.
Methods
Post‐statin changes AST/ALT levels during the first year for 21 233 Korean outpatients at two large academic teaching hospitals from January 2009 to December 2013 were analysed using electronic health record data. The date of the first statin prescription was set as baseline. We also performed a comparative analysis of statin‐related AST/ALT elevations according to the type of statin, followed by an analysis of clinical risk factors.
Results and discussion
The progression rate to abnormal AST/ALT values >×3 the upper normal limit (UNL) was significantly higher (2·4–16% vs. 0·3–1·7%, P < 0·001) in subjects with borderline (>×1, but ≤×3 of UNL) compared with normal AST/ALT values at baseline. Those with normal baseline AST/ALT did not show significantly different progression rate between different statin medications (P = 0·801). However, patients taking pitavastatin (HR = 0·76, P = 0·657) were least likely to develop abnormal AST/ALT, whereas those taking fluvastatin (HR = 2·96, P = 0·029) were the most likely to develop abnormal AST/ALT compared with atorvastatin for patients who were with baseline borderline AST/ALT. However, given the small sample sizes and the observational nature of our study, these need further study.
What is new and conclusion
It is advisable to regularly monitor AST/ALT levels even in patients with AST/ALT increases >×1. Future studies should aim to determine the possible risk factors for each specific statin type by analysing various confounding variables.
The progression rate to abnormal AST/ALT values (>×3 the UNL) was significantly higher in subjects with borderline (>×1, but ≤ ×3 of UNL) compared to normal AST/ALT values at baseline. It is advisable to regularly monitor AST/ALT levels in patients with AST/ALT increases >×1, but ≤×3 of UNL.
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