Validation of the Korean version of the Bayer activities of daily living scale

The Bayer-activities of daily living (B-ADL) is a brief and internationally applicable ADL instrument which has been validated in three European countries. The B-ADL has been developed to provide a tool for the assessment of functional deficits in performance of every day tasks as they are observed in mild to moderate stages of dementia. The B-ADL has been constructed for use in clinical trials as well as in clinical practice. From an international perspective the major application is the evaluation of treatment effects in clinical studies and the current study was to validate the Korean version of the B-ADL. The B-ADL was administered to a total of 129 subjects with varying degrees of cognitive decline. A substantial cross-sectional correlation between B-ADL and MMSE scores was found. The internal consistency of B-ADL was above 0.98. A factor analysis revealed that a one factor solution accounted for most of the total variance. The B-ADL global score significantly increased as the severity of dementia, assessed by global deterioration scale increased from stage 1 to 5. Test-retest reliabilities of B-ADL global score and each item were very high. All of these results were very similar to those from three European countries except for the proportion of 'non-applicability' in some ADL items. These findings provide evidence that the Korean version of B-ADL can be useful not only for clinical purposes but also for international multicentre studies.     

Association of the Tag SNPs in the Human SKT Gene (KIAA1217) With Lumbar Disc Herniation

Lumbar disc herniation (LDH) is one of the most common musculo‐skeletal diseases. Recent studies have indicated that LDH has strong genetic determinants, and several susceptibility genes have been reported to associate with LDH; however, its etiology and pathogenesis still remain unclear. KIAA1217 (alias SKT, the human homolog of murine Skt [Sickle tail]) is a good candidate for an LDH susceptibility gene because SKT is specifically expressed in nucleus pulposa of intervertebral discs (IVDs) in humans and mice, and Skt^Gt mice, which are established through a large‐scale gene‐trap mutagenesis, exhibit progressive, postnatal onset abnormality of the IVDs. Here, we report the association of SKT with LDH. Using tag SNPs, we examined the association in two independent Japanese case‐control populations and found a significant association with SKT rs16924573 in the allele frequency model (p = 0.0015). The association was replicated in a Finnish case‐control population (p = 0.026). The combined p value of the two population by meta‐analysis is 0.00040 (OR, 1.34; 95% CI, 1.14–1.58). Our data indicate that SKT is involved in the etiology of LDH.     

Validation of the Korean version of the Syndrom Kurztest (SKT): a short test for the assessment of memory and attention

The Syndrom Kurztest SKT is a brief neuropsychological test battery that consists of nine subtests and defines two independent factors of memory and attention deficit. The aim of this study was to validate the Korean version of the SKT. The reliability of each subtest among three parallel Forms (A, B and C) of the Korean version was high (r = 0.46-0.95). The SKT had good concurrent validity with the Mini-Mental State Examination (r = -0.83, p < 0.001). Factor analysis confirmed the presence of two primary factors, memory and attention. The overall similarities of the factor structures for the Korean data and those for the data from Germany and the USA provide evidence of the transcultural stability of the SKT.     

Epo-Induced Hemoglobinhation of SKT6 Cells is Mediated by Minimal Cytoplasmic Domains of the Epo or Prolactin Receptors without Modulation of GATA-1 or EKLF

Abstract

Interaction of erythropoietin with its type 1 receptor is essential to the development of late erythroid progenitor cells. Through the ectopic expression of receptor mutants in lymphoid and myeloid cell lines, insight has been gained regarding effectors that regulate Epo-induced proliferation. In contrast, effectors that regulate Epo-induced differentiation events (e.g. globin gene expression) are largely undefined. For in vitro studies of this pathway, erythroleukemic SKT6 cell sublines have been isolated which stably and efficiently hemoglobinize in response to Epo. Epo rapidly activated Jak2, STAT5 and detectably STATs 1 and 3, while no effects on GAIIA-1, EKLF or STAT5 expression were observed. Finally, eficient hemoglobinization of SKT6 cells was shown to be mediated by chimeric receptors comprised of the EGF receptor extracellular domain and truncated cytoplasmic subdomains of either the Epo receptor or the prolactin Nb2 receptor. This work further establishes SKT6 cells as an important model for studies of Epo-stimulated differentiation, and shows that this signaling pathway is promoted by a limited set of membrane-proximal receptor domains and effectors.     

Antispasmodic effect of shakuyakukanzoto extract on experimental muscle cramps in vivo: Role of the active constituents of Glycyrrhizae radix

Ethnopharmacological relevance

Shakuyakukanzoto (SKT) composed of Glycyrrhizae radix (G. radix) and Paeoniae radix (P. radix) has been traditionally used in Japan, Korea and China as an antispasmodic drug for the treatment of skeletal muscle cramps and intestinal cramps.

Aim of this study

To evaluate the antispasmodic activity of SKT and its two components, as well as to identify the key constituents of the components which mediate this effect in skeletal muscles in vivo.

Materials and methods

An experimental cramp model was constructed to evaluate the effects of peripherally-acting muscle relaxants on electrically-induced cramps under physiological conditions. This was accomplished by surgically isolating the motor supply to the gastrocnemius muscle in an anesthetized rat and delivering electrical stimuli to an isolated tibial nerve to induce tetanic contractions. We first tested dantrolene, a well-known peripherally-acting relaxant, to determine the sensitivity and reliability of our experimental model. We then evaluated the effects of SKT, P. radix, G. radix, and the eight active constituents of G. radix against tetanic contractions.

Results

We found that dantrolene (10 and 30 mg/kg, i.d.) rapidly and significantly inhibited tetanic contractions (P<0.01) irrespective of dose. SKT (0.5, 1.0, and 2.0 g/kg, i.d.) and G. radix (0.5 and 1.0 g/kg, i.d.) also significantly inhibited tetanic contractions (P<0.01) but in a dose-dependent manner owing to the actions of six of the eight active constituents in G. radix (liquiritin apioside, liquiritigenin, isoliquiritin apioside, isoliquiritigenin, glycycoumarin, and glycyrrhetinic acid, 20 μmol/kg, i.v.). These constituents, which include flavonoids, a triterpenoid, and a courmarin derivative, demonstrated temporal variations in their inhibitory activity. In contrast, P. radix (0.5 and 1.0 g/kg, i.d.) did not show a statistically significant antispasmodic effect in our study; however, we previously found that it had a significant antinociceptive effect.

Conclusions

Our findings show that SKT inhibits tetanic contractions in vivo and that G. radix is the main antispasmodic component due to the actions of its active constituents, thus supporting the traditional use of SKT. We further propose that SKT containing the antispasmodic G. radix and antinociceptive P. radix is a pharmaceutically elegant option for muscle cramps as treatment requires a two-pronged approach, i.e., inhibition of hyperexcitable skeletal tissues and modulation of the pain accompanying cramps.     

EEG and the Test for the Early Detection of Dementia with Discrimination from Depression (TE4D): a validation study

OBJECTIVE: The Test for the Early Detection of Dementia with Discrimination from Depression (TE4D) was developed as a screening instrument for mild dementia. We investigated the convergent validity of the TE4D to EEG and other psychometric tests in patients suffering from dementia and depression. METHOD: In 47 patients suffering from Alzheimer's disease (ICD-10 F.00) and 16 patients with affective disorders (F30-F39) the tests TE4D, ADAS-cog, SKT, BCRS, MMSE were performed and an EEG recorded. Group differences were compared by t-tests and a regression analysis was calculated. RESULTS: The inter-test-correlations varied between rs = 0.77 and rs = 0.91. Significant differences between the diagnostic groups were found for all tests as well as for the frequency bands alpha and beta. For the qEEG, significant positive correlations were found between TE4D (Dementia subscore) and the mean frequency (r = 0.47), the peak frequency (r = 0.42), the frequency bands alpha (r = 0.59) and beta (r = 0.56) as well as negative correlations in the frequency bands delta (r = -0.23) and theta (r = -0.42). The mean frequency and the activity in the frequency bands alpha, beta2, delta and theta contributed to the regression equation. The correlation between regression equation and the TE4D was rs = 0.87. The other tests also correlated with the TE4D: ADAS rs = -0.75, MMST rs = 0.82, SKT rs = -0.74, BCRS rs = -0.83. CONCLUSION: The TE4D showed convergent validity with the EEG parameters. Both the TE4D-score and the EEG-alterations correlated significantly with the degree of severity of Alzheimer's disease. This result underlines the assumption that the TE4D will be a useful instrument for the diagnostic process in dementia.     

Psychometric properties of Clock Drawing Test and MMSE or Short Performance Test (SKT) in dementia screening in a memory clinic population

OBJECTIVE: To evaluate five different scoring methods of the Clock Drawing Test (CDT) and to examine whether a combination of Mini Mental State Examination (MMSE) or Short Performance Test (Syndrom Kurz Test, SKT), respectively, with CDT can be used for cognitive screening. METHODS: Retrospective blinded analysis of clock drawing performance using five scoring methods (Shulman et al. (1986), Sunderland et al. (1989), Wolf-Klein et al. (1989), Watson et al. (1997), Manos (1997)). A Memory Clinic at an academic psychiatric hospital (University of Frankfurt am Main, Germany). 123 consecutive patients (79 dementia patients, 44 controls). Inter-rater reliability and correlation of five different scoring methods of the CDT with established psychometric tests. Sensitivity and specificity of all five CDT's using the original and modified cut-off scores. Sensitivity, specificity and positive and negative predictive value of a combination of the CDT with MMSE and SKT, respectively. RESULTS: All scoring methods of the CDT showed a highly significant interrater reliability (0.82 to 0.94). Correlation with the MMSE and the SKT was also significant (p < 0.01) for all five CDTs. Highest sensitivity was achieved by the Shulman scoring method (81% sensitivity, specificity 79%). Sensitivity of all scoring methods could be improved up to 89% by modifying the originally proposed cut-off scores at the cost of lower specificity. By combining the CDT with the MMSE or the SKT, respectively, the sensitivity of each of the tests could be improved to 92% (SKT and Shulman scale). In patients with mild dementia (GDS 3), a combination of the Shulman Scale with the SKT (92%) and the MMSE (75%) achieved the highest sensitivity. CONCLUSIONS: The CDT in combination with the MMSE or SKT is an easily administered, non threatening and highly sensitive screening test for dementia in the setting of a memory clinic.