Efficacy of Aquatic Treadmill Training on Gait Symmetry and Balance in Subacute Stroke Patients.

OBJECTIVE: To determine the efficacy of aquatic treadmill training (ATT) as a new modality for stroke rehabilitation, by assessing changes in gait symmetry, balance function, and subjective balance confidence for the paretic and non-paretic leg in stroke patients. METHODS: Twenty-one subacute stroke patients participated in 15 intervention sessions of aquatic treadmill training. The Comfortable 10-Meter Walk Test (CWT), spatiotemporal gait parameters, Berg Balance Scale (BBS), and Activities-specific Balance Confidence scale (ABC) were assessed pre- and post-interventions. RESULTS: From pre- to post-intervention, statistically significant improvements were observed in the CWT (0.471±0.21 to 0.558±0.23, p<0.001), BBS (39.66±8.63 to 43.80±5.21, p<0.001), and ABC (38.39±13.46 to 46.93±12.32, p<0.001). The step-length symmetry (1.017±0.25 to 0.990±0.19, p=0.720) and overall temporal symmetry (1.404±0.36 to 1.314±0.34, p=0.218) showed improvement without statistical significance. CONCLUSION: ATT improves the functional aspects of gait, including CWT, BBS and ABC, and spatiotemporal gait symmetry, though without statistical significance. Further studies are required to examine and compare the potential benefits of ATT as a new modality for stroke therapy, with other modalities.

Cyclooxygenase-2 inhibitors modulate skin aging in a catalytic activity-independent manner.

It has been proposed that the pro-inflammatory catalytic activity of cyclooxygenase-2 (COX-2) plays a key role in the aging process. However, it remains unclear whether the COX-2 activity is a causal factor for aging and whether COX-2 inhibitors could prevent aging. We here examined the effect of COX-2 inhibitors on aging in the intrinsic skin aging model of hairless mice. We observed that among two selective COX-2 inhibitors and one non-selective COX inhibitor studied, only NS-398 inhibited skin aging, while celecoxib and aspirin accelerated skin aging. In addition, NS-398 reduced the expression of p53 and p16, whereas celecoxib and aspirin enhanced their expression. We also found that the aging-modulating effect of the inhibitors is closely associated with the expression of type I procollagen and caveolin-1. These results suggest that pro-inflammatory catalytic activity of COX-2 is not a causal factor for aging at least in skin and that COX-2 inhibitors might modulate skin aging by regulating the expression of type I procollagen and caveolin-1.

Selective COX-2 inhibitors modulate cellular senescence in human dermal fibroblasts in a catalytic activity-independent manner.

It has been recently proposed that pro-inflammatory genes such as cyclooxygenase-2 (COX-2) play a key role in the aging process. However, it remains unclear whether the pro-inflammatory activity of COX-2 is involved in the aging process and whether COX-2 inhibitors prevent aging. We therefore examined the effect of COX-2 inhibitors on aging in the cellular senescence model of human dermal fibroblasts (HDFs). While the catalytic activity of COX-2 was observed to increase in the senescence process, we found that among three selective COX-2 inhibitors studied, only NS-398 inhibited the senescence whereas celecoxib and nimesulide accelerated the senescence. Non-selective COX inhibitors including aspirin, ibuprofen and flurbiprofen accelerated the senescence. The senescence-regulating effect of selective COX-2 inhibitors had no correlation with cellular reactive oxygen species levels, NF-kappaB activities or protein levels of p53 and p21. We instead found that selective COX-2 inhibitors regulate caveolin-1 expression at transcriptional levels, which was closely associated with the inhibitors' effect on the senescence. Collectively, these results suggest that COX-2 catalytic activity does not mediate HDF senescence and that selective COX-2 inhibitors modulate HDF senescence by a catalytic activity-independent mechanism.

Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide.

TLR2 in association with TLR1 or TLR6 plays an important role in the innate immune response by recognizing microbial lipoproteins and lipopeptides. Here we present the crystal structures of the human TLR1-TLR2-lipopeptide complex and of the mouse TLR2-lipopeptide complex. Binding of the tri-acylated lipopeptide, Pam(3)CSK(4), induced the formation of an "m" shaped heterodimer of the TLR1 and TLR2 ectodomains whereas binding of the di-acylated lipopeptide, Pam(2)CSK(4), did not. The three lipid chains of Pam(3)CSK(4) mediate the heterodimerization of the receptor; the two ester-bound lipid chains are inserted into a pocket in TLR2, while the amide-bound lipid chain is inserted into a hydrophobic channel in TLR1. An extensive hydrogen-bonding network, as well as hydrophobic interactions, between TLR1 and TLR2 further stabilize the heterodimer. We propose that formation of the TLR1-TLR2 heterodimer brings the intracellular TIR domains close to each other to promote dimerization and initiate signaling.

Serology of Chlamydia pneumoniae in patients with chronic cough.

OBJECTIVE AND BACKGROUND: Chronic cough is one of the more common respiratory symptoms. Controversy exists as to whether Chlamydia infection is associated with chronic cough. As such, the association of chronic cough with serological evidence of Chlamydia pneumoniae (C. P) infection and a systemic inflammatory marker was assessed. METHODS: Thirty-seven patients who visited Kangwon National University Hospital for chronic cough between September 2003 and August 2004 and 37 age-matched healthy controls were evaluated for C. P. antibodies and C-reactive protein. Chronic infection was defined as an IgG or IgA titre between 1:64 and 1:512, and acute infection was defined as IgM=1:16 or IgG titre of=1:512 or IgA=1:512. A nasopharyngeal swab was evaluated for C. P. DNA using the polymerase chain reaction. RESULTS: The median duration of cough was 3 months (1-240). Nineteen patients (49%) and 19 controls had titres consistent with chronic infection, and the titre difference was not significant (P=0.592). Nine patients and two controls had titres consistent with acute infection (24.3% vs. 5.4%). Acute infection was significantly more prevalent in the patients with chronic cough (P=0.023). There was no difference in the C-reactive protein value (0.13 vs. 0.14, P=0.84). Three patients were positive for C. P. DNA. CONCLUSION: Acute Chlamydia infection was more prevalent in patients with chronic cough, whereas chronic Chlamydia infection was not. There was no elevation of a systemic inflammatory marker in patients with chronic cough.

Seroprevalence of Coxiella burnetii infection in dairy cattle and non-symptomatic people for routine health screening in Korea.

We report results on the seroprevalence of antibodies to Coxiella burnetii in cattle and healthy people in Korea. Upon agreement with dairy owners, serum samples from 414 dairy cattle were collected between March and June 2001 and samples from 205 people for health screening were collected between April and December 2002. The sera were analyzed for the presence of anti-C. burnetii phase II antibodies using an indirect microimmunofluorescence test; strong fluorescence at a 1:32 dilution was regarded as positive. The overall seroprevalence of C. burnetii in cattle in Korea was 25.6%, with regional variation from 8.9 to 59.3%. Of the positive serum samples, 75.5% had antibody titers >or=1:256. By contrast, only 1.5% of people in a rural area were seropositive, and most of the positive samples had low antibody titers. In conclusion, this study showed that relatively high seropositivity of C. burnetii in dairy cattle, accordingly, the studies on the high-risk groups are needed to evaluate the seroprevalence for this organism in Korea.

Crystal structure of the BAFF-BAFF-R complex and its implications for receptor activation.

B-cell activating factor (BAFF) is a key regulator of B-lymphocyte development. Its biological role is mediated by the specific receptors BCMA, TACI and BAFF-R. We have determined the crystal structure of the extracellular domain of BAFF-R bound to BAFF at a resolution of 3.3 A. The cysteine-rich domain (CRD) of the BAFF-R extracellular domain adopts a beta-hairpin structure and binds to the virus-like BAFF cage in a 1:1 molar ratio. The conserved DxL motif of BAFF-R is located on the tip of the beta-turn and is indispensable in the binding of BAFF. The crystal structure shows that a unique dimeric contact occurs between the BAFF-R monomers in the virus-like cage complex. The extracellular domain of TACI contains two CRDs, both of which contain the DxL motif. Modeling of TACI-BAFF complex suggests that both CDRs simultaneously interact with the BAFF dimer in the virus-like cage.

Crystal structure of phosphodiesterase 4D and inhibitor complex(1).

Cyclic nucleotide phosphodiesterases (PDEs) regulate physiological processes by degrading intracellular second messengers, adenosine-3',5'-cyclic phosphate or guanosine-3',5'-cyclic phosphate. The first crystal structure of PDE4D catalytic domain and a bound inhibitor, zardaverine, was determined. Zardaverine binds to a highly conserved pocket that includes the catalytic metal binding site. Zardaverine fills only a portion of the active site pocket. More selective PDE4 inhibitors including rolipram, cilomilast and roflumilast have additional functional groups that can utilize the remaining empty space for increased binding energy and selectivity. In the crystal structure, the catalytic domain of PDE4D possesses an extensive dimerization interface containing residues that are highly conserved in PDE1, 3, 4, 8 and 9. Mutations of R358D or D322R among these interface residues prohibit dimerization of the PDE4D catalytic domain in solution.