Search

OBJECTIVE: To investigate the efficacy of adenovirus vector mediated transduction of heat shock protein 70 (HSP70) gene to human chondrocyte-like cell (HCS-2/8) against heat stress. METHODS: Two adenovirus vectors that contain wild-type (AxSHEwt) or mutant-type (AxSHEmt) HSP70 gene, and that are regulated by SRalpha promoter, were constructed. The mutant-type lacks the area that expresses stress durability. One of the 2 adenovirus vectors was added to the cultures of human chondrocyte-like cells (HCS-2/8). Heat stress (48 degrees C) was applied to the transduced cells for 2 h, and the efficacy of adenovirus vector mediated transduction of HSP70 gene against heat stress in the chondrocytes was investigated using alamar blue assay and MTT assay. RESULTS: Absorbance levels at 48 degrees C were 300.3 +/- 51.9 and 1.173 +/- 0.011 in the controls, 278.5 + 33.8 and 1.217 +/- 0.018 in the AxSHEmt transduced cells, and 349 +/- 14.7 and 1.371 +/- 0.033 in the AxSHEwt transduced cells. The level in the AxSHEwt transduced cells was significantly higher than in the other 2 groups (p < 0.05). With 37 degrees C treatment, no significant difference was observed. CONCLUSION: Chondrocytes to which HSP70 gene was transduced had a significantly higher metabolic activity and viability under heat stress.

We have studied the restoration of sensation in 24 patients after operations involving the digital nerves of the thumb. These comprised 10 neurorrhaphies, two nerve graftings, five replantations, one toe-to-thumb transfer and six neurovascular island flaps. The average follow-up period was 46 months. Greater sensitivity was found in the moving two-point discrimination (2PD) test than in the static 2PD test. The results of the Semmes-Weinstein test showed good correlation with the static 2PD test. Porter's letter test showed correlations with both 2PD tests, and the pulp-writing test showed good correlation with the moving 2PD test. The neurorrhaphy cases had the best results using the static 2PD and Semmes-Weinstein test, and had good restoration of sensation; the replantation cases were next best. After neurovascular island flaps, patients exhibited hypersensitivity, double sensation and distorted images on the pulp-writing test. Using this same test the nerve grafting cases had distorted touch perception and perceived a straight line as a curve. The pulp-writing test, using moving touch, is one method of examining mechanoreceptors and shows to what extent the patient perceives what touches the finger pulp; it gives a better indication of higher functions than the 2PD test.

The authors have treated 14 cases of spontaneous rupture of extensor pollicis longus tendon after fractures of the distal end of the radius, most of which were undisplaced or only slightly displaced. A microvascular study on five cadavers revealed that this tendon is subject to mechanical bending and attrition, has no mesotenon and has a poorly vascularised portion about 5 mm in length, which may be a cause of spontaneous rupture of the tendon.

Summary Objective:: Osteoarthritis (OA) is a debilitating disease of the joints. The joints of affected individuals are characterized by a progressive degeneration of articular cartilage leading to inflammation and pain. The expression of heat shock proteins (HSPs) is a ubiquitous self-protective mechanism of all cells under stress, furthermore, the synovium of osteoarthritic individuals contains high levels of cytokines. This study seeks to establish the role of HSPs and cytokines in OA. Methods:: We have investigated the presence of HSPs and cytokines in articular cartilage during early stages of OA in a mouse that is known to develop spontaneous OA lesions (C57 black mouse). The articular cartilage from closely related mice (C57BL/6) was used as control. Messenger RNAs (mRNAs) for HSPs (HSP32, HSP47, HSP60, HSP70, HSP84 and HSP86) and cytokines [interleukin-1@b (IL-1@b), interleukin-6 (IL-6), tumor necrosis factor-@a (TNF-@a) and interferon-@c (IFN-@c)] were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results:: The mRNA levels of HSP47, HSP70, HSP86, IL-6, and IFN-@c were up-regulated in the cartilage of C57 black mice, whereas, the level of expression of HSP32, HSP60, HSP84 and IL-1@b remained unchanged. Furthermore, the expression of IL-1@b, IL-6, TNF-@a and IFN-@c mRNA was associated with expression of HSP60, HSP47, HSP70 and HSP70/HSP86 mRNA, respectively. Conclusions:: The findings in this study suggest that chondrocytes are conditioned under non-physiological stress during early stages of OA, In addition, among HSPs, HSP70 was associated with two different highly expressed cytokines in C57 black mice, indicating the possible role of HSP70 as a characteristic indicator of early stage of OA.

We examined whether p.o. biological activities of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409), a spontaneous nitric oxide (NO) releaser, and the derivatives, i.e., (+/-)-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-5-nitro-3-hexenyl]-3 - pyridinecarboxamide (FR144420) and (+/-)-N-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-6-methyl-5- nitro-3-heptenyl]-3-pyridinecarboxamide (FR146801), could be accounted for by their NO-releasing rates and p.o. absorption manners. These compounds spontaneously released NO with the rates in the rank order of FK409 > FR144420 > FR146801. Total contribution of these drugs as NO donors in vivo was almost the same from the determination of urinary nitrite/nitrate (NOx) levels after p.o. administration of the compounds at 10 mg/kg to rats. Plasma NOx level after p.o. administration of FK409 at 10 mg/kg to rats reached maximal level at 120 min, and decreased gradually. On the other hand, plasma NOx levels time-dependently increased during 360 min after p.o. administration of FR144420 and FR146801 at the same dose. FK409 and FR144420 showed hypotensive effects immediately after p.o. administration at 10 mg/kg to rats, and the maximum response of FR144420 was less and the duration of the effect was longer than those of FK409, respectively. On the other hand, FR146801, which is most stable in solution, did not show any significant hypotensive effect during 240 min after p.o. administration at the same dose. In conclusion, the response and the duration of biological activity after p.o. administration of three spontaneous NO releasers can be closely accounted for by their NO-releasing rates and p.o. absorption manners.