The relationship of VEGF and PGE2 expression to extracellular matrix remodelling of the tenosynovium in the carpal tunnel syndrome

Tenosynovial thickening within the confined space of the carpal tunnel is thought to be the cause of the carpal tunnel syndrome (CTS). However, little is known about the pathological mechanism of tenosynovial thickening. In this study, the role of prostaglandin E(2) (PGE(2)) and vascular endothelial growth factor (VEGF) (two representative molecules that can induce oedema by increasing vascular permeability) was analysed in CTS by using immunohistochemistry and enzyme-linked immunosorptive assay (ELISA). Expression of these molecules was compared with the patients' clinical histories and a temporary increase in production of these molecules was found in cells within the vessels and synovial lining during the intermediate phase of the syndrome when the histology of the tenosynovium changes from oedematous to fibrotic. Statistical analysis clearly demonstrated that there is a close correlation between the expression of PGE(2) and VEGF. Furthermore, immunohistochemical analysis with anti-proliferating cell nuclear antigen (PCNA) revealed that the area with distinct VEGF expression closely matched the area where endothelial cells, vascular smooth muscle cells, and synovial lining cells proliferate. In contrast, despite marked alteration in the extracellular matrix (ECM) component of the tenosynovium, the fibroblasts responsible for most ECM framework production do not proliferate during any phase of CTS. Histological analysis demonstrated that angiogenesis takes place only during the intermediate phase. Since clusters of capillaries and arterioles are often surrounded by type III collagen-rich, disorganized, degenerate connective tissue, which contains fewer fibroblasts than normal, angiogenesis appears to take place as a part of a regenerative reaction that results in fibrosis. These findings strongly indicate that both PGE(2) and VEGF are expressed in the tenosynovium in CTS during the intermediate phase and induce the histological changes seen in the tenosynovium.     

Ultraviolet B induces mast cell apoptosis: a hypothetical mechanism of ultraviolet B treatment for uraemic pruritus.

The pathogenesis of uraemic pruritus is unclear, although there is some evidence that an increased number of skin-infiltrating mast cells may play a role. Ultraviolet B reduces itchy sensation of uraemic patients by leading to depletion of cutaneous mast cells. This study presents data that both broad-band and narrow-band ultraviolet B irradiation are able to induce apoptosis in transformed mast cells (murine mastocytoma cell line P815) in a dose-dependent manner at a time point of 24 hours. The positive apoptotic rates were as follows: sham-exposed cells (controls) -- 13.3% +/- 0.6%; with broad-band ultraviolet B irradiation -24.5% +/- 1.1% with 10mJ/cm(2), 57.9% +/- 4.6% with 20mJ/cm(2) and 70.9% +/- 4.5% with 30mJ/cm(2); with narrow-band ultraviolet B irradiation -- 29.6% +/- 2.3% with 100mJ/cm(2), 57.3% +/- 4.1% with 200mJ/cm(2) and 81.5% +/- 1.9% with 300mJ/cm(2). The difference between the number of apoptotic cells in all groups of ultraviolet B-irradiated cells and sham-exposed cells was highly significant (P<0.001). Based on these findings, it is hypothesized that ultraviolet B induced mast cell apoptosis could be an important factor in phototherapy for the diseases dependent on increased number of cutaneous mast cells, including uraemic pruritus.     

Protective role of heme oxygenase-1 in renal ischemia

Oxidative stress, which has been implicated in the pathogenesis of ischemic renal injury, degrades heme proteins, such as cytochrome P450, and causes the elevation in the level of cellular free heme, which can catalyze the formation of reactive oxygen species. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is induced not only by its substrate, heme, but also by oxidative stress. In various models of oxidative tissue injuries, the induction of HO-1 confers protection on tissues from further damages by removing the prooxidant heme, or by virtue of the antioxidative, antiinflammatory, and/or antiapoptotic actions of one or more of the three products, i.e., carbon monoxide, biliverdin IXalpha, and iron by HO reaction. In contrast, the abrogation of HO-1 induction, or chemical inhibition of HO activity, abolishes its beneficial effect on the protection of tissues from oxidative damages. In this article, we review the protective role of HO-1 in renal ischemic injury, and its potential therapeutic applications. In addition, we summarize recent findings in the regulatory mechanism of ho-1 gene expression.     

In vivo release of cisplatin from a needle-type copolymer formulation implanted in rat kidney

Cisplatin, cis-dichlorodiamine platinum (II), was incorporated in a needle-type copolymer formulation (0.8 mm diameter, 6 mm long) by radiation-induced polymerization. The copolymer used was copoly(diethylene glycol dimethacrylate/polyethylene glycol #600 dimethacrylate, 80/20 vol%). This copolymer, containing 6 mg of cisplatin, was implanted into the kidney of adult male Wistar rats (420 +/- 20 g). A total of 70 d was required for 100% release of cisplatin in vivo. The kidney tissue surrounding the formulation was strongly necrotized by the action of cisplatin. Two layers of necrosis could be distinguished: necrotic tissue surrounding the formulation and necrobiotic tissue surrounding the necrotic tissue. The amount of necrotic tissue changed markedly over time, but no change was apparent in the amount of necrobiotic tissue. The maximal amounts of necrotized tissue were observed 14 d after implantation: 3100 microns and 600 microns thick for the necrotic and necrobiotic tissues, respectively.     

Responsiveness of the ANP providing system to volume load in conscious dogs

We examined in detail changes in arterial plasma ANP concentration in response to volume load in conscious dogs. In a 5-min volume load experiment, 18 ml/kg of isosmotic and isooncotic 3% Dextran 40 in saline was infused over a period of 5 min. Mean left atrial pressure (MLAP) increased transiently by 7.6±0.9 mm Hg. Plasma ANP level (P-ANP) did not significantly increase. Assayed P-ANP levels were corrected for hemodilution. Corrected P-ANP (C-ANP) significantly increased from 206±17 to 348±34 pg/ml. However, the level of C-ANP did not reach a steady state. No significant linear correlation was found between increases in MLAP and normalized C-ANP. In a 45-min volume load experiment, the elevated level of MLAP caused by the 5-min volume load was maintained for 40 min by supplemental infusion. C-ANP significantly increased from 196±18 pg/ml to 435±73 ng/ml. The level of C-ANP reached a steady state. A close linear correlation was observed between increases in MLAP and normalized C-ANP. However, the peak time of C-ANP lagged 10 min behind MLAP. These results indicate that it takes 10 min for P-ANP to reach a steady state in fully responding to a volume load, and that the long-term volume load is a prerequisite to the response of the ANP providing system.     

Isolation,characterization and chromosomal mapping of an actin gene from the primitive red alga Cyanidioschyzon merolae

Based on the results of cytological studies, it has been assumed that Cyanidioschyzon merolae does not contain actin genes. However, Southern hybridization of C. merolae cell-nuclear DNA with a yeast actin-gene probe has suggested the presence of an actin gene in the C. merolae genome. In the present study, an actin gene was isolated from a C. merolae genomic library using a yeast actin-gene probe. The C. merolae actin gene has no intron. The predicted actin is composed of 377 amino acids and has an estimated molecular mass of 42003 Da. Southern hybridization indicated that the C. merolae genome contains only one actin gene. This gene is transcribed at a size of 2.4 kb. When Southern hybridization was performed with C. merolae chromosomes separated by pulsed-field gel electrophoresis, a band appeared on unseparated chromosomes XI and XII. A phylogenetic tree based on known eucaryote actin-gene sequences revealed that C. merolae diverged after the division of Protozoa, but before the division of Fungi, Animalia and Chlorophyta.     

Dissociation between changes in renal nerve activity and renal vascular resistance in conscious dogs

The effects of acute volume expansion and hemorrhage on renal nerve activity and renal vascular resistance were examined in chronically instrumented conscious dogs. In six conscious dogs, when the blood volume was expanded by 18 ml/kg, the mean arterial pressure increased by 14 +/- 3 mmHg, mean left atrial pressure increased by 5.3 +/- 0.7 mmHg, and renal nerve activity decreased by 87 +/- 3%, while the renal blood flow was not altered significantly and renal vasoconstriction occurred, i.e., the calculated renal vascular resistance increased by 12 +/- 4% from 0.49 +/- 0.05 mmHg/ml/min. Volume depletion, induced by 20 ml/kg hemorrhage, did not alter the mean arterial pressure (-4 +/- 6 mmHg), while it decreased the mean left atrial pressure by 4.0 +/- 0.7 mmHg and increased the renal nerve activity by 200 +/- 67%. However, the renal blood flow was well maintained at the pre-hemorrhagic control level and renal vasoconstriction did not occur. Thus, in conscious dogs, acute volume changes altered the renal nerve activity dramatically, but these changes in renal nerve activity did not exert any significant effects on renal vascular resistance.