Inhibitory action of tranilast, an anti-allergic drug, on the release of cytokines and PGE2 from human monocytes-macrophages.

Tranilast, an anti-allergic drug that inhibits the release of substances such as histamine and prostaglandins from mast cells, has been reported to improve keloids and hypertrophic scars which originate from the abnormal proliferation and excessive collagen accumulation of fibroblasts. It has been considered that various chemical mediators produced by inflammatory cells play important roles in the development of keloids and hypertrophic scars. We therefore studied the effect of tranilast on the release of chemical mediators including transforming growth factor (TGF)-beta 1, interleukin (IL)-1 beta and prostaglandin (PG) E2 which are produced by the human monocytes-macrophages, and estimated whether these mediators induce collagen synthesis and cell proliferation of normal skin fibroblasts. Tranilast inhibited the release of TGF-beta 1, IL-1 beta and PGE2 from the human monocytes-macrophages. TGF-beta 1 (25-200 pM) enhanced the collagen synthesis by fibroblasts. IL-1 (0.1-1 U/ml) increased the proliferation and conversely decreased the collagen synthesis. PGE2 (2 micrograms/ml) enhanced the collagen synthesis. These results suggest that tranilast suppresses collagen synthesis by fibroblasts through inhibiting TGF-beta 1 and PGE2 production and cell proliferation by fibroblasts through inhibiting IL-1 production by inflammatory cells such as macrophages.     

Comparison of flow capacities of arterial and venous grafts for coronary artery bypass grafting: evaluation with exercise thallium-201 single-photon emission tomography

Stress thallium-201 tomography was performed to compare the flow capacities of arterial and saphenous vein grafts in patients with coronary artery bypass grafting (CABG). One hundred and seven consecutive patients (95 male and 12 female; mean age 58±9.1 years) underwent exercise-redistribution ²⁰¹Tl myocardial single-photon emission tomography 4–5 weeks after CABG. When a reversible perfusion defect was present in the area covered by a patent bypass graft, the flow capacity of the graft was defined as insufficient. Of all 285 grafts, 211 were considered as complete bypass. Reversible perfusion defects were present in 29 (27%) of 108 myocardial areas supplied by patent arterial grafts but in only 5 (5%) of 103 myocardial areas supplied by patent saphenous vein grafts (P<0.0001). In the LAD area reversible defects were observed in 22 of 82 areas covered by arterial grafts, in contrast to only 1 of 29 areas covered by venous grafts (P<0.01); in the RCA area reversible defects were observed in 7 of 17 and 4 of 41 areas respectively (P<0.01). There was no difference between the native coronary artery stenosis bypassed by patent arterial and venous grafts (88%±12% vs 86%±14% respectively, P=0.27). In conclusion, flow capacities during peak myocardial demand were more frequently insufficient in arterial bypass grafts than in saphenous vein grafts. Received 23 May and in revised form 7 August 1997     

Clinical statistics on inpatients admitted to the Department of Urology, Hyogo Prefectural Hospital Nishinomiya during 20 years from 1972 to 1991]

A statistic analysis was carried out on the 4,956 inpatients admitted to our Department of Urology from April 1972 to December 1991. The patients included 3,399 males and 1,557 females. A total of 4,105 operations including 255 renal allotransplantations were performed on 3,590 patients. Open surgery for upper urinary tract stones has been replaced by extracorporeal shock-wave lithotripsy (ESWL) in the last three years.     

Hamartoma of the parotid gland: A case report with immunohistochemical and electron microscopic study

Summary A case of a solid parotid tumour in a 16-year-old boy is presented. Histologically, the tumour demonstrated some peculiar findings. An acinar pattern was predominant although every component seen in the normal salivary gland was present, namely, serous and mucous gland acini, ducts, myoepithelial cells, adipose and lymphoid tissue. Large eosinophilic granules were abundant in the large acinar cell cytoplasm. Immunohistochemically, the tumour demonstrated the proteins which are present in the normal parotid gland, for example, amylase, lactoferrin and lysozyme. Electron microscopic features were quite similar to those of normal parotid tissue except for accumulation of a large number of cytoplasmic granules in the acinar cells. There has been no previous report of a tumour with the same features as seen in this case. Our pathological diagnosis is hamartoma, although the possibility of hyperplasia or neoplasia can not be excluded.     

Response of postapoplectic hemichorea/ballism to GPi pallidotomy: progressive improvement resulting in complete relief.

We report on a 66-year-old woman in whom GPi pallidotomy produced progressive and eventually complete relief of hemichorea/ballism (HCB) after a subthalamic hemorrhage. Although choreoballistic movements were unchanged during and immediately after the surgery, the symptoms were gradually improved and consequently abolished by 5 days postoperatively. HCB has never recurred up to the present (9 months follow-up period). This note is the first report describing detailed postsurgical process in HCB relief after pallidotomy.     

Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor).

CTGF/CCN2, a hypertrophic chondrocyte-specific gene product, possessed the ability to repair damaged articular cartilage in two animal models, which were experimental osteoarthritis and full-thickness defects of articular cartilage. These findings suggest that CTGF/CCN2 may be useful in regeneration of articular cartilage. INTRODUCTION: Connective tissue growth factor (CTGF)/CCN2 is a unique growth factor that stimulates the proliferation and differentiation, but not hypertrophy, of articular chondrocytes in vitro. The objective of this study was to investigate the therapeutic use of CTGF/CCN2. MATERIALS AND METHODS: The effects of recombinant CTGF/CCN2 (rCTGF/CCN2) on repair of damaged cartilage were evaluated by using both the monoiodoacetic acid (MIA)-induced experimental rat osteoarthritis (OA) model and full-thickness defects of rat articular cartilage in vivo. RESULTS: In the MIA-induced OA model, quantitative real-time RT-PCR assays showed a significant increase in the level of CTGF/CCN2 mRNA, and immunohistochemical analysis and in situ hybridization revealed that the clustered chondrocytes, in which clustering indicates an attempt to repair the damaged cartilage, produced CTGF/CCN2. Therefore, CTGF/CCN2 was suspected to play critical roles in cartilage repair. In fact, a single injection of rCTGF/CCN2 incorporated in gelatin hydrogel (rCTGF/CCN2-hydrogel) into the joint cavity of MIA-induced OA model rats repaired their articular cartilage to the extent that it became histologically similar to normal articular cartilage. Next, to examine the effect of rCTGF/CCN2 on the repair of articular cartilage, we created defects (2 mm in diameter) on the surface of articular cartilage in situ and implanted rCTGF/CCN2-hydrogel or PBS-hydrogel therein with collagen sponge. In the group implanted with rCTGF/CCN2-hydrogel collagen, new cartilage filled the defect 4 weeks postoperatively. In contrast, only soft tissue repair occurred when the PBS-hydrogel collagen was implanted. Consistent with these in vivo effects, rCTGF/CCN2 enhanced type II collagen and aggrecan mRNA expression in mouse bone marrow-derived stromal cells and induced chondrogenesis in vitro. CONCLUSION: These findings suggest the utility of CTGF/CCN2 in the regeneration of articular cartilage.     

Effect of lactate and bicarbonate on human peritoneal mesothelial cells, fibroblasts and vascular endothelial cells, and the role of basic fibroblast growth factor.

BACKGROUND: In patients on long-term continuous ambulatory peritoneal dialysis (CAPD), peritoneal dysfunction may occur due to loss of peritoneal mesothelial cells, peritoneal fibrosis and neovascularization. Lactate, long used as a buffer in peritoneal dialysates, has been substituted by bicarbonate in recent years. However, their effects on the peritoneum of CAPD patients are unknown. This study investigated the influence of lactate and bicarbonate on peritoneal dysfunction in CAPD patients. METHODS: The mitochondrial activity of human peritoneal mesothelial cells (HPMCs) and their expression of basic fibroblast growth factor (bFGF) were studied after culture under various conditions. We also assessed the mitochondrial-activating effect of the supernatant of those cultures on human peritoneal fibroblasts (HPFBs) and human umbilical vein endothelial cells (HUVECs) and the effect of recombinant human bFGF on the mitochondrial activity of HPFBs and HUVECs. We used the WST-1 assay to determine mitochondrial activity in HPMC. RESULTS: At pH 7.4, the mitochondrial activity of HPMCs was lowest in a medium containing 40 mM (Lac), intermediate in a lactate (15 mM) plus bicarbonate (25 mM) medium (Lac/Bic), and highest in a 40 mM bicarbonate medium (Bic). In culture supernatant, the increase of bFGF was: Lac > Lac/Bic > Bic. Mitochondrial activation of HPFBs and HUVECs was stimulated by HPMC culture supernatants in the following decreasing order: Lac > Lac/Bic > Bic. The effects of these supernatants were suppressed by a bFGF-neutralizing antibody, while recombinant bFGF caused concentration-dependent mitochondrial activation in HPFBs and HUVECs. CONCLUSIONS: The role of bFGF in peritoneal fibrosis and neovascularization may be important. A bicarbonate-containing medium is better than a lactate-containing medium for preserving cell viability in HPMCs and preventing bFGF expression by these cells.     

Mapping of odor-related neuronal activity using a fluorescent derivative of glucose

Activity labeling was applied to the olfactory systems of the terrestrial slug Limax valentianus using 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), a fluorescent derivative of glucose. 2-NBDG was incorporated into cultured Limax olfactory interneurons, and this was partially blocked by the presence of a high concentration of glucose in the medium, indicating that a part of the uptake of 2-NBDG is mediated by glucose transporters. Next, in order to map odor-related neuronal activity in the primary olfactory center, tentacular ganglion, we injected 2-NBDG into the body cavities of slugs and exposed them to odors or clean air (control). In the odor-stimulated animals, the cell mass region was strongly stained. The digit-like extensions and the neuropil region were also stained in some animals. The control animals showed no staining. The neurons in the cell mass are thought to be involved in generating oscillating activities in the tentacular ganglion, and their activation may imply modulation of oscillatory activity during odor processing. Our results show that 2-NBDG is useful for mapping neuronal activity in vivo.     

Calorie restriction increases serum parathyroid hormone and decreases serum calcitonin levels in patients with maturity onset diabetes mellitus

Calorie restriction is important in managing patients with maturity onset diabetes mellitus (NIDDM). The effect of such restriction on calcium metabolism is not known. The objective of this study was to determine whether patients on calorie restricted diets would show any modification of parathyroid hormone (PTH) and calcitonin (CTN). The serum levels of PTH and CTN were measured by radioimmunoassays in 269 patients with NIDDM. The patients were divided into two groups depending on the intake of calorie, and PTH and CTN were monitored for 2 years. Plasma levels of vitamin D were measured by competitive protein binding assays before and after each program. The level of PTH (520.8±266.0 pg/ml) (mean±S.D.) was significantly (P<0.01) higher in 109 diabetic patients whose calorie intake was restricted for 2 years (diet (D) group) as compared with that (256.6±103.8 pg/ml) of 160 diabetic patients whose calorie intake was not restricted (non-diet (ND) group). The daily oral calcium intake of the two groups did not differ significantly. We found no significant difference in the serum PTH level in the ND groupVS. normal control subjects (248.8±98.4, N=78). The serum calcium concentration and the amount of calcium excreted in urine were slightly but significantly (P<0.01) lower in the D than in the ND group. The rate of tubular reabsorption of phosphate (% TRP) was significantly lower in the D group than that in the ND group (P<0.01). The serum CTN level was significantly (P<0.01) lower in the D group (33.9±11.3 pg/ml) than in the ND group (64.9±21.2 pg/ml) 2 years after each treatment. The plasma 1,25-(OH)₂-vitamin D level was significantly (P<0.01) lower in the D group (22.2±6.6 pg/ml) than in the ND group (50.6±4.2 pg/ml). When the restriction of calorie intake in the D group was canceled, their PTH levels decreased, which was accompanied by increase in the 1,25-(OH)₂-vitamin D levels, whereas their CTN levels were unchanged. These observations suggested that a restricted calorie intake is a risk factor for secondary hyperparathyroidism as well as for a low serum level of CTN in patients with NIDDM.