PGE2 signal via EP2 receptors evoked by a selective agonist enhances regeneration of injured articular cartilage.

OBJECTIVE: The effect of the prostaglandin E2 (PGE2) signal through prostaglandin E receptor 2 (EP2) receptors on the repair of injured articular cartilage was investigated using a selective agonist for EP2. METHODS: Chondral and osteochondral defects were prepared on the rabbit femoral concave in both knee joints, and gelatin containing polylactic-co-glycolic acid microspheres conjugated with or without the EP2 agonist was placed nearby. Animals were sacrificed at 4 or 12 weeks post-operation, and regenerated cartilage tissues and subchondral structure remodeling were evaluated by histological scoring. The quality of regenerated tissues was also evaluated by the immunohistochemical staining of EP2, type II collagen, and proliferating cell nuclear antigen (PCNA). As an evaluation of side effects, the inflammatory reaction of the synovial membrane was analyzed based on histology and the mRNA expression of matrix metalloproteinase3 (MMP3), tissue inhibitor of metalloproteinase 3 (TIMP3), and interleukin-1 beta (IL-1 beta). Also, the activity of MMP3 and the amount of tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein in joint fluid were measured. RESULTS: In both models, the EP2 agonist enhanced the regeneration of the type II collagen-positive tissues containing EP2- and PCNA-positive chondrocytes, and the histological scale of regenerated tissue and subchondral bone was better than that of on the control side, particularly at 12 weeks post-operation. No inflammatory reaction in the synovial membrane was observed, and no induction of pro-inflammatory cytokines was found in joint fluid. CONCLUSION: Selective stimulation of the PGE2 signal through EP2 receptors by a specific agonist promoted regeneration of cartilage tissues with a physiological osteochondral boundary, suggesting the potential usefulness of this small molecule for the treatment of injured articular cartilages.

Laboratory-scale bioremediation of oil-contaminated soil of Kuwait with soil amendment materials.

A huge amount of oil-contaminated soil remains unremediated in the Kuwait desert. The contaminated oil has the potentiality to cause pollution of underground water and to effect the health of people in the neighborhood. In this study, laboratory scale bioremediation experiments were carried out. Hyponex (Hyponex, Inc.) and bark manure were added as basic nutrients for microorganisms, and twelve kinds of materials (baked diatomite, microporous glass, coconut charcoal, an oil-decomposing bacterial mixture (Formula X from Oppenheimer, Inc.), and eight kinds of surfactants) were applied to accelerate the biodegradation of oil hydrocarbons. 15% to 33% of the contaminated oil was decomposed during 43 weeks' incubation. Among the materials tested, coconut charcoal enhanced the biodegradation. On the contrary, the addition of an oil-decomposing bacterial mixture impeded the biodegradation. The effects of the other materials were very slight. The toxicity of the biodegraded compounds was estimated by the Ames test and the tea pollen tube growth test. Both of the hydrophobic (dichloromethane extracts) and hydrophilic (methanol extracts) fractions showed a very slight toxicity in the Ames test. In the tea pollen tube growth test, the hydrophobic fraction was not toxic and enhanced the growth of pollen tubes.

Molecular mechanism of angiotensin II type I and type II receptors in cardiac hypertrophy of spontaneously hypertensive rats.

We administered angiotensin (Ang) II receptor type 1 (AT1) blockade (losartan; 10 or 40 mg/kg per day), type II receptor (AT2) blockades (PD123319; 100 mg/kg per day), or angiotensin-converting enzyme (ACE) inhibitor (enalapril; 30 mg/kg per day) to spontaneously hypertensive rats (SHR) from 10 to 20 weeks of age. At the end of the treatment, high doses of losartan and enalapril significantly reduced the arterial systolic blood pressure compared with the untreated SHR to the level of WKY rats. But low doses of losartan and PD123319 were without effect. High doses of losartan and enalapril also significantly reduced both the left ventricular (LV) weight and the ratio of LV to body weight compared with the untreated SHR, which were still larger than that of WKY rats. However, the collagen concentration of SHR treated with high doses of losartan or enalapril was completely reduced to the level of WKY rats. Using reverse transcription polymerase chain reaction, we examined the mRNA expression for ACE, AT1, and AT2 in experimental animals. The enhanced AT1 mRNA expression was significantly decreased in the SHR treated with a high dose of losartan or PD123319 compared with the untreated SHR. The level of ACE mRNA was also decreased in the SHR treated with a high dose of losartan or enalapril. The level of AT2 mRNA was not significantly different between the Wistar-Kyoto rats and the SHR; however, this expression was decreased significantly after the treatment with a high dose of losartan or PD123319. These results indicate that AT1 receptor and ACE, but not AT2 receptor, play a crucial role in the remodeling of matrix tissue but a smaller role in the development of the hypertrophy of LV myocyte in SHR and that the LV/body weight changes do not fully account for the complete suppression of hypertension.

[Endoscopic treatment of early gastric cancer with laser and laserthermia using Nd : YAG laser].

As a therapeutic modality for early gastric cancer, endoscopic laser treatment is indicated in cases where the tumor is an intramucosal carcinoma, the macroscopic type is either I, IIa, or IIc(Ul(-)), and the diameter of the tumor is less than 10 mm. Type I tumors with less than 15 mm diameter and type IIa tumors with less than 20 mm diameter can be included in this indication. Depressed lesions should be treated carefully. Endoscopic laser treatment may be considered for patients who are not candidates for surgery or who refuse surgery.

Protective effect of teprenone on blood flow and incidence of histologic lesions in rat gastric mucosa after hemorrhage and retransfusion.

BACKGROUND: The effects of teprenone (6,10,14,18-tetramethyl-5,9,13, 17-nonadecatetraen-2-one) on changes in gastric mucosal blood flow, adenosine triphosphate (ATP) content, and incidence of histologic lesions were evaluated in rat gastric mucosa after hemorrhage and retransfusion. METHODS: Teprenone (100 mg/kg) was administered orally once a day for 3 consecutive days. On the 3rd day hemorrhage was induced, withdrawn blood (retransfusion) was returned, and the above variables were determined. RESULTS: Teprenone significantly inhibited the decreases in blood flow and index of mucosal oxygen saturation (ISO2) during hemorrhage in the corpus and antral mucosa. However, no effect of teprenone was observed on systemic blood pressure and ATP levels after hemorrhage and retransfusion. Teprenone significantly (p < 0.05) decreased both the incidence of ischemic lesions and the increase in the severity of lesions after retransfusion in both mucosal regions. CONCLUSION: From these results, it is concluded that the protective effect of teprenone on blood flow was partly responsible for its inhibitory effect on the incidence of lesions in the rat stomach in this hypovolemic shock model, although the former effect might be not a direct effect on systemic vascular tone.

[Metastatic liver cancer from the stomach successfully treated by combined immunochemotherapy and transarterial embolization].

A 53-year-old-man, who suffered from advanced gastric carcinoma with liver metastasis (P0H3S2N1; stage IV) underwent simple gastrectomy. After the operation, the patient was treated by chemotherapy (1/2 MFC, M: mitomycin C, F: FT-207, C: Cylocide) combined with immunotherapy (PSK, lentinan) and intraarterial injection (mitomycin C & Lipiodol). Liver metastases disappeared soon after the combined therapy, and these findings were confirmed by CT and US. Moreover, the serum level of CEA and CA 19-9 also decreased from 160 ng/ml and 51 U/ml to the normal level. The duration of the complete disappearance of the liver metastasis was not so long, but quality of life was well maintained for 2 and one half years. This case suggested that combined therapy may well be effective for advanced gastric cancer with liver metastases.