Risk factors for dental findings of the development of medication-related osteonecrosis of the jaw: Investigation of 3734 teeth in cancer patients receiving high dose antiresorptive agents.

Background/purpose: Local infection is a risk factor for medication-related osteonecrosis of the jaw (MRONJ), along with invasive dental treatment of the bone; the tooth that is the source of infection should be extracted prior to the administration of bone resorption inhibitors. However, which teeth should be extracted remains unclear. This study aimed to determine the relationship between dental findings prior to high-dose antiresorptive agent (ARA) administration and the subsequent development of MRONJ. Materials and methods: Patients with cancer who were scheduled to receive high-dose ARAs and referred to our hospital between 2011 and 2020 were included in this retrospective study. Apical lesions, enlargement of the periodontal space, thickening of the lamina dura, alveolar bone resorption of >1/3, periapical osteosclerosis, and local infection symptoms in each tooth were investigated using medical records and panoramic radiographs. Results: A total of 172 patients, 329 jaws, and 3734 teeth were registered. MRONJ developed in 68 teeth in 33 jaws of 32 patients. In tooth-by-tooth analysis, fewer teeth (P < 0.001), apical lesions (P < 0.001), periapical osteosclerosis (P < 0.001), local infection symptoms (P = 0.002), and one or more dental findings (P < 0.001) were significant factors for MRONJ development. In jaw-by-jaw analysis, old age, local infection symptoms, and number of radiographic abnormalities per tooth were significant. In patient-by-patient analysis, patients with diabetes and those with fewer teeth developed MRONJ. Conclusion: Patients with fewer teeth, apical lesions, periapical osteosclerosis, and local infection were more likely to develop MRONJ. Therefore, these teeth should be treated as much as possible before ARA administration.

Essential oil composition of Curcuma species and drugs from Asia analyzed by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry.

Essential oils (EOs) comprised of various bioactive compounds have been widely detected in the Curcuma species. Due to the widespread distribution and misidentification of Curcuma species and differences in processing methods, inconsistent reports on major compounds in rhizomes of the same species from different geographical regions are not uncommon. This inconsistency leads to confusion and inaccuracy in compound detection of each species and also hinders comparative study based on EO compositions. The present study aimed to characterize EO compositions of 12 Curcuma species, as well as to detect the compositional variation among different species, and between the plant specimens and their related genetically validated crude drug samples using headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry. The plant specimens of the same species showed similar EO patterns, regardless of introducing from different geographical sources. Based on the similarity of EO compositions, all the specimens and samples were separated into eight main groups: C. longa; C. phaeocaulis, C. aeruginosa and C. zedoaria; C. zanthorrhiza; C. aromatica and C. wenyujin; C. kwangsiensis; C. amada and C. mangga; C. petiolata; C. comosa. From EOs of all the specimens and samples, 54 major compounds were identified, and the eight groups were chemically characterized. Most of the major compounds detected in plant specimens were also observed in crude drug samples, although a few compounds converted or degraded due to processing procedures or over time. Orthogonal partial least squares-discriminant analysis allowed the marker compounds to discriminate each group or each species to be identified.

Nintedanib-Induced Renal Thrombotic Microangiopathy.

Nintedanib is a unique tyrosine kinase inhibitor used to suppress fibrosis in patients with idiopathic pulmonary fibrosis (IPF). Nintedanib has been shown to suppress multiple processes of fibrosis, thereby reducing the rate of lung function decline in patients with IPF. Since vascular endothelial growth factor is one of this agent's targets, nephrotoxicity, including renal thrombotic microangiopathy (TMA), is a possible major adverse effect. However, only 2 previous cases of nintedanib-induced renal TMA have been published. Our patient was an 83-year-old man with IPF. As adverse effects including liver enzyme level elevation, diarrhoea, anorexia, and nephrotoxicity developed, the nintedanib dosage was reduced after 9 months. The digestive symptoms resolved promptly, but the proteinuria and reduced kidney function remained. Although the kidney injury had improved to some extent, we performed a percutaneous renal biopsy. The biopsy revealed typical TMA findings such as microaneurysms filled with pale material, segmental double contours of glomerular basement membranes, and intracapillary foam cells. After discontinuation of nintedanib, the patient's nephrotoxicity improved. Nintedanib-induced renal TMA is reversible and is possibly dose-dependent. Here, we report the clinical course of our case and review the characteristics of nintedanib-induced renal TMA.

Semi-fixed versus fixed oral appliance therapy for obstructive sleep apnea: A randomized crossover pilot study.

BACKGROUND/PURPOSE: Although mandibular advancement oral appliances (OAs) are the most widely used and accepted therapeutic modality for obstructive sleep apnea (OSA), whether these maxillary and mandibular appliances should be semi-fixed or fixed remains uncertain. This randomized crossover pilot study compared the efficacy, side effects, and patient preference of semi-fixed and fixed OAs for the treatment of OSA. MATERIALS AND METHODS: Patients with mild to moderate OSA were recruited and randomly assigned to either the semi-fixed or fixed OA group, whereby they used their assigned OA for the first 4 weeks, followed by assessments for sleep parameters (including the Apnea-Hypopnea Index [AHI]) and temporomandibular joint pain as a side effect. After a two-week washout period, patients were switched to the alternative OA for 4 weeks, followed by repeated assessments. Patient preference was assessed at the end of the completed treatment period. RESULTS: Fifteen patients were enrolled and completed the full study protocol. Both types of OAs were efficient in reducing the patient's AHI in comparison to baseline (i.e., without OA). However, there was no significant difference in AHI reduction between the semi-fixed and fixed OA devices. Regarding the side effect of temporomandibular joint pain and patient preference, the semi-fixed OA device was superior to the fixed OA device on both measures. CONCLUSION: While both semi-fixed and fixed OAs are effective in treating patients with OSA, semi-fixed OAs are superior in regards to both patient preference and reduced side effects. Thus, semi-fixed OAs may be the preferred therapeutic modality for OSA.

PolyIC Induces Retinoic Acid-inducible Gene-I and Melanoma Differentiation-associated Gene 5 and Modulates Inflammation in Podocytes.

BACKGROUND/AIM: Viral infection often exacerbates proteinuria, which has been suggested to be due to antiviral responses of podocytes. We examined the effect of polyinosinic-polycytidylic acid (polyIC) on the expression of retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) in differentiated human podocytes in culture. MATERIALS AND METHODS: The podocytes were treated with 2 ng/ml to 500 µg/ml of polyIC for 3 to 36 h, and also transfected with siRNA against RIG-I and MDA5. F-actin staining was performed to assess actin reorganization. RESULTS: PolyIC induced the expression of RIG-I and MDA5 in dose- and time-dependent manner, accompanied with interferon-ß (IFN-ß) and interleukin-6 (IL-6) up-regulation and actin reorganization. Temporal knockdown of RIG-I by siRNA decreased IFN-ß expression, while MDA5 siRNA inhibited IFN-ß and IL-6 expression. Actin reorganization was attenuated by RIG-I and MDA5 knockdown. CONCLUSION: RIG-I and MDA5 may play a role in the antiviral responses of podocytes.

Successful Resuscitation of a Patient with Life-Threatening Metabolic Acidosis by Hemodialysis: A Case of Ethylene Glycol Intoxication.

BACKGROUND: Ethylene glycol intoxication causes severe metabolic acidosis and acute kidney injury. Fomepizole has become available as its antidote. Nevertheless, a prompt diagnosis is not easy because patients are often unconscious. Here we present a case of ethylene glycol intoxication who successfully recovered with prompt hemodialysis. CASE PRESENTATION: A 52-year-old Japanese male was admitted to a local hospital due to suspected food poisoning. The patient presented with nausea and vomiting, but his condition rapidly deteriorated, with worsening conscious level, respiratory distress requiring mechanical ventilation, hypotension, and severe acute kidney injury. He was transferred to the university hospital; hemodialysis was initiated because of hyperkalemia and severe metabolic acidosis. On recovering consciousness, he admitted having ingested antifreeze solution. Thirty-seven days after admission, the patient was discharged without requiring HD. CONCLUSIONS: We reported a case of ethylene glycol intoxication who presented with a life-threatening metabolic acidosis. In a state of severe circulatory shock requiring catecholamines, hemodialysis should be avoided, and continuous hemodiafiltration may be a preferred approach. However, one should be aware of the possibility of intoxication by unknown causes, and hemodialysis could be life-saving with its superior ability to remove toxic materials in such cases.

Daclatasvir/asunaprevir based direct-acting antiviral therapy ameliorate hepatitis C virus-associated cryoglobulinemic membranoproliferative glomerulonephritis: a case report.

BACKGROUND: Direct-acting antivirals (DAAs) dramatically improve the treatment of hepatitis C virus (HCV) infections. However, the effects of DAAs on extra-hepatic manifestations such as HCV-associated glomerulonephritis, especially in cases with renal dysfunction, are not well elucidated. CASE PRESENTATION: A 69-year-old Japanese woman was diagnosed as having chronic hepatitis C, genotype 1b at the age of 55. She presented with hypertension, microscopic hematuria, proteinuria, renal dysfunction, purpura, and arthralgia at the age of 61. She also had hypocomplementemia and cryoglobulinemia. Renal biopsy revealed membranoproliferative glomerulonephritis (MPGN), and she was diagnosed as having HCV-associated cryoglobulinemic MPGN. She declined interferon therapy at the time and was treated with antihypertensive medications as well as oral corticosteroid that were effective in reducing proteinuria. However, when the corticosteroid dose was reduced, proteinuria worsened. She began antiviral treatment with daclatasvir/asunaprevir (DCV/ASV). Clearance of HCV-RNA was obtained by 2 weeks and sustained, and liver function was normalized. In addition, microhematuria turned negative, proteinuria decreased, hypocomplementemia and estimated glomerular filtration rate were improved, whereas cryoglobulinemia persisted. She completed 24 weeks of therapy without significant adverse effects. CONCLUSION: In a case of HCV-associated cryoglobulinemic MPGN with renal dysfunction, DCV/ASV -based DAAs ameliorated microhematuria, proteinuria and renal function without significant side effects.

NF-κB-dependent increase in tissue factor expression is responsible for hypoxic podocyte injury.

BACKGROUND: Fibrin deposition within glomeruli is commonly seen in kidney biopsy specimens, suggesting enhanced coagulant activity. Tissue factor (TF) is a coagulation factor which is also related to various biological effects, and TF is upregulated by hypoxia in cancer cells. Recently, hypoxic podocyte injury has been proposed, therefore, we investigated TF expression in hypoxia. METHODS: Conditionally immortalized human podocytes were differentiated and treated under hypoxic or normoxic conditions. mRNA expressions of TF and tissue factor pathway inhibitor (TFPI) were analyzed by quantitative RT-PCR. Protein levels of TF and TFPI were tested by enzyme-linked immunosorbent assay. We employed small interfering RNA (siRNA) to temporary knockdown early growth response protein 1 (Egr-1), hypoxia-inducible factor-1α (HIF-1α) and TF. The expression of CD2-associated protein (CD2AP) mRNA and phalloidin staining was examined to assess podocyte injury. RESULTS: Hypoxia increased mRNA expression of TF (6 h: 2.3 ± 0.05 fold, p < 0.001, 24 h: 5.6 ± 2.4 fold, p < 0.05) and suppressed TFPI (6 h: 0.54 ± 0.04 fold, p < 0.05, 24 h: 0.24 ± 0.06 fold, p < 0.001) compared with normoxia. Similarly, protein levels of TF were increased and TFPI were decreased. Egr-1 siRNA did not change TF mRNA expression. Pyrrolidine dithiocarbamate (PDTC), a nuclear factor kappa B (NF-κB) inhibitor, significantly reduced hypoxia induced TF expression, and HIF-1α knockdown further increased TF. Hypoxia resulted in decreased CD2AP and actin reorganization in podocytes, and these changes were attenuated by TF siRNA. CONCLUSION: Hypoxia increased the expression of TF in human podocytes NF-κB dependently. TF may have a critical role in the hypoxic podocyte injury.

A case of membranoproliferative glomerulonephritis associated with curved fibril deposition.

BACKGROUND: It is sometimes challenging to diagnose unsusual cases of fibrillary glomerulonephritis (FGN) and immunotactoid glomerulopathy (ITG), the rare causes of nephrotic syndrome. CASE PRESENTATION: A 75-year-old Japanese woman presented with nephrotic syndrome, microhematuria and renal insufficiency. Renal biopsy revealed membranoproliferative glomerulonephritis (MPGN) with IgM and weak C3 deposition. Congo red stain was negative. Electron microscopy demonstrated massive fibrils in the subendothelium, mesangium and subepithelium. The fibrils were partially parallel, partially curved and 17 nm in diameter. Cryoglobulin, hepatitis B virus (HBV) antigen, hepatitis C virus (HCV) antibody or antinuclear antibody were negative. CONCLUSION: We report a case of MPGN associated with peculiar non-amyloid fibril deposition corresponding to neither FGN nor ITG.

A case of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis and concurrent membranous nephropathy.

BACKGROUND: Myeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (MPO-ANCA-GN) and concurrent membranous nephropathy (MN) are very rare combination. Their causal relationship has been suggested, but not determined. CASE PRESENTATION: A 73-years-old male with 5-year history of proteinuria underwent an operation for his sigmoid colon cancer. Seven months later, he was referred to a nephrology division due to an exacerbating renal function and hypoalbuminemia. Laboratory examination revealed positive MPO-ANCA in the serum. A renal biopsy revealed a necrotizing extracapillary proliferative glomerulonephritis with crescents, demonstrating MPO-ANCA-GN. Whereas, immunofluorescent staining documented granular deposition of immumoglobulin (Ig) G and C3 along the capillary wall and electron microscopy showed subepithelial deposits in the glomerular basement membrane demonstrating MN. Immunofluorescent staining of IgG subclass showed positive IgG1, IgG2, negative IgG3 and weak positive IgG4 suggested the possibility of malignancy-associated MN. CONCLUSION: Combination of MPO-ANCA-GN and MN are rare. Although the causal relationship has been suggested in some cases, we should consider all the possibilities including idiopathic MN and secondary MN associated with malignancy, drug use or infection.

Mizoribine suppresses proliferation of rat glomerular epithelial cells in culture and inhibits increase of monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 stimulated by thrombin.

Glomerular crescents play an important role in progressive glomerular injury. The lesions consist of epithelial cells, macrophages and fibrin deposition. Macrophage chemoattractant protin-1 (MCP-1) is a chemoattractant of monocytes, which has a potential of procoagulant activity. Macrophage inflammatory protein-2 (MIP-2) is a chemoattractant of neutrophils and acute necrotizing injury is primarily mediated by neutrophils in crescentic glomerulonephritis. Mizoribine (MZR) is an immunosuppressive drug and it has been used for organ transplantation and treatment of various autoimmune diseases. The aim of this study is to investigate the effects of MZR on glomerular epithelial cells (GEC). Rat GEC were cultured with K1 medium and used from 12th to 14th passage. GEC proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MCP-1 and MIP-2 were quantified by enzyme-linked immunosorbent assay (ELISA) in culture supernatants and mRNA expressions of MCP-1 and MIP-2 were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The proliferation of GEC was suppressed by MZR in a dose-dependent manner in the range of 1.0-100.0 µg/mL. These concentrations of MZR had no toxic effect to GEC. Thrombin (1.0-5.0 U/mL) enhanced the production of MCP-1, MIP-2 and the mRNA expressions of MCP-1 and MIP-2. The stimulatory effect of thrombin was inhibited by addition of MZR (10 µg/mL). It is concluded that MZR may be useful for the treatment of crescentic glomerulonephritis.

Thrombin stimulates synthesis of macrophage colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor by human proximal tubular epithelial cells in culture.

BACKGROUND/AIMS: Colony-stimulating factors (CSFs) are well-known hematopoietic growth factors. Although recent studies revealed that CSFs are involved in many inflammatory conditions, the local production of CSFs and its regulation in the kidney is not well elucidated. Therefore, using cultured human proximal tubular epithelial cells (PTEC), we examined the effect of thrombin on CSFs production, since thrombin has been suggested to play an important role in tubulointerstitial injury. METHODS: PTEC were incubated with thrombin (0.5-5.0 U/ml) and the effects on the production of macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF) were measured in the cell supernatant by enzyme-linked immunosorbent assay, and the expressions of mRNA were analyzed by quantitative real-time reverse transcription polymerase chain reaction. Using argatroban, a direct thrombin inhibitor, we also examined the specific effect of thrombin. RESULTS: Thrombin 5.0 U/ml significantly stimulated the production of M-CSF (p < 0.01) and G-CSF (p < 0.01), and 1.0 and 5.0 U/ml thrombin significantly stimulated GM-CSF (p < 0.02 and p < 0.01) in a dose-dependent manner. Thrombin 5.0 U/ml increased CSFs (M-CSF, p < 0.005; GM-CSF, p < 0.0005; G-CSF, p < 0.005) in a time-dependent manner. Thrombin also significantly enhanced the mRNA expressions of M-CSF (p < 0.01), GM-CSF (p < 0.05) and G-CSF (p < 0.01). These effects of thrombin were significantly reduced by the addition of argatroban (M-CSF, p < 0.01; GM-CSF, p < 0.01; G-CSF, p < 0.05). CONCLUSION: We demonstrated that thrombin significantly increased the production of CSFs by PTEC. These data suggest that the local production of CSFs in the tubulointerstitium may affect tubulointerstitial lesions in kidney injury.

A case of familial Mediterranean fever-associated systemic amyloidosis.

Familial Mediterranean fever (FMF) is a chronic inflammatory disease, characterized by recurrent fever and polyserositis (pleuritis and/or peritonitis). The most important complication of FMF is amyloidosis, which causes chronic renal failure. Colchicine is the most effective treatment in acute attacks and amyloidosis development. However, the majority of patients with amyloidosis have a relentless progression to end-stage renal disease despite initiation of colchicine treatment. We present the case of a 38-year-old man with FMF-associated chronic renal failure due to systemic amyloidosis. The patient suffered from periodic fever and renal insufficiency, and was admitted to our hospital. Laboratory examination revealed an inflammatory reaction, renal dysfunction (serum creatinine 2.5 mg/dl), and proteinuria. Renal biopsy revealed segmental mesangial AA amyloid deposits in several glomeruli and the walls of several vessels. Genetic analysis showed that the patient was heterozygous for the MEFV gene (E148Q/M694I). Thus, he was diagnosed with FMF, and colchicine treatment was initiated. He remained almost attack free, with decreasing serum creatinine levels (1.6 mg/dl) and diminishing urinary protein excretion. In conclusion, renal amyloidosis is the most important long-term complication of FMF, and treatment with colchicine is effective for preventing progression. Therefore, colchicine treatment should be initiated as early as possible after the diagnosis of FMF.

Paroxysmal nocturnal hemoglobinuria in systemic lupus erythematosus: a case report.

INTRODUCTION: Paroxysmal nocturnal hemoglobinuria is an acquired disorder of hemopoiesis and is characterized by recurrent episodes of intravascular hemolysis due to an increased sensitivity to complement-mediated hemolysis. Systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. We report a case of paroxysmal nocturnal hemoglobinuria that developed in a patient with systemic lupus erythematosus and lupus nephritis. CASE PRESENTATION: A 29-year-old Mongolian woman had systemic lupus erythematosus, which manifested only as skin lesions when she was 12 years old. She had leg edema and proteinuria when she was 23 years old, and a renal biopsy revealed lupus nephritis (World Health Organization type IV). She had been treated with steroids and immunosuppressant therapy. At 29, she had headaches, nausea, general fatigue, and severe pancytopenia and was admitted to our hospital. A laboratory evaluation showed hemolytic anemia. Further examination showed a neutrophil alkaline phosphatase score of 46 points, a CD55 value of 18%, and a CD59 value of 78.6%. The results of Ham test and sugar water tests were positive. The constellation of symptoms throughout the clinical course and the laboratory findings suggested paroxysmal nocturnal hemoglobinuria. CONCLUSIONS: To the best of our knowledge, systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. Clinicians should be aware of the association between autoimmune and hematological diseases.

Polyunsaturated fatty acids and blood circulation in the forebrain during a mental arithmetic task.

The effects of polyunsaturated fatty acids on human cerebral blood oxygenation have yet to be extensively investigated. In this study, healthy participants (14 men, 40 women) aged between 20 and 49 years were recruited. All female participants entered the trial at the start of their menstrual cycle. Blood was sampled before measuring cerebral blood oxygenation in the prefrontal cortex (PFC) and prior to administering two kinds of questionnaires, the Profile of Mood States (POMS) and a questionnaire regarding participants' arousal level. Blood oxygenation in the PFC was continuously monitored immediately before and during the Uchida-Kraepelin Performance (UKP) test as a mental arithmetic task. Changes in the tissue oxygenation index (the ratio of oxyhemoglobin to oxyhemoglobin+deoxyhemoglobin; TOI, a simplified index for cerebral blood circulation) were measured by near-infrared spectroscopy. Multiple regression analysis was performed with sex, age, smoking and drinking as confounding factors. Eicosapentaenoic acid (EPA) was positively associated with TOI, which was positively associated with arousal level and inversely associated with negative mood (POMS). EPA and docosahexaenoic acid were inversely associated with depression-dejection (POMS) and positively associated with arousal level and overall performance in the UKP test. We suggest that EPA might increase the oxygenation level in the PFC, in turn improving various psychological parameters and performance.

Metabolism and pharmacokinetics in rats of ganoderiol F, a highly cytotoxic and antitumor triterpene from Ganoderma lucidum.

The metabolism of ganoderiol F (GF), a cytotoxic and antitumor triterpene from Ganoderma lucidum, by intestinal bacteria and its pharmacokinetics in rats were investigated by using liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). GF was converted to ganodermatriol by anaerobic incubation with bacterial mixtures from rats and humans. This metabolite was detected in rat feces, but not in plasma and urine, after oral administration of GF. The fate of GF after oral (p.o.) and intravenous (i.v.) administration to rats was examined in pharmacokinetics studies. Plasma samples pretreated by solid-phase extraction were quantified by HPLC/MS/MS over a GF concentration range of 1.25-100 ng/ml (S/N = 5). The intra- and interday precision (CV%) was below 8% and accuracy was within the range of 95.9-103.6% for all samples. The range of recovery ratios was 89.2-98.2%. After the administration of GF at 0.5 mg/kg i.v., the plasma concentrations of GF quickly declined and the elimination half-life values (t(1/2alpha) and t(1/2beta)) were about 2.4 and 34.8 min. On the other hand, the elimination half-life values (t(1/2alpha)) after p.o. administration of GF at doses of 20 and 50 mg/kg were 14.4 and 143.3 min for the former, and 18.6 and 114.6 min for the latter. The AUC(0-t) value was 11.17 (ng/ml) h at a GF dose of 0.5 mg/kg i.v., but 49.4 and 111.6 (ng/ml) h at GF doses of 20 and 50 mg/kg p.o., respectively, indicating that the AUC(0-t) value is proportional to the administered oral doses. The estimated absolute bioavailability of GF in rats was F = 0.105.

Extracellular matrix metalloproteinase inducer is expressed in the proximal tubular epithelial cells of the human kidney.

AIM: Matrix metalloproteinases (MMP) affect matrix remodelling, and extracellular matrix metalloproteinase inducer (EMMPRIN) has been reported to increase the levels of several MMP. However, the expression of EMMPRIN in the human kidney and its regulatory mechanisms are not well known. In this study, we examined EMMPRIN expression in the human kidney with the biopsied specimens, cultured proximal tubular epithelial cells (PTEC) and human mesangial cells (HMC). METHODS: EMMPRIN expression was examined by immunofluorescent (IF) study, reverse transcription polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay. We also examined soluble EMMPRIN in the conditioned medium of PTEC stimulated by various agents and its effect in the activities of MMP-2 and MMP-9. Also, IF study in the several kidney diseases was performed to elucidate its role in pathological condition. RESULTS: EMMPRIN expression was diffusely observed in the tubular epithelial cells of most patients and healthy adults, but was never observed in glomeruli. Cultured PTEC expressed EMMPRIN, while HMC did not. Soluble EMMPRIN was also detected by enzyme-linked immunosorbent assay in the conditioned medium of PTEC. Epidermal growth factor (50 ng/mL) and phorbol 12-myristate 13-acetate (10(-7) mol/L) stimulated the secretion of soluble EMMPRIN and increased the MMP-2 activity, although these agents did not increase the level of EMMPRIN mRNA. From the IF study, EMMPRIN expression was shown to decrease in tubulointerstitial nephritis. CONCLUSION: EMMPRIN is widely distributed in the tubular epithelial cells of the adult human kidney and may regulate MMP-2 activity via its secretion from PTEC.

Two new triterpenes from the Rhizome of Dryopteris crassirhizoma, and inhibitory activities of its constituents on human immunodeficiency virus-1 protease.

Two new hopane type triterpenes, named dryopteric acids A (1) and B (2), were isolated from the Rhizome of Dryopteris crassirhizoma (Aspiadaceae) together with sixteen known compounds (3-18). Of isolated compounds, ursolic acid (15), and dryopteric acid A (1) and B (2) showed potent inhibitory activities against HIV-1 protease with IC50 values of 8.9-44.5 microM. In addition, acetylated compounds 1 and 2 appreciably increased inhibitory activities with their IC50 values of 1.7 and 10.8 microM, respectively.

[Gamma knife radiosurgery for temporal bone chondroblastoma: case report].

A case with chondroblastoma arising from the right temporal bone was reported. A 52-year-old woman demonstrated residual tumor growth after surgical excision. The patient presented continuous right temporalgia and right facial twitch while opening her mouth. The tumor was an expansile mass (tumor volume: 12.8 cm3) and showed homogeneous hypo-intensity on T1 and T2-weighted images, but little contrast enhancement. The patient underwent gamma knife radiosurgery (GKR: marginal dose: 12 Gy, maximum dose: 24 Gy). One month later, her symptoms improved completely. The size of the tumor was reduced to 6.4 cm3 twenty months after GKR. The patient has been free of recurrence and side effects for four years since GKR. GKR may be useful to control residual chondroblastoma of the skull after surgery.