Decreased protein levels of stathmin in adult brains with Down syndrome and Alzheimer's disease

Stathmin, distributed in neurons with high abundance, acts as an intracellular relay, integrating various transduction pathways triggered by extracellular signals and it is involved in physiological regulation of microtubule destabilization. Stathmin has been also shown to be a critical molecule in pathology of neurodegeneration such as Alzheimer's disease (AD), particularly, in neurofibrillary tangle (NFT) formation. Here we evaluated protein levels of stathmin in adult brain from patients with AD and Down syndrome (DS) showing AD-like pathology by applying proteomic technologies with two-dimensional (2-D) gel electrophoresis, matrix-assisted laser desorption ionization mass spectroscopy (MALDI-MS) identification and specific software for quantification of proteins. Significantly decreased protein levels of stathmin were observed in frontal (2.12+/-1.17, n = 6) and temporal (3.05+/-2.81, n = 10) cortices of AD compared to controls (frontal cortex: 4.41+/-1.70, n = 8; temporal cortex: 5.26+/-2.26, n = 13). Stathmin was also significantly decreased in frontal (2.47+/-1.11, n = 7) and temporal (2.02+/-1.18, n = 9) cortices of DS. We also investigated stathmin levels in fetal brain. Stathmin was not significantly changed between fetal DS brain and controls. We suggest that the decreased protein level of stathmin in brains is associated with tangle formation and microtubule instability in DS as well as AD, but stathmin is not involved in the abnormal development of fetal DS brain.     

Effects of prenylated flavonoids and biflavonoids on lipopolysaccharide-induced nitric oxide production from the mouse macrophage cell line RAW 264.7

Certain flavonoid derivatives possess anti-inflammatory activity in vitro and in vivo. Besides their antioxidative properties and effects on the arachidonic acid metabolism including cyclooxygenase/lipoxygenase inhibition, some flavones and flavonols were previously found to show inhibitory activity on nitric oxide production by inducible nitric oxide synthase (iNOS; NOS type 2) through suppression of iNOS induction. As part of our continuing investigations, the effects of unique and minor flavonoids (prenylated flavonoids and biflavonoids) on nitric oxide production from lipopolysaccharide-induced macrophage cell line (RAW 264.7) were evaluated in order to establish their inhibitory activity on NO production and correlate this action with their in vivo anti-inflammatory potential. Among the derivatives tested, prenylated compounds including morusin, kuwanon C, and sanggenon D and biflavonoids such as bilobetin and ginkgetin were found to inhibit NO production from lipopolysaccharide (LPS)-induced RAW 264.7 cells at > 10 microM. Inhibition of nitric oxide production was mediated by suppression of iNOS enzyme induction but not by direct inhibition of iNOS enzyme activity. An exception was echinoisoflavanone that inhibited iNOS enzyme activity (IC50 = 83 microM) and suppressed iNOS enzyme induction as well. While most prenylated derivatives showed cytotoxicity to RAW cells at 10-100 microM, all biflavonoids tested were not cytotoxic. Since nitric oxide (NO) produced by inducible NO synthase (iNOS) plays an important role in inflammatory disorders, inhibition of NO production by these flavonoids may contribute, at least in part, to their anti-inflammatory and immunoregulating potential in vivo.     

Changes on NiTi orthodontic wired due to acidic fluoride solution

The effect of acidic fluoride solution on NiTi arch wires was examined by testing crystal structure, tensile strength, morphology after fracture, and element release from wire under four different test solutions after 1 or 3 d immersion. Three-day immersion in a 0.2%/pH 4 solution did not form any new crystal structure. However, tensile strength after immersion was changed compared to the as-received wires. 3M wires showed increased tensile strength whereas G&H and Ormco wires showed decreased strength. Significant difference in tensile strength was associated with the immersion period. The fractured wires showed dimple patterns in the inner part of the wire, and ductile features on the outer part. Element release in the test solution increased as NaF concentration and the period of immersion increased, and as pH valued decreased. Wires immersed in a 0.2%/pH 4 solution released several-fold greater amount of elements than wires in a 0.05%/pH 4 solution. Tensile strength and element release were affected by acidic fluoride solution. In particular, NaF concentration, pH value, and the period of immersion were the factors affecting these properties.     

Nutcracker syndrome in children with gross haematuria: Doppler sonographic evaluation of the left renal vein

Background: Nutcracker syndrome is characterized by gross haematuria caused by left renal vein (LRV) entrapment. Objective: To assess the role of LRV ultrasonography in the diagnosis of the nutcracker syndrome in children. Materials and methods: Twelve children (eight male, four female; mean age 12.8 years) with venographically confirmed nutcracker syndrome (LRV-IVC pressure gradient ≥3 mm Hg) underwent LRV sonography including Doppler spectral analysis (n=7). The diameter and peak velocity (PV) were measured at two sites of the LRV (renal hilum and aortomesenteric portion). The US findings of nutcracker syndrome were compared with those of 20 control subjects using the t-test. We identified the optimal cut-off value of the US parameters for the diagnosis of the nutcracker syndrome using ROC analysis. Results: The PV at the aortomesenteric portion and the ratio of the PV between the two measured points showed significant differences between the two groups (P<0.0001). The optimum cut-off values were found to be 4.7 for the PV ratio (sensitivity 100%, specificity 90%, accuracy 93%), and 93 cm/s for the PV at the aortomesenteric portion (sensitivity 100%, specificity 85%, accuracy 89%). Conclusion: LRV sonography, including Doppler spectral analysis, can demonstrate LRV entrapment haemodynamically.     

Preparation and biological evaluation of 188Re-ethylenediamine-N,N,N',N'-tetrakis(methylene phosphonic acid) as a potential agent for bone pain palliation.

This study was undertaken in order to prepare 188Re labelled ethylenediamine-N,N,N',N'-tetrakis(methylene phosphonic acid) (EDTMP), and to determine its potential as a therapeutic radiopharmaceutical for the palliation of metastatic bone pain. The effects of pH, incubation methods, and concentrations of stannous chloride, EDTMP, and ammonium perrhenate as a carrier on radiochemical yield and stability were evaluated. Biodistribution studies were performed in male Wistar rats after intravenous injection of 188Re-EDTMP and compared with those of hydroxyethylidene diphosphonate (HEDP). Greater than 95% radiochemical yield of 188Re-EDTMP was obtained under the optimal conditions (0.1 mmol x ml(-1) of EDTMP, 0.5 mg x ml(-1) of stannous chloride, and pH 1.0). Heating the reaction mixture (boiling water for 15 min, and microwave heating for 15 s) and the addition of ammonium perrhenate increased the radiochemical stability (>90% at 3 h, and >80% at 48 h). The biodistribution of 188Re-EDTMP showed high bony uptake and rapid clearance from other organs, and high bone-to-soft tissue ratios, which are similar to 188Re-HEDP. In conclusion, 188Re-EDTMP was prepared with high radiochemical yield and stability, and showed favourable biological characteristics. Microwave heating was a convenient and rapid method for the preparation of 188Re-EDTMP. It is considered that 188Re-EDTMP is a potential therapeutic agent for bone metastasis.     

Two cases of pineal germinoma with granulomatous inflammation.

We report two cases of pineal germinoma with remarkable chronic granulomatous inflammation. In the first case, the pineal mass was totally removed via an occipital transtentorial approach as symptoms were due to direct mass effect. In the second case, endoscopic third ventriculostomy and tissue biopsy was performed to alleviate worsening hydrocephalus. Pathological examination of specimens of both cases showed chronic granulomatous inflammation associated with a few germ cell tumor nests, which demonstrated positive staining for placental alkaline phosphatase. Both patients received post-operative craniospinal irradiation with no subsequent neurological deficits. Follow-up magnetic resonance imaging (MRI) of the second case showed an asymptomatic, shrunken residual tumor mass. MRI of the first case showed no residual or recurrent disease. Thus, a pineal mass with unusual features on MRI and chronic granulomatous inflammation on histopathology, should raise the suspicion of germinoma. In cases with symptomatic mass effect, open resection can be considered. In cases with lesser mass effect, conventional therapeutic modalities without resection can achieve a good outcome, as for other germinomas.     

Chronological changes in the systemic manifestations of intestinal Behcet’s disease and their significance in diagnosis

Purpose

Intestinal Behçet's disease (BD) is challenging to diagnose, especially if the patient presents with typical colonoscopic findings of intestinal BD without systemic manifestations of BD. We performed this study to evaluate the systemic manifestations of BD in patients with typical colonoscopic findings of intestinal BD at the time of initial presentation and to identity the chronologic changes of these features during an extended follow-up period.

Methods

One hundred twenty-six consecutive patients who showed typical colonoscopic findings of intestinal BD at a single institution in Korea were enrolled. Clinical and endoscopic data were collected from a medical database and using a written questionnaire. Parameters including demographic characteristics and the subset type of BD at the initial and endpoints of the follow-up were analyzed.

Results

The mean follow-up period was 63.9?±?50.9 months. The number of cases that satisfied the International Study Group for Behçet’s Disease criteria at initial diagnosis, 19.0%, increased to 53.2% by the end of follow-up. When the Japanese criteria were used for classification, the proportion of complete and incomplete type BD increased (2.4% and 26.2% to 18.3% and 49.2%, respectively), while that of suspected and not-satisfied subtype BD decreased (22.2% and 49.2% to 19.0% and 13.5%, respectively) during the follow-up period.

Conclusions

Our data suggest that patients who lack the systemic manifestations of BD could be included in the category of intestinal BD when typical intestinal lesion is identified, indicating that close examination and early treatment should be considered in such patients.     

Protective role of metabolism by intestinal microflora in butyl paraben-induced toxicity in HepG2 cell cultures

Parabens are alkyl esters of p-hydroxybenzoic acid (BA), including methyl paraben (MP), ethyl paraben, propyl paraben (PP), and butyl paraben (BP). In the present study, possible role of metabolism by fecalase in BP-induced cytotoxicity was investigated in HepG2 cell cultures. As an intestinal bacterial metabolic system, a human fecalase prepared from human fecal specimen was employed. Among the parabens tested, cytotoxicity of BP was most severe. BA, the de-esterified metabolite, did not induce cytotoxicity when compared to other parabens. When BP was incubated with fecalase, it rapidly disappeared, in association with reduced cytotoxicity in HepG2 cells. In addition, BP incubated with fecalase significantly caused an increase in Bcl-2 expression together with a decrease in Bax expression and cleaved caspase-3. Moreover, anti-apoptotic effect by the incubation of BP with fecalase was also confirmed by the TUNEL assay. Furthermore, BP induced a sustained activation of the phosphorylation of JNK only when it was treated alone. Meanwhile, BP-induced cell death was reversed by the pre-incubation of BP with either fecalase or SP600125. Taken together, the findings suggested that metabolism of BP by human fecalase might have protective effects against BP-induced toxicity in HepG2 cells.