Anti-Helicobacter pylori activity of quinolone alkaloids from Evodiae fructus.

A biologically monitored fractionation of methanol extract of the fruit of Evodia rutaecarpa led to the isolation of six quinolone alkaloids, evocarpine (1), 1-methyl-2-[(4Z,7Z)-4,7-tridecadienyl]-4(1H)-quinolone (2), 1-methyl-2-[(6Z,9Z)-6,9-pentadecadienyl]-4(1H)-quinolo ne (3), 1-methyl-2-undecyl-4(1H)-quinolone (4), dihydroevocarpine (5), 1-methyl-2-pentadecyl-4(1H)-quinolone (6). They showed potent anti-Helicobacter pylori activity with the minimum inhibitory concentration (MIC) value of 10-20 microg/ml. However, they had no effect on Helicobacter pylori urease activity at the concentration of 300 microg/ml.     

GABAA receptor-mediated activation of L-type calcium channels induces neuronal excitation in surgically resected human hypothalamic hamartomas.

PURPOSE: The human hypothalamic hamartoma (HH) is a rare, intrinsically epileptogenic lesion associated with gelastic seizures, but the underlying mechanisms remain unclear. Here, we examined the role of GABAA receptors in surgically resected HH tissue. METHODS: HH tissue slices (350 microm) were studied using cellular electrophysiological, calcium imaging, and immunocytochemical techniques. RESULTS: Two neuronal cell types were seen: small (10-16 microm) spontaneously firing GABAergic neurons and large (20-28 microm) quiescent neurons. In gramicidin-perforated patch recordings, muscimol (30 microM) induced membrane depolarization in 70% of large (but not small) neurons and a concomitant rise in intracellular calcium. These responses were blocked by bicuculline methiodide (50 microM). Depolarizing neurons also exhibited more positive reversal potentials (Emuscimol) and significantly higher intracellular chloride concentrations compared to those that hyperpolarized. The cation chloride co-transporters NKCC1 and KCC2 were coexpressed in the majority of large neurons, but fluorometric measurements revealed that 84% of large HH neurons expressed solely or relatively more NKCC1. Bumetanide (20 microM), a NKCC1 antagonist, partially suppressed muscimol-induced excitation in large neurons. Concordant with robust expression of CaV1.2 and CaV1.3 subunits in HH neurons, the L-type calcium channel blocker nifedipine (100 microM) prevented muscimol-induced neuronal excitation. CONCLUSIONS: GABAA receptor-mediated excitation, due in part to differential expression of NKCC1 and KCC2 and subsequent activation of L-type calcium channels, may contribute to seizure genesis in HH tissue. Given the ready availability of L-type calcium channel blockers, our results have clinical ramifications for the treatment of seizures associated with HH lesions.     

Linezolid-associated peripheral neuropathy

Linezolid is the first drug in a new class of synthetic antimicrobials, the oxazolidinones, to be approved by the Food and Drug Administration. Linezolid is active against methicillin- and vancomycin-resistant gram-positive microorganisms. We describe 2 patients who developed peripheral neuropathy after prolonged treatment with linezolid. Linezolid-associated peripheral neuropathy has not been well documented. Most reported cases of linezolid-associated peripheral neuropathy have occurred in patients who took linezolid for a period longer than the recommended 28 or fewer days. Health care providers must be alert to the potential for serious adverse effects associated with linezolid use, including peripheral neuropathy.     

Decreased Total Antioxidant Activity in Major Depressive Disorder Patients Non-Responsive to Antidepressant Treatment

Objective

This study aimed to evaluate the total antioxidant activity (TAA) in patients with major depressive disorder (MDD) and the effect of antidepressants on TAA using a novel potentiometric method.

Methods

Twenty-eight patients with MDD and thirty-one healthy controls were enrolled in this study. The control group comprised 31 healthy individuals matched for gender, drinking and smoking status. We assessed symptoms of depression using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). We measured TAA using potentiometry. All measurements were made at baseline and four and eight weeks later.

Results

There was a significant negative correlation between BDI scores and TAA. TAA was significantly lower in the MDD group than in controls. When the MDD group was subdivided into those who showed clinical response to antidepressant therapy (response group) and those who did not (non-response group), only the non-response group showed lower TAA, while the response group showed no significant difference to controls at baseline. After eight weeks of antidepressant treatment, TAA in both the response and non-response groups was similar, and there was no significant difference among the three groups.

Conclusion

These results suggest that the response to antidepressant treatment in MDD patients might be predicted by measuring TAA.     

Tissue-engineered bone formation using periosteal-derived cells and polydioxanone/pluronic F127 scaffold with pre-seeded adipose tissue-derived CD146 positive endothelial-like cells

The aim of this study was to generate tissue-engineered bone formation using periosteal-derived cells seeded into a polydioxanone/pluronic F127 (PDO/Pluronic F127) scaffold with adipose tissue-derived CD146 positive endothelial-like cells. Considering the hematopoietic and mesenchymal phenotypes of adipose tissue-derived cells cultured in EBM-2 medium, CD146 positive adipose tissue-derived cells was sorted to purify more endothelial cells in characterization. These sorted cells were referred to as adipose tissue-derived CD146 positive endothelial-like cells. Periosteum is a good source of osteogenic cells for tissue-engineered bone formation. Periosteal-derived cells were found to have good osteogenic capacity in a PDO/Pluronic F127 scaffold, which could provide a suitable environment for the osteoblastic differentiation of these cells. Through the investigation of capillary-like tube formation on matrigel and the cellular proliferation of adipose tissue-derived CD146 positive endothelial-like cells cultured in different media conditions, we examined these cells could be cultured in EBM-2 with osteogenic induction factors. We also observed that the osteogenic activity of periosteal-derived cells could be good in EBM-2 with osteogenic induction factors, in the early period of culture. The experimental results obtained in the miniature pig model suggest that tissue-engineered bone formation using periosteal-derived cells and PDO/Pluronic F127 scaffold with pre-seeded adipose tissue-derived CD146 positive endothelial-like cells can be used to restore the bony defects of the maxillofacial region when used in clinics.     

Activation of protein kinase Czeta mediates luteinizing hormone- or forskolin-induced NGFI-B expression in preovulatory granulosa cells of rat ovary

We have previously demonstrated that luteinizing hormone (LH) induces a rapid and transient expression of NGFI-B in the ovary. In this report, we investigated the signaling pathway for LH- and forskolin-induced NGFI-B expression in cultured rat granulosa cells of preovulatory follicles. LH- or forskolin-induced NGFI-B expression was suppressed by high dose of protein kinase C (PKC) inhibitor RO 31-8220 (10 μM), but not by low doses RO 31-8220 (0.1–1.0 μM) or adenylate cyclase inhibitor MDL-12,300A, implicating the involvement of atypical PKCs. Kinase assay revealed that LH treatment of granulosa cells resulted in a rapid stimulation of atypical PKCζ activity. Interestingly, like LH, forskolin was also able to activate PKCζ. Treatment with the cell-permeable PKCζ-specific inhibitor pseudosubstrate peptide inhibited LH-or forskolin-induced NGFI-B expression, indicating the essential role of PKCζ. Consistent with this promise, in granulosa cells depleted of diacylglycerol sensitive PKCs by prolonged treatment with tetradecanoylphobol-13-acetate, LH or forskolin could still induce NGFI-B expression, and RO 31-8220 or the PKCζ pseudosubstrate peptide inhibited LH- or forskolin-induced NGFI-B expression. Furthermore, overexpression of dominant-negative PKCζ in primary granulosa cells using a replication-defective adenovirus vector resulted in the suppression of LH- or forskolin-induced NGFI-B expression. Our findings demonstrate that PKCζ, which is activated by LH or forskolin, contributes to the induction of NGFI-B in granulosa cells of preovulatory follicles.