A phenylpropanoid glycoside with antioxidant activity from picria tel-ferae

A phytochemical study on Picria tel-ferae resulted in the isolation of a phenylpropanoid glycoside (1), which was reported for the first time from this plant. The structure of compound 1 was identified as 1-O-3,4-(dihydroxyphenyl)- ethyl-beta-D- apiofuranosyl- (1-->4)-alpha-L-rharmnopyranosyl- (1-->3)-4-O-caffeoyl- beta-D-glucopyranoside on the basis of spectroscopic analyses. In addition, it was found that 1 exhibited a remarkable inhibitory effect on lipid peroxidation initiated by either a free radical [AAPH; 2,2'-azobis-(2-amidinopropane)dihydrochloride] or generated hydroxyl radical (Fe2+/ascorbate). These findings, together with those of previous studies, suggest that P. tel-ferae possesses abundant phenylpropanoid glycosides, and the plant might be used beneficially in the treatment of oxidative stress-related human diseases.     

Design,Synthesis and Pharmacological Characterization of Endomorphin Analogues with Non‐Cyclic Amino Acid Residues in Position 2

Abstract: A series of endomorphin‐1 (EM‐1) and endomorphin‐2 (EM‐2) analogues, containing non‐cyclic amino acids (Ala, d ‐Ala, β‐Ala, NMeAla, d ‐NMeAla or Sar) instead of Pro in position 2 was synthesized, where NMeAla = N‐methylalanine and Sar = N‐methylglycine, sarcosine. The opioid activity profiles of these peptides were determined in μ and δ opioid receptor (MOR and DOR)‐representative binding assays and bioassays in vitro, as well as in the mouse hot‐plate test in vivo. Finally, the degradation rates of all analogues in the presence of either rat brain homogenate or selected proteolytic enzymes were determined. Analogues of EM‐2 were generally more potent than the respective analogues of EM‐1. EM‐2 analogues with d ‐Ala or d ‐NMeAla were about twofold more potent than the parent peptide and were least prone to degradation by brain homogenate, dipeptydyl peptidase IV and aminopeptidase M. In the in vivo test, [d ‐Ala²]EM‐2 and [d ‐NMeAla²]EM‐2 showed much higher analgesic potency than EM‐2 which confirmed the usefulness of structural modifications in obtaining new leads for pain‐relief therapeutics.     

Toxicometabolomics of urinary biomarkers for human gastric cancer in a mouse model

Toxicometabolomics of urinary biomarkers for human gastric cancer in a mouse model was investigated using (1)H-nuclear magnetic resonance (NMR) spectroscopy. A human gastric adenocarcinoma cell line (1 × 10(7) cells/ml) was grafted onto the skin of the back of intact male BALB/c-nu/nu mice. After the xenografted tumors developed, urine was collected and analyzed for endogenous metabolites. Global profiling combined with principal components analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal projections to latent squares-discriminant analysis (OPLS-DA) showed distinct separation of clusters between control and tumor-bearing mice. Targeted profiling revealed significant changes in trimethylamine oxide (TMAO), 3-indoxylsulfate, hippurate, and citrate levels in mice carrying human gastric cancer cells compared to normal mice. The levels of TMAO (0.41-fold) and hippurate (0.26-fold) in tumor-bearing mice were significantly decreased, whereas the levels of 3-indoxylsulfate (3.39-fold), 2-oxoglutarate (2.32-fold), and citrate (1.9-fold) were significantly increased in urine samples of tumor-bearing mice. Data suggest that TMAO, hippurate, 3-indoxylsulfate, 2-oxoglutarate, and citrate may serve as useful urinary biomarkers for gastric tumorigenesis in a mouse model.     

Phospholipase D1 is up-regulated in the mitochondrial fraction from the brains of Alzheimer's disease patients

Mitochondrial dysfunction may play an important role in sporadic Alzheimer's disease (AD) progression. Recently, we have reported that amyloid precursor protein (APP) stimulates phospholipase D (PLD) activity and beta-amyloid (Abeta) region of APP is involved in the interaction with PLD1. To elucidate the involvement of PLD in the pathophysiology of AD, we examined the expression of PLD1 and alteration of membrane phospholipid in mitochondrial membranes of control and AD brains using Western blot and phospholipid analysis by thin layer chromatography (TLC). We have found that protein expression of PLD1 was significantly increased in mitochondrial fraction of brains of AD patients compared with that in control brains. Furthermore, the concentration of mitochondrial phospholipids such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was increased and the content of phosphatidic acid (PA), a product of PLD activity, was up-regulated in the mitochondrial membrane fractions of AD brain compared with that of control brain. These results suggest that up-regulation of PLD1 in the mitochondrial fraction of AD brain might affect the composition of membrane phospholipids and provide a clue to the mechanism underlying the mitochondrial dysfunction associated with AD.     

Preoperative concurrent radiochemotherapy and surgery for stage IIIA non-small cell lung cancer

This is to examine whether aggressive multimodality therapy improves the treatment outcomes in stage IIIA non-small cell lung cancer (NSCLC). Fifty-three consecutive NSCLC patients with N2 disease, confirmed by mediastinoscopic biopsy, received preoperative thoracic radiation therapy (45 Gy/5 weeks) concurrent with two cycles of oral etoposide and intravenous cisplatin and surgery. Postoperative radiation therapy (PORT, 18 Gy/2 weeks) was optionally recommended for those with the risk factors of loco-regional recurrence based on the surgical and pathological findings. Surgical resection was performed in 38 patients (71.7%), and down-staging was achieved in 19 patients (50%). The median survival period was 27 months in 38 patients who underwent resection, and the rates at 3-yr of overall survival, loco-regional control, distant metastasis-free survival, and disease-free survival were 44.3%, 87.9%, 32.9%, and 29.3%. Significantly favorable factor regarding overall survival was achieving p0/I stage by the multivariate analysis. PORT was successful in reducing locoregional recurrences in patients with the risk factors. Current preoperative concurrent radiochemotherapy and surgery by the authors resulted in comparable survival with other reports, however, further refinement of multimodality approach may be warranted for more effective reduction of distant metastasis.     

Cutaneous polyarteritis nodosa presented with digital gangrene: a case report

Cutaneous polyarteritis nodosa (CPAN) is an uncommon form of vasculitis involving small and medium sized arteries of unknown etiology. The disease can be differentiated from polyarteritis nodosa by its limitation to the skin and lack of progression to visceral involvement. The characteristic manifestations are subcutaneous nodule, livedo reticularis, and ulceration, mostly localized on the lower extremity. Arthralgia, myalgia, peripheral neuropathy, and constitutional symptoms such as fever and malaise may also be present. We describe a 34-yr-old woman presented with severe ischemic change of the fingertip and subcutaneous nodules without systemic manifestations as an unusual initial manifestation of CPAN. Therapy with corticosteroid and alprostadil induce a moderate improvement of skin lesions. However, necrosis of the finger got worse and the finger was amputated.     

Angiogenesis facilitated by autologous whole bone marrow stem cell transplantation for Buerger's disease

We hypothesized that angiogenesis can be triggered by autologous whole bone marrow stem cell transplantation. Twenty-seven patients (34 lower limbs) with Buerger's disease, who were not candidates for surgical revascularization or radiologic intervention, were enrolled in this study. Six sites of the tibia bone were fenestrated using a 2.5-mm-diameter screw under fluoroscopic guidance. Clinical status and outcome were determined using the "Recommended Standards for Reports." To mobilize endothelial progenitor cells (EPCs) from bone marrow, recombinant human granulocyte colony-stimulating factor (r-HuG-CSF) was injected subcutaneously as a dose of 75 microg, preoperatively. During the follow-up period (19.1 +/- 3.5 months), one limb showed a markedly improved outcome (+3), and 26 limbs showed a moderately improved outcome (+2). Thirteen limbs among 17 limbs with nonhealing ulcers healed. Postoperative angiograms were obtained for 22 limbs. Two limbs showed marked (+3), five limbs moderate (+2), and nine limbs slight (+1) collateral development. However, six limbs showed no collateral development (0). Peripheral blood and bone marrow samples were analyzed for CD34 and CD133 molecules to enumerate potential EPCs, and EPC numbers were found to be increased in peripheral blood and in bone marrow after r-HuG-CSF injection. In conclusion, the transplantation of autologous whole BMCs by fenestration of the tibia bone represents a simple, safe, and effective means of inducing therapeutic angiogenesis in patients with Buerger's disease.