Pathological conditions such as hypoxia and inflammation can lead to the development of cell membrane-lesions. The presence of these membrane-lesions leads to egress of intracellular macromolecules as well as exposure of intracellular microenvironment to the extracellular milieu resulting in necrotic cell death. An intracellular structure that becomes exposed to the extracellular environment is myosin, a cytoskeletal antigen. We had hypothesized that cell viability can be preserved in nascent necrotic cells if the cell membrane lesions were sealed and the injurious conditions removed. Cell membrane lesion sealing and preservation of cell viability were achieved by the application of Cytoskeletal-antigen Specific ImmunoLiposomes (CSIL) as molecular “Band-Aid” that initially plugs the holes with subsequent sealing of the lesions. Anti-myosin antibody was chosen as the cytoskeleton-antigen specific antibody to develop CSILs, because antimyosin antibody is highly specific for targeting myosin exposed through myocardial cell membrane lesions in various cardiomyopathies. Liposomes are biocompatible lipid bilayer vesicles that have been used in many biological applications for several decades.

This chapter will be limited to the description of CSIL therapy to ex vivo studies in adult mammalian hearts. Due to page limitations, cell culture, gene delivery and in vivo studies will not be included. Therapeutic efficacy of CSIL in preservation of myocardial viability as well as function (by left ventricular developed pressure measurements) as assessed in globally ischemic Langendorff instrumented hearts is both dose and time dependent. This approach of cell membrane lesion repair and sealing may have broader applications in other cell systems.

The petals of Rosa rugosa and allied plants for medicinal use contain abundant hydrolysable tannins, and they show remarkable biological activities. The activities are dependent on the structures of the hydrolysable tannins, so their contents and compositions are essential for evaluation of medicinal potency. Therefore, we optimized the simultaneous quantitative determination of the hydrolysable tannins using ultra-performance liquid chromatography. A column of ethylene bridged hybrid (BEH) phenyl (C₆ alkyl phenyl group as solid-phase modification) was shown to be most effective for the separation of hydrolysable tannins isolated from R. rugosa and related compounds when the column temperature was kept under 25°C. The efficacy of the BEH phenyl column might be due to the interaction between solid phase and phenolic ester groups of hydrolysable tannins such as galloyl, hexahydroxydiphenoyl and valoneoyl groups. The relation between the retention times on the BEH phenyl column and the column temperature was demonstrated to depend on the structural characteristics of hydrolysable tannins.

Study design:

Case report.

Objectives:

To report the late onset of cervical myelopathy secondary to fibrous scar tissue formation around an epidural electrode implanted for spinal cord stimulation (SCS).

Setting:

Department of Orthopaedic Surgery, Hoshigaoka Koseinenkin Hospital, Osaka, Japan.

Method and results:

A 49-year-old man who had an electrode implanted for SCS 5 years ago was referred to our department on 2 March 2005, complaining of difficulty using chopsticks and walking. A computed tomography scan with myelography revealed severe spinal cord compression around the epidural electrode. Surgical removal of the electrode was not effective. Removal of fibrous scar tissue during a second surgery significantly improved his neurological symptoms.

Conclusion:

Late onset cervical myelopathy secondary to fibrous scar tissue formation around the epidural electrode should be considered a possible event associated with SCS therapy.

Reports of toxicity secondary to Kratom are rare and lack of diagnostic testing in human specimens has prevented confirmatory explanation of observed clinical effects. We present a novel case of serious human toxicity following Kratom use confirmed via quantitative analysis of urine by high performance liquid chromatography coupled to electrospray tandem mass spectrometry. A 64 year-old male was witnessed to have a seizure at home following kratom consumption. Upon arrival to the emergency department (ED), the patient was unresponsive. While in the ED, the patient sustained a second seizure. He was intubated to protect his airway. The remainder of his hospital course was uneventful. A urine specimen was collected shortly after admission and sent for analysis. The mitragynine concentration in the urine was 167 ± 15 ng/ml. We report a rare case of Kratom toxicity characterized by a seizure and coma confirmed by urinary analysis of mitragynine by high performance liquid chromatography coupled to electrospray tandem mass spectrometry. The proposed mechanism for this reaction is unclear but suggested mechanisms include adenosine binding or stimulation of adrenergic and/or serotonergic receptors similar to tramadol.

Background

Chronic inflammation is considered to be implicated in the development of prostate cancer. In this study we are the first to investigate a potential association between variants in an autoimmune related region on chromosome 4q27 and prostate cancer risk. This region harbors two cytokine genes IL-2 and the recently described IL-21.

Methods

We genotyped six variants previously associated with autoimmune disease (namely rs13151961, rs13119723, rs17388568, rs3136534, rs6822844 and rs6840978) and one functional IL-2 promoter variant (rs2069762) for possible association with prostate cancer risk using the Australian Risk Factors for Prostate Cancer case-control Study.

Results

Overall, our results do not support an association between the seven variants at position 4q27 and prostate cancer risk. Per allele odds ratios (ORs) were not significantly different from 1 (all P-values = 0.06). However, we found suggestive evidence for a significant association between the presence of the rs13119723 variant (located in a protein of unknown function) and men with a family history of prostate cancer in first-degree relatives (P-value for interaction 0.02). The per allele OR associated with this variant was significantly higher than 1 (2.37; 95% C.I. = 1.01-5.57).

Conclusions

We suggest that genetic variation within the chromosome 4q27 locus might be associated with prostate cancer susceptibility in men with a family history of the disease. Furthermore, our study alludes to a potential role of unknown protein KIAA1109 in conferring this risk.

Background

Sulfatides (ST) are a category of sulfated galactosylceramides (GalCer) that are elevated in many types of cancer including, possibly, ovarian cancer. Previous evidence for elevation of ST in ovarian cancer was based on a colorimetric reagent that does not provide structural details and can also react with other lipids. Therefore, this study utilized mass spectrometry for a structure-specific and quantitative analysis of the types, amounts, and tissue localization of ST in ovarian cancer, and combined these findings with analysis of mRNAs for the relevant enzymes of ST metabolism to explore possible mechanisms.

Results

Analysis of 12 ovarian tissues graded as histologically normal or having epithelial ovarian tumors by liquid chromatography electrospray ionization-tandem mass spectrometry (LC ESI-MS/MS) established that most tumor-bearing tissues have higher amounts of ST. Because ovarian cancer tissues are comprised of many different cell types, histological tissue slices were analyzed by matrix-assisted laser desorption ionization-tissue-imaging MS (MALDI-TIMS). The regions where ST were detected by MALDI-TIMS overlapped with the ovarian epithelial carcinoma as identified by H & E staining and histological scoring. Furthermore, the structures for the most prevalent species observed via MALDI-TIMS (d18:1/C16:0-, d18:1/C24:1- and d18:1/C24:0-ST) were confirmed by MALDI-TIMS/MS, whereas, a neighboring ion(m/z 885.6) that was not tumor specific was identified as a phosphatidylinositol. Microarray analysis of mRNAs collected using laser capture microdissection revealed that expression of GalCer synthase and Gal3ST1 (3'-phosphoadenosine-5'-phosphosulfate:GalCer sulfotransferase) were approximately 11- and 3.5-fold higher, respectively, in the ovarian epithelial carcinoma cells versus normal ovarian stromal tissue, and they were 5- and 2.3-fold higher in comparison with normal surface ovarian epithelial cells, which is a likely explanation for the higher ST.

Conclusions

This study combined transcriptomic and lipidomic approaches to establish that sulfatides are elevated in ovarian cancer and should be evaluated further as factors that might be important in ovarian cancer biology and, possibly, as biomarkers.