Effect of BDE-209 on glutathione system in Carassius auratus

In this study, the oxidative stress induced by deca-polybromodiphenyl ether (BDE-209) was investigated in livers of Carassius auratus. Six groups of fish were exposed to blank and 0, 0.004, 0.04, 0.4, 4 μM BDE-209 (in 0.1% DMSO) for 1, 4, 7, 10, 13 d, respectively. The following oxidative stress markers were analyzed: reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidases (GPx) and glutathione S-transferases (GSTs). No significant difference was observed in the content of GSH over the whole period of exposure (p > 0.05). Increases in hepatic GR and GPx activities were in concomitant with the decrease in GST activity. GR activity was induced after 1 d exposure, while GPx activity reached maximum at 4 d after exposure to 0.04 μM BDE-209 and GST activity was significantly inhibited at 7-13 d in all the treatment groups (0.004-4 μM group).     

Characteristics of dimeric (bis) bidentate selective high affinity ligands as HLA-DR10 beta antibody mimics targeting non-Hodgkin's lymphoma

Despite their large size, antibodies have proven to be suitable radioisotope carriers to deliver systemic radiotherapy, often molecular image-based, for lymphoma and leukemia. To mimic antibody (Ab) targeting behavior while decreasing size by 50-100x, a combination of computational and experimental methods were used to generate molecules that bind to unique sites within the HLA-DR epitopic region of Lym-1, an Ab shown effective in patients. Lym-1 Ab mimics (synthetic high afinity ligands; SHALs) were generated and studied in vitro, using live cell binding assays, and/or pharmacokinetic studies over 24 h in xenografted mice given 1 or 20 microg SHAL doses i.v. Multimilligram amounts of each of the dimeric (bis) SHALs were synthesized at high purity, and labeled with indium-111 at high specific activity and purity. These SHALs were selective for HLA-DR and HLA-DR expressing malignant cells and had functional affinities that ranged from 10(-9) M (nanomolar) to 10(-10) M. Blood clearances ranged from 3.6 to 9.5 h and body clearances ranged from 15.2 to 43.0 h for the 6 bis DOTA-SHALs studied in a mouse model for non-Hodgkin's lymphoma (NHL). While localization was shown in Raji NHL xenografts, biodistribution was influenced by 'sinks' for individual ligands of the SHALs. Highly pure, dimeric mimics for HLA-DR Ab were synthesized, biotinylated and radiolabeled, and showed selectivity in vitro. Pharmacokinetic behavior in mice was influenced by the ligands and by the linker length of the dimeric SHALs. Nanomolar or better functional affinity was observed when a suitably long linker was used to connect the two bidentate SHALs. The concept and methodology are of interest because applicable for targeting most proteins; the SHAL synthetic platform is highly efficient and adaptive.     

Whole-hand sensorimotor area: cortical stimulation localization and correlation with functional magnetic resonance imaging

OBJECT: The pli de passage moyen (PPM) is an omega-shaped cortical landmark bulging into the central sulcus. There has been considerable interest in the PPM given that hand motor and sensory tasks have been found on functional magnetic resonance (fMR) imaging to activate the structure. Note, however, that the cortical function subserved by the PPM is not completely understood. Finger and thumb function are somatotopically organized over the central area and encompass a larger cortical surface than the anatomical PPM. Therefore, a sensory or motor hand area within the PPM would be redundant with the somatotopically organized digit function in the primary sensorimotor cortex. In this study the authors aimed to clarify the function subserved by the PPM and further evaluate hand area function in the primary sensorimotor cortex. METHODS: To further elucidate the function subserved by the PPM, patients underwent cortical stimulation in the region of the PPM as well as fMR imaging-demonstrated activation of the hand area. Two separate analytical methods were used to correlate hand area functional imaging with whole-hand sensory and motor responses induced by cortical stimulation. RESULTS: A relationship of the anatomical PPM with cortical stimulation responses as well as hand fMR imaging activation was observed. CONCLUSIONS: A strong relationship was identified between the PPM, whole-hand sensory and motor stimulation responses, and fMR imaging hand activation. Whole-hand motor and whole-hand sensory cortical regions were identified in the primary sensorimotor cortex. It was localized to the PPM and exists in addition to the somatotopically organized finger and thumb sensory and motor areas.     

From combinatorial chemistry to cancer-targeting peptides

Several monoclonal antibodies that target cell surface receptors have gained approval by the U.S. Food and Drug Administration and are widely used in the treatment of some cancers. These include but are not limited to the anti-CD20 antibody Rituximab, used in lymphoma treatment, as well as anti-HER-2 antibody for breast cancer therapy. The efficacy of this cancer immunotherapy modality is, however, limited by the large size of the antibody (160 kd) and its relatively nonspecific binding to the reticuloendothelial system. This latter property is particularly problematic if the antibody is used as a vehicle to deliver radionuclides, cytotoxic drugs, or toxins to the tumor site. Peptides, peptidomimetic, or small molecules are thus attractive as alternative cell surface targeting agents for cancer imaging and therapy. Cancer cell surface targeting peptides can be derived from known native peptide hormones such as somatostatin and bombesin, or they can be identified through screening combinatorial peptide libraries against unknown cell surface receptor targets. Phage-display peptide library and one-bead one-compound (OBOC) combinatorial library methods have been successfully used to discover peptides that target cancer cells or tumor blood vessel endothelial cells. The phage-display peptide library method, because of its biological nature, can only display l-amino acid peptides. In contrast, the OBOC combinatorial library method allows for bead-surface display of peptides that contain l-amino acids, d-amino acids, unnatural amino acids, or other organic moieties. We have successfully used the OBOC method to discover and optimize ligands against unique cell surface receptors of prostate cancer, T- and B-cell lymphoma, as well as ovarian and lung cancers, and we have used some of these peptides to image xenografts in nude mice with high specificity. Here, we (i) review the literature on the use of phage-display and OBOC combinatorial library methods to discover cancer and tumor blood vessel targeting ligands, and (ii) report on the use of an ovarian cancer targeting ligand, OA02, as an in vivo PET imaging probe in a xenograft model in nude mice.     

Antibiotic resistance in bacteria - an emerging public health problem

The discovery and eventual introduction of anti-microbial agents to clinical medicine was one of the greatest medical triumphs of the twentieth century that revolutionized the treatment of bacterial diseases. However, the gradual emergence of populations of antibiotic-resistant bacteria resulting from use, misuse and outright abuse of antibiotics has today become a major public health problem of global proportions. This review paper examines the origins and molecular epidemiology of resistance genes, global picture of antibacterial resistance, factors that favour its spread, strategies for its control, problems of control and the consequences of failure to contain antibiotic resistance in bacteria.     

Storage temperature and viability of sporangiospores of potentially human pathogenic species of Rhizomucor from Nigerian tobacco

The effects of temperature on storage and viability of asexual spores of Rhizomucor pusillus (Lindt) Schipper and Rhizomucor miehei (Cooney and Emerson) Schipper were studied. An optimal germination temperature of 35 degrees C was recorded for both species with good results obtained around 40 degrees C. On prolonged storage of the spores at various temperatures (-19 degrees C, 4 degrees C, 30 degrees C, 37 degrees C), the best results were obtained at 4 degrees C and 30 degrees C. Very rapid losses in viability of the spores of both fungi occurred at -19 degrees C reaching a maximum of 68% and 51%, respectively, for R. pusillus and R. miehei after 6 months of storage. Continuous exposure of the spores to 68 degrees C led to rapid losses of viability of up to 100% for those of R. pusillus after 40 min exposure. Sporangiospores of R. miehei showed more gradual losses on exposure to 68 degrees C. The potential health hazards which the presence of these fungi on tobacco products pose to man are discussed.     

Doing participant observation in a psychiatric hospital-- research ethics resumed

Social scientists who employ participant observation methods in medical settings are often held accountable for their research methods, specifically in regard to medical research ethics. However, the medical research ethics tradition rubs uneasily against participant observation and the anthropological understanding of the research process. The underlying premise for considering research ethics in the current case is the notion of the vulnerability of psychiatric patients as a participant group. Based on this notion of vulnerability among psychiatric patients, this article discusses the epistemological grounds for vulnerability in anthropological and medical research ethics. The authors draw on their experience with the Regional Committee for Medical Research Ethics in Norway, and the consequences of the guidelines used for participant observation as a research method in a psychiatric hospital. Social science researchers are required to follow medical ethical guidelines, such as informed consent, the principle of voluntariness, and estimation of risks and benefits. Ethnographers have found these guidelines to be obstructive when doing social science research in a psychiatric hospital. The article suggests the need for reformulation of research guidelines for participant observation in medical settings.     

How bilingualism shapes the functional architecture of the brain: A study on executive control in early bilinguals and monolinguals

The existence of a behavioral advantage of bilinguals over monolinguals during executive tasks is controversial. A new approach to this issue is to investigate the effect of bilingualism on neural control when performing these tasks as a window to understand when behavioral differences are produced. Here, we tested if early bilinguals use more language‐related networks than monolinguals while performing a go/no‐go task that includes infrequent no‐go and go trials. The RTs and accuracy in both groups did not differ. An independent component analyses (ICA) revealed, however, that bilinguals used the left fronto‐parietal network and the salience network more than monolinguals while processing go infrequent cues and no‐go cues, respectively. It was noteworthy that the modulation of these networks had opposite correlates with performance in bilinguals and monolinguals, which suggests that between‐group differences were more qualitative than quantitative. Our results suggest that bilinguals may differently develop the involvement of the executive control networks that comprise the left inferior frontal gyrus during cognitive control tasks than monolinguals. Hum Brain Mapp 36:5101–5112, 2015. © 2015 Wiley Periodicals, Inc.