The Efficacy of Reboxetine as an Antidepressant, a Meta-analysis of Both Continuous (Mean HAM-D Score) and Dichotomous (Response Rate) Outcomes.

Kobe J Med Sci. 2008;54(2):E147-58

Authors: Chuluunkhuu G, Nakahara N, Yanagisawa S, Kamae I

Reboxetine is the first selective Norepinephrine Reuptake Inhibitor (NRI). There are limited numbers of quantitative synthesis studies of the efficacy of this drug in treating depressive disorders. We have meta-analyzed the efficacy of the reboxetine using both continuous and dichotomous outcome measures. Data was collected from the Pubmed search of English-language studies published from 1997 to 2007 and manual search of retrieved articles. We have searched for controlled clinical trials of reboxetine with any other antidepressant comparator or placebo in adults with depressive disorders using HAM-D scale for the outcome measure. After 11 studies were selected, separate meta-analyses for the active drug and for the placebo were performed using random effect model. The overall effect size compared with the other antidepressants was -0.06 (95%CI: -0.19; 0.08), with placebo -1.54 (95%CI: -2.23; -0.85). It was calculated using the final mean HAM-D score (continuous outcome). The pooled SD was used when the variance was not available. Pooled odds ratios for the response rates (dichotomous outcome) were 1.04 (95%CI: 0.75; 1.46) and 2.85 (95%CI: 1.88; 4.31) for the active drug and placebo comparisons accordingly. These results suggest that the efficacy of the reboxetine and the other antidepressants (SSRI, TCA and SNRI) on both measures does not differ while it is significantly superior to placebo.

PMID: 18772616 [PubMed - in process]

Proline-functionalised calix[4]arene: an anion-triggered hydrogelator.

Chem Commun (Camb). 2008 Sep 7;(33):3900-2

Authors: Becker T, Yong Goh C, Jones F, McIldowie MJ, Mocerino M, Ogden MI

A water-soluble, chiral calix[4]arene has been found to form hydrogels when triggered by the presence of specific anions, with efficacy linked to the Hofmeister series; the gel properties are modified by the associated cations, and gelation can be reversibly switched off by increasing pH.

PMID: 18726028 [PubMed - in process]

[Heart tissue from embryonic stem cells.]

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2008 Sep 8;

Authors: Zimmermann WH

Embryonic stem cells can give rise to all somatic cells, making them an attractive cell source for tissue engineering applications. The propensity of cells to form tissue-like structures in a culture dish has been well documented. We and others made use of this intrinsic property to generate bioartificial heart muscle. First proof-of-concept studies involved immature heart cells mainly from fetal chicken, neonatal rats and mice. They eventually provided evidence that force-generating heart muscle can be engineered in vitro. Recently, the focus shifted to the application of stem cells to eventually enable the generation of human heart muscle and reach following long-term goals: (1) development of a simplified in vitro model of heart muscle development; (2) generation of a human test-bed for drug screening and development; (3) allocation of surrogate heart tissue to myocardial repair applications. This overview will provide the background for cell-based myocardial repair, introduce the main myocardial tissue engineering concepts, discuss the use of embryonic and non-embryonic stem cells, and lays out the potential direct and indirect therapeutic use of human tissue engineered myocardium.

PMID: 18773171 [PubMed - as supplied by publisher]

Editing Antigen Presentation: Antigen Transfer between Human B Lymphocytes and Macrophages Mediated by Class A Scavenger Receptors.

J Immunol. 2008 Sep 15;181(6):4043-51

Authors: Harvey BP, Quan TE, Rudenga BJ, Roman RM, Craft J, Mamula MJ

B lymphocytes can function independently as efficient APCs. However, our previous studies demonstrate that both dendritic cells and macrophages are necessary to propagate immune responses initiated by B cell APCs. This finding led us to identify a process in mice whereby Ag-specific B cells transfer Ag to other APCs. In this study, we report the ability and mechanism by which human B lymphocytes can transfer BCR-captured Ag to macrophages. The transfer of Ag involves direct contact between the two cells followed by the capture of B cell-derived membrane and/or intracellular components by the macrophage. These events are abrogated by blocking scavenger receptor A, a receptor involved in the exchange of membrane between APCs. Macrophages acquire greater amounts of Ag in the presence of specific B cells than in their absence. This mechanism allows B cells to amplify or edit the immune response to specific Ag by transferring BCR-captured Ag to other professional APCs, thereby increasing the frequency of its presentation. Ag transfer may perpetuate chronic autoimmune responses to specific self-proteins and help explain the efficacy of B cell-directed therapies in human disease.

PMID: 18768860 [PubMed - in process]

Sulfhydryl-Based Tumor Antigen-Carrier Protein Conjugates Stimulate Superior Antitumor Immunity against B Cell Lymphomas.

J Immunol. 2008 Sep 15;181(6):4131-40

Authors: Betting DJ, Kafi K, Abdollahi-Fard A, Hurvitz SA, Timmerman JM

Therapeutic vaccination of B cell lymphoma patients with tumor-specific Ig (idiotype, or Id) chemically coupled to the immunogenic foreign carrier protein keyhole limpet hemocyanin (KLH) using glutaraldehyde has shown promising results in early clinical trials, and phase III trials are underway. However, glutaraldehyde Id-KLH vaccines fail to elicit anti-Id immune and clinical responses in many patients, possibly because glutaraldehyde reacts with lysine, cysteine, tyrosine, and histidine residues, damaging critical immunogenic epitopes. A sulfhydryl-based tumor Ag-carrier protein conjugation system using maleimide chemistry was used to enhance the efficacy of Id-KLH vaccines. Maleimide Id-KLH conjugates eradicated A20 lymphoma from most tumor-bearing mice, whereas glutaraldehyde Id-KLH had little efficacy. Maleimide Id-KLH elicited tumor-specific IgG Abs and T cells, with CD8(+) T cells being the major effectors of antilymphoma immunity. Maleimide Id-KLH vaccines also demonstrated superior efficacy in 38C13 and BCL-1 lymphoma models, where Abs were shown to be critical for protection. Importantly, standard glutaraldehyde Id-KLH conjugation procedures could result in "overconjugation" of the tumor Ag, leading to decreased efficacy, whereas the heterobifunctional maleimide-based conjugation yielded potent vaccine product regardless of conjugation duration. Under lysosomal processing conditions, the Id-carrier protein linkage was cleavable only after maleimide conjugation. Maleimide KLH conjugation was easily performed with human Igs analogous to those used in Id-KLH clinical trials. These data support the evaluation of sulfhydryl-based Id-KLH vaccines in lymphoma clinical trials and possibly the use of tumor Ag-carrier protein vaccines for other cancers.

PMID: 18768870 [PubMed - in process]

Prevention of malignant seeding at drain sites after invasive procedures (surgery and/or thoracoscopy) by hypofractionated radiotherapy in patients with pleural mesothelioma.

Acta Oncol. 2008;47(6):1094-8

Authors: Di Salvo M, Gambaro G, Pagella S, Manfredda I, Casadio C, Krengli M

Introduction. Literature data show that mesothelioma cells can implant along the surgical pathway of invasive procedures such as thoracotomy and thoracoscopy. We investigated the use of hypofractionated radiotherapy for preventing such malignant seeding. Material and methods. Thirty-two consecutive patients diagnosed with pleural mesothelioma were included in the present retrospective study. All patients underwent surgery and/or thoracoscopy for diagnosis, staging or talc pleurodesis. They were treated with electron external beam radiation therapy (21 Gy in 3 fractions over 1 week), directed to the surgical pathway after the invasive procedure. After completion of radiation treatment, 20 of 32 patients (63%) underwent chemotherapy. Results. After a mean follow-up of 13.6 months (range 3-41) from the end of radiation therapy, no patient had tumour progression in the treated area. The treatment was well tolerated, as only erythema grade I (Radiation Therapy Oncology Group, RTOG, scale) was noted in 11 patients. Seventeen patients died of disease with local progression after a mean survival time of 12.6 months (range 3-27); thirteen patients are alive with disease after a mean follow-up of 13.9 months (range 4-41); two patients are alive without evidence of disease after a mean follow-up of 16.50 months (range 6-27). Discussion. The present study shows the efficacy and safety of local radiotherapy in preventing malignant seeding after thoracoscopy in patients with pleural mesothelioma although larger prospective trials are probably still needed to validate this treatment approach.

PMID: 18770063 [PubMed - in process]

Hyperelongated biglycan: the surreptitious initiator of atherosclerosis.

Curr Opin Lipidol. 2008 Oct;19(5):448-454

Authors: Little PJ, Osman N, Oʼbrien KD

PURPOSE OF REVIEW: To outline a role for the dermatan sulfate proteoglycan biglycan and specifically its growth factor modified form having elongated glycosaminoglycan chains as being a primary initiator of atherosclerosis. RECENT FINDINGS: Antiatherosclerotic therapies have mostly targeted epidemiologically identified, experimentally confirmed risk factors. The efficacy of such therapies is less than optimal, and rates of cardiovascular disease remain stubbornly high. A variety of targets have been actively pursued, but as yet no new therapy has emerged that specifically targets the vessel wall. One area concerns the role of proteoglycans in the trapping of atherogenic lipoproteins as an early and initiating step in atherogenesis. On the basis of studies in human coronary arteries, the prime proteoglycan for lipoprotein retention is biglycan. The glycosaminoglycan chains on biglycan are subject to regulation that yields several structural changes, but most prominently elongation of the chains to form 'hyperelongated biglycan'. Multiple animal studies and a recent human disorder study have demonstrated the colocalization of atherogenic lipoproteins with biglycan in atherosclerotic lesions. Moreover, in the human atherosclerosis, the deposition of lipid appears to precede the chronic inflammatory response typical of atherosclerotic lesions. SUMMARY: The process of biglycan-associated glycosaminoglycan elongation represents a novel potential therapeutic target worthy of full investigation for the prevention of atherosclerosis.

PMID: 18769225 [PubMed - as supplied by publisher]

Diagnosis and treatment of unexplained infertility.

Rev Obstet Gynecol. 2008;1(2):69-76

Authors: Quaas A, Dokras A

Over the past decade, significant advances have occurred in the diagnosis and treatment of reproductive disorders. In this review, we discuss the routine testing performed to diagnose unexplained infertility. We also discuss additional testing, such as assessment of ovarian reserve, and the potential role of laparoscopy in the complete workup of unexplained infertility. Finally, we outline the available therapeutic options and discuss the efficacy and the cost-effectiveness of the existing treatment modalities. The optimal treatment strategy needs to be based on individual patient characteristics such as age, treatment efficacy, side-effect profile, and cost considerations.

PMID: 18769664 [PubMed - in process]

Does Acupuncture Enhance a Woman's Chance for Pregnancy and a Live Birth?

Rev Obstet Gynecol. 2008;1(2):89

Authors: Kent A

PMID: 18769662 [PubMed - in process]

Lapatinib: A dual tyrosine kinase inhibitor for metastatic breast cancer.

Am J Health Syst Pharm. 2008 Sep 15;65(18):1703-10

Authors: Paul B, Trovato JA, Thompson J

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug and food interactions, dosage and administration, and role in therapy of lapatinib in metastatic breast cancer are reviewed. SUMMARY: Lapatinib is a small-molecule tyrosine kinase inhibitor that dually targets human epidermal growth factor receptors 1 and 2 (HER2). Unlike trastuzumab, lapatinib enters the cell and binds to the intracellular domain of the tyrosine kinase receptor, allowing for complete blockage of the autophosphorylation reaction and a complete halt to the downstream cascade of events. After oral administration, lapatinib reaches peak plasma levels within approximately 4 hours, steady-state levels within six to seven days, and has a half-life of 24 hours. Combination therapy with lapatinib and capecitabine has demonstrated superior time to progression compared with capecitabine monotherapy for the treatment of HER2-positive metastatic breast cancer refractory to anthracycline-, taxane-, and trastuzumab-containing regimens. Unlike trastuzumab, lapatinib is an orally active agent with promising clinical activity in metastatic breast cancer and is associated with a better adverse-effect profile. The most frequently reported adverse events in patients receiving combination therapy with lapatinib and capecitabine were diarrhea and hand-foot syndrome. Ongoing research has further evaluated the safety of lapatinib regarding cardiac effects and found that the majority of left ventricular ejection fraction decreases from baseline were asymptomatic and reversible. CONCLUSION: Lapatinib has demonstrated efficacy in combination with capecitabine in patients with previously treated HER2-positive metastatic breast cancer. In patients with metastatic disease refractory to trastuzumab-, anthracycline-, and taxane-containing regimens, the addition of lapatinib to capecitabine may extend the time to disease progression and progression-free survival.

PMID: 18768996 [PubMed - in process]

Modified vancomycin dosing protocol for treatment of diabetic foot infections.

Am J Health Syst Pharm. 2008 Sep 15;65(18):1740-3

Authors: Niu SC, Deng ST, Lee MH, Ho C, Chang HY, Liu FH

PURPOSE: The clinical efficacy of a modified vancomycin dosing protocol with a conventional regimen for managing patients with diabetic foot infections caused by methicillin-resistant Staphylococcus aureus (MRSA) was evaluated. METHODS: This prospective study was conducted from January 2002 to December 2004 at the diabetic ward of Chang Gung Memorial Hospital-Linkou in Taiwan. All diabetic patients with MRSA-related diabetic foot infections confirmed by wound cultures were enrolled in this study. Patients treated with the conventional protocol (from 2002 to 2003) received vancomycin 10-15 mg/kg (up to 1 g) over 60 minutes every 12 hours if their serum creatinine (SCr) concentration was 0.4-1.4 mg/dL according to the estimation of creatinine clearance (CL(cr)). Patients treated with the modified vancomycin dosing protocol (from 2003 to 2004) received vancomycin according to their SCr level, age, and concurrent gentamicin dosage. Data analyzed included patients' age, sex, body weight, SCr level, CL(cr), serum vancomycin peak and trough levels, vancomycin dosage, treatment period, and duration of hospital stay. RESULTS: A total of 85 patients were enrolled in this study. The conventional protocol group achieved substantially higher serum vancomycin levels than those recommended by the British National Formulary (BNF). Although the vancomycin dosage in the modified protocol was lower than that in the conventional protocol, trough and peak vancomycin levels remained within the range recommended by the BNF. The duration of hospitalization and treatment did not significantly differ between the two groups. CONCLUSION: A modified vancomycin dosing protocol for treating diabetic foot infections caused by MRSA was superior to the conventional dosing regimen in achieving therapeutic serum levels of vancomycin.

PMID: 18769001 [PubMed - in process]

Tension neck syndrome treated by acupuncture combined with physiotherapy: A comparative clinical trial (pilot study).

Complement Ther Med. 2008 Oct;16(5):268-77

Authors: França DL, Senna-Fernandes V, Cortez CM, Jackson MN, Bernardo-Filho M, Guimarães MA

OBJECTIVE: To evaluate the effect of acupuncture combined with physiotherapy in comparison with acupuncture and physiotherapy performed alone in different parameters; pain intensity, muscle tension, functional disability and muscle strength in the treatment of tension neck syndrome (TNS). DESIGN: A prospective, comparative clinical trial. SETTING: Acupuncture and Rehabilitation Department. BACKGROUND: TNS can occur in computer users. Acupuncture has been one alternative treatment in physiotherapeutic rehabilitation of musculoskeletal disorders. SUBJECTS: Forty-six patients with TNS. Interventions: Patients were allocated into three groups: Group-1 received physiotherapy (therapeutic exercises) combined with acupuncture; Group-2, acupuncture alone, and Group-3, physiotherapy alone; over a period of 10 weeks, with one or two sessions weekly. OUTCOME ASSESSMENT: All patients had completed the protocols and were assessed using a visual analogue scale for pain intensity (VAS(pain)) and muscle tension (VAS(mt)), the Neck Disability Index: Brazilian Portuguese version for functional disability, and the cranio-cervical Flexion Test for isometric neck muscle strength (INMS); in the periods before treatment (baseline), after 10 weeks of treatment, and after 6 months of follow-up. RESULTS: All groups showed significant improvement (p<0.001) in these parameters after 10 weeks of treatment and after 6 months of follow-up. Group-1 was superior to Group-3 in pain and functional disability improvements (p<0.05); and Group-1 was superior to both Group-2 (p<0.01) and Group-3 (p<0.05) in INMS. After 6 months of follow-up, the improvements of all groups were maintained (p<0.05). CONCLUSION: The data suggested that acupuncture effect may facilitate and/or enhance physiotherapy performance in musculoskeletal rehabilitation for tension neck syndrome.

PMID: 18765182 [PubMed - in process]

Pharmacokinetics, efficacy and safety of IMMUNATE solvent/detergent (IMMUNATE S/D) in previously treated patients with severe hemophilia A: results of a prospective, multicenter, open-label phase III study.

Acta Haematol. 2008;119(2):89-97

Authors: Nemes L, Lissitchkov T, Dobaczewski G, Klukowska A, Komrska V, Zimmermann R, Auerswald G, Engl W, Abbühl B, Pavlova BG, Ehrlich HJ

BACKGROUND: IMMUNATE Solvent/Detergent (S/D) is a plasma-derived, human factor VIII (FVIII)/von Willebrand factor (VWF) complex subjected to S/D and vapor heat treatment. METHODS: This prospective clinical study evaluated the pharmacokinetics (PK) (compared to IMMUNATE), efficacy and safety of IMMUNATE S/D in 56 previously treated patients with severe hemophilia A. Subjects received IMMUNATE S/D either on-demand (47/56), as a prophylactic regimen (49/56), or both (40/56). RESULTS: IMMUNATE and IMMUNATES/D were equivalent with respect to the FVIII and VWF PK parameters assessed. Bleeding episodes (623) were reported in 47/56 subjects. For 89% of episodes, subjects required only 1 infusion with a mean dose of 29.6 IU/kg and 96% of episodes had an excellent or good response. The duration of prophylaxis ranged from 0.1 to 5.2 months. The median number of bleeds per month in subjects on prophylaxis was 0 (range 0-10). No FVIII inhibitory antibodies were observed in 56 subjects after 2,646 treatment exposure days. No related serious adverse events were reported. CONCLUSION: The introduction of S/D treatment did not alter the PK characteristics and function of VWF and FVIII molecules in IMMUNATE S/D which is effective and safe for treatment of bleeding episodes, management of surgical procedures and prophylaxis.

PMID: 18305381 [PubMed - indexed for MEDLINE]

Effects of Tai Chi on gait kinematics, physical function, and pain in elderly with knee osteoarthritis--a pilot study.

Am J Chin Med. 2008;36(2):219-32

Authors: Shen CL, James CR, Chyu MC, Bixby WR, Brismée JM, Zumwalt MA, Poklikuha G

Our previous study has demonstrated that 6 weeks of Tai Chi exercise significantly improves knee pain and stiffness in elderly with knee osteoarthritis. This study also examine the effects of Tai Chi exercise on gait kinematics, physical function, pain, and pain self-efficacy in elderly with knee osteoarthritis. In this prospective, pretest-posttest clinical trial, 40 men and women (64.4+/-8.3 years) diagnosed with knee osteoarthritis participated in 6 weeks of instructed Tai Chi training, 1 hour/session, 2 sessions/week. The following measures were taken at baseline and the conclusion of the intervention: (a) gait kinematics including stride length, stride frequency, and gait speed quantified using video analysis, (b) physical function, (c) knee pain, and (d) pain self-efficacy. Data were analyzed using repeated MANCOVA, MANOVA, ANOVA and Wilcoxon tests. After 6 weeks of Tai Chi exercise, stride length (p=0.023; 1.17+/-0.17 vs. 1.20+/-0.14 m), stride frequency (p=0.014; 0.91+/-0.08 vs. 0.93+/-0.08 strides/s), and consequently gait speed (p<0.025; 1.06+/-0.19 vs. 1.12+/-0.15 m/s) increased in the participants. Physical function was significantly improved (p<0.001) and knee pain was significantly decreased (p=0.002), while no change was observed in pain self-efficacy. In conclusion, these findings support that Tai Chi is beneficial for gait kinematics in elderly with knee osteoarthritis, and a longer term application is needed to substantiate the effect of Tai Chi as an alternative exercise in management of knee osteoarthritis.

PMID: 18457357 [PubMed - indexed for MEDLINE]

Medical device regulations and testing for toxicologic pathologists.

Toxicol Pathol. 2008;36(1):63-9

Authors: Schuh JC

Awareness of the regulatory environment is fundamental to understanding the biological assessment of biomaterials and medical devices. Medical devices are a diverse and heterogeneous group of medical products and technologies defined by the lack of chemical action or requirement for metabolism. Regional activity and the Global Harmonization Task Force are now working on harmonizing the categorization and testing of medical devices. The International Organization for Standardization (ISO) has published 19 standards for biological evaluation. ISO 10993 standards are generally accepted outright or as an alternative to most national regulatory directives or acts, although Japan and the United States require more stringency in some tests. Type of materials, intended use, and risk are the basis for drafting testing programs for biomaterials and medical devices. With growth of the medical device industry and advent of new biomaterials and technologies, the need for toxicologic pathologists in safety (biocompatibility) and efficacy (conditions of use) evaluation of moderate- to high-risk devices is expanding. Preclinical evaluation of biomaterials and medical devices increasingly requires a basic understanding of materials science and bioengineering to facilitate interpretation of complex interface reactions between biomaterials, cellular and secretory factors, and vascular and tissue responses that modulate success or failure of medical devices.

PMID: 18337222 [PubMed - indexed for MEDLINE]

Chapter 4 B cells and autoantibodies in the pathogenesis of multiple sclerosis and related inflammatory demyelinating diseases.

Adv Immunol. 2008;98:121-49

Authors: McLaughlin KA, Wucherpfennig KW

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). The mainstream view is that MS is caused by an autoimmune attack of the CNS myelin by myelin-specific CD4 T cells, and this perspective is supported by extensive work in the experimental autoimmune encephalomyelitis (EAE) model of MS as well as immunological and genetic studies in humans. However, it is important to keep in mind that other cell populations of the immune system are also essential in the complex series of events leading to MS, as exemplified by the profound clinical efficacy of B cell depletion with Rituximab. This review discusses the mechanisms by which B cells contribute to the pathogenesis of MS and dissects their role as antigen-presenting cells (APCs) to T cells with matching antigen specificity, the production of proinflammatory cytokines and chemokines, as well as the secretion of autoantibodies that target structures on the myelin sheath and the axon. Mechanistic dissection of the interplay between T cells and B cells in MS may permit the development of B cell based therapies that do not require depletion of this important cell population.

PMID: 18772005 [PubMed - in process]

Chapter 1 ginsenosides chemistry, biosynthesis, analysis, and potential health effects.

Adv Food Nutr Res. 2008;55:1-99

Authors: Christensen LP

Ginsenosides are a special group of triterpenoid saponins that can be classified into two groups by the skeleton of their aglycones, namely dammarane- and oleanane-type. Ginsenosides are found nearly exclusively in Panax species (ginseng) and up to now more than 150 naturally occurring ginsenosides have been isolated from roots, leaves/stems, fruits, and/or flower heads of ginseng. Ginsenosides have been the target of a lot of research as they are believed to be the main active principles behind the claims of ginsengs efficacy. The potential health effects of ginsenosides that are discussed in this chapter include anticarcinogenic, immunomodulatory, anti-inflammatory, antiallergic, antiatherosclerotic, antihypertensive, and antidiabetic effects as well as antistress activity and effects on the central nervous system. Ginsensoides can be metabolized in the stomach (acid hydrolysis) and in the gastrointestinal tract (bacterial hydrolysis) or transformed to other ginsenosides by drying and steaming of ginseng to more bioavailable and bioactive ginsenosides. The metabolization and transformation of intact ginsenosides, which seems to play an important role for their potential health effects, are discussed. Qualitative and quantitative analytical techniques for the analysis of ginsenosides are important in relation to quality control of ginseng products and plant material and for the determination of the effects of processing of plant material as well as for the determination of the metabolism and bioavailability of ginsenosides. Analytical techniques for the analysis of ginsenosides that are described in this chapter are thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) combined with various detectors, gas chromatography (GC), colorimetry, enzyme immunoassays (EIA), capillary electrophoresis (CE), nuclear magnetic resonance (NMR) spectroscopy, and spectrophotometric methods.

PMID: 18772102 [PubMed - in process]

Selection of IgE-binding aptameric green fluorescent protein (Ap-GFP) by the ribosome display (RD) platform.

Biochem Biophys Res Commun. 2008 Sep 26;374(3):409-14

Authors: Chen SS, Yang YM, Barankiewicz TJ

GFP-Ckappa fusion protein was previously shown selectable on ribosome display platform with solid phase antibodies against GFP determinant [Y.-M. Yang, T.J. Barankiewicz, M. He, M. Taussig, S.-S. Chen, Selection of antigenic markers on a GFP-Ckappa fusion scaffold with high sensitivity by eukaryotic ribosome display, Biochem. Biophys. Res. Commun. 359 (2007) 251-257]. Herein, we show that members of aptameric peptide library constructed within the site 6 and site 8/9 loops of GFP of the ribosome display construct are selectable upon binding to the solid phase IgE antigen. An input of 1.0 microg of the dual site aptameric GFP library exhibiting a diversity of 7.5x10(11) was transcribed, translated and incubated with solid phase IgE. RT-PCR products were amplified from mRNA of the aptamer-ribosome-mRNA (ARM) complex captured on the solid phase IgE. Clones of aptameric GFP were prepared from RT-PCR product of ARM complex following repetitive selection. Recombinant aptameric GFP proteins from the selected clones bind IgE coated on the 96-well plate, and the binding was abrogated by incubation with soluble human IgE but not human IgG. Selected aptameric GFP proteins also exhibit binding to three different sources of human IgE (IgE PS, BED, and JW8) but not irrelevant proteins. These observations indicate that appropriately selected aptameric GFP on a solid phase ligand by ribosome display may serve as an affinity reagent for blocking reactivity of a biological ligand.

PMID: 18619414 [PubMed - indexed for MEDLINE]

Microbiological risk assessment in stem cell manipulation.

Crit Rev Microbiol. 2008;34(1):1-12

Authors: Pessina A, Bonomi A, Baglio C, Cavicchini L, Sisto F, Neri MG, Gribaldo L

Cell therapy based on the use of human stem cells is more complicated than transfusion or organ transplantation because cells may undergo many additional manipulations due to different treatments for isolation, expansion, differentiation, and other types of biological changes. These manipulations require the approval of regulatory agencies (other than ethical) and the processes must be monitored with more tests than the ones applied for minimally manipulated cells. The clinical safety and efficacy of transplanted cells depend on several factors such as homologous or non-homologous sources, extent of manipulation, and culture conditions. Moreover, the kind of information needed to address these issues may differ depending on whether the cells are to be used for tissue reconstruction or repair, or to recover metabolic functions. Also anatomical site, functional integration as well as duration of therapy, are crucial points that indirectly can influence safety. Many important assays have been suggested for environmental monitoring as well as to standardize microbiological controls in stem cell banks to prevent contamination. In order to guarantee safety two main aspects must be considered: one is related to the source of cells (the donor) and the other is depending on cell collection and processing. In this review we critically analyze the steps of the processes (from collection to banking) and consider the main factors involved in the clinical research (continuously in evolution) by suggesting a standardized facsimile form to use in the laboratory for the assessment of the microbiological risk related to the cell manipulations.

PMID: 18259977 [PubMed - indexed for MEDLINE]

The Efficacy of Reboxetine as an Antidepressant, a Meta-analysis of Both Continuous (Mean HAM-D Score) and Dichotomous (Response Rate) Outcomes.

Kobe J Med Sci. 2008;54(2):E147-58

Authors: Chuluunkhuu G, Nakahara N, Yanagisawa S, Kamae I

Reboxetine is the first selective Norepinephrine Reuptake Inhibitor (NRI). There are limited numbers of quantitative synthesis studies of the efficacy of this drug in treating depressive disorders. We have meta-analyzed the efficacy of the reboxetine using both continuous and dichotomous outcome measures. Data was collected from the Pubmed search of English-language studies published from 1997 to 2007 and manual search of retrieved articles. We have searched for controlled clinical trials of reboxetine with any other antidepressant comparator or placebo in adults with depressive disorders using HAM-D scale for the outcome measure. After 11 studies were selected, separate meta-analyses for the active drug and for the placebo were performed using random effect model. The overall effect size compared with the other antidepressants was -0.06 (95%CI: -0.19; 0.08), with placebo -1.54 (95%CI: -2.23; -0.85). It was calculated using the final mean HAM-D score (continuous outcome). The pooled SD was used when the variance was not available. Pooled odds ratios for the response rates (dichotomous outcome) were 1.04 (95%CI: 0.75; 1.46) and 2.85 (95%CI: 1.88; 4.31) for the active drug and placebo comparisons accordingly. These results suggest that the efficacy of the reboxetine and the other antidepressants (SSRI, TCA and SNRI) on both measures does not differ while it is significantly superior to placebo.

PMID: 18772616 [PubMed - in process]

Proline-functionalised calix[4]arene: an anion-triggered hydrogelator.

Chem Commun (Camb). 2008 Sep 7;(33):3900-2

Authors: Becker T, Yong Goh C, Jones F, McIldowie MJ, Mocerino M, Ogden MI

A water-soluble, chiral calix[4]arene has been found to form hydrogels when triggered by the presence of specific anions, with efficacy linked to the Hofmeister series; the gel properties are modified by the associated cations, and gelation can be reversibly switched off by increasing pH.

PMID: 18726028 [PubMed - in process]

[Heart tissue from embryonic stem cells.]

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2008 Sep 8;

Authors: Zimmermann WH

Embryonic stem cells can give rise to all somatic cells, making them an attractive cell source for tissue engineering applications. The propensity of cells to form tissue-like structures in a culture dish has been well documented. We and others made use of this intrinsic property to generate bioartificial heart muscle. First proof-of-concept studies involved immature heart cells mainly from fetal chicken, neonatal rats and mice. They eventually provided evidence that force-generating heart muscle can be engineered in vitro. Recently, the focus shifted to the application of stem cells to eventually enable the generation of human heart muscle and reach following long-term goals: (1) development of a simplified in vitro model of heart muscle development; (2) generation of a human test-bed for drug screening and development; (3) allocation of surrogate heart tissue to myocardial repair applications. This overview will provide the background for cell-based myocardial repair, introduce the main myocardial tissue engineering concepts, discuss the use of embryonic and non-embryonic stem cells, and lays out the potential direct and indirect therapeutic use of human tissue engineered myocardium.

PMID: 18773171 [PubMed - as supplied by publisher]

Editing Antigen Presentation: Antigen Transfer between Human B Lymphocytes and Macrophages Mediated by Class A Scavenger Receptors.

J Immunol. 2008 Sep 15;181(6):4043-51

Authors: Harvey BP, Quan TE, Rudenga BJ, Roman RM, Craft J, Mamula MJ

B lymphocytes can function independently as efficient APCs. However, our previous studies demonstrate that both dendritic cells and macrophages are necessary to propagate immune responses initiated by B cell APCs. This finding led us to identify a process in mice whereby Ag-specific B cells transfer Ag to other APCs. In this study, we report the ability and mechanism by which human B lymphocytes can transfer BCR-captured Ag to macrophages. The transfer of Ag involves direct contact between the two cells followed by the capture of B cell-derived membrane and/or intracellular components by the macrophage. These events are abrogated by blocking scavenger receptor A, a receptor involved in the exchange of membrane between APCs. Macrophages acquire greater amounts of Ag in the presence of specific B cells than in their absence. This mechanism allows B cells to amplify or edit the immune response to specific Ag by transferring BCR-captured Ag to other professional APCs, thereby increasing the frequency of its presentation. Ag transfer may perpetuate chronic autoimmune responses to specific self-proteins and help explain the efficacy of B cell-directed therapies in human disease.

PMID: 18768860 [PubMed - in process]

Sulfhydryl-Based Tumor Antigen-Carrier Protein Conjugates Stimulate Superior Antitumor Immunity against B Cell Lymphomas.

J Immunol. 2008 Sep 15;181(6):4131-40

Authors: Betting DJ, Kafi K, Abdollahi-Fard A, Hurvitz SA, Timmerman JM

Therapeutic vaccination of B cell lymphoma patients with tumor-specific Ig (idiotype, or Id) chemically coupled to the immunogenic foreign carrier protein keyhole limpet hemocyanin (KLH) using glutaraldehyde has shown promising results in early clinical trials, and phase III trials are underway. However, glutaraldehyde Id-KLH vaccines fail to elicit anti-Id immune and clinical responses in many patients, possibly because glutaraldehyde reacts with lysine, cysteine, tyrosine, and histidine residues, damaging critical immunogenic epitopes. A sulfhydryl-based tumor Ag-carrier protein conjugation system using maleimide chemistry was used to enhance the efficacy of Id-KLH vaccines. Maleimide Id-KLH conjugates eradicated A20 lymphoma from most tumor-bearing mice, whereas glutaraldehyde Id-KLH had little efficacy. Maleimide Id-KLH elicited tumor-specific IgG Abs and T cells, with CD8(+) T cells being the major effectors of antilymphoma immunity. Maleimide Id-KLH vaccines also demonstrated superior efficacy in 38C13 and BCL-1 lymphoma models, where Abs were shown to be critical for protection. Importantly, standard glutaraldehyde Id-KLH conjugation procedures could result in "overconjugation" of the tumor Ag, leading to decreased efficacy, whereas the heterobifunctional maleimide-based conjugation yielded potent vaccine product regardless of conjugation duration. Under lysosomal processing conditions, the Id-carrier protein linkage was cleavable only after maleimide conjugation. Maleimide KLH conjugation was easily performed with human Igs analogous to those used in Id-KLH clinical trials. These data support the evaluation of sulfhydryl-based Id-KLH vaccines in lymphoma clinical trials and possibly the use of tumor Ag-carrier protein vaccines for other cancers.

PMID: 18768870 [PubMed - in process]