Probiotics under the regulatory microscope

This review examines current knowledge regarding the safety of probiotic bacteria in man. Tighter and more comprehensive standards and regulations will be developed as probiotic therapy moves from a limited number of products used in the food industry, into more defined therapeutic categories and more complex organisms. A new framework considering probiotics as nonspecific promoters of mucosal immunity, defines probiotic characteristics and the clinical circumstances in which it is used. For example, those with immune deficiency taking a high dose of viable bacteria may have an increased risk. A wider range of bacteria is now being used, sometimes in territories other than the gut mucosa. The question of competition with multiple isolates must be addressed, as does the use of nonselected faecal isolates. Transfer of antibiotic resistance with probiotics acting as a 'shuttle' needs clarification. These issues are addressed and reviewed as probiotics evolve into a new therapeutic arena.     

Probiotics under the regulatory microscope

This review examines current knowledge regarding the safety of probiotic bacteria in man. Tighter and more comprehensive standards and regulations will be developed as probiotic therapy moves from a limited number of products used in the food industry, into more defined therapeutic categories and more complex organisms. A new framework considering probiotics as nonspecific promoters of mucosal immunity, defines probiotic characteristics and the clinical circumstances in which it is used. For example, those with immune deficiency taking a high dose of viable bacteria may have an increased risk. A wider range of bacteria is now being used, sometimes in territories other than the gut mucosa. The question of competition with multiple isolates must be addressed, as does the use of nonselected faecal isolates. Transfer of antibiotic resistance with probiotics acting as a ‘shuttle’ needs clarification. These issues are addressed and reviewed as probiotics evolve into a new therapeutic arena.     

Nanomedicine and the complement paradigm

The role of complement in idiosyncratic reactions to nanopharmaceutical infusion is receiving increasing attention. We discuss this in relation to nanopharmaceutical development and the possible use of complement inhibitors to prevent related adverse reactions. We further call on initiation of genetic association studies to unravel the genetic basis of nanomedicine infusion-related adverse responses, since most of the polymorphic genes in the genome belong to the immune system.From the Clinical EditorIn this paper, idiosyncratic reactions based on complement activation are discussed in the context of newly available complement inhibitors.     

A galpha(s) carboxyl-terminal peptide prevents G(s) activation by the A(2A) adenosine receptor

The molecular mechanisms of interaction between G(s) and the A(2A) adenosine receptor were investigated using synthetic peptides corresponding to various segments of the Galpha(s) carboxyl terminus. Synthetic peptides were tested for their ability to modulate binding of a selective radiolabeled agonist, [(3)H]2-[4-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxam idoade nosine ([(3)H]CGS21680), to A(2A) adenosine receptors in rat striatal membranes. The Galpha(s) peptides stimulated specific binding both in the presence and absence of 100 microM guanosine-5'-O-(3-thiotriphosphate) (GTPgammaS). Three peptides, Galpha(s)(378-394)C(379)A, Galpha(s)(376-394)C(379)A, and Galpha(s)(374-394)C(379)A, were the most effective. In the presence of GTPgammaS, peptide Galpha(s)(374-394)C(379)A increased specific binding in a dose-dependent fashion. However, the peptide did not stabilize the high-affinity state of the A(2A) adenosine receptor for [(3)H]CGS21680. Binding assays with a radiolabeled selective antagonist, [(3)H]5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo[4, 3-e]-1,2,4-triazolo[1,5-c]pyrimidine ([(3)H]SCH58261), showed that the addition of the Galpha(s) peptide modified the slope of the 5'-N-ethylcarboxamidoadenosine (NECA) competition curve, suggesting modulation of receptor affinity states. In the presence of GTPgammaS, the displacement curve was right-shifted, whereas the addition of Galpha(s)(374-394)C(379)A caused a partial left-shift. Both curves were fitted by one-site models. This same Galpha(s) peptide was also able to disrupt G(s)-coupled signal transduction as indicated by inhibition of the A(2A) receptor-stimulated adenylyl cyclase activity without affecting either basal or forskolin-stimulated enzymatic activity in the same membrane preparations. Shorter peptides from Galpha(s) and Galpha(i1/2) carboxyl termini were not effective. NMR spectroscopy showed the strong propensity of peptide Galpha(s)(374-394)C(379)A to assume a compact carboxyl-terminal alpha-helical conformation in solution. Overall, our results point out the conformation requirement of Galpha(s) carboxyl-terminal peptides to modulate agonist binding to rat A(2A) adenosine receptors and disrupt signal transduction.     

Nanomedicine applications towards the cure of HIV

Combination antiretroviral therapy (cART) successfully suppresses HIV replication. However, daily and lifelong treatment is necessary to manage patient illness because cART neither eradicates infected cells from reservoirs nor reconstitutes HIV-specific immunity that could kill infected cells. Toward the cure of HIV, different nanomedicine classes have been developed with the following disease-modifying properties: to eradicate the virus by activation of latently infected CD4+ T-cells and reservoirs flushing; to kill the infected cells in the reservoirs by boosting of HIV-specific T cells; and to prevent infection by the use of microbicides with improved epithelial penetration and drug half-life. Preclinical and clinical trials consistently demonstrated that DermaVir, the most advanced nanomedicine, induces long-lasting memory T-cell responses and reduces viral load in comparison with placebo. DermaVir and the nanomedicine pipelines have the potential to improve the health of HIV-infected people at lower costs, to decrease antiretroviral drug exposure, and to contribute to the cure of HIV/AIDS.From the Clinical EditorDespite the leaps and bounds in the development of antiretroviral therapy, HIV remains a significant public health challenge. In this review, applications of nanomedicine- based technologies are discussed in the context of HIV treatment, including virus elimination by activation of latently infected CD4+ T-cells; infected cell elimination in the reservoirs by boosting HIV-specific T cells, and by preventing infection by the use of microbicides with improved epithelial penetration and drug half-life.     

急诊显微手术治疗泪小管断裂

目的探讨泪小管断裂断端的找寻规律和防止术后瘢痕收缩的方法,提高急诊泪小管断裂吻合术的成功率。方法在眼科手术显微镜下仔细寻找11例泪小管断裂患者(含年龄9个月者)的泪小管断端,以硬膜外麻醉导管作支撑管,以眼科9-0尼龙线行三点对位吻合,支撑管留置至术后20～90d。结果11例均成功吻合泪小管,术后20d至3个月拔管后无泪溢。结论术中耐心寻找泪小管断端,仔细对位缝合皮肤,术后以硬膜外麻醉导管作留置支撑管可以提高手术成功率。     

Nanomedicine in the European Commission policy for nanotechnology

Nanomedicine has a critical role as a key enabling technology offering improved and better targeted health care and well-being to the aging European population, one of the grand societal challenges of Europe.The project Nanoparticles for Alzheimer's Disease (NAD), funded by the European Seventh Framework Programme for Research, Technological Development, aims to develop nanotechnology-based targeted delivery systems for in vivo diagnosis and therapy for Alzheimer's disease (AD). The results of the NAD project can have a huge impact on the lives of diseased people, and on the societal economic and social burden.NAD is also part of a cluster of European projects on targeted nanopharmaceuticals and early diagnostics, aiming to create synergies between European cooperative projects having similar objectives to discuss common interests and challenges and facilitate a cross-fertilization across projects.     

高原人附红细胞体的光镜形态特点

目的了解高原环境条件下人附红细胞体的光镜形态特点。方法采集西藏地区(平均海拔4000米)已被感染附红细胞体者121人的末梢血、骨髓涂片、干燥固定,经瑞氏、吉姆萨氏、革兰氏或活体标本在光镜1000倍视野下观察附红细胞体的形态特点。结果血片、骨髓片可见直径为0.3μm～1.2μm×1.0μm～2.0μm,呈多形性,以圆形为主的附红细胞体:多数附着在红细胞表面,亦可在血浆、骨髓浆中见到;排列呈小簇,有的呈花环状、半月状、串珠状;同一视野中可见紫红色、褐黄色、深褐色,也可见到弱折光性发亮的圆形小体。吉姆萨氏染色后,大小、形态、排列等与瑞氏染色相同。革兰氏染色呈阳性。活体标本观察被寄生或感染附红细胞体的红细胞可塑性、变形性受到影响。结论高原环境条件下人附红细胞体光镜形态与非高原地区大致相同。     

Fourth Annual Conference of the American Society for Nanomedicine

The 20th conference of the Society on NeuroImmune Pharmacology will be held March 26-29, 2014. It features the latest in research examining the intersection of neuroscience, immunology and pharmacology, relevant for human health and disease. Particular emphases are placed on HIV and other infectious diseases, and abused substances, including illicit drugs and alcohol.     

On the mechanism(s) of morphine-induced hypothermia

The effects of morphine on core body temperature of mice in the presence or absence of catecholamine receptor antagonists were examined. Administration of different doses of morphine (20, 30 and 40 mg/kg) to mice caused a hypothermic effect. Pre-treatment of animals with the opioid receptor antagonist naloxone (1, 1.5 and 3 mg/kg), the D-2 receptor antagonists sulpiride (25 and 50 mg/kg), pimozide (0.0625, 0.125 and 0.25 mg/kg) and the adenosine receptor antagonist theophylline (25 and 50 mg/kg) decreased the morphine-induced hypothermia. The D-1 receptor antagonist SCH 23390 (0.1 and 0.2 mg/kg), the peripheral D-2 antagonist domperidone (10 and 30 mg/kg), the serotonin (5-HT) antagonist methysergide (5 and 10 mg/kg), the adrenoceptor antagonist phenoxybenzamine (2.5 and 5 mg/kg) and the β-adrenoceptor antagonist propranolol (5 and 10 mg/kg) did not inhibit the morphine response. The antimuscarinic drug atropine (5 and 10 mg/kg) caused a slight decrease in the morphine response. In animals pre-treated with reserpine (5 mg/kg), a hyperthermic response was observed after morphine injection. It is concluded that indirect dopaminergic or adenosine receptor mechanism(s) may be involved in the morphine-induced hypothermia in mice.     

Autoxidation of catechol(amine)s

The autoxidation of nine catecholamines and two catechols as a function of pH was studied. The reaction rate constants of the distinct charged particles, in which catechol(amine)s can appear, are proved to be independent of pH. Autoxidation appears to be a feasible system for the acquisition of data useful for structure (re)activity relationships.     

Nanomedicine and nanotoxicology: two sides of the same coin

Current advances in nanotechnology have led to the development of the new field of nanomedicine, which includes many applications of nanomaterials and nanodevices for diagnostic and therapeutic purposes. The same unique physical and chemical properties that make nanomaterials so attractive may be associated with their potentially calamitous effects on cells and tissues. Our recent study demonstrated that aspiration of single-walled carbon nanotubes elicited an unusual inflammatory response in the lungs of exposed mice with a very early switch from the acute inflammatory phase to fibrogenic events resulting in pulmonary deposition of collagen and elastin. This was accompanied by a characteristic change in the production and release of proinflammatory to anti-inflammatory profibrogenic cytokines, decline in pulmonary function, and enhanced susceptibility to infection. Chemically unmodified (nonfunctionalized) carbon nanotubes are not effectively recognized by macrophages. Functionalization of nanotubes results in their increased recognition by macrophages and is thus used for the delivery of nanoparticles to macrophages and other immune cells to improve the quality of diagnostic and imaging techniques as well as for enhancement of the therapeutic effectiveness of drugs. These observations on differences in recognition of nanoparticles by macrophages have important implications in the relationship between the potentially toxic health effects of nanomaterials and their applications in the field of nanomedicine.     

New technology and clinical applications of nanomedicine: highlights of the second annual meeting of the American Academy of Nanomedicine (Part I)

The Second Annual Meeting of the American Academy of Nanomedicine (AANM) was held at the National Academy of Science Building in Washington, DC, September 9-10, 2006. The program included two Nobel Prize Laureate Lectures, two Keynote Lectures, and 123 invited outstanding State-in-Art lectures presenting in 23 special concurrent symposia. In addition, there were 22 poster presentations in the meeting addressing different areas in nanomedicine research. All of the presenters at the meeting are outstanding investigators and researchers in the field. The Second Annual Meeting of the AANM was a great success. The meeting provides investigators from different world areas a forum and an opportunity for discussion. We believe that nanomedicine research will develop rapidly in the future. The AANM invites basic and clinical researchers from the world to join this exciting research.