Outbreak of Antiviral Drug�CResistant Influenza A in Long-Term Care Facility, Illinois, USA, 2008

An outbreak of oseltamivir-resistant influenza A (H1N1) occurred in a long-term care facility. Eight (47%) of 17 and 1 (6%) of 16 residents in 2 wards had oseltamivir-resistant influenza A virus (H1N1) infections. Initial outbreak response included treatment and prophylaxis with oseltamivir. The outbreak abated, likely because of infection control measures.     

Protection afforded by intranasal immunization with the neuraminidase-lacking mutant of influenza A virus in a ferret model

Protective efficacy of the intranasal immunization with the neuraminidase (NA)-deficient mutant of the influenza A virus was investigated in ferrets. Despite the highly attenuated replication in vivo, the mutant completely protected the animals against the wild type virus challenge. When challenge was done with antigenic drift variants, significant reductions in the viral titers, inflammatory cell counts, and protein concentrations were observed in the nasal washes of the immunized animals. The genetically engineered NA-deficient mutant also protected animals against the challenge and induced humoral immune response against the foreign protein that replaced the NA. We conclude that the NA as antigen is dispensable in the live attenuated influenza virus vaccine and that the NA-lacking mutant can be used as a virus vector.     

CENTRAL NEUROGENIC NEUROPROTECTION: PROTECTION OF BRAIN FROM FOCAL ISCHEMIA BY CEREBELLAR STIMULATION

Electrical stimulation of the cerebellar fastigial nucleus (FN) elevates regional cerebral blood flow (rCBF) independently of cerebral metabolism (rCGU) throughout brain. One hour of FN stimulation also reduces, by up to 50%, the volume of the focal ischemic infarction produced by occlusion of the middle cerebral artery in rat. Protected areas correspond to the ischemic penumbra. Neuroprotection, while reversible, persists for weeks after 1h of stimulation. It cannot be attributed to increasing rCBF and/or reducing rCGU to improve matching of flow and metabolism. Conditional stimulation of FN initiates long-lived inhibition of expression of peri-infarction depolarizing waves, possibly by altering potassium-channel function and suppresses induction of inducible nitric oxide synthase (iNOS) and ICAM in cerebral microvessels. The brain contains intrinsic networks which may protect the brain from ischemic injury, possibly by producing widespread and longterm suppression of electrical excitability and/or and expression of proinflammatory molecules.     

Morphological Evaluation of the Tissue Reaction to Subcutaneous Implantation of Decellularized Matrices

Bulletin of Experimental Biology and Medicine - Based on the data of morphological analysis, we performed histological evaluation of rat tissue reaction to subcutaneous implantation of...     

Whole Organ and Tissue Reconstruction in Thoracic Regenerative Surgery

Development of novel prognostic, diagnostic, and treatment options will provide major benefits for millions of patients with acute or chronic respiratory dysfunction, cardiac-related disorders, esophageal problems, or other diseases in the thorax. Allogeneic organ transplant is currently available. However, it remains a trap because of its dependency on a very limited supply of donated organs, which may be needed for both initial and subsequent transplants. Furthermore, it requires lifelong treatment with immunosuppressants, which are associated with adverse effects. Despite early clinical applications of bioengineered organs and tissues, routine implementation is still far off. For this review, we searched the PubMed, MEDLINE, and Ovid databases for the following keywords for each tissue or organ: tissue engineering, biological and synthetic scaffold/graft, acellular and decelluar(ized), reseeding, bioreactor, tissue replacement, and transplantation.We identified the current state-of-the-art practices in tissue engineering with a focus on advances during the past 5 years. We discuss advantages and disadvantages of biological and synthetic solutions and introduce novel strategies and technologies for the field. The ethical challenges of innovation in this area are also reviewed.     

Neuraminidase inhibitor susceptibility testing in human influenza viruses: a laboratory surveillance perspective

Neuraminidase inhibitors (NAIs) are vital in managing seasonal and pandemic influenza infections. NAI susceptibilities of virus isolates (n = 5540) collected during the 2008-2009 influenza season were assessed in the chemiluminescent neuraminidase inhibition (NI) assay. Box-and-whisker plot analyses of log-transformed IC(50)s were performed for each virus type/subtype and NAI to identify outliers which were characterized based on a statistical cutoff of IC(50) >3 interquartile ranges (IQR) from the 75(th) percentile. Among 1533 seasonal H1N1 viruses tested, 1431 (93.3%) were outliers for oseltamivir; they all harbored the H275Y mutation in the neuraminidase (NA) and were reported as oseltamivir-resistant. Only 15 (0.7%) of pandemic 2009 H1N1 viruses tested (n = 2259) were resistant to oseltamivir. All influenza A(H3N2) (n = 834) and B (n = 914) viruses were sensitive to oseltamivir, except for one A(H3N2) and one B virus, with D151V and D197E (D198E in N2 numbering) mutations in the NA, respectively. All viruses tested were sensitive to zanamivir, except for six seasonal A(H1N1) and several A(H3N2) outliers (n = 22) which exhibited cell culture induced mutations at residue D151 of the NA. A subset of viruses (n = 1058) tested for peramivir were sensitive to the drug, with exception of H275Y variants that exhibited reduced susceptibility to this NAI. This study summarizes baseline susceptibility patterns of seasonal and pandemic influenza viruses, and seeks to contribute towards criteria for defining NAI resistance.     

Dual resistance to adamantanes and oseltamivir among seasonal influenza A(H1N1) viruses: 2008-2010

Two distinct genetic clades of seasonal influenza A(H1N1) viruses have cocirculated in the recent seasons: clade 2B oseltamivir-resistant and adamantane-susceptible viruses, and clade 2C viruses that are resistant to adamantanes and susceptible to oseltamivir. We tested seasonal influenza A(H1N1) viruses collected in 2008-2010 from the United States and globally for resistance to antivirals approved by the Food and Drug Administration. We report 28 viruses with both adamantane and oseltamivir (dual) resistance from 5 countries belonging to 4 distinct genotypes. Because of limited options for antiviral treatment, emergence of dual-resistant influenza viruses poses a public health concern, and their circulation needs to be closely monitored.     

Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans

Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin. Fourteen healthy male volunteers between 18 and 30 years old were injected intravenously with 3 ng/kg Escherichia coli endotoxin. Concurrent with the injections, nine volunteers received a 3-hour continuous intravenous infusion of IL-1Ra. The other five subjects were given a 3-hour infusion of saline. Volunteers injected with endotoxin experienced a threefold increase in circulating neutrophils over baseline. This neutrophilia was significantly reduced by 48% in subjects administered endotoxin plus IL-1Ra (P = .0253). Ex vivo mitogen-induced peripheral blood mononuclear cell proliferation decreased by greater than 60% at 3 and 6 hours after endotoxin injection (P = .0053). This endotoxin-induced reduction in mitogen response was reversed in subjects coinjected with IL-1Ra (P = .0253). Endotoxin-induced symptoms, fever, and tachycardia were unaffected by IL-1Ra. IL-1 appears to be an important mediator in endotoxemia because some of its hematologic and immunomodulatory effects can be blocked by IL-1Ra.     

Precocious expression of T cell functional response genes in vivo in primitive thymocytes before T lineage commitment

The genes encoding effector molecules of mature T cells, IL-2, perforin and IL-4, were found to be expressed in vivo in the most primitive subsets of thymocytes of adult mice. These subsets have previously been identified by their cell surface markers and by their expression of other T lineage-associated genes. While IL-2, perforin and IL-4 are expressed in distinct patterns, all three are expressed before the induction of RAG-1 and pre-TCR alpha mRNA expression, and are confined to subsets of cells that apparently have not yet undergone commitment to the T lineage. Thus, expression of T cell response genes appears to be one of the earliest markers of lymphocyte differentiation. Activation events marked by CD69 induction occur in these early cell types, but the response gene expression by these cells is separable from CD69 expression. IL-2 and perforin are induced again much later in thymocyte development, during TCR-dependent repertoire selection. At those stages, IL-2 protein and RNA levels per cell are higher, but the fraction of cells expressing IL-2 appears to be much lower than in the most immature stages. In addition, a striking feature of the immature populations is the robust IL-2 expression by presumptive immature NK cells. These findings are discussed in terms of the developmental origins of lineage specificity in T cell response gene regulation.