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  • SpringerLink  (23)
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  • 1
    Language: German
    In: Medizinische Klinik, 2010, Vol.105(6), pp.399-403
    Description: Zur antiviralen Therapie des Zoster stehen in Deutschland fünf Präparate (Aciclovir, Valaciclovir, Famciclovir, Brivudin sowie das Reservemittel Foscarnet) zur Verfügung. Eine gezielte Therapie sollte zur Vermeidung von Spätkomplikationen so schnell wie möglich, spätestens innerhalb von 72 h nach Auftreten der typischen Zostereffloreszenzen, eingeleitet werden. Die effektivste Maßnahme zur Prävention von Windpocken liegt in der Impfung selbst. Es handelt sich um eine attenuierte Lebendvakzine auf der Basis des japanischen Oka-Stammes. Seit 2004 empfiehlt die STIKO (Ständige Impfkommission) die Varizellenimpfung als Standardimpfung für alle Kinder zwischen dem 11. und 14. Lebensmonat. Eine zweite Impfung sollte frühestens nach 4 Wochen und spätestens bis zum 17. Lebensjahr stattfinden. Eine passive Immunglobulingabe ist für Risikogruppen wie Schwangere, Immunsupprimierte oder Neugeborene von Müttern mit einer frischen Varizelleninfektion indiziert und sollte innerhalb von 72–96 h nach Varizellenexposition erfolgen. In der Shingles Prevention Study konnte die Effektivität einer Zosterimpfung nachgewiesen werden. In Germany, five antiviral agents are approved for antiviral therapy in zoster patients (acyclovir, valacyclovir, famciclovir, brivudine, and foscarnet). They should be administered within 72 h after rash onset and can significantly shorten viral replication and reduce the complications. In 2004, the German Standing Committee on Vaccination (STIKO) at the Robert Koch Institute suggested the active immunization against varicella with a live attenuated varicella vaccine (Oka strain) for all children and young persons. The first dose is given between the ages of 11 and 14 months, the second at the earliest 4 weeks later. Passive immunization is indicated as postexposure prophylaxis in high-risk individuals within 72–96 h after exposure. High-risk individuals are pregnant women, immunocompromised patients, or newborns, whose mothers had a primary varicella infection 5 days before or 2 days after birth. The Shingles Prevention Study demonstrated that vaccination is the most effective strategy for prevention of herpes zoster and postherpetic neuralgia.
    Keywords: Varicella-zoster virus infection ; Risk groups ; Pregnancy ; Prevention ; Therapy
    ISSN: 0723-5003
    E-ISSN: 1615-6722
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  • 2
    Language: English
    In: Cellular and Molecular Life Sciences, 2011, Vol.68(6), pp.1079-1090
    Description: Human cytomegalovirus (HCMV) is a major pathogen in immunocompromised individuals. Here, non-toxic concentrations of the anti-cancer kinase inhibitor sorafenib were shown to inhibit replication of different HCMV strains (including a ganciclovir-resistant strain) in different cell types. In contrast to established anti-HCMV drugs, sorafenib inhibited HCMV major immediate early promoter activity and HCMV immediate early antigen (IEA) expression. Sorafenib is known to inhibit Raf. Comparison of sorafenib with the MEK inhibitor U0126 suggested that sorafenib inhibits HCMV IEA expression through inhibition of Raf but independently of signaling through the Raf downstream kinase MEK 1/2. In concordance, siRNA-mediated depletion of Raf but not of MEK-reduced IEA expression. In conclusion, sorafenib diminished HCMV replication in clinically relevant concentrations and inhibited HCMV IEA expression, a pathophysiologically relevant event that is not affected by established anti-HCMV drugs. Moreover, we demonstrated for the first time that Raf activation is involved in HCMV IEA expression.
    Keywords: Human cytomegalovirus ; Sorafenib ; Kinase inhibitor ; Raf ; Immediate early antigen ; Cancer chemotherapy ; Oncomodulation ; Antiviral therapy
    ISSN: 1420-682X
    E-ISSN: 1420-9071
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  • 3
    Language: English
    In: Medical Microbiology and Immunology, 2014, Vol.203(6), pp.365-371
    Description: Vaccination has proven to be one of the best weapons protecting the mankind against infectious diseases. Along with the huge progress in microbiology, numerous highly efficacious and safe vaccines have been produced by conventional technology (cultivation), by the use of molecular biology (genetic modification), or by synthetic chemistry. Sterilising prevention is achieved by the stimulation of antibody production, while the stimulation of cell-mediated immune responses may prevent the outbreak of disease in consequence of an acute or reactivated infection. From several examples, two rules are deduced to evaluate the perspectives of future vaccine developments: They are promising, if (1) the natural infectious disease induces immunity or (2) passive immunisation (transfer of antibodies, adoptive transfer of lymphocytes) is successful in preventing infection.
    Keywords: Vaccines ; Passive immunisation ; Adoptive transfer of lymphocytes ; Hepatitis virus ; Influenza virus ; Herpes viruses ; HIV ; Tuberculosis ; Diphtheria ; Tetanus ; Oncogenic HPV
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 4
    Language: English
    In: Medical Microbiology and Immunology, 2018, Vol.207(5), pp.249-253
    Description: Several virus infections affect the pregnancy itself as well as the foetal development (rubella, PVB19, VZV, HSV, HCMV, HBV, HIV). Prevention can be established by vaccination or an assessment of the immunity status as well as by chemotherapy. The following review provides an update to current aspects focusing on the role of serologic screening.
    Keywords: Pregnancy ; Vertical virus infections ; Serologic screening
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 5
    Language: German
    In: Medizinische Klinik, 2010, Vol.105(5), pp.334-338
    Description: Das Varicella-Zoster-Virus (VZV) gehört zu den acht bisher bekannten Herpesviren des Menschen, zeigt ein ubiquitäres Vorkommen und verursacht die akute exanthematöse Kinderkrankheit „Windpocken“. Typisch ist der hohe Kontagiositätsindex. Die Hauptübertragung erfolgt über Aerosole, seltener über direkten Kontakt mit Bläschenflüssigkeit. Eine Eigenschaft aller Herpesviren ist ihre Latenz. Nach der Primärinfektion wandert das Virus retrograd mit dem Zytoplasmastrom der Neurone zum Spinalganglion. Das Virusgenom verbleibt dort latent, weitgehend inaktiv im Kern der Spinalganglienzelle. Reaktivierungen sind bei allen latent Infizierten möglich. Gewöhnlich werden Reaktivierungen im höheren Alter (〉 50 Jahre) sowie bei Abfall der Gedächtniszellen für die T-Lymphozyten beobachtet. Gerade bei älteren Menschen und Risikogruppen (Immunsupprimierte) werden im Zusammenhang mit Reaktivierungen schwere Krankheitsverläufe beschrieben. Eine häufig auftretende und schwer behandelbare Komplikation stellt die postzosterische Neuralgie (PZN) dar, ein neuropathischer Schmerz, der definitionsgemäß 〉 6 Wochen nach dem akuten Infekt persistiert und eine adäquate antivirale Therapie und Schmerzbehandlung erfordert. Varicella-zoster virus (VZV), known as one of the eight human herpesviridae, shows a ubiquitous distribution and is the cause for acute exanthema in childhood (chickenpox). VZV is highly infectious, spread by respiratory droplets and direct contact with fluid in vesicles. As a characteristic of the α-herpesviridae, VZV establishes latency in the nucleus of the paraspinal cells. Reactivation of VZV (zoster) is possible in all infected persons, but becomes more common with increasing age and a decline of VZV-specific cell-mediated immunity. Immunocompromised patients and older people (〉 50 years) have an increased risk for a severe course of disease. The postherpetic neuralgia (PHN), as one of the most common and feared complications, is defined as a neuropathic pain (burning character), which persists for 〉 6 weeks after onset of disease and needs adequate antiviral and pain treatment.
    Keywords: VZV epidemiology ; Postherpetic neuralgia ; VZV diagnostics
    ISSN: 0723-5003
    E-ISSN: 1615-6722
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  • 6
    Language: English
    In: Medical Microbiology and Immunology, 2011, Vol.200(1), pp.1-5
    Description: The question whether human cytomegalovirus may affect cancer diseases has been discussed (very controversially) for decades. There are convinced believers and strict opponents of the idea that HCMV might be able to play a role in the course of cancer diseases. In parallel, the number of published reports on the topic is growing. Recently published and presented (Ranganathan P, Clark P, Kuo JS, Salamat S, Kalejta RF. A Survey of Human Cytomegalovirus Genomic Loci Present in Glioblastoma Multiforme Tissue Samples. 35th Annual International Herpes Workshop, Salt Lake City, 2010) data on HCMV detection in glioblastoma tissues and colocalisation of HCMV proteins with cellular proteins known to be relevant for glioblastoma progression motivated us to recapitulate the current state of evidence.
    Keywords: Cytomegalovirus ; Cancer ; Oncomodulation ; Tumour virus ; Glioblastoma ; Neuroblastoma
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 7
    Language: English
    In: Medical Microbiology and Immunology, 2010, Vol.199(1), pp.45-51
    Description: Coxsackie A16 (CA16) and Enterovirus 71 (EV71) are members of the picornaviridae family and are associated with hand, foot and mouth disease (HFMD), in rare cases also to acute neurological diseases. HFMD outbreaks have been reported from many parts of the world, especially Southeast Asia. The objective of the study was to analyze CA16 and EV71 seroepidemiologically in the population of Frankfurt/M., Germany. A total of 696 individuals (349 males and 347 females, divided into seven different age groups, 1–4, 5–9, 10–14, 15–19, 20–39, 40–59 and 〉60 years) were tested for serum antibodies against CA16 and EV71 by the use of a microneutralization test. Sera were collected at the Frankfurt university hospital from patients suffering from other diseases between March and September 2006. CA16 and EV71 infections were observed to be widely present in the population. The age-adjusted seroprevalence for individuals ≥1 year was found to be 62.9% for CA16 and 42.8% for EV71 without a gender-specific significant difference. Only 12.0 and 27.0% of the children aged 1–4 had antibodies to EV71 and CA16, respectively – indicating that 88 and 73% of the children in this age group were susceptible to the infection. A total of 213 individuals (30.6%) was seropositive for both viruses, 303 (43.5%) showed neutralizing antibodies (NtAb) to at least one of the two viruses. A total of 180 individuals (25.9%) revealed no antibodies. High CA16 and EV71 antibody titers were found especially in the age group of the 10- to 14-year-olds, without gender-specific difference. The seroprevalence study demonstrates a common spread of CA16 and EV71 in Germany, but a relatively high susceptibility of the younger population to CA16 and EV71. Obviously, the manifestation rate, i.e., distinct disease of these infections is low.
    Keywords: Hand, foot and mouth disease ; Seroprevalence ; Coxsackie A16 ; Enterovirus 71 ; Neutralization assay
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 8
    Language: English
    In: Medical Microbiology and Immunology, 2010, Vol.199(1), pp.53-60
    Description: Since the dynamics of transmission of human cytomegalovirus (HCMV) have not been clarified yet, we assessed a possible change in HCMV seroprevalence in Frankfurt am Main, Germany during the past twenty years and tried to detect variables with an impact on epidemiology. Between 1/1/1988 and 10/15/2008, a total of 54443 serum samples were collected for routine diagnostics and analyzed using Enzygnost Anti HCMV-IgG enzyme immunoassay (Siemens/Dade Behring, Marburg, Germany). Two decades, 1/1/1988–12/31/1997 and 1/1/1998–10/15/2008, and several groups (type of health insurance, gender, age, HIV-status) were evaluated to assess changes in seroprevalence. Regarding both decades, the overall age-adjusted prevalence of HIV-negative patients dropped from 63.70% (confidence interval (CI) 95% 63.15–64.25) to 57.25% (CI 95% 56.57–57.93; P  〈 0.0001). Private health insurance (PHI) patients showed significant lower HCMV seroprevalences than members of obligatory health insurances (OHI) in both decades (1988–1997: PHI = 55.79%, OHI = 64.27%; P  〈 0.0001; 1998–1908: PHI = 47.02%, OHI = 58.74%; P  〈 0.0001). Furthermore, comparing the two decades, there was generally a gender-specific statistically significant decrease in HCMV seroprevalence for males (63.54–55.54%) and females (63.83–58.73%) as well as for members of PHI and OHI (PHI males: 57.59% to 47.19%, PHI females 54.10–46.80%; OHI males: 64.00–57.06%, OHI females 64.50–60.11%). Also, while female HIV-positive patients showed significant difference in HCMV seroprevalence between the two decades (83.17 and 87.80%, P  = 0.023), there was no significant difference in male patients with HIV (88.76 and 87.32% in the first and second decade, respectively ( P  = 0.196). The cumulative HCMV prevalence of all HIV-negative patients tested in the past 20 years demonstrates a biphasic, age-related rise of HCMV seroprevalence throughout all age-groups. The seroprevalence of HCMV has declined between 1988–1997 and 1998–2008 in Frankfurt am Main, Germany. The decline varied between different age-groups. HCMV prevalence correlates with the type of health insurance, gender, age, and HIV-status.
    Keywords: Cytomegalovirus ; Seroepidemiology ; HCMV ; Germany ; Prevalence
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 9
    Language: English
    In: Medical Microbiology and Immunology, 2013, Vol.202(1), pp.37-47
    Description: Although several host factors have been identified to influence the course of HCMV infection, it still remains unclear why in AIDS patients without highly active antiretroviral therapy human cytomegalovirus (HCMV) retinitis is one of the most common opportunistic infections, whereas in other immunosuppressed individuals it has a low incidence. It was suggested that HCMV glycoprotein B strains may be suitable as marker for virulence and HCMV retinitis. Moreover, UL144 ORF, a member of the TNF-α receptor superfamily, may play a crucial role in innate defences and adaptive immune response of HCMV infection. Furthermore, sequence analyses of HCMV genes UL128, UL130, and UL131A as major determinants of virus entry and replication in epithelial and other cell types were performed. To evaluate the association of sequence variability of depicted viral genes with HCMV retinitis and in vitro growth properties in retinal pigment epithelial cells (RPE) and human foreskin fibroblasts (HFF), we compared 14 HCMV isolates obtained from vitreous fluid and urine of AIDS patients with clinically proven HCMV retinitis. Isolates were analyzed by PCR cycle sequencing and phylogenetic analysis. In addition, sequences of HCMV strains AF1, U8, U11, VR1814, and its cell culture adapted derivates were included. Sequence analysis of gB yielded three genetic subtypes (gB type 1 (5 isolates), gB type 2 (12 isolates), and gB type 3 (5 Isolates)), whereas sequence analysis of UL144 showed a greater diversity (7 isolates type 1A, 2 isolates type 1C, 7 isolates type 2, and 3 isolates type 3). In contrast, the UL128, UL130, and UL131A genes of all low-passage isolates were highly conserved and showed no preferential clustering. Moreover, in HFF and RPE cells, all of our HCMV isolates replicated efficiently independently of their genetic subtype. In conclusion, beside a possible link between the gB subtype 2 and HCMV retinitis, our study found no direct evidence for a connection between UL144/UL128/UL130/UL131A genotypes and the incidence of HCMV retinitis in AIDS patients.
    Keywords: Cytomegalovirus ; Viral tropism and virulence ; Retinitis ; AIDS
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 10
    Language: English
    In: Medical Microbiology and Immunology, 2010, Vol.199(4), pp.291-297
    Description: Hypercytokinaemia is thought to contribute to highly pathogenic H5N1 influenza A virus disease. Glycyrrhizin is known to exert immunomodulatory and anti-inflammatory effects and therefore a candidate drug for the control of H5N1-induced pro-inflammatory gene expression. Here, the effects of an approved parenteral glycyrrhizin preparation were investigated on H5N1 virus replication, H5N1-induced pro-inflammatory responses, and H5N1-induced apoptosis in human monocyte-derived macrophages. Glycyrrhizin 100 μg/ml, a therapeutically achievable concentration, impaired H5N1-induced production of CXCL10, interleukin 6, and CCL5 and inhibited H5N1-induced apoptosis but did not interfere with H5N1 replication. Global inhibition of immune responses may result in the loss of control of virus replication by cytotoxic immune cells including natural killer cells and cytotoxic CD8 + T-lymphocytes. Notably, glycyrrhizin concentrations that inhibited H5N1-induced pro-inflammatory gene expression did not affect cytolytic activity of natural killer cells. Since H5N1-induced hypercytokinaemia is considered to play an important role within H5N1 pathogenesis, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease.
    Keywords: Glycyrrhizin ; H5N1 ; Cytokines ; Monocyte-derived macrophages
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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