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Sample records for adenoviruses eradicate pancreatic

  1. Experimental virotherapy of chemoresistant pancreatic carcinoma using infectivity-enhanced fiber-mosaic oncolytic adenovirus

    PubMed Central

    Kaliberov, Sergey A.; Kaliberova, Lyudmila N.; Buchsbaum, Donald J.; Curiel, David T.

    2014-01-01

    Pancreatic cancer is a significant clinical problem and novel therapeutic approaches are desperately needed. Recent advances in conditionally replicative adenovirus-based (CRAd) oncolytic virus design allow the application of CRAd vectors as a therapeutic strategy to efficiently target and eradicate chemoresistant pancreatic cancer cells thereby improving the efficacy of pancreatic cancer treatment. The goal of this study was to construct and validate the efficacy of an infectivity-enhanced, liver-untargeted, tumor-specific CRAd vector. A panel of CRAds has been derived which embody the C-X-C chemokine receptor type 4 promoter for conditional replication, two fiber complex mosaicism for targeting expansion, and hexon hypervariable region 7 (HVR7) modification for liver untargeting. We evaluated CRAds for cancer virotherapy using a human pancreatic tumor xenograft model. Employment of the fiber mosaic approach improved CRAd replication in pancreatic tumor xenografts. Substitution of the HVR7 of the Ad5 hexon for Ad serotype 3 hexon resulted in decreased liver tropism of systemically administrated CRAd. Obtained data demonstrated that employment of complex mosaicism increased efficacy of the combination of oncolytic virotherapy with chemotherapy in a human pancreatic tumor xenograft model. PMID:24903014

  2. Eradication of melanoma in vitro and in vivo via targeting with a Killer-Red-containing telomerase-dependent adenovirus.

    PubMed

    Takehara, Kiyoto; Yano, Shuya; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Narii, Nobuhiro; Mizuguchi, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M

    2017-01-05

    Melanoma is a highly recalcitrant cancer and transformative therapy is necessary for the cure of this disease. We recently developed a telomerase-dependent adenovirus containing the fluorescent protein Killer-Red. In the present report, we first determined the efficacy of Killer-Red adenovirus combined with laser irradiation on human melanoma cell lines in vitro. Cell viability of human melanoma cells was reduced in a dose-dependent and irradiation time-dependent manner. We used an intradermal xenografted melanoma model in nude mice to determine efficacy of the Killer-Red adenovirus. Intratumoral injection of Killer-Red adenovirus, combined with laser irradiation, eradicated the melanoma indicating the potential of a new paradigm of cancer therapy.

  3. Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts.

    PubMed

    José, Anabel; Sobrevals, Luciano; Miguel Camacho-Sánchez, Juan; Huch, Meritxell; Andreu, Núria; Ayuso, Eduard; Navarro, Pilar; Alemany, Ramon; Fillat, Cristina

    2013-01-01

    Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p less than 0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors.

  4. Intraductal Delivery of Adenoviruses Targets Pancreatic Tumors in Transgenic Ela-myc Mice and Orthotopic Xenografts

    PubMed Central

    José, Anabel; Sobrevals, Luciano; Camacho-Sánchez, Juan Miguel; Huch, Meritxell; Andreu, Núria; Ayuso, Eduard; Navarro, Pilar; Alemany, Ramon; Fillat, Cristina

    2013-01-01

    Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p<0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors. PMID:23328228

  5. Targeting notch to eradicate pancreatic cancer stem cells for cancer therapy.

    PubMed

    Wang, Zhiwei; Ahmad, Aamir; Li, Yiwei; Azmi, Asfar S; Miele, Lucio; Sarkar, Fazlul H

    2011-04-01

    Pancreatic cancer is the most aggressive malignant disease once it is diagnosed and it remains the fourth leading cause of cancer-related death in the U.S.A. Recent data indicates that the Notch signaling pathway plays an important role in the development and progression of pancreatic cancer. Emerging evidence also suggests that the activation of the Notch signaling pathway is mechanistically associated with molecular characteristics of cancer stem cells (CSCs) in pancreatic cancer. Moreover, CSCs are known to be highly drug-resistant, suggesting that targeted inactivation of Notch signaling would be useful for overcoming drug resistance and the elimination of CSCs. This review describes the roles of the Notch signaling pathway in pancreatic cancer with a special emphasis on its novel functions in the regulation of pancreatic CSC. Moreover, the review also proposes that targeting the Notch signaling pathway by natural agents may represent a novel strategy for overcoming drug resistance and the elimination of CSCs, which would be useful for the successful treatment of patients diagnosed with pancreatic cancer.

  6. An epithelial cell adhesion molecule- and CD3-bispecific antibody plus activated T-cells can eradicate chemoresistant cancer stem-like pancreatic carcinoma cells in vitro.

    PubMed

    Umebayashi, Masayo; Kiyota, Akifumi; Koya, Norihiro; Tanaka, Hiroto; Onishi, Hideya; Katano, Mitsuo; Morisaki, Takashi

    2014-08-01

    Cancer stem-like properties of various types of cancer, including pancreatic cancer, one of the most aggressive types, correlate with metastasis, invasion, and therapeutic resistance. More importantly, chemoresistance in cancer stem-like cells (CSLCs) is a critical problem for eradication of pancreatic cancer. Several cell surface markers, such as CD44 and epithelial cell adhesion molecule (EpCAM), are molecular targets on CSLCs of pancreatic carcinoma. In this study, we investigated whether catumaxomab, a clinical-grade bi-specific antibody that binds to both EpCAM on tumor cells and CD3 on T-cells, combined with activated T-cells can eliminate chemoresistant pancreatic CSLCs in vitro. Firstly, we established a CSLC line (MU-PK1) from human pancreatic carcinoma cells derived from a patient with chemoresistant and disseminated pancreatic cancer. These CSLCs were almost completely resistant to gemcitabine-mediated cytotoxicity up to a concentration of 10 μg/ml. The cells expressed high levels of CSLC markers (CD44 and EpCAM) and had significantly higher capacities for sphere formation, invasion, and aldehyde dehydrogenase-1 expression, which are associated with cancer stemness properties. We found that pre-treatment with catumaxomab and subsequent addition of interleukin-2/OKT3 activated autologous T-cells eliminated CSLCs during a short incubation period. Moreover, when MU-PK1 cells were cultured under hypoxic conditions, the CSLCs became more aggressive. However, the combination of cytokine-activated killer T-cells with catumaxomab successfully lysed almost all these cells. In conclusion, catumaxomab combined with activated T-cells may be a potent therapeutic modality to eradicate chemoresistant pancreatic CSLCs.

  7. Targeted oncolytic herpes simplex virus type 1 eradicates experimental pancreatic tumors.

    PubMed

    Gayral, Marion; Lulka, Hubert; Hanoun, Naima; Biollay, Coline; Sèlves, Janick; Vignolle-Vidoni, Alix; Berthommé, Hervé; Trempat, Pascal; Epstein, Alberto L; Buscail, Louis; Béjot, Jean-Luc; Cordelier, Pierre

    2015-02-01

    As many other cancers, pancreatic ductal adenocarcinoma (PDAC) progression is associated with a series of hallmark changes for cancer cells to secure their own growth success. Yet, these very changes render cancer cells highly sensitive to viral infection. A promising strategy may rely on and exploit viral replication for tumor destruction, whereby infection of tumor cells by a replication-conditional virus may lead to cell destruction and simultaneous release of progeny particles that can spread and infect adjacent tumor cells, while sparing healthy tissues. In the present study, we used Myb34.5, a second-generation replication-conditional herpes simplex virus type 1 (HSV-1) mutant in which ICP6 gene expression is defective and expression of the HSV-1 γ134.5 gene is regulated by the cellular B-myb promoter. We found that B-myb is present in experimental PDAC and tumors, and is overexpressed in patients' tumors, as compared with normal adjacent pancreas. Myb34.5 replicates to high level in human PDAC cell lines and is associated with cell death by apoptosis. In experimental models of PDAC, mice receiving intratumoral Myb34.5 injections appeared healthy and tumor progression was inhibited, with evidence of tumor necrosis, hemorrhage, viral replication, and cancer cell death by apoptosis. Combining standard-of-care chemotherapy with Myb34.5 successfully led to a very impressive antitumoral effect that is rarely achieved in this experimental model, and resulted in a greater reduction in tumor growth than chemotherapy alone. These promising results warrant further evaluation in early phase clinical trial for patients diagnosed with PDAC for whom no effective treatment is available.

  8. A NOTCH-sensitive uPAR-regulated oncolytic adenovirus effectively suppresses pancreatic tumor growth and triggers synergistic anticancer effects with gemcitabine and nab-paclitaxel.

    PubMed

    Mato-Berciano, Ana; Raimondi, Giulia; Maliandi, Maria Victoria; Alemany, Ramon; Montoliu, Lluis; Fillat, Cristina

    2017-02-07

    Notch signaling pathway is an embryonic program that becomes reactivated in pancreatic cancer and contributes to cancer stem cell (CSC) maintenance. We explored the concept of oncolytic adenoviral activity in response to Notch activation signaling, in the context of a chimeric promoter with uPAR regulatory sequences, as a strategy to drive its activity in neoplastic and CSC. We explored the advantages of a chemo-virotherapy approach based on synergistic combinations. Regulatory sequences recognized by the transcriptional factor CSL upstream a minimal uPAR promoter were engineered in adenoviral vectors and in the oncolytic adenovirus AdNuPARmE1A. Viral response to Notch signaling, and viral potency in cell lines and pancreatic cancer stem cells (PCSC) was tested. Preclinical toxicity and antitumor efficacy in xenografts and Patient-derived xenografts (PDX) mouse models was evaluated, as unimodal or in combination with gemcitabine+nab-paclitaxel. Mechanistic studies were conducted to explore the synergism of combined therapies.We demonstrate that CSL-binding site optimized-engineered sequences respond to Notch activation in AdNuPARmLuc and AdNuPARmE1A. AdNuPARmE1A showed strong lytic effects in pancreatic cancer cell lines and PCSC. AdNuPARmE1A displayed attenuated activity in normal tissues, but robust antitumor effects in xenograft and PDX models, leading to a reduced capacity of treated tumors to form tumorspheres. Chemo-virotherapy treatment enlarged therapeutic response in both tumor models. Synergistic effects of the combination resulted from viral sensitization of apoptotic cell death triggered by chemotherapy.In summary we present a novel effective oncolytic adenovirus, AdNuPARmE1A that reduces PCSC and presents synergistic effects with gemcitabine and nab-paclitaxel, supporting further clinical development.

  9. Adenovirus-mediated p53 gene transduction inhibits telomerase activity independent of its effects on cell cycle arrest and apoptosis in human pancreatic cancer cells.

    PubMed

    Kusumoto, M; Ogawa, T; Mizumoto, K; Ueno, H; Niiyama, H; Sato, N; Nakamura, M; Tanaka, M

    1999-08-01

    Evidence for a relationship between overexpression of wild-type p53 and telomerase activity remains controversial. We investigated whether p53 gene transduction could cause telomerase inhibition in pancreatic cancer cell lines, focusing on the relation of transduction to growth arrest, cell cycle arrest, and apoptotic cell death. The cells were infected with recombinant adenovirus expressing wild-type p53 or p21WAF1 at a multiplicity of infection of 100 or were continuously exposed to 10 microM VP-16, which is well known to induce apoptosis. Adenovirus-mediated p53 gene transduction caused G1 cell cycle arrest, apoptosis, and resultant growth inhibition in MIA PaCa-2 cells; the cell number 2 days after infection was 50% of preinfection value, and 13% of the cells were dead. Moreover, the transduction resulted in complete depression of telomerase activity through down-regulation of hTERT mRNA expression. In contrast, p21WAF1 gene transduction only arrested cell growth and cell cycle at G1 phase, and VP-16 treatment inhibited cell growth with G2-M arrest and apoptosis; after treatment, the cell number was 73% of pretreatment, and 12% of the cells were dead. Neither p21WAF1 gene transduction nor VP-16 treatment caused telomerase inhibition. Similar results were obtained in two other pancreatic cancer cell lines, SUIT-2 and AsPC-1. Thus, our results demonstrate that the p53 gene transduction directly inhibits telomerase activity, independent of its effects on cell growth arrest, cell cycle arrest, and apoptosis.

  10. Preclinical Evaluation of Sequential Combination of Oncolytic Adenovirus Delta-24-RGD and Phosphatidylserine-Targeting Antibody in Pancreatic Ductal Adenocarcinoma.

    PubMed

    Dai, Bingbing; Roife, David; Kang, Ya'an; Gumin, Joy; Rios Perez, Mayrim V; Li, Xinqun; Pratt, Michael; Brekken, Rolf A; Fueyo-Margareto, Juan; Lang, Frederick F; Fleming, Jason B

    2017-04-01

    Delta-24-RGD (DNX-2401) is a conditional replication-competent oncolytic virus engineered to preferentially replicate in and lyse tumor cells with abnormality of p16/RB/E2F pathway. In a phase I clinical trial, Delta-24-RGD has shown favorable safety profile and promising clinical efficacy in brain tumor, which prompted us to evaluate its anticancer activity in pancreatic ductal adenocarcinoma (PDAC), which also has high frequency of homozygous deletion and promoter methylation of CDKN2A encoding the p16 protein. Our results demonstrate that Delta-24-RGD can induce dramatic cytotoxicity in a subset of PDAC cell lines with high cyclin D1 expression. Induction of autophagy and apoptosis by Delta-24-RGD in sensitive PDAC cells was confirmed with LC3B-GFP autophagy reporter and acridine orange staining as well as Western blotting analysis of LC3B-II expression. Notably, we found that Delta-24-RGD induced phosphatidylserine exposure in infected cells independent of cells' sensitivity to Delta-24-RGD, which renders a rationale for combination of Delta-24-RGD viral therapy and phosphatidylserine targeting antibody for PDAC. In a mouse PDAC model derived from a liver metastatic pancreatic cancer cell line, Delta-24-RGD significantly inhibited tumor growth compared with control (P < 0.001), and combination of phosphatidylserine targeting antibody 1N11 further enhanced its anticancer activity (P < 0.01) possibly through inducing synergistic anticancer immune responses. Given that these 2 agents are currently in clinical evaluation, our study warrants further clinical evaluation of this novel combination strategy in pancreatic cancer therapy. Mol Cancer Ther; 16(4); 662-70. ©2016 AACR.

  11. Waterborne adenovirus.

    PubMed

    Mena, Kristina D; Gerba, Charles P

    2009-01-01

    Adenoviruses are associated with numerous disease outbreaks, particularly those involving d-cares, schools, children's camps, hospitals and other health care centers, and military settings. In addition, adenoviruses have been responsible for many recreational water outbreaks, including a great number of swimming pool outbreaks than any other waterborne virus (Gerba and Enriquez 1997). Two drinking water outbreaks have been documented for adenovirus (Divizia et al. 2004; Kukkula et al. 1997) but none for food. Of the 51 known adenovirus serotypes, one third are associated with human disease, while other infections are asymptomatic. Human disease associated with adenovirus infections include gastroenteritis, respiratory infections, eye infections, acute hemorrhagic cystitis, and meningoencephalitis (Table 2). Children and the immunocompromised are more severely impacted by adenovirus infections. Subsequently, adenovirus is included in the EPA's Drinking Water Contaminant Candidate List (CCL), which is a list of unregulated contaminants found in public water systems that may pose a risk to public health (National Research Council 1999). Adenoviruses have been detected in various waters worldwide including wastewater, river water, oceans, and swimming pools (Hurst et al. 1988; Irving and Smith 1981; Pina et al. 1998). Adenoviruses typically outnumber the enteroviruses, when both are detected in surface waters. Chapron et al. (2000) found that 38% of 29 surface water samples were positive for infectious Ad40 and Ad41. Data are lacking regarding the occurrence of adenovirus in water in the US, particularly for groundwater and drinking water. Studies have shown, however, that adenoviruses survive longer in water than enteroviruses and hepatitis A virus (Enriquez et al. 1995), which may be due to their double-stranded DNA. Risk assessments have been conducted on waterborne adenovirus (Crabtree et al. 1997; van Heerden et al. 2005c). Using dose-response data for inhalation

  12. Pancreatitis

    MedlinePlus

    ... removal is sometimes performed along with a sphincterotomy. Stent placement. Using the endoscope, the doctor places a ... a narrowed pancreatic or bile duct. A temporary stent may be placed for a few months to ...

  13. Pertussis-like syndrome associated with adenovirus presenting with hyperleukocytosis: Case report

    PubMed Central

    Sarbay, Hakan; Polat, Aziz; Mete, Emin; Balci, Yasemin Isik; Akin, Mehmet

    2016-01-01

    Adenovirus is an infectious viral agent that causes variety of clinical presentations such as respiratory disease, conjunctivitis, and gastroenteritis. Hepatitis, pancreatitis, myocarditis, encephalitis, and disseminated infection are primarily seen in immunocompromised patients. Rarely, adenovirus infection can present with pertussis-like syndrome. Described here is case of pertussis-like syndrome associated with adenovirus presenting with hyperleukocytosis. PMID:28058402

  14. Adenovirus vector-mediated Gli1 siRNA induces growth inhibition and apoptosis in human pancreatic cancer with Smo-dependent or Smo-independent Hh pathway activation in vitro and in vivo.

    PubMed

    Guo, Jiefang; Gao, Jun; Li, Zhaoshen; Gong, Yanfang; Man, Xiaohua; Jin, Jing; Wu, Hongyu

    2013-10-10

    Activation of Hedgehog (Hh) signaling pathway is a core molecular mechanism in pancreatic carcinogenesis. However, the inhibition of upstream Hh signals does not inhibit the growth of a subset of pancreatic cancer (PC). This study was to examine the effect of siRNA targeting Gli1, the downstream component of Hh pathway, on PC cells and to provide some insight into the underlying mechanisms. A Gli1siRNA-expressing adenovirus (Ad-U6-Gli1siRNA) was constructed, and its effect on PC cells was investigated in vitro and in vivo. Gli1 was expressed in 83.3% (20/24) PC tissues, whereas no expression was found in normal pancreatic ductal epithelium. Gli1 was expressed in SW1990 and CFPAC cells in which Smo was completely absent, as well as in PaTu8988, Panc-1 and BxPC-3 cells in which Smo was concomitantly present. Ad-U6-Gli1siRNA induced cell growth inhibition, strong G0/G1 cell cycle arrest and apoptosis in all five human PC cell lines. Meanwhile, Ad-U6-Gli1siRNA significantly suppressed the expression of Gli1, Ptch1 and two target genes, Cyclin D2 and Bcl-2, in all five lines. Furthermore, two tumor xenograft nude mice models were established by subcutaneously injecting Smo-positive Panc-1 cells or Smo-negative SW1990 cells. The in vivo experimental results demonstrated that Ad-U6-Gli1siRNA inhibited the growth of both Panc1-derived and SW1990-derived tumors and induced cell apoptosis. Our study indicates that Gli1-targeting siRNA could induce growth inhibition and apoptosis in PC through knockdown of Gli1 and its target genes; and this method may represent a more effective therapeutic strategy for PC with Smo-dependent or Smo-independent Hh pathway activation.

  15. Activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, C.W.; Mangel, W.F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described. 29 figs.

  16. Activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, Carl W.; Mangel, Walter F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  17. Adenovirus structure.

    PubMed

    Rux, John J; Burnett, Roger M

    2004-12-01

    Structural studies continue to play an essential role as the focus of adenovirus research shifts in emphasis from basic biology to adenovirus-based vector technologies. A crucial step in developing novel therapeutics for gene replacement, cancer, and vaccines is often to modify the virion. Such engineered changes are designed to retarget the virus, or to reduce the immunological responses to infection. These efforts are far more effective when they are based on detailed structural knowledge. This minireview provides a brief summary of the wealth of information that has been obtained from the combined application of X-ray crystallography and electron microscopy. This knowledge now includes a good working model for the architectural organization of the virion, and atomic resolution molecular structures for all the major capsid proteins, hexon, penton, and fiber. We highlight new developments, which include the structure of the penton base and the discovery that adenovirus has several relatives. We sketch how the structural information can be used to engineer novel virions and conclude with the prospects for future progress.

  18. Eradicating chancroid.

    PubMed Central

    Steen, R.

    2001-01-01

    Genital ulcers are important cofactors of HIV transmission in the countries most severely affected by HIV/AIDS. Chancroid is a common cause of genital ulcer in all 18 countries where adult HIV prevalence surpasses 8% and is rare in countries with low-level HIV epidemics. Haemophilus ducreyi, the causative organism of chancroid, is biologically vulnerable and occupies a precarious epidemiological niche. Both simple, topical hygiene and male circumcision greatly reduce risk of infection and several classes of antibiotics--some of which can be administered in single-dose treatment regimens--provide rapid cure. H. ducreyi depends on sexual networks with high rates of partner change for its survival, thriving in environments characterized by male mobility and intensive commercial sex activity. Elimination of H. ducreyi infection from vulnerable groups results in disappearance of chancroid from the larger community. Once endemic in Europe and North America, chancroid began a steady decline early in the twentieth century, well before the discovery of antibiotics. Social changes--resulting in changing patterns of commercial sex--probably disrupted the conditions needed to sustain chancroid as an endemic disease. Sporadic outbreaks are now easily controlled when effective curative and preventive services are made available to sex workers and their clients. More recently, chancroid prevalence has declined markedly in countries such as the Philippines. Senegal, and Thailand, a development that may contribute to stabilization of the HIV epidemics in these countries. Eradication of chancroid is a feasible public health objective. Protecting sex workers and their clients from exposure to sexually transmitted diseases (STDs) and improving curative services for STDs are among the proven strategies that could be employed. PMID:11584729

  19. Innate Immunity to Adenovirus

    PubMed Central

    Hendrickx, Rodinde; Stichling, Nicole; Koelen, Jorien; Kuryk, Lukasz; Lipiec, Agnieszka

    2014-01-01

    Abstract Human adenoviruses are the most widely used vectors in gene medicine, with applications ranging from oncolytic therapies to vaccinations, but adenovirus vectors are not without side effects. In addition, natural adenoviruses pose severe risks for immunocompromised people, yet infections are usually mild and self-limiting in immunocompetent individuals. Here we describe how adenoviruses are recognized by the host innate defense system during entry and replication in immune and nonimmune cells. Innate defense protects the host and represents a major barrier to using adenoviruses as therapeutic interventions in humans. Innate response against adenoviruses involves intrinsic factors present at constant levels, and innate factors mounted by the host cell upon viral challenge. These factors exert antiviral effects by directly binding to viruses or viral components, or shield the virus, for example, soluble factors, such as blood clotting components, the complement system, preexisting immunoglobulins, or defensins. In addition, Toll-like receptors and lectins in the plasma membrane and endosomes are intrinsic factors against adenoviruses. Important innate factors restricting adenovirus in the cytosol are tripartite motif-containing proteins, nucleotide-binding oligomerization domain-like inflammatory receptors, and DNA sensors triggering interferon, such as DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 and cyclic guanosine monophosphate–adenosine monophosphate synthase. Adenovirus tunes the function of antiviral autophagy, and counters innate defense by virtue of its early proteins E1A, E1B, E3, and E4 and two virus-associated noncoding RNAs VA-I and VA-II. We conclude by discussing strategies to engineer adenovirus vectors with attenuated innate responses and enhanced delivery features. PMID:24512150

  20. Adenovirus (For Parents)

    MedlinePlus

    ... common in late winter, spring, and early summer conjunctivitis (pinkeye) and pharyngoconjunctival fever caused by adenovirus tend to ... cystitis usually resolves on its own. Eye infections: Pinkeye (conjunctivitis) is a mild inflammation of the conjunctiva ( ...

  1. Hereditary Pancreatitis

    MedlinePlus

    ... meals throughout the day that are high in carbohydrates and low in protein and fat. Pancreatic enzymes ... the Pancreas NPF Centers Pancreatitis Centers Pancreatitis Center Application Pancreatic Cancer Centers Diagnosis of Pancreatic Cancer Pancreas ...

  2. [Chronic pancreatitis, acute pancreatitis].

    PubMed

    Mabuchi, T; Katada, N; Nishimura, D; Hoshino, H; Shimizu, F; Suzuki, R; Sano, H; Kato, K

    1998-11-01

    MRCP has been recognized as a safe and noninvasive diagnostic method. In the present study we evaluated the usefulness of MRCP in diagnosis of chronic and acute pancreatitis. Two-dimensional fast asymmetric spin-echo (FASE) MRCP was performed in 40 patients with chronic pancreatitis and 13 with acute pancreatitis. In 29 patients (72.5%) with chronic pancreatitis and 9 (66.7%) with acute pancreatitis, main pancreatic duct (MPD) was visualized entirely. MRCP could demonstrate the characteristic findings of chronic pancreatitis such as dilatation and irregularity of MPD in most cases. In acute pancreatitis, MRCP indicated that MPD was normal in diameter, but irregular in configuration compared with that of the control group. MRCP may facilitate the diagnosis of chronic and acute pancreatitis.

  3. Pancreatitis - discharge

    MedlinePlus

    Chronic pancreatitis - discharge; Pancreatitis - chronic - discharge; Pancreatic insufficiency - discharge; Acute pancreatitis - discharge ... fluids through an intravenous (IV) tube in your vein and nutrition through a feeding tube or IV. ...

  4. Chronic pancreatitis

    MedlinePlus

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... hospital for: Pain medicines Fluids given through a vein (IV) Stopping food or fluid by mouth to ...

  5. Co-factor activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, C.W.; Mangel, W.F.

    1996-08-06

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying the peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described. 29 figs.

  6. Co-factor activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, Carl W.; Mangel, Walter F.

    1996-08-06

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  7. Helicobacter pylori eradication therapy.

    PubMed

    Suzuki, Hidekazu; Nishizawa, Toshihiro; Hibi, Toshifumi

    2010-04-01

    Helicobacter pylori infection is the main cause of gastritis, gastroduodenal ulcers and gastric cancer. H. pylori eradication has been shown to have a prophylactic effect against gastric cancer. According to several international guidelines, the first-line therapy for treating H. pylori infection consists of a proton pump inhibitor (PPI) or ranitidine bismuth citrate, with any two antibiotics among amoxicillin, clarithromycin and metronidazole, given for 7-14 days. However, even with these recommended regimens, H. pylori eradication failure is still seen in more than 20% of patients. The failure rate for first-line therapy may be higher in actual clinical practice, owing to the indiscriminate use of antibiotics. The recommended second-line therapy is a quadruple regimen composed of tetracycline, metronidazole, a bismuth salt and a PPI. The combination of PPI-amoxicillin-levofloxacin is a good option as second-line therapy. In the case of failure of second-line therapy, the patients should be evaluated using a case-by-case approach. European guidelines recommend culture before the selection of a third-line treatment based on the microbial antibiotic sensitivity. H. pylori isolates after two eradication failures are often resistant to both metronidazole and clarithromycin. The alternative candidates for third-line therapy are quinolones, tetracycline, rifabutin and furazolidone; high-dose PPI/amoxicillin therapy might also be promising.

  8. Recombinant soluble adenovirus receptor

    DOEpatents

    Freimuth, Paul I.

    2002-01-01

    Disclosed are isolated polypeptides from human CAR (coxsackievirus and adenovirus receptor) protein which bind adenovirus. Specifically disclosed are amino acid sequences which corresponds to adenovirus binding domain D1 and the entire extracellular domain of human CAR protein comprising D1 and D2. In other aspects, the disclosure relates to nucleic acid sequences encoding these domains as well as expression vectors which encode the domains and bacterial cells containing such vectors. Also disclosed is an isolated fusion protein comprised of the D1 polypeptide sequence fused to a polypeptide sequence which facilitates folding of D1 into a functional, soluble domain when expressed in bacteria. The functional D1 domain finds application for example in a therapeutic method for treating a patient infected with a virus which binds to D1, and also in a method for identifying an antiviral compound which interferes with viral attachment. Also included is a method for specifically targeting a cell for infection by a virus which binds to D1.

  9. [Worldwide eradication of poliomyelitis].

    PubMed

    Rasch, G; Schreier, E; Kiehl, W; Kurth, R

    2001-10-30

    Poliomyelitis, an infectious disease with acute and persistent flaccid paralysis is caused by poliovirus (types 1, 2 or 3), an enterovirus. The infection is asymptomatic in 95% of infected subjects. Most of the paralytic cases occur in adolescents or adults in the course of polio type 1 infection. In the prevaccination era, in countries with poor hygienic conditions, infection in early childhood was common, mostly asymptomatic, and immunity in the population prevailed. In developed countries polio often struck adolescents and adults taking its toll in paralytic disease. The introduction of vaccination with the Salk vaccine (IPV Inactivated Polio Vaccine) in the USA and in Europe in 1956 and with the Oral Polio Vaccine (OPV) developed by Sabin worldwide in the early sixties made it possible to control the epidemic in large geographic areas, but it could not eliminate the disease worldwide. Poliomyelitis is still endemic in Central Africa and in the Indian sub-continent. Acts of war led to the reduction in the vaccination rate in different geographic areas, and smaller epidemics with wild virus but also with reverted vaccine strains occurred. In some parts of the world the rate of vaccination also declined due to elimination of poliomyelitis, and it came to small epidemics of paralytic polio mainly caused by reverted vaccine strains circulating in the population. Reverted vaccine strains also remain a central problem in the eradication of poliomyelitis projected for 2005 by the World Health Organisation. A high vaccination rate, preferably with 3 doses of OPV in infancy or early childhood, and exact worldwide monitoring of cases is indispensable for the eradication. For the complete eradication of poliovirus the live vaccine OPV would have to be changed to an inactivated vaccine IPV worldwide. However, this is presently unachieveable, because of logistic problems and high costs.

  10. HIV/AIDS eradication.

    PubMed

    Marsden, Matthew D; Zack, Jerome A

    2013-07-15

    Antiretroviral therapy can inhibit HIV replication in patients and prevent progression to AIDS. However, it is not curative. Here we provide an overview of what antiretroviral drugs do and how the virus persists during therapy in rare reservoirs, such as latently infected CD4+ T cells. We also outline several innovative methods that are currently under development to eradicate HIV from infected individuals. These strategies include gene therapy approaches intended to create an HIV-resistant immune system, and activation/elimination approaches directed towards flushing out latent virus. This latter approach could involve the use of novel chemically synthesized analogs of natural activating agents.

  11. Pancreatic Cancer

    MedlinePlus

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  12. Pancreatic pseudocyst

    MedlinePlus

    ... More Acute pancreatitis Chronic pancreatitis Pancreatic abscess Shock Review Date 10/27/2015 Updated by: Subodh K. ... gastroenterologist with Gastrointestinal Specialists of Georgia, Austell, GA. Review provided by VeriMed Healthcare Network. Also reviewed by ...

  13. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  14. Eradication of tetanus

    PubMed Central

    Thwaites, C. L.; Loan, H. T.

    2015-01-01

    Introduction The causative agent of tetanus, Clostridium tetani is widespread in the environment throughout the world and cannot be eradicated. To reduce the number of cases of tetanus efforts are focussed on prevention using vaccination and post-exposure wound care. Sources of data Medline, Pubmed and Cochrane databases; World Health Organization and United Nations Children's Fund publications. Areas of agreement The maternal and neonatal tetanus elimination initiative has resulted in significant reductions in mortality from neonatal tetanus throughout the world. Areas of controversy Although there are few data available it is likely that large numbers of children and adults, particularly men, remain unprotected due to lack of booster immunization. Areas timely for developing research It remains unclear how HIV and malaria affect both responses to vaccination and transplacental transfer of antibodies or how this might affect timing of vaccination doses. PMID:26598719

  15. 21 CFR 866.3020 - Adenovirus serological reagents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and antisera used in serological tests to identify antibodies to adenovirus in serum. Additionally... identify adenoviruses directly from clinical specimens. The identification aids in the diagnosis of disease caused by adenoviruses and provides epidemiological information on these diseases. Adenovirus...

  16. Treponematosis eradication, with special reference to yaws eradication in Haiti*

    PubMed Central

    Samame, G. E.

    1956-01-01

    This paper outlines the general administrative and therapeutic principles governing yaws eradication campaigns, with particular reference to the operational problems encountered in Haiti. The ways in which those problems were solved are described in the course of a relatively detailed account of the yaws eradication programme which began in that country in 1950 and which has now reached the end of the “mopping-up” phase. The author points out that lessons learnt in this mass treatment campaign can usefully be applied to eradication programmes against other diseases. PMID:13404466

  17. Eradicating rabies at source.

    PubMed

    Pastoret, P-P; Van Gucht, S; Brochier, B

    2014-08-01

    Along with zoonotic influenza and antimicrobial resistance, rabies has been identified as a key One Health issue by the World Organisation for Animal Health (OIE), World Health Organization (WHO) and Food and Agriculture Organization of the United Nations (FAO). It provides an excellent example of a disease that has an impact on public, animal and environmental health, and therefore benefits from a One Health approach to management. Regrettably, this zoonotic disease is still neglected despite the fact that, annually, it kills as many as 70,000 people worldwide (chiefly children in Asia and Africa), millions of dogs suffer and die, and the disease threatens some populations of endangered wildlife. This is particularly unfortunate, given that effective means of prevention exist. As Her Royal Highness Princess Haya of Jordan pointed out in a video to mark World Rabies Day on 28 September 2013, rabies is a serious world public health problem that is all too often underestimated and even neglected. Yet we know it can be eliminated. By combatting rabies at its source in animals and vaccinating 70% of dogs, we can eradicate it.

  18. Chronic Pancreatitis in Children

    MedlinePlus

    ... Chronic Pancreatitis in Children Childhood Inherited Disorders Pancreatic Cancer Pancreatic Cancer Risks and Symptoms Staging of Pancreatic Cancer Treatment of Pancreatic Cancer Whipple Procedure Complementary Therapies Pancreatic Cancer Support ...

  19. Acute Pancreatitis in Children

    MedlinePlus

    ... Chronic Pancreatitis in Children Childhood Inherited Disorders Pancreatic Cancer Pancreatic Cancer Risks and Symptoms Staging of Pancreatic Cancer Treatment of Pancreatic Cancer Whipple Procedure Complementary Therapies Pancreatic Cancer Support ...

  20. Mankind's Magnificent Milestone: Smallpox Eradication.

    ERIC Educational Resources Information Center

    Small, Parker A., Jr.; Small, Natalie S.

    1996-01-01

    Illustrates the complex interactions between disease, societal attitudes, and technology by looking at the history of smallpox. Describes one of mankind's most magnificent accomplishments--the eradication of smallpox from the earth. (JRH)

  1. India eradicates guinea worm disease.

    PubMed

    Sharma, R

    2000-03-11

    The WHO officially certifies India and other countries of the South East Asian regions as free of guinea worm disease. The eradication was made possible through the efforts of the Indian government to launch a national guinea worm eradication program in 1983-84, and a sustained campaign at the grass-roots level by agencies such as the UN International Children's Fund and the WHO in collaboration with the government. The recognition was based on the report gathered by three members of the 4th International Commission for Certification of Dracunculiasis Eradication, who visited India in November 1999 and conducted an investigation in 62 villages in 5 states where the disease had been endemic. Also, the national eradication program had been evaluated 7 times and showed remarkable achievement.

  2. Tuberculosis eradication versus control.

    PubMed

    Schito, Marco; Hanna, Debra; Zumla, Alimuddin

    2017-03-01

    According to the World Health Organization (WHO), 10.4 million people died of tuberculosis (TB) in 2015, and the disease is now the number one cause of death from a preventable infectious disease worldwide. A bold vision is needed from global leaders to end the TB epidemic and plans to this end have been proposed. However enthusiasm must be matched by tangible and achievable goals based on the science and available funding. In order to reach the target and goals set by the WHO End TB Strategy, the challenges for TB eradication need to be addressed. In order to achieve the targets, several areas need to be bolstered, including the requirement to better identify and treat existing drug-susceptible cases and diagnose all the drug-resistant forms of the disease. Although treatment is available for most TB patients, stock-outs and other delays are problematic in some settings, resulting in ongoing transmission, especially for the drug-resistant forms of the disease. Despite the fact that a majority of multidrug-resistant cases are linked to treatment, the cure rate is only 50%, which highlights the need for safer, shorter, and more efficacious drug regimens that are more tolerable to patients. Prospects for a more efficacious vaccine are limited, with no correlates of protection identified; thus the availability of a vaccine by 2025 is highly improbable. Support for instituting infection control methods should be prioritized to subvert transmission while patients seek treatment and care. Finally, more adequate financial mechanisms should be instituted to reduce patient expenditures and support national TB programs. Moreover, funding to support basic science, drug development, clinical trials, vaccine development, diagnostics, and implementation research needs to be secured in order to reduce global TB incidence in the future.

  3. Pancreatic cancer

    MedlinePlus

    ... cancer, cystic pancreatic neoplasms, and other nonendocrine pancreatic tumors. In: Feldman M, Friedman LS, Brandt LJ, ... by: Yi-Bin Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital, Boston, MA. ...

  4. Canine adenovirus based rabies vaccines.

    PubMed

    Tordo, N; Foumier, A; Jallet, C; Szelechowski, M; Klonjkowski, B; Eloit, M

    2008-01-01

    Adenovirus based vectors are very attractive candidates for vaccination purposes as they induce in mammalian hosts potent humoral, mucosal and cellular immune responses to antigens encoded by the inserted genes. We have generated E1-deleted and replication-competent recombinant canine type-2 adenoviruses expressing the rabies virus glycoprotein (G). The effectiveness of both vectors to express a native G protein has been characterized in vitro in permissive cell lines. We compared the humoral and cellular immune responses induced in mice by intramuscular injection of the recombinant canine adenovirus vectors with those induced by a human (Ad5) E1-deleted virus expressing the same rabies G protein. Humoral responses specific to the adenoviruses or the rabies glycoprotein antigens were studied. The influence of the mouse strain was observed using replication-competent canine adenovirus. A high level of rabies neutralizing antibody was observed upon i.m. inoculation, and 100% of mice survived lethal challenge. These results are very promising in the perspective of oral vaccine for dog rabies control.

  5. Can measles be eradicated globally?

    PubMed Central

    de Quadros, Ciro A.

    2004-01-01

    Measles is one of the most infectious diseases. Before measles vaccine was introduced, nearly everyone contracted the disease at some point in childhood. By the late 1980s, most countries had incorporated measles vaccine into their routine immunization programmes. Globally, about 800 000 children nevertheless still die from measles annually, half of them in Africa. Eradicating measles would therefore play an important role in improving children's survival. The 24th Pan American Sanitary Conference in 1994 established a goal of eradicating measles from the Americas. Progress to date has been remarkable and the disease is no longer endemic in the Americas, with most countries having documented interruption of transmission. As of November 2003, 12 months had elapsed since the last indigenous case was detected in Venezuela. This experience shows that measles transmission can be interrupted, and that this can be sustained over a long period of time. Global eradication is feasible if an appropriate strategy is implemented. Even under a new paradigm in which immunization is not discontinued after measles is eradicated, eradication will be a good investment to avoid expensive epidemics and save the lives of almost one million children annually. A world free of measles by 2015 is not a dream. PMID:15042236

  6. Adenoviruses in the immunocompromised host.

    PubMed Central

    Hierholzer, J C

    1992-01-01

    Adenoviruses are among the many pathogens and opportunistic agents that cause serious infection in the congenitally immunocompromised, in patients undergoing immunosuppressive treatment for organ and tissue transplants and for cancers, and in human immunodeficiency virus-infected patients. Adenovirus infections in these patients tend to become disseminated and severe, and the serotypes involved are clustered according to the age of the patient and the nature of the immunosuppression. Over 300 adenovirus infections in immunocompromised patients, with an overall case fatality rate of 48%, are reviewed in this paper. Children with severe combined immunodeficiency syndrome and other primary immunodeficiencies are exposed to the serotypes of subgroups B and C that commonly infect young children, and thus their infections are due to types 1 to 7 and 31 of subgenus A. Children with bone marrow and liver transplants often have lung and liver adenovirus infections that are due to an expanded set of subgenus A, B, C, and E serotypes. Adults with kidney transplants have viruses of subgenus B, mostly types 11, 34, and 35, which cause cystitis. This review indicates that 11% of transplant recipients become infected with adenoviruses, with case fatality rates from 60% for bone marrow transplant patients to 18% for renal transplant patients. Patients with AIDS become infected with a diversity of serotypes of all subgenera because their adult age and life-style expose them to many adenoviruses, possibly resulting in antigenically intermediate strains that are not found elsewhere. Interestingly, isolates from the urine of AIDS patients are generally of subgenus B and comprise types 11, 21, 34, 35, and intermediate strains of these types, whereas isolates from stool are of subgenus D and comprise many rare, new, and intermediate strains that are untypeable for practical purposes. It has been estimated that adenoviruses cause active infection in 12% of AIDS patients and that 45% of

  7. Global eradication of Guinea worm.

    PubMed

    Periès, H; Cairncross, S

    1997-11-01

    Little more than a decade ago, it was estimated that over three million cases of dracunculiasis occurred worldwide. Since then, the numbers have fallen dramatically, thanks to the water supply initiatives of the 1980s and, more recently, the national guinea worm eradication programmes implemented in a score of endemic countries. Hervé Periès and Sandy Cairncross discuss how eradication will require the containment of cases in the remaining endemic areas, together with the simultaneous strengthening of surveillance to permit the certification of eradication. This aim requires existing strategies to be adapted to maintain their efficacy and also to improve their sustainability and cost-effectiveness. Sudan with its civil war, and more than a hundred thousand reported cases, remains a major obstacle to rapid achievement of the goal.

  8. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    ClinicalTrials.gov

    2016-09-14

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  9. [Polio vaccines, eradication and posterradication].

    PubMed

    Salmerón García, Francisco; Portela Moreira, Agustín; Soler Soneira, Marta; López Hernández, Susana; Chamorro Somoza Díaz-Sarmiento, María; Pérez González, Isabel; Rubio Gómez, María Isabel; Pérez González, Alicia; Sagredo Rodríguez, Ana; Ruiz Antúnez, Sol; Timón Jiménez, Marcos; Frutos Cabanillas, Gloria

    2013-01-01

    Vaccination against polio generates herd immunity (both with the attenuated (OPV) and inactivated (IPV) vaccines) and this will allow the eradication of the disease. The OPV vaccine produces 2-4 polio cases per cohort of one million children and therefore IPV is used in countries that can afford its cost (about 15 times more expensive than OPV). In 1988 the World Health Assembly established the polio eradication goal as "interruption of wild poliovirus transmission". If the elimination of wild poliovirus were achieved, the use of OPV will produce annually between 250 and 500 cases of polio in the world. From 1999, it was clear that eradication would require ending of immunization with OPV. On the 25th of January, 2013 it is approved the plan for the eradication and containment of all polioviruses, wild or not, so that no child suffers paralytic poliomyelitis. The most important landmarks include the lack of wild polio cases after 2014, the introduction of at least one dose of IPV in all immunization programs and to cease the type 2 OPV vaccination by the end of 2016 and to stop the use of the oral bivalent vaccine in 2019. To achieve all this, a complex scientific work and economic solidarity will be required.

  10. Vector control after malaria eradication

    PubMed Central

    Micks, D. W.

    1963-01-01

    In considerable areas now in or near the consolidation phase of malaria eradication, other vector-borne diseases present serious public health problems, even though not susceptible to control on the same world-wide scale as malaria. Several of these areas are already making plans for converting their malaria eradication services to vector control services. While it is possible to use essentially the same personnel and equipment, the methods must be adapted to the biology and habits of the vector. For a smooth and rapid transition, considerable advance planning is therefore needed—preferably well ahead of the consolidation phase. The author gives several examples of the need for flexibility in effecting the changeover and of the problems likely to arise after the completion of malaria eradication programmes. He recommends that epidemiological studies should be extended to vector-borne diseases other than malaria while eradication programmes are still in progress and that vector control programmes should be integrated into the basic health services of the country as soon as possible. He also underlines the importance of water management and other aspects of environmental sanitation in vector control programmes. PMID:20604169

  11. Eradicating Helicobacter pylori and symptoms of non-ulcer dyspepsia.

    PubMed Central

    Patchett, S; Beattie, S; Leen, E; Keane, C; O'Morain, C

    1991-01-01

    OBJECTIVE--To examine the effect of eradication of Helicobacter pylori on symptoms of non-ulcer dyspepsia. DESIGN--Four week prospective study. SETTING--One hospital outpatient and endoscopy department. PATIENTS--90 adults with persistent symptoms typical of non-ulcer dyspepsia but no clinical or endoscopic evidence of other peptic, biliary, pancreatic, or malignant disease; all had histological and microbiological evidence of infection with H pylori. 83 patients completed the treatment regimen. INTERVENTION--Colloidal bismuth subcitrate 120 mg four times a day for four weeks (27 patients); metronidazole 400 mg and amoxycillin 500 mg each three times a day for one week (27); and bismuth subcitrate 120 mg four times a day for four weeks, metronidazole 400 mg three times a day for one week, plus amoxycillin 500 mg three times a day for the first week (29). MAIN OUTCOME MEASURES--Change in symptom scores determined with questionnaire; histological evidence of gastritis and microbiological evidence of presence of H pylori in biopsy specimens. RESULTS--Overall, H pylori was eradicated in 41 (49%) patients. Although gastritis scores improved significantly in only patients in whom H pylori had been eradicated (from 1.56 to 0.61, p less than 0.01 v from 1.83 to 1.07, p = 0.52) mean symptom scores after treatment were similar in patients in whom H pylori had or had not been eradicated (3.0 v 2.3, NS). Similarly the mean symptom score improved whether or not gastritis improved (2.8 v 3.1 respectively, p = 0.72). The observations were similar for treatment groups analysed individually. CONCLUSION--Antral infection with the organism does not seem to have an important aetiological role in non-ulcer dyspepsia short term. PMID:1747644

  12. Adenovirus Early Proteins and Host Sumoylation

    PubMed Central

    Sohn, Sook-Young

    2016-01-01

    ABSTRACT The human adenovirus genome is transported into the nucleus, where viral gene transcription, viral DNA replication, and virion assembly take place. Posttranslational modifications by small ubiquitin-like modifiers (SUMOs) are implicated in the regulation of diverse cellular processes, particularly nuclear events. It is not surprising, therefore, that adenovirus modulates and utilizes the host sumoylation system. Adenovirus early proteins play an important role in establishing optimal host environments for virus replication within infected cells by stimulating the cell cycle and counteracting host antiviral defenses. Here, we review findings on the mechanisms and functional consequences of the interplay between human adenovirus early proteins and the host sumoylation system. PMID:27651358

  13. Combination therapy with conditionally replicating adenovirus and replication defective adenovirus.

    PubMed

    Lee, Choon-Taek; Park, Kyung-Ho; Yanagisawa, Kiyoshi; Adachi, Yasushi; Ohm, Joyce E; Nadaf, Sorena; Dikov, Mikhail M; Curiel, David T; Carbone, David P

    2004-09-15

    Low gene transfer rate is the most substantial hurdle in the practical application of gene therapy. One strategy to improve transfer efficiency is the use of a conditionally replicating adenovirus (CRAD) that can selectively replicate in tumor cells. We hypothesized that conventional E1-deleted adenoviruses (ad) can become replication-competent when cotransduced with a CRAD to selectively supply E1 in trans in tumors. The resulting selective production of large numbers of the E1-deleted ad within the tumor mass will increase the transduction efficiency. We used a CRAD (Delta24RGD) that produces a mutant E1 without the ability to bind retinoblastoma but retaining viral replication competence in cancer cells with a defective pRb/p16. Ad-lacZ, adenovirus-luciferase (ad-luc), and adenovirus insulin-like growth factor-1R/dominant-negative (ad-IGF-1R/dn; 482, 950) are E1-deleted replication-defective adenoviruses. The combination of CRAD and ad-lacZ increased the transduction efficiency of lacZ to 100% from 15% observed with ad-lacZ alone. Transfer of media of CRAD and ad-lacZ cotransduced cells induced the transfer of lacZ (media transferable bystander effect). Combination of CRAD and ad-IGF-1R/dn increased the production of truncated IGF-1R or soluble IGF-1R > 10 times compared with transduction with ad-IGF-1R/dn alone. Combined intratumoral injection of CRAD and ad-luc increased the luciferase expression about 70 times compared with ad-luc alone without substantial systemic spread. Combined intratumoral injection of CRAD and ad-IGF-1R/482 induced stronger growth suppression of established lung cancer xenografts than single injections. The combination of CRAD and E1-deleted ad induced tumor-specific replication of CRAD and E1-deleted ad and increased the transduction rate and therapeutic efficacy of these viruses in model tumors.

  14. Poliomyelitis eradication: Rhetoric or reality

    PubMed Central

    Bhatnagar, Nidhi; Grover, Manoj; Sinha, Smita; Kaur, Ravneet

    2013-01-01

    Since the launch of Global Polio Eradication Initiative in 1988, disease burden has been reduced by more than 99% globally. Lately, India has witnessed a year without a case of poliomyelitis. It no longer stands endemic and is being regarded as a model for polio eradication efforts in other low income endemic countries: Pakistan, Nigeria and Afghanistan. The near elimination of wild polio virus in India has set forth new challenges of vaccine derived polio virus and need for newer strategies in oral poliomyelitis vaccine cessation preparatory phase. Stricter surveillance measures are needed to check for importations, any spread of virus in migratory populations and rapid containment of newly found virus. No stone should be left unturned in this last ditch effort for extermination of polio virus form environmental circulation. India's battle against polio will be cited as the biggest public health achievement or the most expensive public health failure.

  15. Acute Pancreatitis

    PubMed Central

    Geokas, Michael C.

    1972-01-01

    For many decades two types of acute pancreatitis have been recognized: the edematous or interstitial and the hemorrhagic or necrotic. In most cases acute pancreatitis is associated with alcoholism or biliary tract disease. Elevated serum or urinary α-amylase is the most important finding in diagnosis. The presence of methemalbumin in serum and in peritoneal or pleural fluid supports the diagnosis of the hemorrhagic form of the disease in patients with a history and enzyme studies suggestive of pancreatitis. There is no characteristic clinical picture in acute pancreatitis, and its complications are legion. Pancreatic pseudocyst is probably the most common and pancreatic abscess is the most serious complication. The pathogenetic principle is autodigestion, but the precise sequence of biochemical events is unclear, especially the mode of trypsinogen activation and the role of lysosomal hydrolases. A host of metabolic derangements have been identified in acute pancreatitis, involving lipid, glucose, calcium and magnesium metabolism and changes of the blood clotting mechanism, to name but a few. Medical treatment includes intestinal decompression, analgesics, correction of hypovolemia and other supportive and protective measures. Surgical exploration is advisable in selected cases, when the diagnosis is in doubt, and is considered imperative in the presence of certain complications, especially pancreatic abscess. PMID:4559467

  16. Chronic Pancreatitis

    PubMed Central

    DiMagno, Matthew J.; DiMagno, Eugene P.

    2012-01-01

    Purpose of review We review important new clinical observations in chronic pancreatitis (CP) reported in 2011. Recent findings Smoking increases the risk of non-gallstone acute pancreatitis (AP) and the progression of AP to CP. Binge drinking during Oktoberfest did not associate with increased hospital admissions for AP. The unfolded protein response is an adaptive mechanism to maintain pancreatic health in response to noxious stimuli such as alcohol. Onset of diabetes mellitus in CP is likely due to progressive disease rather than individual variables. Insufficient pancreatic enzyme dosing is common for treatment of pancreatic steatorrhea; 90,000 USP U of lipase should be given with meals. Surgical drainage provides sustained, superior pain relief compared to endoscopic treatment in patients advanced CP with a dilated main duct +/− pancreatic stones. The central acting gabapentoid pregabalin affords a modest 12% pain reduction in patients with CP but ~30% of patients have significant side effects. Summary Patients with non-gallstone related AP or CP of any etiology should cease smoking. Results of this year’s investigations further elucidated the pancreatic pathobiology due to alcohol, onset of diabetes mellitus in CP, and the mechanisms and treatment of neuropathic pain in CP. PMID:22782018

  17. Chronic pancreatitis.

    PubMed

    Lindley, Keith J

    2006-10-01

    Chronic pancreatitis (CP) is characterised by pancreatic inflammation and fibrosis leading eventually to destruction of pancreatic parenchyma and loss of exocrine and endocrine function. A model of interactions between environmental triggers of pancreatic inflammation and disease susceptibility or modifying genes (including PRSS1, SPINK1 and CFTR) provides a framework within which to understand disease pathogenesis. Early in the disease, when fibrosis is mild and pancreatic damage limited, it is difficult to distinguish CP from recurrent acute pancreatitis (RAP) although it is likely these represent opposite ends of a spectrum of disease with a common aetiology in which CP represents either a later disease stage or disease in individuals predisposed to generate a chronic fibrogenic inflammatory response. Pain is a dominant feature resulting in part from neuroimmune interactions within the pancreas. Diagnosis at an early stage of disease is challenging, though in later stages is dependent upon the demonstration of pancreatic fibrosis and duct ectasia using one or more imaging modalities including transabdominal and endoscopic ultrasound, CT and MRCP or ERCP. Current treatments are largely supportive and reactive. The challenge for pediatricians is to achieve diagnosis at an early stage of the disease and to develop treatments that can alter its natural history.

  18. Pancreatic Cysts

    MedlinePlus

    ... fluid can be collected from the cyst for analysis in a laboratory for possible signs of cancer. The characteristics and location of the pancreatic cyst, with your age and sex, can help doctors pinpoint the type of cyst ...

  19. Acute pancreatitis

    MedlinePlus

    ... mg/dL Injury to the pancreas from an accident Other causes include: After certain procedures used to ... pressure Rapid heart rate Rapid breathing (respiratory) rate Lab tests that show the release of pancreatic enzymes ...

  20. Pancreatitis - children

    MedlinePlus

    ... an organ or bone marrow transplant Cystic fibrosis Crohn disease and other disorders when the body's immune system ... lab tests to check the release of pancreatic enzymes. These include tests to check the: Blood amylase ...

  1. Pancreatic abscess

    MedlinePlus

    ... high. Possible Complications Complications may include: Multiple abscesses Sepsis When to Contact a Medical Professional Call your ... 2016:chap 144. Read More Abscess Pancreatic pseudocyst Sepsis Review Date 10/27/2015 Updated by: Subodh ...

  2. Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

    DOE PAGES

    Abbink, Peter; Maxfield, Lori F.; Ng'ang'a, David; ...

    2014-11-19

    Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. Furthermore, the phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. We describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved tomore » have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors.« less

  3. Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

    SciTech Connect

    Abbink, Peter; Maxfield, Lori F.; Ng'ang'a, David; Borducchi, Erica N.; Iampietro, M. Justin; Bricault, Christine A.; Teigler, Jeffrey E.; Blackmore, Stephen; Parenteau, Lily; Wagh, Kshitij; Handley, Scott A.; Zhao, Guoyan; Virgin, Herbert W.; Korber, Bette; Barouch, Dan H.

    2014-11-19

    Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. Furthermore, the phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. We describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors.

  4. Autoimmune pancreatitis

    PubMed Central

    2016-01-01

    Autoimmune pancreatitis (AIP) is a rare, distinct and increasingly recognized form of pancreatitis which has autoimmune features. The international consensus diagnostic criteria (ICDC) for AIP recently described two subtypes; type 1[lymphoplasmacytic sclerosing pancreatitis (LPSP)] and type 2 [idiopathic duct-centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesion (GEL)]. Type 1 is the more common form of the disease worldwide and current understanding suggests that it is a pancreatic manifestation of immunoglobulin G4-related disease (IgG4-RD). In contrast, type 2 AIP is a pancreas-specific disease not associated with IgG4 and mostly without the overt extra-pancreatic organ involvement seen in type 1. The pathogenesis of AIP is not completely understood and its clinical presentation is non-specific. It shares overlapping features with more sinister pathologies such as cancer of the pancreas, which continues to pose a diagnostic challenge for clinicians. The diagnostic criteria requires a variable combination of histopathological, imaging and serological features in the presence of typical extrapancreatic lesions and a predictable response to steroids. PMID:27294040

  5. Economic considerations for the eradication endgame

    PubMed Central

    Barrett, Scott

    2013-01-01

    An infectious disease will be eradicated only if it is eliminated everywhere, including in the hardest-to-reach, most vaccine-wary communities. If eradication is successful, it promises a dividend in the form of avoided infections and vaccinations. However, success is never certain unless and until eradication is achieved, and claiming the dividend means bearing the possibly great risk of re-emergence. Economic analysis of eradication evaluates these risks and rewards relative to the alternative of ‘optimal control’, and also exposes the incentives for achieving and capitalizing on eradication. Eradication is a ‘game’, because some countries may be willing to eliminate the disease within their borders only if assured that all others will eliminate the disease within their borders. International financing is also a game, because each country would rather free ride than contribute. Finally, for diseases such as polio, capitalizing on eradication is a game, for should any country continue to vaccinate in the post-eradication era using the live-attenuated polio vaccine, the countries that stop vaccinating will be exposed to the risk of vaccine-derived polioviruses. In the framework developed in this paper, eradication is a seductive goal, its attainment fraught with peril. PMID:23798697

  6. ERAD and how viruses exploit it

    PubMed Central

    Byun, Hyewon; Gou, Yongqiang; Zook, Adam; Lozano, Mary M.; Dudley, Jaquelin P.

    2014-01-01

    Endoplasmic reticulum (ER)-associated degradation (ERAD) is a universally important process among eukaryotic cells. ERAD is necessary to preserve cell integrity since the accumulation of defective proteins results in diseases associated with neurological dysfunction, cancer, and infections. This process involves recognition of misfolded or misassembled proteins that have been translated in association with ER membranes. Recognition of ERAD substrates leads to their extraction through the ER membrane (retrotranslocation or dislocation), ubiquitination, and destruction by cytosolic proteasomes. This review focuses on ERAD and its components as well as how viruses use this process to promote their replication and to avoid the immune response. PMID:25071743

  7. Pancreatic Cancer Early Detection Program

    ClinicalTrials.gov

    2014-07-30

    Pancreatic Cancer; Pancreas Cancer; Pancreatic Adenocarcinoma; Familial Pancreatic Cancer; BRCA 1/2; HNPCC; Lynch Syndrome; Hereditary Pancreatitis; FAMMM; Familial Atypical Multiple Mole Melanoma; Peutz Jeghers Syndrome

  8. Immunological effects of a tumor necrosis factor alpha-armed oncolytic adenovirus.

    PubMed

    Hirvinen, Mari; Rajecki, Maria; Kapanen, Mika; Parviainen, Suvi; Rouvinen-Lagerström, Noora; Diaconu, Iulia; Nokisalmi, Petri; Tenhunen, Mikko; Hemminki, Akseli; Cerullo, Vincenzo

    2015-03-01

    For long it has been recognized that tumor necrosis factor alpha (TNFa) has anticancer characteristics, and its use as a cancer therapeutic was proposed already in the 1980s. However, its systemic toxicity has limited its usability. Oncolytic viruses, selectively cancer-killing viruses, have shown great potency, and one of their most useful aspects is their ability to produce high amounts of transgene products locally, resulting in high local versus systemic concentrations. Therefore, the overall magnitude of tumor cell killing results from the combination of oncolysis, transgene-mediated direct effect such as TNFa-mediated apoptosis, and, perhaps most significantly, from activation of the host immune system against the tumor. We generated a novel chimeric oncolytic adenovirus expressing human TNFa, Ad5/3-D24-hTNFa, whose efficacy and immunogenicity were tested in vitro and in vivo. The hTNFa-expressing adenovirus showed increased cancer-eradicating potency, which was shown to be because of elevated apoptosis and necrosis rates and induction of various immune responses. Interestingly, we saw increase in immunogenic cell death markers in Ad5/3-d24-hTNFa-treated cells. Moreover, tumors treated with Ad5/3-D24-hTNFa displayed enhanced presence of OVA-specific cytotoxic T cells. We thus can conclude that tumor eradication and antitumor immune responses mediated by Ad5/3-d24-hTNFa offer a new potential drug candidate for cancer therapy.

  9. Phylogenetic analysis of adenovirus sequences.

    PubMed

    Harrach, Balázs; Benko, Mária

    2007-01-01

    Members of the family Adenoviridae have been isolated from a large variety of hosts, including representatives from every major vertebrate class from fish to mammals. The high prevalence, together with the fairly conserved organization of the central part of their genomes, make the adenoviruses one of (if not the) best models for studying viral evolution on a larger time scale. Phylogenetic calculation can infer the evolutionary distance among adenovirus strains on serotype, species, and genus levels, thus helping the establishment of a correct taxonomy on the one hand, and speeding up the process of typing new isolates on the other. Initially, four major lineages corresponding to four genera were recognized. Later, the demarcation criteria of lower taxon levels, such as species or types, could also be defined with phylogenetic calculations. A limited number of possible host switches have been hypothesized and convincingly supported. Application of the web-based BLAST and MultAlin programs and the freely available PHYLIP package, along with the TreeView program, enables everyone to make correct calculations. In addition to step-by-step instruction on how to perform phylogenetic analysis, critical points where typical mistakes or misinterpretation of the results might occur will be identified and hints for their avoidance will be provided.

  10. Eradicating a Disease: Lessons from Mathematical Epidemiology

    ERIC Educational Resources Information Center

    Glomski, Matthew; Ohanian, Edward

    2012-01-01

    Smallpox remains the only human disease ever eradicated. In this paper, we consider the mathematics behind control strategies used in the effort to eradicate smallpox, from the life tables of Daniel Bernoulli, to the more modern susceptible-infected-removed (SIR)-type compartmental models. In addition, we examine the mathematical feasibility of…

  11. H pylori recurrence after successful eradication

    PubMed Central

    Niv, Yaron

    2008-01-01

    Recurrence of H pylori after eradication is rare in developed countries and more frequent in developing countries. Recrudescence (recolonization of the same strain within 12 mo after eradication) rather than reinfection (colonization with a new strain, more than 12 mo after eradication) is considered to be responsible for most of the cases. This observation was confirmed only in developed countries, while in developing countries a recent meta-analysis demonstrated a high rate of reinfection. The proportion of H pylori annual recurrence was 2.67% and 13.00% in developed and developing countries, respectively. Nested meta-analysis (only cases with a longer follow-up and a negative 13CUBT a year after eradication) revealed annual recurrence rate of 1.45% [relative risk (RR), 0.54] and 12.00% (RR, 0.92) in developed and developing countries, respectively. These findings support the notion that in developed countries many cases of recurrence are due to recrudescence within the first year after eradication, with a 46% drop in the recurrence rate after the first year post eradication, while in developing countries reinfection is more pronounced, and continue at the same rate since eradication. A different approach for follow-up after H pylori eradication is probably needed in patients of developing countries, since reinfection is highly prevalent. PMID:18330934

  12. Adenovirus Replaces Mitotic Checkpoint Controls

    PubMed Central

    Turner, Roberta L.; Groitl, Peter; Dobner, Thomas

    2015-01-01

    ABSTRACT Infection with adenovirus triggers the cellular DNA damage response, elements of which include cell death and cell cycle arrest. Early adenoviral proteins, including the E1B-55K and E4orf3 proteins, inhibit signaling in response to DNA damage. A fraction of cells infected with an adenovirus mutant unable to express the E1B-55K and E4orf3 genes appeared to arrest in a mitotic-like state. Cells infected early in G1 of the cell cycle were predisposed to arrest in this state at late times of infection. This arrested state, which displays hallmarks of mitotic catastrophe, was prevented by expression of either the E1B-55K or the E4orf3 genes. However, E1B-55K mutant virus-infected cells became trapped in a mitotic-like state in the presence of the microtubule poison colcemid, suggesting that the two viral proteins restrict entry into mitosis or facilitate exit from mitosis in order to prevent infected cells from arresting in mitosis. The E1B-55K protein appeared to prevent inappropriate entry into mitosis through its interaction with the cellular tumor suppressor protein p53. The E4orf3 protein facilitated exit from mitosis by possibly mislocalizing and functionally inactivating cyclin B1. When expressed in noninfected cells, E4orf3 overcame the mitotic arrest caused by the degradation-resistant R42A cyclin B1 variant. IMPORTANCE Cells that are infected with adenovirus type 5 early in G1 of the cell cycle are predisposed to arrest in a mitotic-like state in a p53-dependent manner. The adenoviral E1B-55K protein prevents entry into mitosis. This newly described activity for the E1B-55K protein appears to depend on the interaction between the E1B-55K protein and the tumor suppressor p53. The adenoviral E4orf3 protein facilitates exit from mitosis, possibly by altering the intracellular distribution of cyclin B1. By preventing entry into mitosis and by promoting exit from mitosis, these adenoviral proteins act to prevent the infected cell from arresting in a

  13. Percutaneous catheter drainage of pancreatic pseudocysts.

    PubMed

    Adams, D B; Harvey, T S; Anderson, M C

    1991-01-01

    Pancreatic pseudocysts represent a complication of severe pancreatic inflammatory disease. Although operative drainage is the cornerstone of therapy for pseudocysts, we have undertaken percutaneous catheter drainage in a selected group of 28 patients over a six-year period (1982-88). This represents 42 per cent of pseudocyst patients managed by the senior author and 1.7 per cent of admissions for pancreatitis at the Medical University Hospitals during that period of time. There were 26 men and two women with an age range of 26-66 years (mean = 42.1). Twenty-six patients had alcohol abuse as the cause of pancreatitis; two were due to surgical trauma. Nondilated pancreatic ducts were demonstrated in 25 patients. Six had pancreatic ascites associated with pseudocysts. Four had previous operative drainage (2 internal and 2 external drainage procedures). Five patients received octreotide acetate, a synthetic peptide which mimics the action of somatostatin, in an attempt to aid closure of external fistulas. The mean length of catheter drainage was 48 days (range 7-210 days). Eight (29%) patients developed procedure-related complications (1 pneumothorax, 1 sheared guidewire, six drain tract infections). There was no mortality. Successful resolution of pseudocysts was achieved in 26 patients (93%). Two patients subsequently had elective caudal pancreaticojejunostomy (CPJ), and one lateral pancreaticojejunostomy (LPJ) to drain obstructed pancreatic ducts. One patient has required repeat external drainage. Percutaneous external drainage is successful in pseudocyst eradication. When underlying pancreatic pathology remains uncorrected, elective surgical decompression of obstructed, dilated ducts may be necessary.

  14. [Acute pancreatitis].

    PubMed

    Hecker, M; Mayer, K; Askevold, I; Collet, P; Weigand, M A; Krombach, G A; Padberg, W; Hecker, A

    2014-03-01

    Acute pancreatitis is a potentially fatal disease with individually differing expression of systemic involvement. For this reason early diagnosis with subsequent risk stratification is essential in the clinical management of this frequent gastroenterological disorder. Severe forms of acute pancreatitis occur in approximately 20 % of cases often requiring intensive care monitoring and interdisciplinary therapeutic approaches. In the acute phase adequate fluid replacement and sufficient analgesic therapy is of major therapeutic importance. Concerning the administration of antibiotics and the nutritional support of patients with acute pancreatitis a change in paradigms could be observed in recent years. Furthermore, endoscopic, radiological or surgical interventions can be necessary depending on the severity of the disease and potential complications.

  15. [Pancreatic ultrasonography].

    PubMed

    Fernández-Rodríguez, T; Segura-Grau, A; Rodríguez-Lorenzo, A; Segura-Cabral, J M

    2015-04-01

    Despite the recent technological advances in imaging, abdominal ultrasonography continues to be the first diagnostic test indicated in patients with a suspicion of pancreatic disease, due to its safety, accessibility and low cost. It is an essential technique in the study of inflammatory processes, since it not only assesses changes in pancreatic parenchyma, but also gives an indication of the origin (bile or alcoholic). It is also essential in the detection and tracing of possible complications as well as being used as a guide in diagnostic and therapeutic punctures. It is also the first technique used in the study of pancreatic tumors, detecting them with a sensitivity of around 70% and a specificity of 90%.

  16. Adenovirus sensing by the immune system.

    PubMed

    Atasheva, Svetlana; Shayakhmetov, Dmitry M

    2016-12-01

    The host immune system developed multiple ways for recognition of viral pathogens. Upon disseminated adenovirus infection, the immune system senses adenovirus invasion from the moment it enters the bloodstream. The soluble blood factors, FX, antibodies, and complement, can bind and activate plethora of host-protective immune responses. Adenovirus binding to the cellular β3 integrin and endosomal membrane rupture trigger activation of IL-1α/IL-1R1 proinflammatory cascade leading to attraction of cytotoxic immune cells to the site of infection. Upon cell entry, adenovirus exposes its DNA genome in the cytoplasm and triggers DNA sensors signaling. Even when inside the nucleus, the specialized cellular machinery that recognizes the double-strand DNA breaks become activated and triggers viral DNA replication arrest. Thus, the host employs very diverse mechanisms to prevent viral dissemination.

  17. Core labeling of adenovirus with EGFP

    SciTech Connect

    Le, Long P.; Le, Helen N.; Nelson, Amy R.; Matthews, David A.; Yamamoto, Masato; Curiel, David T. . E-mail: curiel@uab.edu

    2006-08-01

    The study of adenovirus could greatly benefit from diverse methods of virus detection. Recently, it has been demonstrated that carboxy-terminal EGFP fusions of adenovirus core proteins Mu, V, and VII properly localize to the nucleus and display novel function in the cell. Based on these observations, we hypothesized that the core proteins may serve as targets for labeling the adenovirus core with fluorescent proteins. To this end, we constructed various chimeric expression vectors with fusion core genes (Mu-EGFP, V-EGFP, preVII-EGFP, and matVII-EGFP) while maintaining expression of the native proteins. Expression of the fusion core proteins was suboptimal using E1 expression vectors with both conventional CMV and modified (with adenovirus tripartite leader sequence) CMV5 promoters, resulting in non-labeled viral particles. However, robust expression equivalent to the native protein was observed when the fusion genes were placed in the deleted E3 region. The efficient Ad-wt-E3-V-EGFP and Ad-wt-E3-preVII-EGFP expression vectors were labeled allowing visualization of purified virus and tracking of the viral core during early infection. The vectors maintained their viral function, including viral DNA replication, viral DNA encapsidation, cytopathic effect, and thermostability. Core labeling offers a means to track the adenovirus core in vector targeting studies as well as basic adenovirus virology.

  18. Autoimmune pancreatitis mimicking pancreatic tumor

    PubMed Central

    Dede, Kristóf; Salamon, Ferenc; Taller, András; Teknős, Dániel; Bursics, Attila

    2012-01-01

    Autoimmune pancreatitis (AIP) is a rare disease of unknown pathomechanism. It belongs to the IgG4-related disease family and responds well to steroids, although the relapse rate can reach up to 20–30%. Differentiating AIP from the more common pancreatic cancer can be very challenging. About 20% of AIP is diagnosed postoperatively during final histological examination. Each of the investigative tools can add something to the definitive diagnosis; the question remains whether it is possible to prevent an unnecessary resection. Through our case we would like to demonstrate the differential diagnostic opportunities and present the literary background of this issue. In conclusion, we can state that whenever a focal pancreatic lesion is encountered AIP should always be considered. PMID:24968399

  19. Adenovirus as a gene therapy vector for hematopoietic cells.

    PubMed

    Marini, F C; Yu, Q; Wickham, T; Kovesdi, I; Andreeff, M

    2000-06-01

    Adenovirus (Adv)-mediated gene transfer has recently gained new attention as a means to deliver genes for hematopoietic stem cell (HSC) or progenitor cell gene therapy. In the past, HSCs have been regarded as poor Adv targets, mainly because they lack the specific Adv receptors required for efficient and productive Adv infection. In addition, the nonintegrating nature of Adv has prevented its application to HSC and bone marrow transduction protocols where long-term expression is required. There is even controversy as to whether Adv can infect hematopoietic cells at all. In fact, the ability of Adv to infect epithelium-based targets and its inability to effectively transfect HSCs have been used in the development of eradication schemes that use Adv to preferentially infect and "purge" tumor cell-contaminating HSC grafts. However, there are data supporting the existence of productive Adv infections into HSCs. Such protocols involve the application of cytokine mixtures, high multiplicities of infection, long incubation periods, and more recently, immunological and genetic modifications to Adv itself to enable it to efficiently transfer genes into HSCs. This is a rapidly growing field, both in terms of techniques and applications. This review examines the two sides of the Adv/CD34 controversy as well as the current developments in this field.

  20. The Challenge of Global Poliomyelitis Eradication.

    PubMed

    Garon, Julie R; Cochi, Stephen L; Orenstein, Walter A

    2015-12-01

    In the United States during the 1950's, polio was on the forefront of every provider and caregiver's mind. Today, most providers in the United States have never seen a case. The Global Polio Eradication Initiative (GPEI), which began in 1988 has reduced the number of cases by over 99%. The world is closer to achieving global eradication of polio than ever before but as long as poliovirus circulates anywhere in the world, every country is vulnerable. The global community can support the polio eradication effort through continued vaccination, surveillance, enforcing travel regulations and contributing financial support, partnerships and advocacy.

  1. Dracunculiasis (Guinea worm disease) eradication.

    PubMed

    Ruiz-Tiben, Ernesto; Hopkins, Donald R

    2006-01-01

    Since the seminal review by Ralph Muller about Dracunculus and dracunculiasis in this serial publication in 1971, the Centers for Disease Control and Prevention and The Carter Center forged, during the 1980s, a coalition of organizations to support a campaign to eradicate dracunculiasis. Eighteen of 20 countries were known in 1986 to have endemic dracunculiasis, i.e., Benin, Burkina Faso, Cameroon, Chad, Côte d'Ivoire, Ethiopia, Ghana, India, Kenya, Mali, Mauritania, Niger, Nigeria, Pakistan, Senegal, Sudan, Togo, and Uganda. Transmission of the disease in Yemen was documented in 1995, and the World Health Organization (WHO) declared Central African Republic endemic in 1995. As of the end of 2004, a total of 16026 cases of dracunculiasis were reported from 12 endemic countries (91% of these cases were reported from Ghana and Sudan, combined), a reduction greater than 99% from the 3.5 million cases of dracunculiasis estimated in 1986 to occur annually; the number of endemic villages has been reduced by >91%, from the 23475 endemic villages in 1991; disease transmission has been interrupted in 9 of the 20 endemic countries; and WHO has certified 168 countries free of dracunculiasis, including Pakistan (1996), India (2000), Senegal and Yemen (2004). Asia is now free of dracunculiasis.

  2. Poverty eradication: a new paradigm.

    PubMed

    Pethe, V P

    1998-08-01

    This article offers a new paradigm for eradicating poverty in India. It was assumed incorrectly by Mahatma Gandhi that a good society without mass poverty would follow after independence. India copied Western models of development and developed giant factories, big dams, and megacities. Agriculture did not expand the number of jobs for people. The Western paradigm failed in India because of the false assumption of "trickle down" of income to the masses. The targeted programs to the poor did not directly benefit enough of the poor. Mega-industrialization led to reduced employment and higher skill needs. The model failed mainly because it was a proxy and relied on indirect ways of reaching the poor. The models failed to be adapted to conditions in India. The Swadeshi paradigm is a direct model for addressing mass poverty. Poverty is affected by immediate, intermediate, and ultimate determinants. Poverty begets social and economic problems, such as ignorance, ill health, high fertility, unemployment, and crime. In India and developing countries, mass poverty results from under use of human resources; lack of equal opportunities; and an outdated non-egalitarian social structure, an unjust global economic order, human cruelty, and erosion of ethical values. Indians are squandering their precious resources mimicking Western consumerism. Poverty leads to rapid population growth. People become productive assets with universal literacy, compulsory and free education, health services and sanitation, vocational training, and work ethics. India needs people-oriented policies with less emphasis on capital accumulation.

  3. Is Pancreatic Cancer Hereditary?

    MedlinePlus

    ... Trials Database Supporting Research Raising Awareness Our Blog Patient Education Pancreas News Basics of Pancreatic Cancer FAQs The ... Detection- Goggins Lab Sol Goldman Center Discussion Board Patient Education / Basics of Pancreatic Cancer Is pancreatic cancer hereditary? ...

  4. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as the sudden inflammation ... the incidence of recurrent attacks minimized. Timothy Gardner, MD is Director of Pancreatic Disorders at Dartmouth-Hitchcock ...

  5. Molecular Analysis of Adenovirus Isolates from Previously Vaccinated Young Adults

    DTIC Science & Technology

    2004-04-01

    NAVAL HEALTH RESEARCH CENTER MOLECULAR ANALYSIS OF ADENOVIRUS ISOLATES FROM PREVIOUSLY VACCINATED YOUNG ADULTS D. A. Blasiole...Molecular Analysis of Adenovirus Isolates From Previously Vaccinated Young Adults . 6. AUTHORS Daniel A Blasiole, David Metzgar, Luke T Daum, Margaret AK

  6. Eradication of infectious diseases in heterogeneous populations

    SciTech Connect

    Travis, C.C.; Lenhart, S.M.

    1987-04-01

    A model is presented of infectious disease in heterogeneous populations, which allows for variable intra- to intergroup contact ratios. The authors give necessary and sufficient conditions for disease eradication by means of vaccination. Smallpox is used as an illustrative example.

  7. Malaria research and eradication in the USSR

    PubMed Central

    Bruce-Chwatt, Leonard J.

    1959-01-01

    Relatively little is known outside the USSR about the past history of malaria in that country, the contribution of its scientists to malaria research, the recent progress of Soviet malariology, or the achievements of the Soviet Union in the eradication of malaria. These achievements are of particular interest because the general strategy of malaria eradication in the USSR has many technical, administrative, and economic and social features not seen elsewhere. PMID:13805136

  8. Eradication of Ebola Based on Dynamic Programming

    PubMed Central

    Zhu, Jia-Ming; Wang, Lu; Liu, Jia-Bao

    2016-01-01

    This paper mainly studies the eradication of the Ebola virus, proposing a scientific system, including three modules for the eradication of Ebola virus. Firstly, we build a basic model combined with nonlinear incidence rate and maximum treatment capacity. Secondly, we use the dynamic programming method and the Dijkstra Algorithm to set up M-S (storage) and several delivery locations in West Africa. Finally, we apply the previous results to calculate the total cost, production cost, storage cost, and shortage cost. PMID:27313655

  9. Are probiotics useful in Helicobacter pylori eradication?

    PubMed Central

    Homan, Matjaž; Orel, Rok

    2015-01-01

    Helicobacter pylori (H. pylori) is considered an etiologic factor for the development of peptic ulcer disease, gastric adenocarcinoma, and MALT lymphoma. Therapeutic schemes to eradicate the bacteria are based on double antibiotic therapy and proton pump inhibitor. Despite many therapeutic improvements in H. pylori eradication treatment, it is still associated with high infection rate also in developed countries. Bacterial resistance and adverse events occurrence are among most frequent causes for anti- H. pylori treatment failure. Several studies have reported that certain probiotic strains can exhibit inhibitory activity against H. pylori bacteria. In addition, some probiotic strains can reduce the occurrence of side effects due to antibiotic therapy and consequently increase the H. pylori eradication rate. The results of the prospective double-blind placebo-controlled studies suggest that specific probiotics, such as S. boulardii and L. johnsonni La1 probably can diminish the bacterial load, but not completely eradicate the H. pylori bacteria. Furthermore, it seems that supplementation with S. boulardii is a useful concomitant therapy in the standard H. pylori eradication treatment protocol and most probably increases eradication rate. L. reuteri is equally effective, but more positive studies are needed. Finally, probiotic strains, such as S. boulardii, L. reuteri and L. GG, decrease gastrointestinal antibiotic associated adverse effects. PMID:26457024

  10. Adenovirus Serotype 14 Infection, New Brunswick, Canada, 2011

    PubMed Central

    Garceau, Richard; Thibault, Louise; Oussedik, Youcef; Bastien, Nathalie; Li, Yan

    2013-01-01

    We describe 3 culture-proven cases of adenovirus serotype 14 infection in New Brunswick, Canada, during the summer of 2011. Strains isolated from severely ill patients were closely related to strains of a genomic variant, adenovirus 14p1, circulating in the United States and Ireland. Physicians in Canada should be aware of this emerging adenovirus. PMID:23260201

  11. Pancreatic abscesses.

    PubMed

    Shi, E C; Yeo, B W; Ham, J M

    1984-09-01

    This paper presents the clinical features and problems in the management of 34 patients with pancreatic abscesses. In the majority of patients the abscesses developed following an attack of pancreatitis due to alcohol or gallstones. The abscesses were usually multilocular, and often had spread widely in the retroperitoneal space. Invasion into surrounding viscera or the peritoneal cavity occurred in 12 instances, and eight patients developed major bleeding into the abscess cavity. Obstructive complications (affecting bowel, common bile duct and large veins) occurred in eight patients. Twelve of the 34 patients (35 per cent) died, most deaths being due to failure to control sepsis (seven patients) or to massive bleeding from the abscess cavity (three patients). The mortality of this condition is likely to remain high, but may be reduced by better drainage techniques at the initial exploration. The importance of the infra-mesocolic approach for drainage is emphasized.

  12. Elasticity and Binding of Adenovirus

    NASA Astrophysics Data System (ADS)

    Matthews, Garrett; Negishi, Atsuko; Seeger, Adam; McCarty, Doug; Taylor, Russell; Samulshi, Jude; Superfine, Richard

    1999-11-01

    Adenovirus was the first human virus found to cause the transformation of cells and is one of the more common vectors being used for the development of gene therapy. As such, much is known about the viral structure and genome; however, the events of the early infection cycle, such as binding of the virus to the cell membrane and the release of genetic material from the capsid, for this and other nonenveloped viruses, are not fully understood. With the atomic force microscope (AFM) we are able to image the virus in both air and liquids, allowing us to change the surrounding environment, varying such physiologically relevant parameters as osmolality or pH. We additionally have the ability to do manipulations on single virus particles in these environments using the nanoManipulator. The nanoManipulator is an advanced interface for AFM that allows real time three dimensional rendering of the topographical data, allows the sample surface to be non-destructively felt using a hand held stylus that responds to the information being sensed at the tip, and allows controlled modification of the surface. Using this tool we have translated single virions over various surfaces, allowing us to measure the adhesion between the capsid and these surfaces. Additionally, we are able to place the tip directly atop individual viruses and measure their elasticity under a compressive load being supplied by that tip. We can explore how this property changes as a function of the properties of the surrounding liquid.

  13. Components of Adenovirus Genome Packaging

    PubMed Central

    Ahi, Yadvinder S.; Mittal, Suresh K.

    2016-01-01

    Adenoviruses (AdVs) are icosahedral viruses with double-stranded DNA (dsDNA) genomes. Genome packaging in AdV is thought to be similar to that seen in dsDNA containing icosahedral bacteriophages and herpesviruses. Specific recognition of the AdV genome is mediated by a packaging domain located close to the left end of the viral genome and is mediated by the viral packaging machinery. Our understanding of the role of various components of the viral packaging machinery in AdV genome packaging has greatly advanced in recent years. Characterization of empty capsids assembled in the absence of one or more components involved in packaging, identification of the unique vertex, and demonstration of the role of IVa2, the putative packaging ATPase, in genome packaging have provided compelling evidence that AdVs follow a sequential assembly pathway. This review provides a detailed discussion on the functions of the various viral and cellular factors involved in AdV genome packaging. We conclude by briefly discussing the roles of the empty capsids, assembly intermediates, scaffolding proteins, portal vertex and DNA encapsidating enzymes in AdV assembly and packaging. PMID:27721809

  14. Pancreatic Exocrine Insufficiency in Pancreatic Cancer.

    PubMed

    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J-Matthias

    2017-02-23

    Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  15. Eradication of measles: remaining challenges.

    PubMed

    Holzmann, Heidemarie; Hengel, Hartmut; Tenbusch, Matthias; Doerr, H W

    2016-06-01

    , epidemiological and virological surveillance by the use of modern laboratory diagnostics and reporting systems. By consequent implementation of carefully designed epidemiologic and prophylactic measures, it should be possible to eradicate MeV globally out of mankind, as the closely related morbillivirus of rinderpest could be successfully eliminated out of the cattle on a global scale.

  16. Arterio-Pancreatic Syndrome

    PubMed Central

    Lee, Ser Yee; Ng, Kheng Hong; Sebastian, Mathew George

    2011-01-01

    Acute pancreatitis is a single-organ disorder that has multi-organ sequelae. As a result, it can have varied presentations. Acute pancreatitis presenting as acute limb ischemia is rare. We present a patient with acute pancreatitis presenting with bilateral lower limb ischemia. The episode of acute pancreatitis resolved but the acute lower limb ischemia precipitated as the pancreatitis progressed, and necessitated bilateral above-knee amputations. We review the literature and discuss the pathogenesis of such a phenomenon. PMID:22347150

  17. Immunologic and Genetic Selection of Adenovirus Vaccine Strains: Synthesis and Characterization of Adenovirus Antigens.

    DTIC Science & Technology

    1984-08-01

    exhibited strikingly different chromatographic characteristics. 2. Effect of proflavine on the synthesis of adenovirus, type 5, and associated soluble...antigens. The synthesis of type 5 adenovirus in HeLa cells was suppressed to a considerable extent by low concentrations of proflavine , an acridine dye...chemical. Addition of proflavine to infected cells at different times during the virus growth cycle revealed that the processes leading to the synthesis

  18. EUS-Guided Antitumor Therapy for Pancreatic Tumors

    PubMed Central

    2010-01-01

    Endoscopic ultrasound (EUS) is a very useful modality for the diagnosis and staging of pancreatic masses. With the advent of EUS-guided fine-needle aspiration technology, this modality has made a tremendous leap from imaging modality to histologic diagnosis and therapeutic intervention. EUS offers high-resolution images of and unparalleled access to the pancreas. After locating the tip of the echoendoscope in the duodenum or stomach, several drugs or local treatment modalities can be delivered directly into the pancreas. EUS-guided ethanol lavage with/without paclitaxel injection has been tested for the treatment of cystic tumors of the pancreas, with complete resolution of cystic tumor being observed in up to 70-80% of patients. Ethanol injection is also performed for the management of solid neuroendocrine tumors of the pancreas. Various type of EUS-guided injection have also been investigated for the treatment of pancreatic cancer. An activated allogenic mixed lymphocyte culture (Cytoimplant) was injected in patients with advanced pancreatic cancer. A replication-deficient adenovirus vector carrying the tumor necrosis factor-alpha gene was also delivered intratumorally by EUS. ONYX-015 is an oncolytic attenuated adenovirus that exhibits replication preferentially in malignant cells, causing cell death, and this has also been injected into pancreatic cancers under EUS guidance. EUS-guided local ablation therapies such as radiofrequency ablation, photodynamic therapy, and brachytherapy are also under investigation. EUS-guided fine-needle injection for various solid or cystic lesions is a rapidly expanding field. This article reviews the various applications of EUS for the treatment of pancreatic tumors. PMID:21103299

  19. The eradication of Simulium neavei from Kenya

    PubMed Central

    McMahon, J. P.; Highton, R. B.; Goiny, H.

    1958-01-01

    S. neavei, the vector of onchocerciasis, has been virtually eradicated from Kenya by larviciding measures in which DDT was used. Only a very small area remains infested and this is in the course of being treated by the Uganda medical authorities as it is part of a much larger focus occurring in that country. An account is given of the various surveys which have been carried out during the last ten years in Nyanza Province, involving 15 000 square miles (about 40 000 km2), and survey techniques are described. An account is given of the eradication measures carried out in North and South Nyanza, and techniques in connexion with dosing and checking operations are described. Costs for both surveys and eradication schemes are given, and minimum requirements for transport are indicated. PMID:13585062

  20. Problems of epidemiology in malaria eradication

    PubMed Central

    Yekutiel, P.

    1960-01-01

    With an increasing number of malaria eradication programmes approaching or entering the consolidation phase, the epidemiological features of disappearing malaria are getting better known and defined. At the same time, the old classical methods of measuring malaria prevalence have become inadequate and new methods for the epidemiological assessment of the progress of eradication are being developed. In this article the new methods of assessment and epidemiological and statistical criteria for discontinuing residual spraying and for the stability of consolidation are discussed on the basis of field experience in several countries during the past two or three years. Some prominent epidemiological features of malaria at reduced levels of transmission are described, special attention being given to the role of the asymptomatic carrier in malaria eradication. PMID:13846510

  1. Structure and Uncoating of Immature Adenovirus

    SciTech Connect

    Perez-Berna, A.J.; Mangel, W.; Marabini, R.; Scheres, S. H. W., Menendez-Conejero, R.; Dmitriev, I. P.; Curiel, D. T.; Flint, S. J.; San Martin, C.

    2009-09-18

    Maturation via proteolytic processing is a common trait in the viral world and is often accompanied by large conformational changes and rearrangements in the capsid. The adenovirus protease has been shown to play a dual role in the viral infectious cycle: (a) in maturation, as viral assembly starts with precursors to several of the structural proteins but ends with proteolytically processed versions in the mature virion, and (b) in entry, because protease-impaired viruses have difficulties in endosome escape and uncoating. Indeed, viruses that have not undergone proteolytic processing are not infectious. We studied the three-dimensional structure of immature adenovirus particles as represented by the adenovirus type 2 thermosensitive mutant ts1 grown under non-permissive conditions and compared it with the mature capsid. Our three-dimensional electron microscopy maps at subnanometer resolution indicate that adenovirus maturation does not involve large-scale conformational changes in the capsid. Difference maps reveal the locations of unprocessed peptides pIIIa and pVI and help define their role in capsid assembly and maturation. An intriguing difference appears in the core, indicating a more compact organization and increased stability of the immature cores. We have further investigated these properties by in vitro disassembly assays. Fluorescence and electron microscopy experiments reveal differences in the stability and uncoating of immature viruses, both at the capsid and core levels, as well as disassembly intermediates not previously imaged.

  2. Malaria control and eradication in Taiwan

    PubMed Central

    1958-01-01

    An intensive programme of residual spraying with DDT carried out over a period of 5 years in Taiwan has reduced malaria morbidity to a very low level. Since 1955, the goal has been complete eradication. Some foci of transmission and/or infection remain, however, and although no resistance problems have been encountered, the principal vector, A. minimus minimus, is still widely distributed. An elaborate surveillance organization is now in the process of creation, with the object of detecting and eliminating all residual foci of transmission and preventing the importation of fresh cases. It is hoped to complete eradication in another 3-5 years. PMID:13596886

  3. Yaws: towards the WHO eradication target

    PubMed Central

    Marks, Michael

    2016-01-01

    In 2012 WHO declared a target to eradicate yaws by 2020. The cornerstone of this strategy is community mass treatment with azithromycin. Initial studies suggest this is a very effective tool that may be capable of interrupting transmission. Alongside this there has been progress in the development and validation of diagnostic tests for yaws. Several new challenges have also emerged, in particular, evidence that Haemophilus ducreyi can cause phenotypically similar ulcers in yaws endemic communities, and evidence for a possible non-human primate reservoir. The 2020 eradication target remains ambitious and more challenges should be expected on the journey. PMID:27268712

  4. Yaws: towards the WHO eradication target.

    PubMed

    Marks, Michael

    2016-06-01

    In 2012 WHO declared a target to eradicate yaws by 2020. The cornerstone of this strategy is community mass treatment with azithromycin. Initial studies suggest this is a very effective tool that may be capable of interrupting transmission. Alongside this there has been progress in the development and validation of diagnostic tests for yaws. Several new challenges have also emerged, in particular, evidence that Haemophilus ducreyi can cause phenotypically similar ulcers in yaws endemic communities, and evidence for a possible non-human primate reservoir. The 2020 eradication target remains ambitious and more challenges should be expected on the journey.

  5. Disease eradication as a public health strategy: a case study of poliomyelitis eradication.

    PubMed Central

    Aylward, R. B.; Hull, H. F.; Cochi, S. L.; Sutter, R. W.; Olivé, J. M.; Melgaard, B.

    2000-01-01

    Disease eradication as a public health strategy was discussed at international meetings in 1997 and 1998. In this article, the ongoing poliomyelitis eradication initiative is examined using the criteria for evaluating candidate diseases for eradication proposed at these meetings, which covered costs and benefits, biological determinants of eradicability (technical feasibility) and societal and political considerations (operational feasibility). The benefits of poliomyelitis eradication are shown to include a substantial investment in health services delivery, the elimination of a major cause of disability, and far-reaching intangible effects, such as establishment of a "culture of prevention". The costs are found to be financial and finite, despite some disturbances to the delivery of other health services. The "technical" feasibility of poliomyelitis eradication is seen in the absence of a non-human reservoir and the presence of both an effective intervention and delivery strategy (oral poliovirus vaccine and national immunization days) and a sensitive and specific diagnostic tool (viral culture of specimens from acute flaccid paralysis cases). The certification of poliomyelitis eradication in the Americas in 1994 and interruption of endemic transmission in the Western Pacific since March 1997 confirm the operational feasibility of this goal. When the humanitarian, economic and consequent benefits of this initiative are measured against the costs, a strong argument is made for eradication as a valuable disease control strategy. PMID:10812724

  6. Chimpanzee Adenovirus Vector Ebola Vaccine.

    PubMed

    Ledgerwood, Julie E; DeZure, Adam D; Stanley, Daphne A; Coates, Emily E; Novik, Laura; Enama, Mary E; Berkowitz, Nina M; Hu, Zonghui; Joshi, Gyan; Ploquin, Aurélie; Sitar, Sandra; Gordon, Ingelise J; Plummer, Sarah A; Holman, LaSonji A; Hendel, Cynthia S; Yamshchikov, Galina; Roman, Francois; Nicosia, Alfredo; Colloca, Stefano; Cortese, Riccardo; Bailer, Robert T; Schwartz, Richard M; Roederer, Mario; Mascola, John R; Koup, Richard A; Sullivan, Nancy J; Graham, Barney S

    2017-03-09

    Background The unprecedented 2014 epidemic of Ebola virus disease (EVD) prompted an international response to accelerate the availability of a preventive vaccine. A replication-defective recombinant chimpanzee adenovirus type 3-vectored ebolavirus vaccine (cAd3-EBO), encoding the glycoprotein from Zaire and Sudan species, that offers protection in the nonhuman primate model, was rapidly advanced into phase 1 clinical evaluation. Methods We conducted a phase 1, dose-escalation, open-label trial of cAd3-EBO. Twenty healthy adults, in sequentially enrolled groups of 10 each, received vaccination intramuscularly in doses of 2×10(10) particle units or 2×10(11) particle units. Primary and secondary end points related to safety and immunogenicity were assessed throughout the first 8 weeks after vaccination; in addition, longer-term vaccine durability was assessed at 48 weeks after vaccination. Results In this small study, no safety concerns were identified; however, transient fever developed within 1 day after vaccination in two participants who had received the 2×10(11) particle-unit dose. Glycoprotein-specific antibodies were induced in all 20 participants; the titers were of greater magnitude in the group that received the 2×10(11) particle-unit dose than in the group that received the 2×10(10) particle-unit dose (geometric mean titer against the Zaire antigen at week 4, 2037 vs. 331; P=0.001). Glycoprotein-specific T-cell responses were more frequent among those who received the 2×10(11) particle-unit dose than among those who received the 2×10(10) particle-unit dose, with a CD4 response in 10 of 10 participants versus 3 of 10 participants (P=0.004) and a CD8 response in 7 of 10 participants versus 2 of 10 participants (P=0.07) at week 4. Assessment of the durability of the antibody response showed that titers remained high at week 48, with the highest titers in those who received the 2×10(11) particle-unit dose. Conclusions Reactogenicity and immune responses

  7. Suppression of Adenovirus Replication by Cardiotonic Steroids.

    PubMed

    Grosso, Filomena; Stoilov, Peter; Lingwood, Clifford; Brown, Martha; Cochrane, Alan

    2017-02-01

    The dependence of adenovirus on the host pre-RNA splicing machinery for expression of its complete genome potentially makes it vulnerable to modulators of RNA splicing, such as digoxin and digitoxin. Both drugs reduced the yields of four human adenoviruses (HAdV-A31, -B35, and -C5 and a species D conjunctivitis isolate) by at least 2 to 3 logs by affecting one or more steps needed for genome replication. Immediate early E1A protein levels are unaffected by the drugs, but synthesis of the delayed protein E4orf6 and the major late capsid protein hexon is compromised. Quantitative reverse transcription-PCR (qRT-PCR) analyses revealed that both drugs altered E1A RNA splicing (favoring the production of 13S over 12S RNA) early in infection and partially blocked the transition from 12S and 13S to 9S RNA at late stages of virus replication. Expression of multiple late viral protein mRNAs was lost in the presence of either drug, consistent with the observed block in viral DNA replication. The antiviral effect was dependent on the continued presence of the drug and was rapidly reversible. RIDK34, a derivative of convallotoxin, although having more potent antiviral activity, did not show an improved selectivity index. All three drugs reduced metabolic activity to some degree without evidence of cell death. By blocking adenovirus replication at one or more steps beyond the onset of E1A expression and prior to genome replication, digoxin and digitoxin show potential as antiviral agents for treatment of serious adenovirus infections. Furthermore, understanding the mechanism(s) by which digoxin and digitoxin inhibit adenovirus replication will guide the development of novel antiviral therapies.

  8. [External pancreatic fistulas management].

    PubMed

    Stepan, E V; Ermolov, A S; Rogal', M L; Teterin, Yu S

    2017-01-01

    The main principles of treatment of external postoperative pancreatic fistulas are viewed in the article. Pancreatic trauma was the reason of pancreatic fistula in 38.7% of the cases, operations because of acute pancreatitis - in 25.8%, and pancreatic pseudocyst drainage - in 35.5%. 93 patients recovered after the treatment. Complex conservative treatment of EPF allowed to close fistulas in 74.2% of the patients with normal patency of the main pancreatic duct (MPD). The usage of octreotide 600-900 mcg daily for at least 5 days to decrease pancreatic secretion was an important part of the conservative treatment. Endoscopic papillotomy was performed in patients with major duodenal papilla obstruction and interruption of transporting of pancreatic secretion to duodenum. Stent of the main pancreatic duct was indicated in patients with extended pancreatic duct stenosis to normalize transport of pancreatic secretion to duodenum. Surgical formation of anastomosis between distal part of the main pancreatic duct and gastro-intestinal tract was carried out when it was impossible to fulfill endoscopic stenting of pancreatic duct either because of its interruption and diastasis between its ends, or in the cases of unsuccessful conservative treatment of external pancreatic fistula caused by drainage of pseudocyst.

  9. Therapy of human pancreatic carcinoma based on suppression of HMGA1 protein synthesis in preclinical models.

    PubMed

    Trapasso, Francesco; Sarti, Manuela; Cesari, Rossano; Yendamuri, Sai; Dumon, Kristoffel R; Aqeilan, Rami I; Pentimalli, Francesca; Infante, Luisa; Alder, Hansjuerg; Abe, Nobutsugu; Watanabe, Takashi; Viglietto, Giuseppe; Croce, Carlo M; Fusco, Alfredo

    2004-09-01

    Pancreatic carcinoma is one of the most aggressive tumors, and, being refractory to conventional therapies, is an excellent target for new therapeutic approaches. Based on our previous finding of high HMGA1 expression in pancreatic cancer cells compared to normal pancreatic tissue, we evaluated whether suppression of HMGA1 protein expression could be a treatment option for patients affected by pancreatic cancer. Here we report that HMGA1 proteins are overexpressed in pancreatic carcinoma cell lines, and their downregulation through an adenovirus carrying the HMGA1 gene in an antisense orientation (Ad Yas-GFP) results in the death of three human pancreatic carcinoma cell lines (PANC1, Hs766T and PSN1). Pretreatment of PANC1 and PSN1 cells with Ad Yas-GFP suppressed and reduced, respectively, their ability to form xenograft tumors in nude mice. To further verify the role of HMGA1 in pancreatic tumorigenesis, we used a HMGA1 antisense phosphorothioate oligodeoxynucleotide (ODN); its addition induced a decrease in HMGA1 protein levels and a significant reduction of the proliferation rate of PANC1-, Hs766T- and PSN1-treated cells. Therefore, suppression of HMGA1 protein synthesis by an HMGA1 antisense approach seems to be a feasible treatment strategy in pancreatic carcinomas.

  10. The screwworm eradication data system archives

    NASA Technical Reports Server (NTRS)

    Barnes, C. M.; Spaulding, R. R.; Giddings, L. E.

    1977-01-01

    The archives accumulated during 1 year of operation of the Satellite Temperature-Monitoring System during development of the Screwworm Eradication Data System are reported. Brief descriptions of all the kinds of tapes, as well as their potential uses, are presented. Reference is made to other documents that explain the generation of these data.

  11. How viruses hijack the ERAD tuning machinery.

    PubMed

    Noack, Julia; Bernasconi, Riccardo; Molinari, Maurizio

    2014-09-01

    An essential step during the intracellular life cycle of many positive-strand RNA viruses is the rearrangement of host cell membranes to generate membrane-bound replication platforms. For example, Nidovirales and Flaviviridae subvert the membrane of the endoplasmic reticulum (ER) for their replication. However, the absence of conventional ER and secretory pathway markers in virus-induced ER-derived membranes has for a long time hampered a thorough understanding of their biogenesis. Recent reports highlight the analogies between mouse hepatitis virus-, equine arteritis virus-, and Japanese encephalitis virus-induced replication platforms and ER-associated degradation (ERAD) tuning vesicles (or EDEMosomes) that display nonlipidated LC3 at their cytosolic face and segregate the ERAD factors EDEM1, OS-9, and SEL1L from the ER lumen. In this Gem, we briefly summarize the current knowledge on ERAD tuning pathways and how they might be hijacked for viral genome replication. As ERAD tuning components, such as SEL1L and nonlipidated LC3, appear to contribute to viral infection, these cellular pathways represent novel candidate drug targets to combat positive-strand RNA viruses.

  12. Adapting Nepal’s polio eradication programme

    PubMed Central

    Paudel, Krishna P; Hampton, Lee M; Bohara, Rajendra; Rai, Indra K; Anaokar, Sameer; Swift, Rachel D; Cochi, Stephen

    2017-01-01

    Abstract Problem Many countries have weak disease surveillance and immunization systems. The elimination of polio creates an opportunity to use staff and assets from the polio eradication programme to control other vaccine-preventable diseases and improve disease surveillance and immunization systems. Approach In 2003, the active surveillance system of Nepal’s polio eradication programme began to report on measles and neonatal tetanus cases. Japanese encephalitis and rubella cases were added to the surveillance system in 2004. Staff from the programme aided the development and implementation of government immunization policies, helped launch vaccination campaigns, and trained government staff in reporting practices and vaccine management. Local setting Nepal eliminated indigenous polio in 2000, and controlled outbreaks caused by polio importations between 2005 and 2010. Relevant changes In 2014, the surveillance activities had expanded to 299 sites, with active surveillance for measles, rubella and neonatal tetanus, including weekly visits from 15 surveillance medical officers. Sentinel surveillance for Japanese encephalitis consisted of 132 sites. Since 2002, staff from the eradication programme have helped to introduce six new vaccines and helped to secure funding from Gavi, the Vaccine Alliance. Staff have also assisted in responding to other health events in the country. Lesson learnt By expanding the activities of its polio eradication programme, Nepal has improved its surveillance and immunization systems and increased vaccination coverage of other vaccine-preventable diseases. Continued donor support, a close collaboration with the Expanded Programme on Immunization, and the retention of the polio eradication programme’s skilled workforce were important for this expansion. PMID:28250536

  13. Molecular characterization of adenoviruses among finnish military conscripts.

    PubMed

    Mölsä, Markos; Hemmilä, Heidi; Rönkkö, Esa; Virkki, Maria; Nikkari, Simo; Ziegler, Thedi

    2016-04-01

    Although adenoviruses were identified as important respiratory pathogens many years ago, little information is available concerning the prevalence of different adenovirus serotypes, which are circulating and causing epidemics in Finnish military training centers. Over a period of five years from 2008 to 2012, 3577 respiratory specimens were collected from military conscripts presenting with symptoms compatible with acute respiratory tract infection. Upon initial testing for certain respiratory viruses by real-time PCR, 837 of these specimens were identified as adenovirus-positive. For 672 of these specimens, the serotype of the adenovirus responsible was successfully determined by DNA sequencing. Serotypes 1, 2, 3, and 4 were detected in 1, 3, 181, and 487 samples, respectively. Adenovirus epidemics were observed during each year of this study. Based on these findings, adenovirus vaccination should be considered for military conscripts in the Finnish Defence Forces.

  14. Pancreatic Cancer Stage 3

    MedlinePlus

    ... 3 Description: Stage III pancreatic cancer; drawing shows cancer in the pancreas, common hepatic artery, and portal vein. Also shown ... and superior mesenteric artery. Stage III pancreatic cancer. Cancer ... near the pancreas. These include the superior mesenteric artery, celiac axis, ...

  15. Surgery for pancreatic cancer

    MedlinePlus

    ... medlineplus.gov/ency/article/007649.htm Surgery for pancreatic cancer To use the sharing features on this page, ... surgery are used in the surgical treatment of pancreatic cancer. Whipple procedure: This is the most common surgery ...

  16. Pancreatic pseudocysts and aneurysms

    PubMed Central

    Andrén-Sandberg, Åke

    2010-01-01

    A number of methods are available for the drainage of pancreatic pseudocysts, including percutaneous, endoscopic and open approaches. The author reviewed the most rently reports, and and summarized the latest advances in the pancreatic pseudocysts. PMID:22558566

  17. Systemic adenovirus infection in Bearded Dragons (Pogona vitticeps): histological, ultrastructural and molecular findings.

    PubMed

    Moormann, S; Seehusen, F; Reckling, D; Kilwinski, J; Puff, C; Elhensheri, M; Wohlsein, P; Peters, M

    2009-07-01

    Three Inland Bearded Dragons (Pogona vitticeps) from two breeding groups were humanely destroyed following a period of anorexia. Two of the animals were 8-months old and related and one animal was approximately 2-weeks old. Necropsy examination revealed poor bodily condition but no other gross abnormalities. Microscopically there was non-suppurative hepatitis and interstitial nephritis. Multiple large, amphophilic, intranuclear inclusion bodies were present within hepatocytes and epithelial cells of the bile ducts, renal tubules, small and large intestinal mucosa, pancreatic acini and oral mucous membranes. Transmission electron microscopy (TEM) demonstrated that the inclusions comprised viral particles with morphology consistent with an adenovirus. A fragment of the adenoviral polymerase gene was amplified, sequenced and compared with other reptilian adenoviral sequences.

  18. Adenovirus dodecahedron, a new vector for human gene transfer.

    PubMed

    Fender, P; Ruigrok, R W; Gout, E; Buffet, S; Chroboczek, J

    1997-01-01

    Recombinant adenovirus is one of most efficient delivery vehicles for gene therapy. However, the initial enthusiasm for the use of recombinant adenovirus for gene therapy has been tempered by strong immune responses that develop to the virus and virus-infected cells. Even though recombinant adenoviruses are replication-defective, they introduce into the recipient cell, together with the gene of interest, viral genetes that might lead to fortuitous recombination if the recipient is infected by wild-type adenovirus. We propose the use of a dodecahedron made of adenovirus pentons or penton bases as an alternative vector for human gene therapy. The penton is a complex of two oligomeric proteins, a penton base and fiber, involved in the cell attachment, internalization, and liberation of virus into the cytoplasm. The dodecahedron retains many of the advantages of adenovirus for gene transfer such as efficiency of entry, efficient release of DNA from endosomes, and wide range of cell and tissue targets. Because it consists of only one or two adenovirus proteins instead of the 11 contained in an adenovirus virion and it does not contain the viral genome, it is potentially a safer alternative to recombinant adenovirus.

  19. [Effect of eradication of Helicobacter pylori infection on endoscopic findings and symptoms of gastroesophageal reflux].

    PubMed

    Mesihović, Rusmir; Vucelić, Boris; Bratović, Ismet; Gribajcević, Mehmed; Selak, Ivan

    2002-01-01

    Gastroesophageal reflux disease (GORD) represents an illness which reflects a syndrome caused by returning of acid gastric, alkaline pancreatic and bowels content into the oesophagus, which is in the stomach, because of the protective mechanisms of oesophageal loss. The aim of this study was that this prospective study should explain the role of Helicobacter pylori infection in modification of GORD, respectively whether the Helicobacter pylori infection acts protectively or by deterioration of the disease. According to the settled rules, the inquiry was performed as well as the selection of 97 candidates to undergo research in this study. Helicobacter pylori infection has been proved by immunoassay in all pts in the beginning of this study. Endoscopy has been performed in all pts, the degree of gastroesophageal reflux disease by Sawary-Miller was done. The main group consisted of 50 candidates in whom the eradication of Helicobacter pylori infection was done with triple therapy, pantoprazol + amoxycilin + klaritromicin, which was proven by an immunoassay test. Two groups of pts were formed: the main one with eradicated Helicobacter infection, and a controlled one with a Helicobacter positive infection, which was subject to modification of life style. During 12 months, this study consisted of endoscopic evaluations and monthly evaluation of pts daily difficulties. The eradication of Helicobacter pylori infection acts on the improvement of gastroesophageal disease course by improvement of endoscopic findings by Sawary-Miller, and by decreasing daily acid symptoms. The eradication of Helicobacter pylori infection in gastroesophageal reflux disease does it act at the symptoms such as heartburn, weekly acid symptoms and chest pain.

  20. Pathogenic mechanisms of pancreatitis.

    PubMed

    Manohar, Murli; Verma, Alok Kumar; Venkateshaiah, Sathisha Upparahalli; Sanders, Nathan L; Mishra, Anil

    2017-02-06

    Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in promoting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways (i.e., Transforming growth factor-β/SMAD, mitogen-activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8 IL-10, IL-18, IL-33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for

  1. Pathogenic mechanisms of pancreatitis

    PubMed Central

    Manohar, Murli; Verma, Alok Kumar; Venkateshaiah, Sathisha Upparahalli; Sanders, Nathan L; Mishra, Anil

    2017-01-01

    Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in promoting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways (i.e., Transforming growth factor-β/SMAD, mitogen-activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8 IL-10, IL-18, IL-33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for

  2. The eradication treatments of Helicobacter pylori.

    PubMed

    Wermeille, J; Zelger, G; Cunningham, M

    1998-02-01

    The eradication of Helicobacter pylori is at present widely recognized as the adequate therapeutic approach for gastric and duodenal ulcers in infected patients. In those with dyspepsia but no ulcer as well as in those with type B chronic gastritis, eradication remains controversial. It is difficult to have a clear opinion on the advantages and disadvantages of the numerous existing therapies. Therefore, a systematic review of published treatments has been made by the authors. Ideally, the eradication treatment of H. pylori should have the following advantages: 1. eradication superior to 90%, 2. simplicity, 3. short duration, 4. safety, 5. low cost, 6. reproducibility of results. Dual therapies (2 antibiotics or a proton pump inhibitor in combination with an antibiotic) rarely allow an eradication greater than 90% and the results have poor reproducibility. Consequently, they do not represent an ideal anti-H. pylori treatment. Triple therapies come closer to the requirements for an ideal treatment, with eradication rates generally close to 90%, varying little between studies and the countries in which they were performed. The triple therapy bismuth-imidazole-tetracycline (or amoxicillin) still represents for many authors the standard reference therapy. It has the advantage of low cost, high efficacy and widespread use. It is the therapy that has been the most studied. However, the increasing emergence of strains resistant to imidazoles, the complexity of the treatment (10 to 12 tablets per day), the numerous adverse effects and the lack of availability of bismuth salts in certain countries has led to the elaboration of therapeutic schemes combining an antisecretory drug with 2 antibiotics. Among these, the combination PPI-clarithromycine-imidazole during 7 days represents the most studied triple therapy of short duration for some authors, it already represents a new standard. However, the efficacy of this therapy seems dependent on the sensitivity of the bacteria to

  3. Experimental Models of Pancreatitis

    PubMed Central

    Hyun, Jong Jin

    2014-01-01

    Acute pancreatitis is an inflammatory disease characterized by interstitial edema, inflammatory cell infiltration, and acinar cell necrosis, depending on its severity. Regardless of the extent of tissue injury, acute pancreatitis is a completely reversible process with evident normal tissue architecture after recovery. Its pathogenic mechanism has been known to be closely related to intracellular digestive enzyme activation. In contrast to acute pancreatitis, chronic pancreatitis is characterized by irreversible tissue damage such as acinar cell atrophy and pancreatic fibrosis that results in exocrine and endocrine insufficiency. Recently, many studies of chronic pancreatitis have been prompted by the discovery of the pancreatic stellate cell, which has been identified and distinguished as the key effector cell of pancreatic fibrosis. However, investigations into the pathogenesis and treatment of pancreatitis face many obstacles because of its anatomical location and disparate clinical course. Due to these difficulties, most of our knowledge on pancreatitis is based on research conducted using experimental models of pancreatitis. In this review, several experimental models of pancreatitis will be discussed in terms of technique, advantages, and limitations. PMID:24944983

  4. Epidemiological, evolutionary, and economic determinants of eradication tails.

    PubMed

    Mazzucco, Rupert; Dieckmann, Ulf; Metz, Johan A J

    2016-09-21

    Despite modern medical interventions, infectious diseases continue to generate huge socio-economic losses. The benefits of eradicating a disease are therefore high. While successful with smallpox and rinderpest, many other eradication attempts have failed. Eradications require huge and costly efforts, which can be sustained only if sufficient progress can be achieved. While initial successes are usually obtained more easily, progress often becomes harder as a disease becomes rare in the eradication endgame. A long eradication tail of slowly decreasing incidence levels can frustrate eradication efforts, as it becomes unclear whether progress toward eradication is still being made and how much more needs to be invested to push the targeted disease beyond its extinction threshold. Realistic disease dynamics are complicated by evolutionary responses to interventions and by interactions among different temporal and spatial scales. Models accounting for these complexities are required for understanding the shapes of eradication tails. In particular, such models allow predicting how hard or costly eradication will be, and may even inform in which manner progress has to be assessed during the eradication endgame. Here we outline a general procedure by analyzing the eradication tails of generic SIS diseases, taking into account two major ingredients of realistic complexity: a group-structured host population in which host contacts within groups are more likely than host contacts between groups, and virulence evolution subject to a trade-off between host infectivity within groups and host mobility among groups. Disentangling the epidemiological, evolutionary, and economic determinants of eradication tails, we show how tails of different shapes arise depending on salient model parameters and on how the extinction threshold is approached. We find that disease evolution generally extends the eradication tail and show how the cost structure of eradication measures plays a key

  5. Structure, function and dynamics in adenovirus maturation.

    PubMed

    Mangel, Walter F; San Martín, Carmen

    2014-11-21

    Here we review the current knowledge on maturation of adenovirus, a non-enveloped icosahedral eukaryotic virus. The adenovirus dsDNA genome fills the capsid in complex with a large amount of histone-like viral proteins, forming the core. Maturation involves proteolytic cleavage of several capsid and core precursor proteins by the viral protease (AVP). AVP uses a peptide cleaved from one of its targets as a "molecular sled" to slide on the viral genome and reach its substrates, in a remarkable example of one-dimensional chemistry. Immature adenovirus containing the precursor proteins lacks infectivity because of its inability to uncoat. The immature core is more compact and stable than the mature one, due to the condensing action of unprocessed core polypeptides; shell precursors underpin the vertex region and the connections between capsid and core. Maturation makes the virion metastable, priming it for stepwise uncoating by facilitating vertex release and loosening the condensed genome and its attachment to the icosahedral shell. The packaging scaffold protein L1 52/55k is also a substrate for AVP. Proteolytic processing of L1 52/55k disrupts its interactions with other virion components, providing a mechanism for its removal during maturation. Finally, possible roles for maturation of the terminal protein are discussed.

  6. Structure, function and dynamics in adenovirus maturation

    DOE PAGES

    Mangel, Walter F.; San Martín, Carmen

    2014-11-21

    Here we review the current knowledge on maturation of adenovirus, a non-enveloped icosahedral eukaryotic virus. The adenovirus dsDNA genome fills the capsid in complex with a large amount of histone-like viral proteins, forming the core. Maturation involves proteolytic cleavage of several capsid and core precursor proteins by the viral protease (AVP). AVP uses a peptide cleaved from one of its targets as a “molecular sled” to slide on the viral genome and reach its substrates, in a remarkable example of one-dimensional chemistry. Immature adenovirus containing the precursor proteins lacks infectivity because of its inability to uncoat. The immature core ismore » more compact and stable than the mature one, due to the condensing action of unprocessed core polypeptides; shell precursors underpin the vertex region and the connections between capsid and core. Maturation makes the virion metastable, priming it for stepwise uncoating by facilitating vertex release and loosening the condensed genome and its attachment to the icosahedral shell. The packaging scaffold protein L1 52/55k is also a substrate for AVP. Proteolytic processing of L1 52/55k disrupts its interactions with other virion components, providing a mechanism for its removal during maturation. In conclusion, possible roles for maturation of the terminal protein are discussed.« less

  7. Structure and uncoating of immature adenovirus

    PubMed Central

    Pérez-Berná, Ana J.; Marabini, Roberto; Scheres, Sjors H. W.; Menéndez-Conejero, Rosa; Dmitriev, Igor P.; Curiel, David T.; Mangel, Walter F.; Flint, S. Jane; Martín, Carmen San

    2009-01-01

    Summary Maturation via proteolytical processing is a common trait in the viral world, and is often accompanied by large conformational changes and rearrangements in the capsid. The adenovirus protease has been shown to play a dual role in the viral infectious cycle: (a) in maturation, as viral assembly starts with precursors to several of the structural proteins, but ends with proteolytically processed versions in the mature virion; and (b) in entry, because protease-impaired viruses have difficulties in endosome escape and uncoating. Indeed, viruses that have not undergone proteolytical processing are not infectious. We present the 3D structure of immature adenovirus particles, as represented by the thermosensitive mutant Ad2 ts1 grown under non-permissive conditions, and compare it with the mature capsid. Our 3DEM maps at subnanometer resolution indicate that adenovirus maturation does not involve large scale conformational changes in the capsid. Difference maps reveal the location of unprocessed peptides pIIIa and pVI and help to define their role in capsid assembly and maturation. An intriguing difference appears in the core, indicating a more compact organization and increased stability of the immature cores. We have further investigated these properties by in vitro disassembly assays. Fluorescence and electron microscopy experiments reveal differences in the stability and uncoating of immature viruses, both at the capsid and core levels, as well as disassembly intermediates not previously imaged. PMID:19563809

  8. Structure, Function and Dynamics in Adenovirus Maturation

    PubMed Central

    Mangel, Walter F.; San Martín, Carmen

    2014-01-01

    Here we review the current knowledge on maturation of adenovirus, a non-enveloped icosahedral eukaryotic virus. The adenovirus dsDNA genome fills the capsid in complex with a large amount of histone-like viral proteins, forming the core. Maturation involves proteolytic cleavage of several capsid and core precursor proteins by the viral protease (AVP). AVP uses a peptide cleaved from one of its targets as a “molecular sled” to slide on the viral genome and reach its substrates, in a remarkable example of one-dimensional chemistry. Immature adenovirus containing the precursor proteins lacks infectivity because of its inability to uncoat. The immature core is more compact and stable than the mature one, due to the condensing action of unprocessed core polypeptides; shell precursors underpin the vertex region and the connections between capsid and core. Maturation makes the virion metastable, priming it for stepwise uncoating by facilitating vertex release and loosening the condensed genome and its attachment to the icosahedral shell. The packaging scaffold protein L1 52/55k is also a substrate for AVP. Proteolytic processing of L1 52/55k disrupts its interactions with other virion components, providing a mechanism for its removal during maturation. Finally, possible roles for maturation of the terminal protein are discussed. PMID:25421887

  9. Structure, function and dynamics in adenovirus maturation

    SciTech Connect

    Mangel, Walter F.; San Martín, Carmen

    2014-11-21

    Here we review the current knowledge on maturation of adenovirus, a non-enveloped icosahedral eukaryotic virus. The adenovirus dsDNA genome fills the capsid in complex with a large amount of histone-like viral proteins, forming the core. Maturation involves proteolytic cleavage of several capsid and core precursor proteins by the viral protease (AVP). AVP uses a peptide cleaved from one of its targets as a “molecular sled” to slide on the viral genome and reach its substrates, in a remarkable example of one-dimensional chemistry. Immature adenovirus containing the precursor proteins lacks infectivity because of its inability to uncoat. The immature core is more compact and stable than the mature one, due to the condensing action of unprocessed core polypeptides; shell precursors underpin the vertex region and the connections between capsid and core. Maturation makes the virion metastable, priming it for stepwise uncoating by facilitating vertex release and loosening the condensed genome and its attachment to the icosahedral shell. The packaging scaffold protein L1 52/55k is also a substrate for AVP. Proteolytic processing of L1 52/55k disrupts its interactions with other virion components, providing a mechanism for its removal during maturation. In conclusion, possible roles for maturation of the terminal protein are discussed.

  10. ADENOVIRUS INTERACTION WITH ITS CELLULAR RECEPTOR CAR.

    SciTech Connect

    HOWITT,J.; ANDERSON,C.W.; FREIMUTH,P.

    2001-08-01

    The mechanism of adenovirus attachment to the host cell plasma membrane has been revealed in detail by research over the past 10 years. It has long been known that receptor binding activity is associated with the viral fibers, trimeric spike proteins that protrude radially from the vertices of the icosahedral capsid (Philipson et al. 1968). In some adenovirus serotypes, fiber and other virus structural proteins are synthesized in excess and accumulate in the cell nucleus during late stages of infection. Fiber protein can be readily purified from lysates of cells infected with subgroup C viruses, for example Ad2 and Ad5 (Boulanger and Puvion 1973). Addition of purified fiber protein to virus suspensions during adsorption strongly inhibits infection, indicating that fiber and intact virus particles compete for binding sites on host cells (Philipson et al. 1968; Hautala et al. 1998). Cell binding studies using purified radiolabeled fiber demonstrated that fiber binds specifically and with high affinity to the cell plasma membrane, and that cell lines typically used for laboratory propagation of adenovirus have approximately 10{sup 4} high-affinity receptor sites per cell (Persson et al. 1985; Freimuth 1996). Similar numbers of high-affinity binding sites for radiolabeled intact virus particles also were observed (Seth et al. 1994).

  11. Adenovirus DNA polymerase is a phosphoprotein.

    PubMed

    Ramachandra, M; Nakano, R; Mohan, P M; Rawitch, A B; Padmanabhan, R

    1993-01-05

    Biological activities of many of the eukaryotic DNA replication proteins are modulated by protein phosphorylation. Investigations of the phosphorylation of adenovirus DNA polymerase (AdPol) have been difficult mainly because of its low level of synthesis in adenovirus-infected HeLa cells. However, when AdPol was overproduced using the recombinant vaccinia virus (RV-AdPol) and the baculovirus expression systems, or by a large scale metabolic labeling of adenovirus 2-infected HeLa cells (native AdPol), in vivo phosphorylation of AdPol could be demonstrated. Phosphoamino acid analysis of [32P]AdPol indicated the presence of phosphoserine independent of the source of AdPol. Comparison of tryptic peptide maps of native AdPol and RV-AdPol revealed that the majority of phosphopeptides were common. Fractionation by high performance liquid chromatography and sequencing of one of the major phosphopeptides revealed serine 67 as a site of phosphorylation. Interestingly, this site is located close to the nuclear localization signal of AdPol and has a consensus substrate recognition sequence for histone H1 (cdc2-related) kinases and mitogen-activated protein kinases. Dephosphorylation of AdPol with calf intestinal alkaline phosphatase resulted in significant decrease in its activity in the in vitro DNA replication initiation assay, suggesting that phosphorylation is important for its biological activity.

  12. Chronic pancreatitis: relation to acute pancreatitis and pancreatic cancer.

    PubMed

    Uomo, G; Rabitti, P G

    2000-01-01

    The relationship between chronic pancreatitis (CP) and other pancreatic diseases, such as acute pancreatitis (AP) and pancreatic cancer (PK), remains a fairly debated question. The progression from alcoholic AP to CP is controversial, and some long-term epidemiological studies suggest that alcoholic CP might be the result of recurrent alcoholic AP (necrosis-fibrosis sequence) and a subgroup of alcoholics may present recurrent AP without progression to CP. Other predisposing factors (genetic, nutritional, environmental) seems to be important in inducing different outcomes of pancreatic damage due to alcohol. However, recurrent episodes of AP are clearly involved in pathophysiology of CP in patients with hereditary pancreatitis. A relationship between CP and subsequent PK development has long been suspected, but we actually don't know whether this association is direct or is the result of confounding factors, such as alcohol intake or cigarette smoking. Many issues should be considered as indicators of a causal association, and several of them are not fulfilled. Nonetheless, epidemiological studies (case-control or cohort studies) showed that the risk of PK is increased in patients with CP; the risk is significantly higher in tropical calcifying CP and hereditary pancreatitis. Studies on growth factors, oncogenes, tumor-suppressor genes, and angiogenesis suggest that the sequence PC-KP is plausible from the biological standpoint.

  13. Criticism of WHO's revised malaria eradication strategy.

    PubMed

    Litsios, S

    2000-06-01

    Fred L. Soper played a key role in promoting the idea that malaria could be eradicated world-wide. He believed eradication to be feasible based on the ability of household insecticide spraying to interrupt malaria transmission. He opposed WHO's strategy to reduce the number of years devoted to spraying and to rely instead on chemotherapy to wipe out remaining foci of malaria. While his criticism was intense, it neither featured in the discussions of the World Health Assembly nor the WHO malaria Expert Committee. The author concludes that had his criticism been heard the global campaign could have been stopped far earlier than in fact it was. Furthermore, failure to openly address Soper's criticism represented a major failure on the part of the WHO Secretariat to ensure that policy decisions reflected a full consideration of all underlying issues, technical or otherwise.

  14. Rinderpest: the veterinary perspective on eradication

    PubMed Central

    Roeder, Peter; Mariner, Jeffrey; Kock, Richard

    2013-01-01

    Rinderpest was a devastating disease of livestock responsible for continent-wide famine and poverty. Centuries of veterinary advances culminated in 2011 with the UN Food and Agriculture Organization and the World Organization for Animal Health declaring global eradication of rinderpest; only the second disease to be eradicated and the greatest veterinary achievement of our time. Conventional control measures, principally mass vaccination combined with zoosanitary procedures, led to substantial declines in the incidence of rinderpest. However, during the past decades, innovative strategies were deployed for the last mile to overcome diagnostic and surveillance challenges, unanticipated variations in virus pathogenicity, circulation of disease in wildlife populations and to service remote and nomadic communities in often-unstable states. This review provides an overview of these challenges, describes how they were overcome and identifies key factors for this success. PMID:23798687

  15. HIV-1 Eradication: Early Trials (and Tribulations).

    PubMed

    Spivak, Adam M; Planelles, Vicente

    2016-01-01

    Antiretroviral therapy (ART) has rendered HIV-1 infection a manageable illness for those with access to treatment. However, ART does not lead to viral eradication owing to the persistence of replication-competent, unexpressed proviruses in long-lived cellular reservoirs. The potential for long-term drug toxicities and the lack of access to ART for most people living with HIV-1 infection have fueled scientific interest in understanding the nature of this latent reservoir. Exploration of HIV-1 persistence at the cellular and molecular level in resting memory CD4(+) T cells, the predominant viral reservoir in patients on ART, has uncovered potential strategies to reverse latency. We review recent advances in pharmacologically based 'shock and kill' HIV-1 eradication strategies, including comparative analysis of early clinical trials.

  16. Pancreatic Exocrine Insufficiency in Pancreatic Cancer

    PubMed Central

    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J.-Matthias

    2017-01-01

    Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor’s metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes. PMID:28241470

  17. Experiences with smallpox eradication in Ethiopia.

    PubMed

    de Quadros, Ciro A

    2011-12-30

    The smallpox eradication campaign operated in Ethiopia from 1970 until 1977. During this time Ethiopia had only 84 hospitals, 64 health centres and fewer than 400 physicians in a country of 25 million people. In 1970 smallpox vaccination was relatively unknown in the country, and the government actually contested the fact that smallpox was present in the country. Most of the resources of the Ministry of Health were used for malaria eradication. Initial pessimism from the Ministry of Health and others was eventually overcome as the smallpox eradication campaign continued to pick up steam but many remained unenthusiastic. Ethiopia was the first country in the world to start its smallpox eradication campaign from day one with the strategy of "Surveillance and Containment". Establishing a surveillance system in a country with a limited health infrastructure was a daunting challenge. At the end of the first year of the programme in 1971, 26,000 cases of smallpox had been registered through the growing surveillance system. Throughout revolution of 1974 the smallpox campaign was the only UN program to operate in the country; in fact it expanded with the hire of many locals leading to a "nationalized" program. This development ushered in the most successful final phase of the program. As the program progressed cases were diminishing in most regions, however transmission continued in the Ogaden desert. Over the course of the campaign approximately 14.3 million US dollars was spent. Working conditions were extremely challenging and a variety of chiefs, guerrillas, landowners and governments had to be appeased. The programme was successful due to the dedicated national and international staff on the ground and by having the full support of the WHO HQ in Geneva.

  18. Eradication versus control: the economics of global infectious disease policies.

    PubMed Central

    Barrett, Scott

    2004-01-01

    A disease is controlled if, by means of a public policy, the circulation of an infectious agent is restricted below the level that would be sustained by individuals acting independently to control the disease. A disease is eliminated if it is controlled sufficiently to prevent an epidemic from occurring in a given geographical area. Control and elimination are achieved locally, but a disease can only be eradicated if it is eliminated everywhere. Eradication is plainly a more demanding goal, but it has two advantages over control. First, the economics of eradication can be very favourable when eradication not only reduces infections but also avoids the need for vaccinations in future. Indeed, when eradication is feasible, it will either pay to control it to a fairly low level or to eradicate it. This suggests that, from an economics perspective, diseases that are eliminated in high-income countries are prime candidates for future eradication efforts. Second, the incentives for countries to participate in an eradication initiative can be strong; indeed they can be even stronger than an international control programme. Moreover, high-income countries typically benefit so much that they will be willing to finance elimination in developing countries. Full financing of an eradication effort by nation-states is not always guaranteed, but it can be facilitated by a variety of means. Hence, from the perspective of economics and international relations, eradication has a number of advantages over control. The implications for smallpox and polio eradication programmes are discussed. PMID:15628206

  19. So close: remaining challenges to eradicating polio.

    PubMed

    Toole, Michael J

    2016-03-14

    The Global Polio Eradication Initiative, launched in 1988, is close to achieving its goal. In 2015, reported cases of wild poliovirus were limited to just two countries - Afghanistan and Pakistan. Africa has been polio-free for more than 18 months. Remaining barriers to global eradication include insecurity in areas such as Northwest Pakistan and Eastern and Southern Afghanistan, where polio cases continue to be reported. Hostility to vaccination is either based on extreme ideologies, such as in Pakistan, vaccination fatigue by parents whose children have received more than 15 doses, and misunderstandings about the vaccine's safety and effectiveness such as in Ukraine. A further challenge is continued circulation of vaccine-derived poliovirus in populations with low immunity, with 28 cases reported in 2015 in countries as diverse as Madagascar, Ukraine, Laos, and Myanmar. This paper summarizes the current epidemiology of wild and vaccine-derived poliovirus, and describes the remaining challenges to eradication and innovative approaches being taken to overcome them.

  20. A Research Agenda for Malaria Eradication: Vaccines

    PubMed Central

    2011-01-01

    Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of “vaccines that interrupt malaria transmission” (VIMT), which includes not only “classical” transmission-blocking vaccines that target the sexual and mosquito stages but also pre-erythrocytic and asexual stage vaccines that have an effect on transmission. VIMT may also include vaccines that target the vector to disrupt parasite development in the mosquito. Importantly, if eradication is to be achieved, malaria vaccine development efforts will need to target other malaria parasite species, especially Plasmodium vivax, where novel therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple stages could have enormous impact. A target product profile (TPP) for VIMT is proposed and a research agenda to address current knowledge gaps and develop tools necessary for design and development of VIMT is presented. PMID:21311586

  1. A Research Agenda for Malaria Eradication: Modeling

    PubMed Central

    2011-01-01

    Malaria modeling can inform policy and guide research for malaria elimination and eradication from local implementation to global policy. A research and development agenda for malaria modeling is proposed, to support operations and to enhance the broader eradication research agenda. Models are envisioned as an integral part of research, planning, and evaluation, and modelers should ideally be integrated into multidisciplinary teams to update the models iteratively, communicate their appropriate use, and serve the needs of other research scientists, public health specialists, and government officials. A competitive and collaborative framework will result in policy recommendations from multiple, independently derived models and model systems that share harmonized databases. As planned, modeling results will be produced in five priority areas: (1) strategic planning to determine where and when resources should be optimally allocated to achieve eradication; (2) management plans to minimize the evolution of drug and pesticide resistance; (3) impact assessments of new and needed tools to interrupt transmission; (4) technical feasibility assessments to determine appropriate combinations of tools, an associated set of target intervention coverage levels, and the expected timelines for achieving a set of goals in different socio-ecological settings and different health systems; and (5) operational feasibility assessments to weigh the economic costs, capital investments, and human resource capacities required. PMID:21283605

  2. A Research Agenda to Underpin Malaria Eradication

    PubMed Central

    Alonso, Pedro L.; Brown, Graham; Arevalo-Herrera, Myriam; Binka, Fred; Chitnis, Chetan; Collins, Frank; Doumbo, Ogobara K.; Greenwood, Brian; Hall, B. Fenton; Levine, Myron M.; Mendis, Kamini; Newman, Robert D.; Plowe, Christopher V.; Rodríguez, Mario Henry; Sinden, Robert; Slutsker, Laurence; Tanner, Marcel

    2011-01-01

    The interruption of malaria transmission worldwide is one of the greatest challenges for international health and development communities. The current expert view suggests that, by aggressively scaling up control with currently available tools and strategies, much greater gains could be achieved against malaria, including elimination from a number of countries and regions; however, even with maximal effort we will fall short of global eradication. The Malaria Eradication Research Agenda (malERA) complements the current research agenda—primarily directed towards reducing morbidity and mortality—with one that aims to identify key knowledge gaps and define the strategies and tools that will result in reducing the basic reproduction rate to less than 1, with the ultimate aim of eradication of the parasite from the human population. Sustained commitment from local communities, civil society, policy leaders, and the scientific community, together with a massive effort to build a strong base of researchers from the endemic areas will be critical factors in the success of this new agenda. PMID:21311579

  3. A research agenda for malaria eradication: vaccines.

    PubMed

    2011-01-25

    Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of "vaccines that interrupt malaria transmission" (VIMT), which includes not only "classical" transmission-blocking vaccines that target the sexual and mosquito stages but also pre-erythrocytic and asexual stage vaccines that have an effect on transmission. VIMT may also include vaccines that target the vector to disrupt parasite development in the mosquito. Importantly, if eradication is to be achieved, malaria vaccine development efforts will need to target other malaria parasite species, especially Plasmodium vivax, where novel therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple stages could have enormous impact. A target product profile (TPP) for VIMT is proposed and a research agenda to address current knowledge gaps and develop tools necessary for design and development of VIMT is presented.

  4. A Research Agenda for Malaria Eradication: Drugs

    PubMed Central

    2011-01-01

    Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or “attack” phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection. Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. The ideal malaria eradication drug is a coformulated drug combination suitable for mass administration that can be administered in a single encounter at infrequent intervals and that results in radical cure of all life cycle stages of all five malaria species infecting humans. Short of this optimal goal, highly desirable drugs might have limitations such as targeting only one or two parasite species, the priorities being Plasmodium falciparum and Plasmodium vivax. The malaria research agenda for eradication should include research aimed at developing such drugs and research to develop situation-specific strategies for using both current and future drugs to interrupt malaria transmission. PMID:21311580

  5. The role of research in viral disease eradication and elimination programs: lessons for malaria eradication.

    PubMed

    Breman, Joel G; de Quadros, Ciro A; Dowdle, Walter R; Foege, William H; Henderson, Donald A; John, T Jacob; Levine, Myron M

    2011-01-25

    By examining the role research has played in eradication or regional elimination initiatives for three viral diseases--smallpox, poliomyelitis, and measles--we derive nine cross-cutting lessons applicable to malaria eradication. In these initiatives, some types of research commenced as the programs began and proceeded in parallel. Basic laboratory, clinical, and field research all contributed notably to progress made in the viral programs. For each program, vaccine was the lynchpin intervention, but as the programs progressed, research was required to improve vaccine formulations, delivery methods, and immunization schedules. Surveillance was fundamental to all three programs, whilst polio eradication also required improved diagnostic methods to identify asymptomatic infections. Molecular characterization of pathogen isolates strengthened surveillance and allowed insights into the geographic source of infections and their spread. Anthropologic, sociologic, and behavioural research were needed to address cultural and religious beliefs to expand community acceptance. The last phases of elimination and eradication became increasingly difficult, as a nil incidence was approached. Any eradication initiative for malaria must incorporate flexible research agendas that can adapt to changing epidemiologic contingencies and allow planning for posteradication scenarios.

  6. Pancreatic Cancer Genetics

    PubMed Central

    Amundadottir, Laufey T.

    2016-01-01

    Although relatively rare, pancreatic tumors are highly lethal [1]. In the United States, an estimated 48,960 individuals will be diagnosed with pancreatic cancer and 40,560 will die from this disease in 2015 [1]. Globally, 337,872 new pancreatic cancer cases and 330,391 deaths were estimated in 2012 [2]. In contrast to most other cancers, mortality rates for pancreatic cancer are not improving; in the US, it is predicted to become the second leading cause of cancer related deaths by 2030 [3, 4]. The vast majority of tumors arise in the exocrine pancreas, with pancreatic ductal adenocarcinoma (PDAC) accounting for approximately 95% of tumors. Tumors arising in the endocrine pancreas (pancreatic neuroendocrine tumors) represent less than 5% of all pancreatic tumors [5]. Smoking, type 2 diabetes mellitus (T2D), obesity and pancreatitis are the most consistent epidemiological risk factors for pancreatic cancer [5]. Family history is also a risk factor for developing pancreatic cancer with odds ratios (OR) ranging from 1.7-2.3 for first-degree relatives in most studies, indicating that shared genetic factors may play a role in the etiology of this disease [6-9]. This review summarizes the current knowledge of germline pancreatic cancer risk variants with a special emphasis on common susceptibility alleles identified through Genome Wide Association Studies (GWAS). PMID:26929738

  7. Inherited pancreatic cancer syndromes.

    PubMed

    Solomon, Sheila; Das, Siddhartha; Brand, Randall; Whitcomb, David C

    2012-01-01

    Pancreatic cancer remains one of the most challenging of all cancers. Genetic risk factors are believed to play a major role, but other than genes coding for blood group, genetic risks for sporadic cases remain elusive. However, several germline mutations have been identified that lead to hereditary pancreatic cancer, familial pancreatic cancer, and increased risk for pancreatic cancer as part of a familial cancer syndrome. The most important genes with variants increasing risk for pancreatic cancer include BRCA1, BRCA2, PALB2, ATM, CDKN2A, APC, MLH1, MSH2, MSH6, PMS2, PRSS1, and STK11. Recognition of members of high-risk families is important for understanding pancreatic cancer biology, for recommending risk reduction strategies and, in some cases, initiating cancer surveillance programs. Because the best methods for surveillance have not been established, the recommendation to refer at-risk patients to centers with ongoing research programs in pancreatic cancer surveillance is supported.

  8. Enhanced inactivation of adenovirus under polychromatic UV lamps

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adenovirus is recognized as the most UV-resistant waterborne pathogen of concern to public health microbiologists. The US EPA has stipulated that a UV fluence (dose) of 186 mJ cm-2 is required for 4-log inactivation credit in water treatment. However, all adenovirus inactivation data to date publi...

  9. Capturing and concentrating adenovirus using magnetic anionic nanobeads

    PubMed Central

    Sakudo, Akikazu; Baba, Koichi; Ikuta, Kazuyoshi

    2016-01-01

    We recently demonstrated how various enveloped viruses can be efficiently concentrated using magnetic beads coated with an anionic polymer, poly(methyl vinyl ether-maleic anhydrate). However, the exact mechanism of interaction between the virus particles and anionic beads remains unclear. To further investigate whether these magnetic anionic beads specifically bind to the viral envelope, we examined their potential interaction with a nonenveloped virus (adenovirus). The beads were incubated with either adenovirus-infected cell culture medium or nasal aspirates from adenovirus-infected individuals and then separated from the supernatant by applying a magnetic field. After thoroughly washing the beads, adsorption of adenovirus was confirmed by a variety of techniques, including immunochromatography, polymerase chain reaction, Western blotting, and cell culture infection assays. These detection methods positively identified the hexon and penton capsid proteins of adenovirus along with the viral genome on the magnetic beads. Furthermore, various types of adenovirus including Types 5, 6, 11, 19, and 41 were captured using the magnetic bead procedure. Our bead capture method was also found to increase the sensitivity of viral detection. Adenovirus below the detectable limit for immunochromatography was efficiently concentrated using the magnetic bead procedure, allowing the virus to be successfully detected using this methodology. Moreover, these findings clearly demonstrate that a viral envelope is not required for binding to the anionic magnetic beads. Taken together, our results show that this capture procedure increases the sensitivity of detection of adenovirus and would, therefore, be a valuable tool for analyzing both clinical and experimental samples. PMID:27274228

  10. The search for adenovirus 14 in children in Houston, Texas.

    PubMed

    Laham, Federico R; Jewell, Alan M; Schoonover, Shauna L; Demmler, Gail J; Piedra, Pedro A

    2008-07-01

    Adenovirus (Ad)14 has recently emerged in the United States causing outbreaks of severe respiratory disease. To determine if Ad14 circulated in Houston, Texas, during the same time as an outbreak in military recruits in nearby San Antonio, 215 pediatric adenovirus isolates were serotyped using microneutralization. None were Ad14; Ad1, Ad2, and Ad3 were the most common identified serotypes.

  11. A novel adenovirus in Chinstrap penguins (Pygoscelis antarctica) in Antarctica.

    PubMed

    Lee, Sook-Young; Kim, Jeong-Hoon; Park, Yon Mi; Shin, Ok Sarah; Kim, Hankyeom; Choi, Han-Gu; Song, Jin-Won

    2014-05-07

    Adenoviruses (family Adenoviridae) infect various organ systems and cause diseases in a wide range of host species. In this study, we examined multiple tissues from Chinstrap penguins (Pygoscelis antarctica), collected in Antarctica during 2009 and 2010, for the presence of novel adenoviruses by PCR. Analysis of a 855-bp region of the hexon gene of a newly identified adenovirus, designated Chinstrap penguin adenovirus 1 (CSPAdV-1), showed nucleotide (amino acid) sequence identity of 71.8% (65.5%) with South Polar skua 1 (SPSAdV-1), 71% (70%) with raptor adenovirus 1 (RAdV-1), 71.4% (67.6%) with turkey adenovirus 3 (TAdV-3) and 61% (61.6%) with frog adenovirus 1 (FrAdV-1). Based on the genetic and phylogenetic analyses, CSPAdV-1 was classified as a member of the genus, Siadenovirus. Virus isolation attempts from kidney homogenates in the MDTC-RP19 (ATCC® CRL-8135™) cell line were unsuccessful. In conclusion, this study provides the first evidence of new adenovirus species in Antarctic penguins.

  12. Adenovirus dodecahedron allows large multimeric protein transduction in human cells.

    PubMed

    Fender, P; Schoehn, G; Foucaud-Gamen, J; Gout, E; Garcel, A; Drouet, E; Chroboczek, J

    2003-04-01

    Adenovirus dodecahedron is a virus-like particle composed of only two viral proteins of human adenovirus serotype 3 that are responsible for virus attachment and internalization. We show here that this dodecameric particle, devoid of genetic information, efficiently penetrates human cells and can deliver large multimeric proteins such as immunoglobulins.

  13. The other 'neglected' eradication programme: achieving the final mile for Guinea worm disease eradication?

    PubMed

    Al-Awadi, Abdul Rahman; Karam, Marc V; Molyneux, David H; Breman, Joel G

    2007-08-01

    Guinea worm disease is one of two diseases targeted for eradication, the other being polio. Since the late 1980s, the number of new cases per year has been reduced from approximately one million to some 25 000 in 2006. However, there was an increase from 2005 owing to improved surveillance in Sudan and problems in Ghana. The International Commission argues that more resources are required to ensure that the goal of eradication is completed. Elimination of transmission throughout Asia has now been confirmed and the disease is now confined to a small number of African countries requiring increased efforts to achieve the global goal.

  14. Pancreatic Cancer Stage 2A

    MedlinePlus

    ... 2A Description: Stage IIA pancreatic cancer; drawing shows cancer in the pancreas and duodenum. The bile duct and pancreatic duct are also shown. Stage IIA pancreatic cancer. Cancer has spread to nearby tissue and organs ...

  15. Pancreatic Cancer Stage 2B

    MedlinePlus

    ... 2B Description: Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum. Stage IIB pancreatic cancer. Cancer has spread to nearby lymph nodes and ...

  16. Dracunculiasis Eradication: And Now, South Sudan

    PubMed Central

    Hopkins, Donald R.; Ruiz-Tiben, Ernesto; Weiss, Adam; Withers Jr., P. Craig; Eberhard, Mark L.; Roy, Sharon L.

    2013-01-01

    This report summarizes the status of the global Dracunculiasis Eradication Program as of the end of 2012. Dracunculiasis (Guinea worm disease) has been eliminated from 17 of 21 countries where it was endemic in 1986, when an estimated 3.5 million cases occurred worldwide. Only 542 cases were reported from four countries in 2012, and 103 villages still had indigenous transmission. Most remaining cases were reported from the new Republic of South Sudan, whereas Chad, Ethiopia, and Mali each reported 10 cases or less. Political instability and insecurity in Mali may become the main obstacles to interrupting dracunculiasis transmission forever. PMID:23843492

  17. Eradication of Invading Insect Populations: From Concepts to Applications.

    PubMed

    Liebhold, Andrew M; Berec, Ludek; Brockerhoff, Eckehard G; Epanchin-Niell, Rebecca S; Hastings, Alan; Herms, Daniel A; Kean, John M; McCullough, Deborah G; Suckling, David M; Tobin, Patrick C; Yamanaka, Takehiko

    2016-01-01

    Eradication is the deliberate elimination of a species from an area. Given that international quarantine measures can never be 100% effective, surveillance for newly arrived populations of nonnative species coupled with their eradication represents an important strategy for excluding potentially damaging insect species. Historically, eradication efforts have not always been successful and have sometimes been met with public opposition. But new developments in our understanding of the dynamics of low-density populations, the availability of highly effective treatment tactics, and bioeconomic analyses of eradication strategies offer new opportunities for developing more effective surveillance and eradication programs. A key component that connects these new developments is the harnessing of Allee effects, which naturally promote localized species extinction. Here we review these developments and suggest how research might enhance eradication strategies.

  18. [Possible method of eradication of poliomyelitis as an infection].

    PubMed

    Seĭbil', V B; Malyshkina, L P

    2012-01-01

    Problem of poliomyelitis eradication is examined in the review. After the eradication of wild poliovirus, vaccine poliomyelitis virus continues to circulate in the human population. In rare cases it can cause the development of the disease. The authors describe disadvantages of the use of oral and inactivated poliomyelitis vaccines and note that by using oral poliomyelitis vaccine and eradication only of wild poliovirus, eradication of poliomyelitis as an infection will not succeed. As one of the approaches to reach this goal the authors propose the use of various enterovirus interference. Use of live enterovirus vaccine is described and its advantages and disadvantages are examined.

  19. Pro and contra IBR-eradication.

    PubMed

    Ackermann, Mathias; Engels, Monika

    2006-03-31

    Bovine herpesvirus type 1 (BoHV-1) is the causative agent of respiratory and genital tract infections such as infectious rhinotracheitis (IBR), infectious pustular vulvovaginitis (IPV, balanoposthitis (IBP), and abortion. Despite of a pronounced immune response, the virus is never eliminated from an infected host but establishes life-long latency and may be reactivated at intervals. Europe has a long history of fighting against BoHV-1 infections, yet, only a small number of countries has achieved IBR-eradication. Therefore, it seemed appropriate to review the reasoning pro and contra such a task. Clearly, the goal can indeed be achieved as has been demonstrated by a number of European countries. However, detection and stamping out of seemingly healthy virus carriers is inevitable in the process. Unfortunately, the use of vaccines is only of temporary and limited value. Therefore, there are numerous considerations to be put forward against such plans, including the high costs, the great risks, and the unsatisfactory quality of tools. If either control or eradication of IBR is nonetheless a goal, then better vaccines are needed as well as better companion tests. Moreover, better tools for the characterization of viral isolates are required. Collaborative actions to gather viral strains from as many countries as possible for inclusion into a newly created clustering library would be most advantageous.

  20. Regulation of Human Adenovirus Replication by RNA Interference

    PubMed Central

    Nikitenko, N. A.; Speiseder, T.; Lam, E.; Rubtsov, P. M.; Tonaeva, Kh. D.; Borzenok, S. A.; Dobner, T.; Prassolov, V. S.

    2015-01-01

    Adenoviruses cause a wide variety of human infectious diseases. Adenoviral conjunctivitis and epidemic keratoconjunctivitis are commonly associated with human species D adenoviruses. Currently, there is no sufficient or appropriate treatment to counteract these adenovirus infections. Thus, there is an urgent need for new etiology-directed therapies with selective activity against human adenoviruses. To address this problem, the adenoviral early genes E1A and E2B (viral DNA polymerase) seem to be promising targets. Here, we propose an effective approach to downregulate the replication of human species D adenoviruses by means of RNA interference. We generated E1A expressing model cell lines enabling fast evaluation of the RNA interference potential. Small interfering RNAs complementary to the E1A mRNA sequences of human species D adenoviruses mediate significant suppression of the E1A expression in model cells. Furthermore, we observed a strong downregulation of replication of human adenoviruses type D8 and D37 by small hairpin RNAs complementary to the E1A or E2B mRNA sequences in primary human limbal cells. We believe that our results will contribute to the development of efficient anti-adenoviral therapy. PMID:26483965

  1. Regulation of Human Adenovirus Replication by RNA Interference.

    PubMed

    Nikitenko, N A; Speiseder, T; Lam, E; Rubtsov, P M; Tonaeva, Kh D; Borzenok, S A; Dobner, T; Prassolov, V S

    2015-01-01

    Adenoviruses cause a wide variety of human infectious diseases. Adenoviral conjunctivitis and epidemic keratoconjunctivitis are commonly associated with human species D adenoviruses. Currently, there is no sufficient or appropriate treatment to counteract these adenovirus infections. Thus, there is an urgent need for new etiology-directed therapies with selective activity against human adenoviruses. To address this problem, the adenoviral early genes E1A and E2B (viral DNA polymerase) seem to be promising targets. Here, we propose an effective approach to downregulate the replication of human species D adenoviruses by means of RNA interference. We generated E1A expressing model cell lines enabling fast evaluation of the RNA interference potential. Small interfering RNAs complementary to the E1A mRNA sequences of human species D adenoviruses mediate significant suppression of the E1A expression in model cells. Furthermore, we observed a strong downregulation of replication of human adenoviruses type D8 and D37 by small hairpin RNAs complementary to the E1A or E2B mRNA sequences in primary human limbal cells. We believe that our results will contribute to the development of efficient anti-adenoviral therapy.

  2. Structure of adenovirus bound to cellular receptor car

    DOEpatents

    Freimuth, Paul I.

    2004-05-18

    Disclosed is a mutant adenovirus which has a genome comprising one or more mutations in sequences which encode the fiber protein knob domain wherein the mutation causes the encoded viral particle to have significantly weakened binding affinity for CARD1 relative to wild-type adenovirus. Such mutations may be in sequences which encode either the AB loop, or the HI loop of the fiber protein knob domain. Specific residues and mutations are described. Also disclosed is a method for generating a mutant adenovirus which is characterized by a receptor binding affinity or specificity which differs substantially from wild type. In the method, residues of the adenovirus fiber protein knob domain which are predicted to alter D1 binding when mutated, are identified from the crystal structure coordinates of the AD12knob:CAR-D1 complex. A mutation which alters one or more of the identified residues is introduced into the genome of the adenovirus to generate a mutant adenovirus. Whether or not the mutant produced exhibits altered adenovirus-CAR binding properties is then determined.

  3. Hypermutation In Pancreatic Cancer.

    PubMed

    Humphris, Jeremy L; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J; Johns, Amber L; McKay, Skye; Chang, David K; Miller, David K; Pajic, Marina; Kassahn, Karin S; Quinn, Michael C J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Stone, Andrew; Wilson, Peter J; Anderson, Matthew; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Mead, Ronald S; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Nagrial, Adnan M; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Rooman, Ilse; Giry-Laterriere, Marc; Samra, Jaswinder S; Kench, James G; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; McKay, Colin J; Carter, C Ross; Dickson, Euan J; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Morton, Jennifer P; Sansom, Owen J; Grützmann, Robert; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Rusev, Borislav; Corbo, Vincenzo; Salvia, Roberto; Cataldo, Ivana; Tortora, Giampaolo; Tempero, Margaret A; Hofmann, Oliver; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Gill, Anthony J; Pearson, John V; Grimmond, Sean M; Waddell, Nicola; Biankin, Andrew V

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.

  4. Mechanisms of pathogenesis of emerging adenoviruses

    PubMed Central

    Cook, James; Radke, Jay

    2017-01-01

    Periodic outbreaks of human adenovirus infections can cause severe illness in people with no known predisposing conditions. The reasons for this increased viral pathogenicity are uncertain. Adenoviruses are constantly undergoing mutation during circulation in the human population, but related phenotypic changes of the viruses are rarely detected because of the infrequency of such outbreaks and the limited biological studies of the emergent strains. Mutations and genetic recombinations have been identified in these new strains. However, the linkage between these genetic changes and increased pathogenicity is poorly understood. It has been observed recently that differences in virus-induced immunopathogenesis can be associated with altered expression of non-mutant viral genes associated with changes in viral modulation of the host innate immune response. Initial small animal studies indicate that these changes in viral gene expression can be associated with enhanced immunopathogenesis in vivo. Available evidence suggests the hypothesis that there is a critical threshold of expression of certain viral genes that determines both the sustainability of viral transmission in the human population and the enhancement of immunopathogenesis. Studies of this possibility will require extension of the analysis of outbreak viral strains from a sequencing-based focus to biological studies of relationships between viral gene expression and pathogenic responses. Advances in this area will require increased coordination among public health organizations, diagnostic microbiology laboratories, and research laboratories to identify, catalog, and systematically study differences between prototype and emergent viral strains that explain the increased pathogenicity that can occur during clinical outbreaks. PMID:28184296

  5. Isolation and Epidemiology of Falcon Adenovirus

    PubMed Central

    Oaks, J. Lindsay; Schrenzel, Mark; Rideout, Bruce; Sandfort, Cal

    2005-01-01

    An adenovirus was detected by electron microscopy in tissues from falcons that died during an outbreak of inclusion body hepatitis and enteritis that affected neonatal Northern aplomado (Falco femoralis septentrionalis) and peregrine (Falco peregrinus anatum) falcons. Molecular characterization has identified the falcon virus as a new member of the aviadenovirus group (M. Schrenzel, J. L. Oaks, D. Rotstein, G. Maalouf, E. Snook, C. Sandfort, and B. Rideout, J. Clin. Microbiol. 43:3402-3413, 2005). In this study, the virus was successfully isolated and propagated in peregrine falcon embryo fibroblasts, in which it caused visible and reproducible cytopathology. Testing for serum neutralizing antibodies found that infection with this virus was limited almost exclusively to falcons. Serology also found that wild and captive peregrine falcons had high seropositivity rates of 80% and 100%, respectively, although clinical disease was rarely reported in this species. These data implicate peregrine falcons as the natural host and primary reservoir for the virus. Other species of North American falcons, including aplomado falcons, had lower seropositivity rates of 43 to 57%. Falcon species of tropical and/or island origin were uniformly seronegative, although deaths among adults of these species have been described, suggesting they are highly susceptible. Chickens and quail were uniformly seronegative and not susceptible to infection, indicating that fowl were not the source of infection. Based on the information from this study, the primary control of falcon adenovirus infections should be based on segregation of carrier and susceptible falcon species. PMID:16000467

  6. Proinflammatory Effects of Interferon Gamma in Mouse Adenovirus 1 Myocarditis

    PubMed Central

    McCarthy, Mary K.; Procario, Megan C.; Twisselmann, Nele; Wilkinson, J. Erby; Archambeau, Ashley J.; Michele, Daniel E.; Day, Sharlene M.

    2014-01-01

    ABSTRACT Adenoviruses are frequent causes of pediatric myocarditis. Little is known about the pathogenesis of adenovirus myocarditis, and the species specificity of human adenoviruses has limited the development of animal models, which is a significant barrier to strategies for prevention or treatment. We have developed a mouse model of myocarditis following mouse adenovirus 1 (MAV-1) infection to study the pathogenic mechanisms of this important cause of pediatric myocarditis. Following intranasal infection of neonatal C57BL/6 mice, we detected viral replication and induction of interferon gamma (IFN-γ) in the hearts of infected mice. MAV-1 caused myocyte necrosis and induced substantial cellular inflammation that was composed predominantly of CD3+ T lymphocytes. Depletion of IFN-γ during acute infection reduced cardiac inflammation in MAV-1-infected mice without affecting viral replication. We observed decreased contractility during acute infection of neonatal mice, and persistent viral infection in the heart was associated with cardiac remodeling and hypertrophy in adulthood. IFN-γ is a proinflammatory mediator during adenovirus-induced myocarditis, and persistent adenovirus infection may contribute to ongoing cardiac dysfunction. IMPORTANCE Studying the pathogenesis of myocarditis caused by different viruses is essential in order to characterize both virus-specific and generalized factors that contribute to disease. Very little is known about the pathogenesis of adenovirus myocarditis, which is a significant impediment to the development of treatment or prevention strategies. We used MAV-1 to establish a mouse model of human adenovirus myocarditis, providing the means to study host and pathogen factors contributing to adenovirus-induced cardiac disease during acute and persistent infection. The MAV-1 model will enable fundamental studies of viral myocarditis, including IFN-γ modulation as a therapeutic strategy. PMID:25320326

  7. Structure of adenovirus bound to cellular receptor car

    DOEpatents

    Freimuth, Paul I.

    2007-01-02

    Disclosed is a mutant CAR-DI-binding adenovirus which has a genome comprising one or more mutations in sequences which encode the fiber protein knob domain wherein the mutation causes the encoded viral particle to have a significantly weakened binding affinity for CAR-DI relative to wild-type adenovirus. Such mutations may be in sequences which encode either the AB loop, or the HI loop of the fiber protein knob domain. Specific residues and mutations are described. Also disclosed is a method for generating a mutant adenovirus which is characterized by a receptor binding affinity or specificity which differs substantially from wild type.

  8. Lymphoplasmacytic sclerosing pancreatitis (autoimmune pancreatitis): evaluation with multidetector CT.

    PubMed

    Kawamoto, Satomi; Siegelman, Stanley S; Hruban, Ralph H; Fishman, Elliot K

    2008-01-01

    Lymphoplasmacytic sclerosing pancreatitis is a form of chronic pancreatitis characterized by a mixed inflammatory infiltrate that centers on the pancreatic ducts. It is a cause of benign pancreatic disease that can clinically mimic pancreatic cancer. Preoperative detection of lymphoplasmacytic sclerosing pancreatitis is important because patients usually respond to steroid therapy. Patients with lymphoplasmacytic sclerosing pancreatitis are often referred for computed tomography (CT) when they are suspected of having a pancreatic or biliary neoplasm; therefore, it is important to search for potential findings suggestive of lymphoplasmacytic sclerosing pancreatitis when typical findings of a pancreatic or biliary neoplasm are not found. Typical CT findings include diffuse or focal enlargement of the pancreas without dilatation of the main pancreatic duct. Focal enlargement is most commonly seen in the head of the pancreas, and the involved pancreas on contrast material-enhanced CT images may be iso-attenuating relative to the rest of the pancreas, or hypo-attenuating, especially during the early postcontrast phase. Thickening and contrast enhancement of the wall of the common bile duct and gallbladder may reflect inflammatory infiltrate and fibrosis associated with lymphoplasmacytic sclerosing pancreatitis. There are several features seen at CT that may help to differentiate lymphoplasmacytic sclerosing pancreatitis from pancreatic cancer, such as diffuse enlargement of the pancreas with minimal peripancreatic stranding in patients with obstructive jaundice, an absence of significant pancreatic atrophy, and an absence of significant main pancreatic duct dilatation. When these findings are encountered, clinical, other imaging, and serologic data should be evaluated.

  9. IMMUNOFLUORESCENT STUDIES OF THE POTENTIATION OF AN ADENOVIRUS-ASSOCIATED VIRUS BY ADENOVIRUS 7

    PubMed Central

    Blacklow, Neil R.; Hoggan, M. David; Rowe, Wallace P.

    1967-01-01

    A quantitative immunofluorescent procedure for detection of viral antigen was used to study the potentiation of AAV-1 by Ad.7. AAV viral antigen formed only when the cells were also infected with adenovirus, and only in cell culture systems in which the adenovirus infection proceeded to completion. Ad. 7 infection of AGMK. cell cultures did not potentiate AAV unless the Ad. 7 infection was itself potentiated by SV40. Dose-response studies indicated that a single AAV particle and a single infectious Ad. 7 particle sufficed to initiate AAV antigen synthesis. Sequential inoculation studies showed that AAV antigen formed simultaneously with Ad. 7 viral antigen when the AAV was inoculated any time between 15 hr before to 10 hr after the Ad. 7, both antigens appearing about 15 hr after inoculation of Ad. 7. The AAV-1 antigen formation had a minimum latent period of 5 hr, as seen with Ad. 7 preinfection of 10 hr or more. When UV-irradiated Ad. 7 was used as helper, the AAV antigen still appeared simultaneously with the Ad. 7 viral antigen, even though the latter was delayed by 23 hr compared to nonirradiated virus. When the early replicative events of both viruses were allowed to proceed in FUDR-inhibited cells, and then the FUDR inhibition was reversed, AAV antigen formed within 2 hr, which was 3 hr before the Ad. 7 viral antigen appeared. It was inferred that the event in the adenovirus cycle that renders a cell competent to synthesize AAV occurs after the 10th hr and may be temporally associated with replication of the adenovirus DNA. PMID:4225814

  10. Lymphoplasmacytic sclerosing pancreatitis.

    PubMed

    Plaza, Jose Antonio; Colonna, Jorge; Vitellas, Kenneth M; Frankel, Wendy L

    2005-10-01

    Lymphoplasmacytic sclerosing pancreatitis is a rare entity that has been described under many different names and constitutes a diagnostic challenge as it may simulate a neoplastic process. Herein, we report a case of a 61-year-old woman who presented to our institution complaining of left flank pain and was found to have normal levels of amylase and lipase. An abdominal magnetic resonance image showed thickening of the pancreatic tail and compression of the pancreatic duct. The radiographic differential included both chronic pancreatitis and a neoplastic process. She underwent an exploratory laparotomy, during which a pancreatectomy and splenectomy were performed. Grossly, the pancreas contained a yellowish white, firm homogeneous mass measuring 6.5 x 3.3 x 2.9 cm involving the entire pancreatic tail and hilum of the spleen. Histologically, pancreatic sections showed extensive fibrosis admixed with an inflammatory infiltrate. This infiltrate was composed mainly of lymphocytes with multiple germinal centers, as well as plasma cells and eosinophils that surrounded pancreatic ducts and extended into the peripancreatic adipose tissue. No malignancy was identified, and the process was diagnosed as lymphoplasmacytic sclerosing pancreatitis.

  11. Uganda's successful Guinea Worm Eradication Program.

    PubMed

    Rwakimari, John B; Hopkins, Donald R; Ruiz-Tiben, Ernesto

    2006-07-01

    Having begun its national Guinea Worm Eradication Program (UGWEP) in 1991 (1991 population, 16.6 million) with the third-highest number of cases reported by any endemic country, and ranked as the second-highest endemic country in the world in 1993, by 2004, Uganda celebrated its first full calendar year with no indigenous cases of the disease. Systematic interventions began in 1992 and were gradually intensified until the final indigenous case occurred in July 2003. The favorable concentration of most cases in relatively few northern districts of the country was partly offset by chronic insecurity in much of the endemic area and by repeated importations of cases from neighboring Sudan. Strong support and dedicated leadership by government officials and external partners were keys to this program's dramatic success. This program cost approximately US dollar 5.6 million.

  12. Malaria: progress, perils, and prospects for eradication

    PubMed Central

    Greenwood, Brian M.; Fidock, David A.; Kyle, Dennis E.; Kappe, Stefan H.I.; Alonso, Pedro L.; Collins, Frank H.; Duffy, Patrick E.

    2008-01-01

    There are still approximately 500 million cases of malaria and 1 million deaths from malaria each year. Yet recently, malaria incidence has been dramatically reduced in some parts of Africa by increasing deployment of anti-mosquito measures and new artemisinin-containing treatments, prompting renewed calls for global eradication. However, treatment and mosquito control currently depend on too few compounds and thus are vulnerable to the emergence of compound-resistant parasites and mosquitoes. As discussed in this Review, new drugs, vaccines, and insecticides, as well as improved surveillance methods, are research priorities. Insights into parasite biology, human immunity, and vector behavior will guide efforts to translate parasite and mosquito genome sequences into novel interventions. PMID:18382739

  13. Eradication of Mycoplasma contaminations from cell cultures.

    PubMed

    Uphoff, Cord C; Drexler, Hans G

    2014-04-14

    Mycoplasma contaminations have a multitude of effects on cultured cell lines that may influence the results of experiments or pollute bioactive substances isolated from the eukaryotic cells. The elimination of mycoplasma contaminations from cell cultures with antibiotics has been proven to be a practical alternative to discarding and re-establishing important or irreplaceable cell lines. Different fluoroquinolones, tetracyclins, pleuromutilins, and macrolides shown to have strong anti-mycoplasma properties are employed for the decontamination. These antibiotics are applied as single treatments, as combination treatment of two antibiotics in parallel or successively, or in combination with a surface-active peptide to enhance the action of the antibiotic. The protocols in this unit allow eradication of mycoplasmas, prevention of the development of resistant mycoplasma strains, and potential cure of heavily contaminated and damaged cells. Consistent and permanent alterations to eukaryotic cells attributable to the treatment have not been demonstrated.

  14. Broadly Neutralizing Antibodies for HIV Eradication.

    PubMed

    Stephenson, Kathryn E; Barouch, Dan H

    2016-02-01

    Passive transfer of antibodies has long been considered a potential treatment modality for infectious diseases, including HIV. Early efforts to use antibodies to suppress HIV replication, however, were largely unsuccessful, as the antibodies that were studied neutralized only a relatively narrow spectrum of viral strains and were not very potent. Recent advances have led to the discovery of a large portfolio of human monoclonal antibodies that are broadly neutralizing across many HIV-1 subtypes and are also substantially more potent. These antibodies target multiple different epitopes on the HIV envelope, thus allowing for the development of antibody combinations. In this review, we discuss the application of broadly neutralizing antibodies (bNAbs) for HIV treatment and HIV eradication strategies. We highlight bNAbs that target key epitopes, such as the CD4 binding site and the V2/V3-glycan-dependent sites, and we discuss several bNAbs that are currently in the clinical development pipeline.

  15. Best strategies for global HCV eradication

    PubMed Central

    Hagan, Liesl M.; Schinazi, Raymond F.

    2014-01-01

    Worldwide eradication of hepatitis C virus (HCV) is possible through a combination of prevention education, universal clinical and targeted community screening, effective linkage to care, and treatment with promising new direct-acting antiviral drug regimens. Universal screening should be offered in all healthcare visits, and parallel community screening efforts should prioritize high-prevalence, high-transmission populations including injection drug users, prison inmates, and those with HIV/HCV co-infection. Increasing awareness of HCV infection through screening, improving treatment uptake and cure rates by providing linkage to care and more effective treatment, and ultimately combining education efforts with vaccination campaigns to prevent transmission and reinfection can slow and eventually stop the “silent epidemic.” PMID:23286849

  16. Invasive mammal eradication on islands results in substantial conservation gains.

    PubMed

    Jones, Holly P; Holmes, Nick D; Butchart, Stuart H M; Tershy, Bernie R; Kappes, Peter J; Corkery, Ilse; Aguirre-Muñoz, Alfonso; Armstrong, Doug P; Bonnaud, Elsa; Burbidge, Andrew A; Campbell, Karl; Courchamp, Franck; Cowan, Philip E; Cuthbert, Richard J; Ebbert, Steve; Genovesi, Piero; Howald, Gregg R; Keitt, Bradford S; Kress, Stephen W; Miskelly, Colin M; Oppel, Steffen; Poncet, Sally; Rauzon, Mark J; Rocamora, Gérard; Russell, James C; Samaniego-Herrera, Araceli; Seddon, Philip J; Spatz, Dena R; Towns, David R; Croll, Donald A

    2016-04-12

    More than US$21 billion is spent annually on biodiversity conservation. Despite their importance for preventing or slowing extinctions and preserving biodiversity, conservation interventions are rarely assessed systematically for their global impact. Islands house a disproportionately higher amount of biodiversity compared with mainlands, much of which is highly threatened with extinction. Indeed, island species make up nearly two-thirds of recent extinctions. Islands therefore are critical targets of conservation. We used an extensive literature and database review paired with expert interviews to estimate the global benefits of an increasingly used conservation action to stem biodiversity loss: eradication of invasive mammals on islands. We found 236 native terrestrial insular faunal species (596 populations) that benefitted through positive demographic and/or distributional responses from 251 eradications of invasive mammals on 181 islands. Seven native species (eight populations) were negatively impacted by invasive mammal eradication. Four threatened species had their International Union for the Conservation of Nature (IUCN) Red List extinction-risk categories reduced as a direct result of invasive mammal eradication, and no species moved to a higher extinction-risk category. We predict that 107 highly threatened birds, mammals, and reptiles on the IUCN Red List-6% of all these highly threatened species-likely have benefitted from invasive mammal eradications on islands. Because monitoring of eradication outcomes is sporadic and limited, the impacts of global eradications are likely greater than we report here. Our results highlight the importance of invasive mammal eradication on islands for protecting the world's most imperiled fauna.

  17. System development of the Screwworm Eradication Data System (SEDS) algorithm

    NASA Technical Reports Server (NTRS)

    Arp, G.; Forsberg, F.; Giddings, L.; Phinney, D.

    1976-01-01

    The use of remotely sensed data is reported in the eradication of the screwworm and in the study of the role of the weather in the activity and development of the screwworm fly. As a result, the Screwworm Eradication Data System (SEDS) algorithm was developed.

  18. Polio eradication: how long and how much to the end?

    PubMed

    Rodríguez-Álvarez, Mauricio; Jiménez-Corona, María Eugenia; Cervantes-Rosales, Rocío; Ponce de León-Rosales, Samuel

    2013-07-01

    Eradication of poliomyelitis seems to be more feasible than ever. During recent years the strategy has reached milestone goals, faced new challenges, and re-configured by itself. In this text we describe the current situation of the polio eradication efforts worldwide and present an analysis of the potential implications and needs regarding vaccination in the coming years.

  19. Insect Eradication and Containment of Invasive Alien Species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insect eradication programs are nearly always targeted at recently arrived invasive species with significant pest potential. They attempt to contain a pest to a defined area and then completely eliminate the pest from that area. From a Federal regulatory standpoint, eradication programs are undert...

  20. Invasive mammal eradication on islands results in substantial conservation gains

    PubMed Central

    Jones, Holly P.; Holmes, Nick D.; Butchart, Stuart H. M.; Tershy, Bernie R.; Kappes, Peter J.; Corkery, Ilse; Aguirre-Muñoz, Alfonso; Armstrong, Doug P.; Bonnaud, Elsa; Burbidge, Andrew A.; Campbell, Karl; Courchamp, Franck; Cowan, Philip E.; Cuthbert, Richard J.; Ebbert, Steve; Genovesi, Piero; Howald, Gregg R.; Keitt, Bradford S.; Kress, Stephen W.; Miskelly, Colin M.; Oppel, Steffen; Poncet, Sally; Rauzon, Mark J.; Rocamora, Gérard; Russell, James C.; Samaniego-Herrera, Araceli; Seddon, Philip J.; Spatz, Dena R.; Towns, David R.; Croll, Donald A.

    2016-01-01

    More than US$21 billion is spent annually on biodiversity conservation. Despite their importance for preventing or slowing extinctions and preserving biodiversity, conservation interventions are rarely assessed systematically for their global impact. Islands house a disproportionately higher amount of biodiversity compared with mainlands, much of which is highly threatened with extinction. Indeed, island species make up nearly two-thirds of recent extinctions. Islands therefore are critical targets of conservation. We used an extensive literature and database review paired with expert interviews to estimate the global benefits of an increasingly used conservation action to stem biodiversity loss: eradication of invasive mammals on islands. We found 236 native terrestrial insular faunal species (596 populations) that benefitted through positive demographic and/or distributional responses from 251 eradications of invasive mammals on 181 islands. Seven native species (eight populations) were negatively impacted by invasive mammal eradication. Four threatened species had their International Union for the Conservation of Nature (IUCN) Red List extinction-risk categories reduced as a direct result of invasive mammal eradication, and no species moved to a higher extinction-risk category. We predict that 107 highly threatened birds, mammals, and reptiles on the IUCN Red List—6% of all these highly threatened species—likely have benefitted from invasive mammal eradications on islands. Because monitoring of eradication outcomes is sporadic and limited, the impacts of global eradications are likely greater than we report here. Our results highlight the importance of invasive mammal eradication on islands for protecting the world's most imperiled fauna. PMID:27001852

  1. Smallpox: emergence, global spread, and eradication.

    PubMed

    Fenner, F

    1993-01-01

    Speculatively, it is suggested that variola virus, the cause of smallpox, evolved from an orthopoxvirus of animals of the central African rain forests (possibly now represented by Tatera poxvirus), some thousands of years ago, and first became established as a virus specific for human beings in the dense populations of the Nile valley perhaps five thousand years ago. By the end of the first millennium of the Christian era, it had spread to all the densely populated parts of the Eurasian continent and along the Mediterranean fringe of north Africa. It became established in Europe during the times of the Crusades. The great voyages of European colonization carried smallpox to the Americas and to Africa south of the Sahara. Transported across the Atlantic by Europeans and their African slaves, it played a major role in the conquest of Mexico and Peru and the European settlement of north America. Variolation, an effective preventive inoculation, was devised as early as the tenth century. In 1798 this practice was supplanted by Jenner's cowpox vaccine. In 1967, when the disease was still endemic in 31 countries and caused ten to fifteen million cases and about two million deaths annually, the World Health Organization embarked on a programme that was to see the disease eradicated globally just over ten years later, and the world was formally declared to be free of smallpox in May 1980. Smallpox is unique--a specifically human disease that emerged from some animal reservoir, spread to become a worldwide, severe and almost universal affliction, and finally underwent the reverse process to emergence, namely global eradication.

  2. [Clinical analysis of unsuccessful Helicobacter pylori eradication].

    PubMed

    Szadkowski, Aleksander; Chojnacki, Jan; Klupińska, Grazyna; Wojtuń, Stanisław

    2004-01-01

    Numerous medical reports claim that the effectiveness of H. pylori therapy decreases. The aim of the study was the analysis of the reasons of this phenomenon on own material. The study included 437 subjects, aged 19-64 years with chronic gastritis with H. pylori infection. All patients were subjected to: endoscopy, fast urease test, breath test (UBT-13C) and antibody titer in IgG class was determined. In the case of ineffective therapy bacteriological examination was performed. In the first stage of the therapy pantoprazol (2 x 40 mg) and amoxicillin (2 x 1000 mg) with metronidazol (2 x 500 mg) were applied in 282 subjects for 7 days (group I), amoxicillin with clarithromycin (2 x 500 mg) in 182 subjects (group II) and clarithromycin with metronidazol in 43 subjects (group III). After 6 weeks negative breath test was observed on average in 65.68% without significant differences between the groups. Ineffective therapy was more frequent in subjects over 45 years of age with high intensity of H. pylori colonization and earlier treated with antibiotics due to other reasons; such differences were not observed dependently on the antibody titer. In the second stage of the therapy pantoprazol was still administered but antibacterial drugs were changed among the groups. From among 150 subjects eradication was obtained in 117 (78.0%). In 33 subjects with ineffective therapy bacteriological examination of gastric bioptates confirmed antibiotic resistance in 75.76%. It results from the study that the applied therapy, consistent with current recommendations of the experts, does not ensure H. pylori eradication in part of the patients, what points to the necessity of searching for other effective antibiotics.

  3. Review of idiopathic pancreatitis

    PubMed Central

    Lee, Jason Kihyuk; Enns, Robert

    2007-01-01

    Recent advances in understanding of pancreatitis and advances in technology have uncovered the veils of idiopathic pancreatitis to a point where a thorough history and judicious use of diagnostic techniques elucidate the cause in over 80% of cases. This review examines the multitude of etiologies of what were once labeled idiopathic pancreatitis and provides the current evidence on each. This review begins with a background review of the current epidemiology of idiopathic pancreatitis prior to discussion of various etiologies. Etiologies of medications, infections, toxins, autoimmune disorders, vascular causes, and anatomic and functional causes are explored in detail. We conclude with management of true idiopathic pancreatitis and a summary of the various etiologic agents. Throughout this review, areas of controversies are highlighted. PMID:18081217

  4. [Pancreatic cancer stem cell].

    PubMed

    Hamada, Shin; Masamune, Atsushi; Shimosegawa, Tooru

    2015-05-01

    Prognosis of pancreatic cancer remains dismal due to the resistance against conventional therapies. Metastasis and massive invasion toward surrounding organs hamper radical resection. Small part of entire cancer cells reveal resistance against chemotherapy or radiotherapy, increased tumorigenicity and migratory phenotype. These cells are called as cancer stem cells, as a counter part of normal stem cells. In pancreatic cancer, several cancer stem cell markers have been identified, which enabled detailed characterization of pancreatic cancer stem cells. Recent researches clarified that conventional chemotherapy itself could increase cancer cells with stem cell-phenotype, suggesting the necessity of cancer stem cell-targeting therapy. Based on these observations, pancreatic cancer stem cell-targeting therapies have been tested, which effectively eliminated cancer stem cell fraction and attenuated cancer progression in experimental models. Clinical efficacy of these therapies need to be evaluated, and cancer stem cell-targeting therapy will contribute to improve the prognosis of pancreatic cancer.

  5. Temporal regulation of adenovirus major late alternative RNA splicing.

    PubMed

    Akusjarvi, Goran

    2008-05-01

    Adenovirus makes extensive use of alternative RNA splicing to produce a complex set of spliced mRNAs during replication. The accumulation of viral mRNAs is subjected to a temporal regulation, a mechanism that ensures that proteins that are needed at certain stages of the virus life cycle are produced in a timely fashion. The complex interactions between the virus and the host cell RNA splicing machinery has been studied in detail during the last decade. These studies have resulted in the characterization of two viral proteins, E4-ORF4 and L4-33K, that adenovirus uses to remodel the host cell RNA splicing machinery. Here I will review the current knowledge of how mRNA expression from the adenovirus major late transcription unit is controlled with a particular emphasis on how cis-acting sequence element, trans-acting factors and mechanisms regulating adenovirus major late L1 alternative RNA splicing is controlled.

  6. Probiotics as an adjuvant treatment in Helicobacter pylori eradication therapy.

    PubMed

    Zhu, Xinyan; Liu, Fei

    2017-03-10

    Over 80% population with Helicobacter pylori (H. pylori) infection is asymptomatic. H. pylori was considered as a primary reason for various natural gastric physiopathology. Increased antibiotic resistance and less medication compliance lead to the failure of antibiotic eradication therapy. Probiotics have been applied as a supplementary treatment in H. pylori eradication therapy in recent years. They have direct and indirect inhibitory effects on H. pylori in both animal models and clinical trials. Because of the improvement in eradication rates and therapy-related side effects, probiotics have been considered as the useful supplementation to current eradication therapy although the treatment outcomes were controversial due to the heterogeneity of probiotics in species, strains, doses and therapeutic duration. Despite the positive role of probiotics, several factors need to be further considered during the application of probiotics. At last, the adverse effects of probiotics are notable. Further investigation into the safety of adjuvant probiotics to present H. pylori eradication therapy is still needed.

  7. Poliovirus Studies during the Endgame of the Polio Eradication Program.

    PubMed

    Arita, Minetaro

    2017-01-24

    Since the beginning of Global Polio Eradication Initiative in 1988, poliomyelitis cases caused by wild poliovirus (PV) have been drastically reduced, with only 74 cases reported in 2 endemic countries in 2015. The current limited PV transmission suggests that we are in the endgame of the polio eradication program. However, specific challenges have emerged in the endgame, including tight budget, switching of the vaccines, and changes in biorisk management of PV. To overcome these challenges, several PV studies have been implemented in the eradication program. Some of the responses to the emerging challenges in the polio endgame might be valuable in other infectious diseases eradication programs. Here, I will review challenges that confront the polio eradication program and current research to address these challenges.

  8. An Oncotropic Adenovirus Vector System for Breast Cancer Treatment

    DTIC Science & Technology

    2005-09-01

    AD Award Number: DAMD17-03-1-0629 TITLE: An Oncotropic Adenovirus Vector System for Breast Cancer Treatment PRINCIPAL INVESTIGATOR: Igor P. Dmitriev...Aug 2005 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER An Oncotropic Adenovirus Vector System for Breast Cancer Treatment 5b. GRANT NUMBER DAMD17-03-1...epithelial cells, the origin of most human cancers. However, realization of the full potential of Ad vectors for targeted cancer treatment is currently

  9. Adenovirus-receptor interaction with human lymphocytes.

    PubMed

    Mentel, R; Döpping, G; Wegner, U; Seidel, W; Liebermann, H; Döhner, L

    1997-03-01

    Lymphocytes play a key role in cell-mediated immunity and are host cells for several viral and bacterial pathogens. Their importance in adenovirus (Ad) infections is not yet fully understood. The initial event, the attachment of Ad to lymphocytes and their subsets, was examined using flow cytometry. The study included analysis of stimulated T cells in binding assays with FITC-labeled Ad fiber. The results confirm that native peripheral lymphocytes express very small amounts of Ad receptors. Stimulation with PHA and interleukin 2 induced the expression. The presence of Ad DNA as a sign of internalization in stimulated cells was demonstrated using the polymerase chain reaction. The findings suggest that lymphocytes after stimulation can turn into target cells for Ad. This is particularly important if there are indications for persistence of Ad, and in the case of immunocompromised patients severe, life-threatening diseases can develop.

  10. [Gene engineering of the adenovirus vector].

    PubMed

    Kondo, Saki; Terashima, Miho; Fukuda, Hiromitsu; Saito, Izumu; Kanegae, Yumi

    2007-06-01

    The adenovirus vector is very attractive tool not only for the gene therapy but also for the basic sciences. However, because a construction method of this vector had been complex, only limited scientists had constructed and enjoyed the benefits. Recently, various methods were developed and the researchers came to be able to choose an efficient method, which is the COS-TPC method, or a concise procedure, which is the intact-genome transfection method (in vitro ligation method). Here we described not only these methods but also new method to construct the various Ads simultaneously using the recombinase-mediated cassette exchange (RMCE) by the site-specific recombinase. And also we want to refer the possibility to the worth of the vector, especially the vector of the expression-switch.

  11. Adenovirus Infections in Immunocompetent and Immunocompromised Patients

    PubMed Central

    2014-01-01

    SUMMARY Human adenoviruses (HAdVs) are an important cause of infections in both immunocompetent and immunocompromised individuals, and they continue to provide clinical challenges pertaining to diagnostics and treatment. The growing number of HAdV types identified by genomic analysis, as well as the improved understanding of the sites of viral persistence and reactivation, requires continuous adaptions of diagnostic approaches to facilitate timely detection and monitoring of HAdV infections. In view of the clinical relevance of life-threatening HAdV diseases in the immunocompromised setting, there is an urgent need for highly effective treatment modalities lacking major side effects. The present review summarizes the recent progress in the understanding and management of HAdV infections. PMID:24982316

  12. Vaccine Design: Replication-Defective Adenovirus Vectors.

    PubMed

    Zhou, Xiangyang; Xiang, Zhiquan; Ertl, Hildegund C J

    2016-01-01

    Replication-defective adenovirus (Ad) vectors were initially developed for gene transfer for correction of genetic diseases. Although Ad vectors achieved high levels of transgene product expression in a variety of target cells, expression of therapeutic proteins was found to be transient as vigorous T cell responses directed to components of the vector as well as the transgene product rapidly eliminate Ad vector-transduced cells. This opened the use of Ad vectors as vaccine carriers and by now a multitude of preclinical as well as clinical studies has shown that Ad vectors induce very potent and sustained transgene product-specific T and B cell responses. This chapter provides guidance on developing E1-deleted Ad vectors based on available viral molecular clones. Specifically, it describes methods for cloning, viral rescue and purification as well as quality control studies.

  13. Neoadjuvant treatment for resectable pancreatic adenocarcinoma

    PubMed Central

    Wong, John; Solomon, Naveenraj L; Hsueh, Chung-Tsen

    2016-01-01

    Pancreatic adenocarcinoma is the fourth leading cause of cancer mortality in the United States in both men and women, with a 5-year survival rate of less than 5%. Surgical resection remains the only curative treatment, but most patients develop systemic recurrence within 2 years of surgery. Adjuvant treatment with chemotherapy or chemoradiotherapy has been shown to improve overall survival, but the delivery of treatment remains problematic with up to 50% of patients not receiving postoperative treatment. Neoadjuvant therapy can provide benefits of eradication of micrometastasis and improved delivery of intended treatment. We have reviewed the findings from completed neoadjuvant clinical trials, and discussed the ongoing studies. Combinational cytotoxic chemotherapy such as fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel, active in the metastatic setting, are being studied in the neoadjuvant setting. In addition, novel targeted agents such as inhibitor of immune checkpoint are incorporated with cytotoxic chemotherapy in early-phase clinical trial. Furthermore we have explored the utility of biomarkers which can personalize treatment and select patients for target-driven therapy to improve treatment outcome. The treatment of resectable pancreatic adenocarcinoma requires multidisciplinary approach and novel strategies including innovative trials to make progress. PMID:26862486

  14. Boll weevil eradication: a model for sea lamprey control?

    USGS Publications Warehouse

    Smith, James W.; Swink, William D.

    2003-01-01

    Invasions of boll weevil (Anthonomus grandis) into the United States and sea lamprey (Petromyzon marinus) into the Great Lakes were similar in many ways. Important species (American cotton, Gossypium hirsutum, and lake trout, Salvelinus namaycush) and the industries they supported were negatively affected. Initial control efforts were unsuccessful until pesticides and application technologies were developed. For boll weevils, controls relying on pesticides evolved into an integrated program that included recommended farming practices and poisoned baits. However, the discovery of a boll weevil sex pheromone in 1964 allowed adoption of an ongoing program of eradication. Despite opposition over concept and cost, insecticides, pheromone traps, poisoned baits, and approved farming practices were used to eradicate boll weevils from Virginia, North Carolina, South Carolina, Georgia, Florida, and Alabama by 1999. Using the working back approach along the path of the original invasion, eradication was nearly completed by 2002 in Mississippi and eradication programs were underway in Arkansas, Tennessee, Oklahoma, Louisiana, and parts of Texas. Insecticide use for cotton production decreased 50 to 90%, and cotton yields and farm income increased an average of 78 kg/ha and $190 U.S./ha in areas where boll weevils were eradicated. For sea lampreys, integrated management uses lampricides, barriers to migration, trapping, and release of sterilized males. Although sea lamprey eradication is not currently feasible, recent research on larval and sex pheromones might provide the tools to make it possible. A successful eradication program for sea lampreys starting in Lake Superior and expanding to the lower Great Lakes would ultimately provide huge ecological and economic benefits by eliminating lampricide applications, removing barriers that block teleost fishes, and facilitating the recovery of lake trout. Should the opportunity arise, the concept of sea lamprey eradication should

  15. Endgame for polio eradication? Options for overcoming social and political factors in the progress to eradicating polio.

    PubMed

    Ganapathiraju, Pavan V; Morssink, Christiaan B; Plumb, James

    2015-01-01

    In 1988, the Global Polio Eradication Initiative (GPEI) was launched with the goal of eradicating polio by the year 2000. After 25 years, several dynamics still challenge this large public health campaign with new cases of polio being reported annually. We examine the roots of this initiative to eradicate polio, its scope, the successes and setbacks during the last 25 years and reflect on the current state of affairs. We examine the social and political factors that are barriers to polio eradication. Options are discussed for solving the current impasse of polio eradication: using force, respecting individual freedoms and gaining support from those vulnerable to fundamentalist 'propaganda'. The travails of the GPEI indicate the need for expanding the Convention on the Rights of the Child to address situations of war and civic strife. Such a cultural and structural reference will provide the basis for global stakeholders to engage belligerent local actors whose local political conflicts are barriers to the eradication of polio. Disregard for these actors will result in stagnation of polio eradication policy, delaying eradication beyond 2018.

  16. Eradication rate and histological changes after Helicobacter pylori eradication treatment in gastric cancer patients following subtotal gastrectomy

    PubMed Central

    Hwang, Jae Jin; Lee, Dong Ho; Kang, Kyu Keun; Lee, Ae-Ra; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung

    2015-01-01

    AIM: To investigate the eradication rate and histological changes after Helicobacter pylori (H. pylori) eradication treatment following subtotal gastrectomy for gastric cancer. METHODS: A total of 610 patients with H. pylori infection who had undergone surgery for either early or advanced gastric adenocarcinoma between May 2004 and December 2010 were retrospectively studied. A total of 584 patients with proven H. pylori infection after surgery for gastric cancer were enrolled in this study. Patients received a seven day standard triple regimen as first-line therapy and a 10 d bismuth-containing quadruple regimen as second-line therapy in cases of eradication failure. The patients underwent an esophagogastroduodenoscopy (EGD) between six and 12 mo after surgery, followed by annual EGDs. A further EGD was conducted 12 mo after confirming the result of the eradication and the histological changes. A gastric biopsy specimen for histological examination and Campylobacter-like organism testing was obtained from the lesser and greater curvature of the corpus of the remnant stomach. Histological changes in the gastric mucosa were assessed using the updated Sydney system before eradication therapy and at follow-up after 12 mo. RESULTS: Eradication rates with the first-line and second-line therapies were 78.4% (458/584) and 90% (36/40), respectively, by intention-to-treat analysis and 85.3% (458/530) and 92.3% (36/39), respectively, by per-protocol analysis. The univariate and multivariate analyses revealed that Billroth II surgery was an independent factor predictive of eradication success in the eradication success group (OR = 1.53, 95%CI: 1.41-1.65, P = 0.021). The atrophy and intestinal metaplasia (IM) scores 12 mo after eradication were significantly lower in the eradication success group than in the eradication failure group (0.25 ± 0.04 vs 0.47 ± 0.12, P = 0.023; 0.27 ± 0.04 vs 0.51 ± 0.12, P = 0.015, respectively). The atrophy and IM scores 12 mo after successful

  17. Managing breaches of containment and eradication of invasive plant populations

    PubMed Central

    Fletcher, Cameron S; Westcott, David A; Murphy, Helen T; Grice, Anthony C; Clarkson, John R

    2015-01-01

    Containment can be a viable strategy for managing invasive plants, but it is not always cheaper than eradication. In many cases, converting a failed eradication programme to a containment programme is not economically justified. Despite this, many contemporary invasive plant management strategies invoke containment as a fallback for failed eradication, often without detailing how containment would be implemented. We demonstrate a generalized analysis of the costs of eradication and containment, applicable to any plant invasion for which infestation size, dispersal distance, seed bank lifetime and the economic discount rate are specified. We estimate the costs of adapting eradication and containment in response to six types of breach and calculate under what conditions containment may provide a valid fallback to a breached eradication programme. We provide simple, general formulae and plots that can be applied to any invasion and show that containment will be cheaper than eradication only when the size of the occupied zone exceeds a multiple of the dispersal distance determined by seed bank longevity and the discount rate. Containment becomes proportionally cheaper than eradication for invaders with smaller dispersal distances, longer lived seed banks, or for larger discount rates. Both containment and eradication programmes are at risk of breach. Containment is less exposed to risk from reproduction in the ‘occupied zone’ and three types of breach that lead to a larger ‘occupied zone’, but more exposed to one type of breach that leads to a larger ‘buffer zone’. For a well-specified eradication programme, only the three types of breach leading to reproduction in or just outside the buffer zone can justify falling back to containment, and only if the expected costs of eradication and containment were comparable before the breach. Synthesis and applications. Weed management plans must apply a consistent definition of containment and provide sufficient

  18. Managing breaches of containment and eradication of invasive plant populations.

    PubMed

    Fletcher, Cameron S; Westcott, David A; Murphy, Helen T; Grice, Anthony C; Clarkson, John R

    2015-02-01

    Containment can be a viable strategy for managing invasive plants, but it is not always cheaper than eradication. In many cases, converting a failed eradication programme to a containment programme is not economically justified. Despite this, many contemporary invasive plant management strategies invoke containment as a fallback for failed eradication, often without detailing how containment would be implemented.We demonstrate a generalized analysis of the costs of eradication and containment, applicable to any plant invasion for which infestation size, dispersal distance, seed bank lifetime and the economic discount rate are specified. We estimate the costs of adapting eradication and containment in response to six types of breach and calculate under what conditions containment may provide a valid fallback to a breached eradication programme.We provide simple, general formulae and plots that can be applied to any invasion and show that containment will be cheaper than eradication only when the size of the occupied zone exceeds a multiple of the dispersal distance determined by seed bank longevity and the discount rate. Containment becomes proportionally cheaper than eradication for invaders with smaller dispersal distances, longer lived seed banks, or for larger discount rates.Both containment and eradication programmes are at risk of breach. Containment is less exposed to risk from reproduction in the 'occupied zone' and three types of breach that lead to a larger 'occupied zone', but more exposed to one type of breach that leads to a larger 'buffer zone'.For a well-specified eradication programme, only the three types of breach leading to reproduction in or just outside the buffer zone can justify falling back to containment, and only if the expected costs of eradication and containment were comparable before the breach.Synthesis and applications. Weed management plans must apply a consistent definition of containment and provide sufficient implementation detail

  19. Epidemiology of pancreatic cancer

    PubMed Central

    Ilic, Milena; Ilic, Irena

    2016-01-01

    Cancer of the pancreas remains one of the deadliest cancer types. Based on the GLOBOCAN 2012 estimates, pancreatic cancer causes more than 331000 deaths per year, ranking as the seventh leading cause of cancer death in both sexes together. Globally, about 338000 people had pancreatic cancer in 2012, making it the 11th most common cancer. The highest incidence and mortality rates of pancreatic cancer are found in developed countries. Trends for pancreatic cancer incidence and mortality varied considerably in the world. A known cause of pancreatic cancer is tobacco smoking. This risk factor is likely to explain some of the international variations and gender differences. The overall five-year survival rate is about 6% (ranges from 2% to 9%), but this vary very small between developed and developing countries. To date, the causes of pancreatic cancer are still insufficiently known, although certain risk factors have been identified, such as smoking, obesity, genetics, diabetes, diet, inactivity. There are no current screening recommendations for pancreatic cancer, so primary prevention is of utmost importance. A better understanding of the etiology and identifying the risk factors is essential for the primary prevention of this disease. PMID:27956793

  20. Pancreatic groove cancer

    PubMed Central

    Ku, Yuan-Hao; Chen, Shih-Chin; Shyr, Bor-Uei; Lee, Rheun-Chuan; Shyr, Yi-Ming; Wang, Shin-E.

    2017-01-01

    Abstract Pancreatic groove cancer is very rare and can be indistinguishable from groove pancreatitis. This study is to clarify the characteristics, clinical features, managements, and survival outcomes of this rare tumor. Brief descriptions were made for each case of pancreatic groove cancer encountered at our institute. Individualized data of pancreatic groove cancer cases described in the literature were extracted and added to our database to expand the study sample size for a more complete analysis. A total of 33 patients with pancreatic groove cancer were included for analysis, including 4 cases from our institute. The median tumor size was 2.7 cm. The most common symptom was nausea or vomiting (89%), followed by jaundice (67%). Duodenal stenosis was noted by endoscopy in 96% of patients. The histopathological examination revealed well differentiated tumor in 43%. Perineural invasion was noted in 90%, and lymphovascular invasion and lymph node involvement in 83%. Overall 1-year survival rate was 93.3%, and 3- or 5-year survival rate was 62.2%, with a median survival of 11.0 months. Survival outcome for the well-differentiated tumors was better than those of the moderate/poorly differentiated ones. Early involvement of duodenum causing vomiting is often the initial presentation, but obstructive jaundice does not always happen until the disease progresses. Tumor differentiation is a prognostic factor for survival outcome. The possibility of pancreatic groove cancer should be carefully excluded before making the diagnosis of groove pancreatitis for any questionable case. PMID:28079795

  1. Pathophysiology of acute pancreatitis.

    PubMed

    Bhatia, Madhav; Wong, Fei Ling; Cao, Yang; Lau, Hon Yen; Huang, Jiali; Puneet, Padmam; Chevali, Lakshmi

    2005-01-01

    Acute pancreatitis is a common clinical condition. It is a disease of variable severity in which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The exact mechanisms by which diverse etiological factors induce an attack are still unclear. It is generally believed that the earliest events in acute pancreatitis occur within acinar cells. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction. If this inflammatory reaction is marked, it leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. Recent studies have established the role played by inflammatory mediators in the pathogenesis of acute pancreatitis and the resultant MODS. At the same time, recent research has demonstrated the importance of acinar cell death in the form of apoptosis and necrosis as a determinant of pancreatitis severity. In this review, we will discuss about our current understanding of the pathophysiology of acute pancreatitis.

  2. Pancreatitis following liver transplantation.

    PubMed

    Alexander, J A; Demetrius, A J; Gavaler, J S; Makowka, L; Starzl, T E; Van Thiel, D H

    1988-06-01

    Since 1981, when the liver transplantation program was initiated at the University of Pittsburgh, we have been impressed with the prevalence of pancreatitis occurring following liver transplantation in patients transplanted for hepatitis B-related liver disease. To either confirm this clinical impression or refute it, the records of the 27 HbsAg+ patients and those of an additional 24 HbsAg- but HbcAb and/or HbsAb+ patients who underwent orthotopic liver transplantation were reviewed to determine the prevalence of clinical pancreatitis and hyperamylasemia (biochemical pancreatitis) following liver transplantation (OLTx). Post-OLTx hyperamylasemia occurred significantly more frequently in HbsAg+ patients (6/27) than it did in the HbsAg- patients (0/24) (P less than 0.05). More importantly, clinical pancreatitis occurred in 14% (4/27) of the HbsAg+ patients and 0% (0/24) of the HbsAg- patients. Interestingly, in each case, the pancreatitis was associated with the occurrence of acute hepatitis B infection of the allograft. Based upon these data, we conclude that pancreatitis occurring after liver transplantation is more common in patients transplanted for active viral liver disease caused by hepatitis B than in those with inactive viral liver disease. These observations suggest that pancreatitis occurring in, at least some cases following liver transplantation for viral liver disease, may result from hepatitis B virus infection of the pancreas.

  3. Diagnosis of autoimmune pancreatitis.

    PubMed

    Matsubayashi, Hiroyuki; Kakushima, Naomi; Takizawa, Kohei; Tanaka, Masaki; Imai, Kenichiro; Hotta, Kinichi; Ono, Hiroyuki

    2014-11-28

    Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis that is increasingly being reported. The presentation and clinical image findings of AIP sometimes resemble those of several pancreatic malignancies, but the therapeutic strategy differs appreciably. Therefore, accurate diagnosis is necessary for cases of AIP. To date, AIP is classified into two distinct subtypes from the viewpoints of etiology, serum markers, histology, other organ involvements, and frequency of relapse: type 1 is related to IgG4 (lymphoplasmacytic sclerosing pancreatitis) and type 2 is related to a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis). Both types of AIP are characterized by focal or diffuse pancreatic enlargement accompanied with a narrowing of the main pancreatic duct, and both show dramatic responses to corticosteroid. Unlike type 2, type 1 is characteristically associated with increasing levels of serum IgG4 and positive serum autoantibodies, abundant infiltration of IgG4-positive plasmacytes, frequent extrapancreatic lesions, and relapse. These findings have led several countries to propose diagnostic criteria for AIP, which consist of essentially similar diagnostic items; however, several differences exist for each country, mainly due to differences in the definition of AIP and the modalities used to diagnose this disease. An attempt to unite the diagnostic criteria worldwide was made with the publication in 2011 of the international consensus diagnostic criteria for AIP, established at the 2010 Congress of the International Association of Pancreatology (IAP).

  4. Pleuropulmonary complications of pancreatitis

    PubMed Central

    Kaye, Michael D.

    1968-01-01

    Pancreatitis, in common with many other upper abdominal diseases, often leads to pleuropulmonary complications. Radiological evidence of pleuropulmonary abnormality was found in 55% of 58 cases examined retrospectively. The majority of such abnormalities are not specific for pancreatitis; but a particular category of pleural effusions, rich in pancreatic enzymes, is a notable exception. A patient with this type of effusion, complicated by a spontaneous bronchopleural fistula and then by an empyema, is reported. The literature relating to pancreatic enzyme-rich pleural effusions (pathognomonic of pancreatitis) is reviewed. Of several possible mechanisms involved in pathogenesis, transdiaphragmatic lymphatic transfer of pancreatic enzymes, intrapleural rupture of mediastinal extensions of pseudocysts, and diaphragmatic perforation are the most important. The measurement of pleural fluid amylase, at present little employed in this country, has considerable diagnostic value. Enzyme-rich effusions are more commonly left-sided, are often blood-stained, are frequently associated with pancreatic pseudocysts, and—if long standing—may be complicated by a bronchopleural fistula. Images PMID:4872925

  5. shRNA-armed conditionally replicative adenoviruses: a promising approach for cancer therapy

    PubMed Central

    Zhang, Jie; Ding, Meng; Xu, Kai; Mao, Lijun; Zheng, Junian

    2016-01-01

    The small-interfering RNAs (siRNAs) have been employed to knockdown the expression of cancer-associated genes and shown some promise in cancer therapy. However, synthetic siRNA duplexes or plasmid mediated delivery of siRNAs have several problems, such as short half-life, low transfection efficiency and cytotoxicity associated with transfection. Conditionally replicating adenovirus (CRAds) as the delivery vector for short hairpin RNAs (shRNAs) could overcome these limitations and have shown augmented anti-tumor effects in experimental studies and preclinical trials. In this review, we summarize recent progress in the development of CRAds-shRNA for cancer treatment. Combination of CRAds-shRNA with chemotherapeutics, radiation, dendritic cells, monoclonal antibodies and small-molecule inhibitors will be necessary to eradicate cancer cells and cancer stem cells and achieve superior outcomes. The use of CRAd platform for efficient delivery of shRNAs and foreign genes will open a new avenue for cancer therapy. PMID:26980708

  6. PKD signaling and pancreatitis

    PubMed Central

    Yuan, Jingzhen; Pandol, Stephen J.

    2016-01-01

    Background Acute pancreatitis is a serious medical disorder with no current therapies directed to the molecular pathogenesis of the disorder. Inflammation, inappropriate intracellular activation of digestive enzymes, and parenchymal acinar cell death by necrosis are the critical pathophysiologic processes of acute pancreatitis. Thus, it is necessary to elucidate the key molecular signals that mediate these pathobiologic processes and develop new therapeutic strategies to attenuate the appropriate signaling pathways in order to improve outcomes for this disease. A novel serine/threonine protein kinase D (PKD) family has emerged as key participants in signal transduction, and this family is increasingly being implicated in the regulation of multiple cellular functions and diseases. Methods This review summarizes recent findings of our group and others regarding the signaling pathway and the biological roles of the PKD family in pancreatic acinar cells. In particular, we highlight our studies of the functions of PKD in several key pathobiologic processes associated with acute pancreatitis in experimental models. Results Our findings reveal that PKD signaling is required for NF-κB activation/inflammation, intracellular zymogen activation, and acinar cell necrosis in rodent experimental pancreatitis. Novel small-molecule PKD inhibitors attenuate the severity of pancreatitis in both in vitro and in vivo experimental models. Further, this review emphasizes our latest advances in the therapeutic application of PKD inhibitors to experimental pancreatitis after the initiation of pancreatitis. Conclusions These novel findings suggest that PKD signaling is a necessary modulator in key initiating pathobiologic processes of pancreatitis, and that it constitutes a novel therapeutic target for treatments of this disorder. PMID:26879861

  7. Can Pancreatic Cancer Be Found Early?

    MedlinePlus

    ... Team About Pancreatic Cancer? Pancreatic Cancer Early Detection, Diagnosis, and Staging Can Pancreatic Cancer Be Found Early? Pancreatic cancer is hard to find early. The pancreas is deep inside the body, so early tumors ...

  8. The Opportunity To Eradicate Peste des Petits Ruminants.

    PubMed

    Mariner, Jeffrey C; Jones, Bryony A; Rich, Karl M; Thevasagayam, Samuel; Anderson, John; Jeggo, Martyn; Cai, Yi; Peters, Andrew R; Roeder, Peter L

    2016-05-01

    Peste des petits ruminants (PPR) is a highly infectious disease of sheep and goats that is caused by PPR virus, a member of the genus Morbillivirus that includes the viruses that cause rinderpest (RP) in cattle. RP was the first animal disease to be globally eradicated in 2011 and is only the second disease, after smallpox, to have ever been eradicated. PPR is one of the principal constraints to small ruminant production in Africa, Asia, and the Middle East. The epidemiology of PPR and RP as well as the technologies available for their diagnosis and control are similar. The conditions that favored the eradication of RP are also largely present for PPR. In this work, we outline the evolving strategy for eradication in light of current opportunities and challenges, as well as the lessons from other eradication programs in animal and human health. The global PPR situation and technology for its control are summarized. A strategy based on the lessons from previous eradication efforts that integrate epidemiology, social science, and economics as tools to target and motivate vaccination is summarized. Major aspects of the cost and benefit-cost analysis of the indicated program are presented. The overall undiscounted cost of eradication was estimated as $3.1 billion, and the benefit-cost ratio for the most likely scenario was estimated at 33.8. We close with a discussion of the possible next steps.

  9. Quinolone-containing therapies in the eradication of Helicobacter pylori.

    PubMed

    Chuah, Seng-Kee; Tai, Wei-Chen; Lee, Chen-Hsiang; Liang, Chih-Ming; Hu, Tsung-Hui

    2014-01-01

    Fluoroquinolones, especially levofloxacin, are used in the eradication of Helicobacter pylori worldwide. Many consensus guidelines recommend that the second-line rescue therapy for H. pylori eradication consists of a proton pump inhibitor, a quinolone, and amoxicillin as an option. Unfortunately, quinolone is well associated with a risk of developing bacterial resistance. In this paper, we review quinolone-containing H. pylori eradication regimens and the challenges that influence the efficacy of eradication. It is generally suggested that the use of levofloxacin should be confined to "rescue" therapy only, in order to avoid a further rapid increase in the resistance of H. pylori to quinolone. The impact of quinolone-containing H. pylori eradication regimens on public health issues such as tuberculosis treatment must always be taken into account. Exposure to quinolone is relevant to delays in diagnosing tuberculosis and the development of drug resistance. Extending the duration of treatment to 14 days improves eradication rates by >90%. Tailored therapy to detect fluoroquinolone-resistant strains can be done by culture-based and molecular methods to provide better eradication rates. Molecular methods are achieved by using a real-time polymerase chain reaction to detect the presence of a gyrA mutation, which is predictive of treatment failure with quinolones-containing triple therapy.

  10. Non-technical constraints to eradication: the Italian experience.

    PubMed

    Moda, Giuliana

    2006-02-25

    Although technical constraints to eradication of bovine tuberculosis are well-recognised, non-technical constraints can also delay progress towards eradication, leading to inefficiency and increased programme costs. This paper seeks to analyse the main non-technical constraints that can interfere with the successful implementation of tuberculosis eradication plans, based on experiences from an area of high tuberculosis prevalence in Regione Piemonte, Italy. The main social and economic constraints faced in the past 20 years are reviewed, including a social reluctance to recognise the importance of seeking eradication as the goal of disease control, effective communication of technical issues, the training and the organization of veterinary services, the relationship between the regional authority and farmers and their representatives, and data management and epidemiological reporting. The paper analyses and discusses the solutions that were applied in Regione Piemonte and the benefits that were obtained. Tuberculosis eradication plans are one of the most difficult tasks of the Veterinary Animal Health Services, and non-technical constraints must be considered when progress towards eradication is less than expected. Organizational and managerial resources can help to overcome social or economic obstacles, provided the veterinary profession is willing to address technical, but also non-technical, constraints to eradication.

  11. Recurrent acute pancreatitis.

    PubMed

    Khurana, Vishal; Ganguly, Ishita

    2014-09-28

    Recurrent acute pancreatitis (RAP) is commonly encountered, but less commonly understood clinical entity, especially idiopathic RAP, with propensity to lead to repeated attacks and may be chronic pancreatitis if attacks continue to recur. A great number of studies have been published on acute pancreatitis, but few have focused on RAP. Analysing the results of clinical studies focusing specifically on RAP is problematic in view due to lack of standard definitions, randomised clinical trials, standard evaluation protocol used and less post intervention follow-up duration. With the availability of newer investigation modalities less number of etiologies will remains undiagnosed. This review particularly is focused on the present knowledge in understanding of RAP.

  12. [Primary pancreatic plasmacytoma].

    PubMed

    Sánchez Acevedo, Z; Pomares Rey, B; Alpera Tenza, M R; Andrada Becerra, E

    2014-01-01

    Extramedullary plasmacytomas are uncommon malignant plasma cell tumors that present outside the bone marrow; 80% of extramedullary plasmacytomas are located in the upper respiratory tract, and gastrointestinal plasmacytomas are rare. We present the case of an asymptomatic 65-year-old man in whom a pancreatic mass was found incidentally. The lesion was determined to be a pancreatic plasmacytoma after fine-needle aspiration cytology and surgical resection. No clinical, laboratory, or imaging findings indicative of multiple myeloma or association with other plasmacytomas were found, so the tumor was considered to be a primary pancreatic plasmacytoma.

  13. Coxsackie–adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes

    PubMed Central

    Hodik, M; Anagandula, M; Fuxe, J; Krogvold, L; Dahl-Jørgensen, K; Hyöty, H; Sarmiento, L; Frisk, G

    2016-01-01

    Objectives One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie–adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. Design Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells. Results An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p<0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p<0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p<0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR. Conclusions CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory

  14. Tumor Associated Stromal Cells Play a Critical Role on the Outcome of the Oncolytic Efficacy of Conditionally Replicative Adenoviruses

    PubMed Central

    Lopez, M. Verónica; Viale, Diego L.; Cafferata, Eduardo G. A.; Bravo, Alicia I.; Carbone, Cecilia; Gould, David; Chernajovsky, Yuti; Podhajcer, Osvaldo L.

    2009-01-01

    The clinical efficacy of conditionally replicative oncolytic adenoviruses (CRAd) is still limited by the inefficient infection of the tumor mass. Since tumor growth is essentially the result of a continuous cross-talk between malignant and tumor-associated stromal cells, targeting both cell compartments may profoundly influence viral efficacy. Therefore, we developed SPARC promoter-based CRAds since the SPARC gene is expressed both in malignant cells and in tumor-associated stromal cells. These CRAds, expressing or not the Herpes Simplex thymidine kinase gene (Ad-F512 and Ad(I)-F512-TK, respectively) exerted a lytic effect on a panel of human melanoma cells expressing SPARC; but they were completely attenuated in normal cells of different origins, including fresh melanocytes, regardless of whether cells expressed or not SPARC. Interestingly, both CRAds displayed cytotoxic activity on SPARC positive-transformed human microendothelial HMEC-1 cells and WI-38 fetal fibroblasts. Both CRAds were therapeutically effective on SPARC positive-human melanoma tumors growing in nude mice but exhibited restricted efficacy in the presence of co-administered HMEC-1 or WI-38 cells. Conversely, co-administration of HMEC-1 cells enhanced the oncolytic efficacy of Ad(I)-F512-TK on SPARC-negative MIA PaCa-2 pancreatic cancer cells in vivo. Moreover, conditioned media produced by stromal cells pre-infected with the CRAds enhanced the in vitro viral oncolytic activity on pancreatic cancer cells, but not on melanoma cells. The whole data indicate that stromal cells might play an important role on the outcome of the oncolytic efficacy of conditionally replicative adenoviruses. PMID:19337591

  15. Loose ends in the eradication of Helicobacter pylori infection

    PubMed Central

    Silva, Marco; Gaspar, Rui; Morais, Rui; Ramalho, Rosa; Macedo, Guilherme; Santos-Antunes, João

    2016-01-01

    Abstract The eradication of Helicobacter pylori is essential for prevention and treatment of various conditions associated with this infection. However, its effectiveness is limited and influenced by factors linked to the bacteria and the host. In particular, influence of the biotype, smoking, diabetes mellitus, and previous treatment failure in eradication is understudied. Our center proposed to evaluate these aspects in a real life cohort by applying a questionnaire with demographic and lifestyle variables in patients who consecutively underwent urease breath test after the eradication therapy. PMID:28191542

  16. The polio eradication campaign: time to shift the goal.

    PubMed

    Baron, Emmanuel; Magone, Claire

    2014-03-01

    The social rejection of the polio eradication campaign in endemic countries challenges an assumption underlying the goal itself: the full compliance of an entire population to a public health programme. The polio campaign, which has been an extraordinary public health enterprise, is at risk of becoming irremediably unpopular if the eradication goal is pursued at all costs. The Global Polio Eradication Initiative (GPEI) should not be driven by the fear of failure, because the greatest benefit of the polio campaign is that it has demonstrated how simple, community-wide actions can contribute to a dramatic decrease in the incidence of a disease.

  17. [Experimental models of acute pancreatitis].

    PubMed

    Ceranowicz, Piotr; Cieszkowski, Jakub; Warzecha, Zygmunt; Dembiński, Artur

    2015-02-21

    Acute pancreatitis is a severe disease with high mortality. Clinical studies can bring some data about etiology, pathogenesis and the course of acute pancreatitis. However, studies concerning early events of this disease and the new concepts of treatment cannot be performed on humans, due to ethical reasons. Animal models of acute pancreatitis have been developed to solve this problem. This review presents currently used experimental models of acute pancreatitis, their properties and clinical relevance. Experimental models of acute pancreatitis can be divided into in vivo (non-invasive and invasive) and ex vivo models. The onset, development, severity and extent of acute pancreatitis, as well as the mortality, vary considerably between these different models. Animal models reproducibly produce mild, moderate or severe acute pancreatitis. One of the most commonly used models of acute pancreatitis is created by administration of supramaximal doses of cerulein, an analog of cholecystokinin. This model produces acute mild edematous pancreatitis in rats, whereas administration of cerulein in mice leads to the development of acute necrotizing pancreatitis. Acute pancreatitis evoked by retrograde administration of sodium taurocholate into the pancreatic duct is the most often used model of acute severe necrotizing pancreatitis in rats. Ex vivo models allow to eliminate the influence of hormonal and nervous factors on the development of acute pancreatitis.

  18. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez Muñoz, J Enrique

    2015-09-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the treatment of symptoms and complications, mainly pain and pancreatic exocrine insufficiency, and the diagnosis and therapy of autoimmune pancreatitis. The multimodal dynamic endoscopic ultrasound-guided secretin-stimulated evaluation of the pancreas provides relevant morphological and functional information for the diagnosis of chronic pancreatitis at early stages. Extracorporeal shock wave lithotripsy in patients with calcifying pancreatitis and endoscopic pancreatic stent placement are effective alternatives for pain therapy in patients with chronic pancreatitis. Presence of pancreatic exocrine insufficiency in patients with chronic pancreatitis is associated with a significantly increase of mortality rate. Despite that, pancreatic enzyme replacement therapy is not prescribed in the majority of patients with pancreatic exocrine insufficiency, or it is prescribed at a low dose. The newly developed and commercialized needles for endoscopic ultrasound-guided pancreatic biopsy are effective in retrieving appropriate tissue samples for the histological diagnosis of autoimmune pancreatitis. Maintenance therapy with azathioprine is effective and safe to prevent relapses in patients with autoimmune pancreatitis.

  19. Support growing for eradicating female genital cutting.

    PubMed

    1999-12-01

    Female genital cutting (FGC), a prevalent practice in most African countries not just seriously endangers a girl's lifetime health, but it is also considered a human rights violation. In June 1999, the Intra-Agency Working Group on FGC held a symposium with US Agency for International Development (USAID) staff to explore ways of incorporating into USAID program activities to eradicate the practice of FGC. One of the presentations at the symposium concerned "circumcision with words". This ceremony is an alternative rite of passage; it is conducted through a 5-day seclusion, culminating in a 1-day celebration including feasting and gift giving. The alternative rites include 1) self-esteem and coping with criticism; 2) responsibility for one¿s own decision; 3) dating and courtship; 4) coping with peer pressure; 5) personal hygiene; 6) marriage; 7) pregnancy and sexually transmitted disease and AIDS prevention; 8) contraception; 9) FGC, early marriage, and gender empowerment, including the rights of the girl child; 10) respect for community; and 11) respect for elders. Alternative rites of passage are gaining community acceptance and by Kenya Medical Association. None of the girls who participated in the ceremony were circumcised later.

  20. Eradicating blinding trachoma: What is working?

    PubMed

    Chaudhry, Imtiaz A

    2010-01-01

    Trachoma remains the leading cause of preventable corneal blindness in developing countries. The disease is contracted in early childhood by repeated infection of the ocular surface by C. trachomatis. Initial clinical manifestation is a follicular conjunctivitis which if not treated on timely basis, may lead to conjunctival and eyelid scarring that may eventually result in corneal scarring and loss of vision. Over the past two decades, a remarkable reduction in the prevalence of active trachoma has occurred due to the World Health Organization's (WHOs) program GET 2020 for the elimination of trachoma with adoption of the SAFE strategy incorporating Surgery, Antibiotic treatment, Facial cleanliness and Environmental hygiene. However, patients who already had infection at young age may present with adnexal-related complications of trachomatous scarring that may cause corneal scarring and visual loss. These patients may present with evidence of trichiasis/entropion as well as eyelid retraction. Lacrimal complications may include nasolacrimal-duct obstruction, dacryocystitis and canaliculitis requiring intervention. In addition to the increased risk for corneal scarring, trichiasis/entropion may further increase the risks for microbial keratitis in patients who may have unrecognized dacryocystitis and canaliculitis. Female patients may have more trachomtous-related complications and may present at an early age. Available evidence indicates that SAFE strategy may be effective and on the right track towards achieving GET 2020 goal for the eradication of trachoma.

  1. Pancreatic Islet Transplantation

    MedlinePlus

    ... allo-transplantation?" For each pancreatic islet allo-transplant infusion, researchers use specialized enzymes to remove islets from ... in a lab. Transplant patients typically receive two infusions with an average of 400,000 to 500, ...

  2. Surgery for Pancreatic Cancer

    MedlinePlus

    ... the abdomen. The surgeon can look at the pancreas and other organs for tumors and take biopsy ... pancreatic cancers appear to be confined to the pancreas at the time they are found. Even then, ...

  3. Chronic Pancreatitis in Children

    MedlinePlus

    ... years to appear, but this, too, is highly variable; some patients with chronic pancreatitis will develop diabetes ... of modifying factors include other genes or environmental variables, which is a term that scientists use to ...

  4. Pancreatic exocrine function testing

    SciTech Connect

    Goff, J.S.

    1981-11-01

    It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of all these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weaknesses of each.

  5. Pancreatic Cancer Risk Factors

    MedlinePlus

    ... age at the time of diagnosis is 71. Gender Men are slightly more likely to develop pancreatic ... would like to unsubscribe/opt out from our communications, please follow this link: http://www.cancer.org/ ...

  6. [Management of postoperative pancreatic fistula].

    PubMed

    Hackert, T; Büchler, M W

    2015-06-01

    The occurrence of a postoperative pancreatic fistula is one of the most important complications following pancreatic resections. The frequency of this complication varies between 3 % after pancreatic head resection and up to 35 % following distal pancreatectomy. In 2005, the international definition of postoperative pancreatic fistula was standardized according to the approach of the International Study Group of Pancreatic Surgery (ISGPS) including an A-C grading system of the severity. Consequently, results from different studies have become comparable and the historically reported fistula rates can be evaluated more critically. The present review summarises the currently available data on incidence, risk factors, fistula-associated complications and management of postoperative pancreatic fistula.

  7. Arsenic-Induced Pancreatitis

    PubMed Central

    Connelly, Sean; Zancosky, Krysia; Farah, Katie

    2011-01-01

    The introduction of all-trans retinoic acid (ATRA) and arsenic trioxide has brought about tremendous advancement in the treatment of acute promyelocytic myelogenous leukemia (APML). In most instances, the benefits of these treatments outweigh the risks associated with their respective safety profiles. Although acute pancreatitis is not commonly associated with arsenic toxicity, it should be considered as a possible side effect. We report a case of arsenic-induced pancreatitis in a patient with APML. PMID:22606427

  8. Isolation and Characterization of Adenoviruses Persistently Shed from the Gastrointestinal Tract of Non-Human Primates

    PubMed Central

    Kryazhimskiy, Sergey; Grant, Rebecca; Calcedo, Roberto; Yuan, Xin; Keough, Martin; Sandhu, Arbans; Wang, Qiang; Medina-Jaszek, C. Angelica; Plotkin, Joshua B.; Wilson, James M.

    2009-01-01

    Adenoviruses are important human pathogens that have been developed as vectors for gene therapies and genetic vaccines. Previous studies indicated that human infections with adenoviruses are self-limiting in immunocompetent hosts with evidence of some persistence in adenoid tissue. We sought to better understand the natural history of adenovirus infections in various non-human primates and discovered that healthy populations of great apes (chimpanzees, bonobos, gorillas, and orangutans) and macaques shed substantial quantities of infectious adenoviruses in stool. Shedding in stools from asymptomatic humans was found to be much less frequent, comparable to frequencies reported before. We purified and fully sequenced 30 novel adenoviruses from apes and 3 novel adenoviruses from macaques. Analyses of the new ape adenovirus sequences (as well as the 4 chimpanzee adenovirus sequences we have previously reported) together with 22 complete adenovirus genomes available from GenBank revealed that (a) the ape adenoviruses could clearly be classified into species corresponding to human adenovirus species B, C, and E, (b) there was evidence for intraspecies recombination between adenoviruses, and (c) the high degree of phylogenetic relatedness of adenoviruses across their various primate hosts provided evidence for cross species transmission events to have occurred in the natural history of B and E viruses. The high degree of asymptomatic shedding of live adenovirus in non-human primates and evidence for zoonotic transmissions warrants caution for primate handling and housing. Furthermore, the presence of persistent and/or latent adenovirus infections in the gut should be considered in the design and interpretation of human and non-human primate studies with adenovirus vectors. PMID:19578438

  9. Insights into Adenovirus Uncoating from Interactions with Integrins and Mediators of Host Immunity

    PubMed Central

    Nemerow, Glen R.; Stewart, Phoebe L.

    2016-01-01

    Human adenoviruses are large (150 MDa) nonenveloped double-stranded DNA (dsDNA) viruses that cause acute respiratory, gastrointestinal and ocular infections. Despite these disease associations, adenovirus has aided basic and clinical research efforts through studies of its association with cells and as a target of host antiviral responses. This review highlights the knowledge of adenovirus disassembly and nuclear transport gleaned from structural, biophysical and functional analyses of adenovirus interactions with soluble and membrane-associated host molecules. PMID:28009821

  10. Hereditary pancreatitis: current perspectives.

    PubMed

    Raphael, Kara L; Willingham, Field F

    2016-01-01

    Hereditary pancreatitis (HP) is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life) and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy.

  11. Silencing E1A mRNA by RNA interference inhibits adenovirus replication.

    PubMed

    Chung, Y-S; Kim, M-K; Lee, W-J; Kang, C

    2007-01-01

    The adenovirus family contains 51 human serotypes, and most human adenoviruses cause widespread respiratory tract infections. Adenovirus infections can result in severe complications in some cases, such as in adenovirus type 11 infection in immunocompromised patients. However, effective treatment methods for adenovirus infections are currently unavailable. This prompted the search for antiviral agents effective against adenovirus infections. In the present study, adenovirus E1A was targeted by RNA interference (RNAi) using synthetic small interfering RNAs (siRNAs) in an attempt to inhibit viral replication, since adenovirus E1A proteins are known to be involved in the transcriptional activation of the viral and cellular genes necessary for controlling the cell cycle and viral replication. The results indicated that the siRNAs effectively reduced the amount of adenovirus E1A mRNA and the levels of replicative intermediates. Additionally, siRNA-mediated gene silencing inhibited adenovirus replication by suppressing the E1A mRNA. These results suggest that the RNAi-mediated targeting of adenovirus E1A may have a potentially therapeutic effect in controlling adenovirus infections.

  12. Exploiting features of adenovirus replication to support mammalian kinase production

    PubMed Central

    Cotten, Matt; Stegmueller, Kerstin; Eickhoff, Jan; Hanke, Miriam; Herzberger, Katrin; Herget, Thomas; Choidas, Axel; Daub, Henrik; Godl, Klaus

    2003-01-01

    Faced with the current wealth of genomic data, it is essential to have robust and reliable methods of converting DNA sequences into their functional gene products. We demonstrate here that when conditions are established that take advantage of the replication-associated virus amplification, the virus-induced shutdown of host protein synthesis as well as the activation of signalling pathways that normally occur during virus replication, adenovirus biology can be exploited to generate a potent kinase expression system. Residual virus in the protein production has always been a limitation for adenovirus systems and we describe a DNA intercalator/ultraviolet light treatment that eliminates residual adenovirus in protein preparations that has no deleterious effect on enzyme activity. The use of mammalian cells in combination with adenovirus generated a variety of active enzymes which could not be produced in Escherichia coli or baculovirus-infected insect cells. Thus, the utility of adenovirus-mediated enzyme expression as a versatile alternative to established protein production technologies is demonstrated. PMID:14576328

  13. Exploiting features of adenovirus replication to support mammalian kinase production.

    PubMed

    Cotten, Matt; Stegmueller, Kerstin; Eickhoff, Jan; Hanke, Miriam; Herzberger, Katrin; Herget, Thomas; Choidas, Axel; Daub, Henrik; Godl, Klaus

    2003-11-01

    Faced with the current wealth of genomic data, it is essential to have robust and reliable methods of converting DNA sequences into their functional gene products. We demonstrate here that when conditions are established that take advantage of the replication-associated virus amplification, the virus-induced shutdown of host protein synthesis as well as the activation of signalling pathways that normally occur during virus replication, adenovirus biology can be exploited to generate a potent kinase expression system. Residual virus in the protein production has always been a limitation for adenovirus systems and we describe a DNA intercalator/ultraviolet light treatment that eliminates residual adenovirus in protein preparations that has no deleterious effect on enzyme activity. The use of mammalian cells in combination with adenovirus generated a variety of active enzymes which could not be produced in Escherichia coli or baculovirus-infected insect cells. Thus, the utility of adenovirus-mediated enzyme expression as a versatile alternative to established protein production technologies is demonstrated.

  14. Oncolytic virotherapy for osteosarcoma using midkine promoter-regulated adenoviruses.

    PubMed

    Takagi-Kimura, M; Yamano, T; Tagawa, M; Kubo, S

    2014-03-01

    Oncolytic virotherapy using adenoviruses has potential therapeutic benefits for a variety of cancers. We recently developed MOA5, a tumor-specific midkine promoter-regulated oncolytic vector based on human adenovirus serotype 5 (Ad5). We modified the binding tropism of MOA5 by replacing the cell-binding domain of the Ad5 fiber knob with that from another adenovirus serotype 35 (Ad35); the resulting vector was designated MOA35. Here we evaluated the therapeutic efficacies of MOA5 and MOA35 for human osteosarcoma. Midkine mRNA expression and its promoter activity was significantly high in five human osteosarcoma cell lines, but was restricted in normal cells. Very low levels of adenovirus cellular receptor coxsackievirus/adenovirus receptor (CAR) (Ad5 receptor) expression were observed in MNNG-HOS and MG-63 cells, whereas high levels of CAR expression were seen in the other osteosarcoma cell lines. By contrast, CD46 (Ad35 receptor) was highly expressed in all osteosarcoma cell lines. Infectivity and in vitro cytocidal effect of MOA35 was significantly enhanced in MNNG-HOS and MG-63 cells compared with MOA5, although the cytocidal effects of MOA5 were sometimes higher in high CAR-expressing cell lines. In MG-63 xenograft models, MOA35 significantly enhanced antitumor effects compared with MOA5. Our findings indicate that MOA5 and MOA35 allow tailored virotherapy and facilitate more effective treatments for osteosarcoma.

  15. Retargeted adenoviruses for radiation-guided gene delivery

    PubMed Central

    Kaliberov, S A; Kaliberova, L N; Yan, H; Kapoor, V; Hallahan, D E

    2016-01-01

    The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment. PMID:27492853

  16. Bovine adenovirus-3 as a vaccine delivery vehicle.

    PubMed

    Ayalew, Lisanework E; Kumar, Pankaj; Gaba, Amit; Makadiya, Niraj; Tikoo, Suresh K

    2015-01-15

    The use of vaccines is an effective and relatively inexpensive means of controlling infectious diseases, which cause heavy economic losses to the livestock industry through animal loss, decreased productivity, treatment expenses and decreased carcass quality. However, some vaccines produced by conventional means are imperfect in many respects including virulence, safety and efficacy. Moreover, there are no vaccines for some animal diseases. Although genetic engineering has provided new ways of producing effective vaccines, the cost of production for veterinary use is a critical criterion for selecting the method of production and delivery of vaccines. The cost effective production and intrinsic ability to enter cells has made adenovirus vectors a highly efficient tool for delivery of vaccine antigens. Moreover, adenoviruses induce both humoral and cellular immune responses to expressed vaccine antigens. Since nonhuman adenoviruses are species specific, the development of animal specific adenoviruses as vaccine delivery vectors is being evaluated. This review summarizes the work related to the development of bovine adenovirus-3 as a vaccine delivery vehicle in animals, particularly cattle.

  17. Gene targeting with a replication-defective adenovirus vector.

    PubMed Central

    Fujita, A; Sakagami, K; Kanegae, Y; Saito, I; Kobayashi, I

    1995-01-01

    Wide application of the gene-targeting technique has been hampered by its low level of efficiency. A replication-defective adenovirus vector was used for efficient delivery of donor DNA in order to bypass this problem. Homologous recombination was selected between a donor neo gene inserted in the adenovirus vector and a target mutant neo gene on a nuclear papillomavirus plasmid. These recombinant adenoviruses allowed gene transfer to 100% of the treated cells without impairing their viability. Homologous recombinants were obtained at a level of frequency much higher than that obtained by electroporation or a calcium phosphate procedure. The structure of the recombinants was analyzed in detail after recovery in an Escherichia coli strain. All of the recombinants examined had experienced a precise correction of the mutant neo gene. Some of them had a nonhomologous rearrangement of their sequences as well. One type of nonhomologous recombination took place at the end of the donor-target homology. The vector adenovirus DNA was inserted into some of the products obtained at a high multiplicity of infection. The insertion was at the end of the donor-target homology with a concomitant insertion of a 10-bp-long filler sequence in one of the recombinants. The possible relationship between these rearrangements and the homologous recombination is discussed. These results demonstrate the applicability of adenovirus-mediated gene delivery in gene targeting and gene therapy. PMID:7666520

  18. New Diagnostic and Therapeutic Approaches to Eradicating Recurrent Breast Cancer

    DTIC Science & Technology

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0191 TITLE: New Diagnostic and Therapeutic Approaches to Eradicating Recurrent Breast Cancer PRINCIPAL...31Aug2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-14-1-0191 New Diagnostic and Therapeutic Approaches to Eradicating Recurrent Breast Cancer 5...AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Some breast cancer patients have no evidence

  19. Latest insights on adenovirus structure and assembly.

    PubMed

    San Martín, Carmen

    2012-05-01

    Adenovirus (AdV) capsid organization is considerably complex, not only because of its large size (~950 Å) and triangulation number (pseudo T = 25), but also because it contains four types of minor proteins in specialized locations modulating the quasi-equivalent icosahedral interactions. Up until 2009, only its major components (hexon, penton, and fiber) had separately been described in atomic detail. Their relationships within the virion, and the location of minor coat proteins, were inferred from combining the known crystal structures with increasingly more detailed cryo-electron microscopy (cryoEM) maps. There was no structural information on assembly intermediates. Later on that year, two reports described the structural differences between the mature and immature adenoviral particle, starting to shed light on the different stages of viral assembly, and giving further insights into the roles of core and minor coat proteins during morphogenesis [1,2]. Finally, in 2010, two papers describing the atomic resolution structure of the complete virion appeared [3,4]. These reports represent a veritable tour de force for two structural biology techniques: X-ray crystallography and cryoEM, as this is the largest macromolecular complex solved at high resolution by either of them. In particular, the cryoEM analysis provided an unprecedented clear picture of the complex protein networks shaping the icosahedral shell. Here I review these latest developments in the field of AdV structural studies.

  20. Latest Insights on Adenovirus Structure and Assembly

    PubMed Central

    San Martín, Carmen

    2012-01-01

    Adenovirus (AdV) capsid organization is considerably complex, not only because of its large size (~950 Å) and triangulation number (pseudo T = 25), but also because it contains four types of minor proteins in specialized locations modulating the quasi-equivalent icosahedral interactions. Up until 2009, only its major components (hexon, penton, and fiber) had separately been described in atomic detail. Their relationships within the virion, and the location of minor coat proteins, were inferred from combining the known crystal structures with increasingly more detailed cryo-electron microscopy (cryoEM) maps. There was no structural information on assembly intermediates. Later on that year, two reports described the structural differences between the mature and immature adenoviral particle, starting to shed light on the different stages of viral assembly, and giving further insights into the roles of core and minor coat proteins during morphogenesis [1,2]. Finally, in 2010, two papers describing the atomic resolution structure of the complete virion appeared [3,4]. These reports represent a veritable tour de force for two structural biology techniques: X-ray crystallography and cryoEM, as this is the largest macromolecular complex solved at high resolution by either of them. In particular, the cryoEM analysis provided an unprecedented clear picture of the complex protein networks shaping the icosahedral shell. Here I review these latest developments in the field of AdV structural studies. PMID:22754652

  1. Adenovirus 36 and Obesity: An Overview

    PubMed Central

    Ponterio, Eleonora; Gnessi, Lucio

    2015-01-01

    There is an epidemic of obesity starting about 1980 in both developed and undeveloped countries definitely associated with multiple etiologies. About 670 million people worldwide are obese. The incidence of obesity has increased in all age groups, including children. Obesity causes numerous diseases and the interaction between genetic, metabolic, social, cultural and environmental factors are possible cofactors for the development of obesity. Evidence emerging over the last 20 years supports the hypothesis that viral infections may be associated with obesity in animals and humans. The most widely studied infectious agent possibly linked to obesity is adenovirus 36 (Adv36). Adv36 causes obesity in animals. In humans, Adv36 associates with obesity both in adults and children and the prevalence of Adv36 increases in relation to the body mass index. In vivo and in vitro studies have shown that the viral E4orf1 protein (early region 4 open reading frame 1, Adv) mediates the Adv36 effect including its adipogenic potential. The Adv36 infection should therefore be considered as a possible risk factor for obesity and could be a potential new therapeutic target in addition to an original way to understand the worldwide rise of the epidemic of obesity. Here, the data indicating a possible link between viral infection and obesity with a particular emphasis to the Adv36 will be reviewed. PMID:26184280

  2. After Beijing: emphasis on poverty eradication.

    PubMed

    1996-01-01

    In March 1996, during its first meeting since the Fourth World Conference on Women, the UN Commission on the Status of Women (CSW), called for a gender perspective to be integrated into policies and programs dealing with poverty, child and dependent care, and the media. Three expert panels examined each of these areas through a format which encouraged dialogue and led to the adoption of 17 resolutions, decisions, and agreed conclusions as well as a recommendation that the UN adopt a multi-year work program for the CSW to allow it to review progress in elimination of the 12 main obstacles to women's advancement identified at Beijing. Among the resolutions adopted by the CSW were calls to 1) take a broad and integrated approach to poverty eradication, 2) enhance women's empowerment and autonomy, 3) promote equity and equality in the public domain, 4) promote women's employment, 5) give women social and economic protection when they are unable to work, 6) counteract negative images of women and sex-stereotyping in the media, 7) reduce the representation of violence against women in the media, 8) strengthen the role of women in global communications, 9) encourage the participation of men in child and dependent care, and 10) recognize women's double burden of work. The CSW also agreed to pursue further discussions about drafting an optional protocol to the 1979 Convention on the Elimination of All Forms of Discrimination Against Women. Among its other actions, the CSW called for mechanisms to protect the rights of women migrant workers, to protect women and children during armed conflicts, to include gender-based human rights violations in UN activities, and to address the root factors which lead to social ills such as trafficking in women and girls. In addition, the CSW submitted a draft resolution demanding that Israel protect the rights of Palestinian women and their families.

  3. Leprosy - evolution of the path to eradication

    PubMed Central

    Dogra, Sunil; Narang, Tarun; Kumar, Bhushan

    2013-01-01

    Leprosy is among the world's oldest and most dreaded diseases and it has been synonymous with stigma and discrimination due to the hideous deformities it produced, mystery around its aetiology and transmission and lack of any effective remedy till recently. Leprosy control started with the use of chaulmoogra oil and for the last three decades, multi drug therapy (MDT) has been our main tool against leprosy. In the last two decades, the reported global prevalence of active leprosy infection has dropped by almost 90 per cent by the combined efforts of the World Health Organization (WHO), local governments, health professionals, and non-governmental organizations (NGOs), however, a parallel drop in the incidence or new case detection rate (NCDR) has not occurred. From 1994 through 2011, more than 100,000 new cases are being detected annually, of whom maximum case load is from India. There is need for research on tools for early diagnosis, short and effective treatment, and prevention of deformities and disabilities. Evaluating the role of immunotherapy and immunoprophylaxis will also lead us to better understanding of their mode of action. Further molecular analysis of Mycobacterium leprae genome may provide the requisite basis for all this. The current reality is that there is a need to sustain and provide quality leprosy services to all persons through general health services, including good referral system. All these provisions in the integrated health care approach will go a long way in further reducing the stigma. Efforts need to be made to reduce deformity through early detection, self care, physiotherapy and reconstructive surgery and developing sound surveillance systems. With all the remarkable achievements in the fight against leprosy, the stage is now set for the final assault. It is hoped that with the efforts of all the stake holders and strong political will, the disease will be eradicated in the near future. PMID:23481049

  4. Successes and shortcomings of polio eradication: a transmission modeling analysis.

    PubMed

    Mayer, Bryan T; Eisenberg, Joseph N S; Henry, Christopher J; Gomes, M Gabriela M; Ionides, Edward L; Koopman, James S

    2013-06-01

    Polio eradication is on the cusp of success, with only a few regions still maintaining transmission. Improving our understanding of why some regions have been successful and others have not will help with both global eradication of polio and development of more effective vaccination strategies for other pathogens. To examine the past 25 years of eradication efforts, we constructed a transmission model for wild poliovirus that incorporates waning immunity (which affects both infection risk and transmissibility of any resulting infection), age-mediated vaccination rates, and transmission of oral polio vaccine. The model produces results consistent with the 4 country categories defined by the Global Polio Eradication Program: elimination with no subsequent outbreaks; elimination with subsequent transient outbreaks; elimination with subsequent outbreaks and transmission detected for more than 12 months; and endemic polio transmission. Analysis of waning immunity rates and oral polio vaccine transmissibility reveals that higher waning immunity rates make eradication more difficult because of increasing numbers of infectious adults, and that higher oral polio vaccine transmission rates make eradication easier as adults become reimmunized. Given these dynamic properties, attention should be given to intervention strategies that complement childhood vaccination. For example, improvement in sanitation can reduce the reproduction number in problematic regions, and adult vaccination can lower adult transmission.

  5. Mathematical Modeling of Programmatic Requirements for Yaws Eradication

    PubMed Central

    Mitjà, Oriol; Fitzpatrick, Christopher; Asiedu, Kingsley; Solomon, Anthony W.; Mabey, David C.W.; Funk, Sebastian

    2017-01-01

    Yaws is targeted for eradication by 2020. The mainstay of the eradication strategy is mass treatment followed by case finding. Modeling has been used to inform programmatic requirements for other neglected tropical diseases and could provide insights into yaws eradication. We developed a model of yaws transmission varying the coverage and number of rounds of treatment. The estimated number of cases arising from an index case (basic reproduction number [R0]) ranged from 1.08 to 3.32. To have 80% probability of achieving eradication, 8 rounds of treatment with 80% coverage were required at low estimates of R0 (1.45). This requirement increased to 95% at high estimates of R0 (2.47). Extending the treatment interval to 12 months increased requirements at all estimates of R0. At high estimates of R0 with 12 monthly rounds of treatment, no combination of variables achieved eradication. Models should be used to guide the scale-up of yaws eradication. PMID:27983500

  6. The final stages of the global eradication of poliomyelitis

    PubMed Central

    Grassly, Nicholas C.

    2013-01-01

    The global incidence of poliomyelitis has dropped by more than 99 per cent since the governments of the world committed to eradication in 1988. One of the three serotypes of wild poliovirus has been eradicated and the remaining two serotypes are limited to just a small number of endemic regions. However, the Global Polio Eradication Initiative (GPEI) has faced a number of challenges in eradicating the last 1 per cent of wild-virus transmission. The polio endgame has also been complicated by the recognition that vaccination with the oral poliovirus vaccine (OPV) must eventually cease because of the risk of outbreaks of vaccine-derived polioviruses. I describe the major challenges to wild poliovirus eradication, focusing on the poor immunogenicity of OPV in lower-income countries, the inherent limitations to the sensitivity and specificity of surveillance, the international spread of poliovirus and resulting outbreaks, and the potential significance of waning intestinal immunity induced by OPV. I then focus on the challenges to eradicating all polioviruses, the problem of vaccine-derived polioviruses and the risk of wild-type or vaccine-derived poliovirus re-emergence after the cessation of oral vaccination. I document the role of research in the GPEI's response to these challenges and ultimately the feasibility of achieving a world without poliomyelitis. PMID:23798688

  7. [PRRSV-eradication: an option for pig herds in Germany?].

    PubMed

    Grosse Beilage, Elisabeth; Bätza, Hans-Joachim

    2007-01-01

    The problem of successfully controling PRRS with traditional methods has led to a growing interest in eradication. This review summarizes the current literature on topics of PRRS-eradication, including the relevant routine diagnostic procedures, routes of virus transmission between pig herds (as i.e. pig movement, semen, aerosols, insects, fomites, transport vehicles) and eradication by close&rollover and test&removal, respectively. On the basis of this knowledge and experiences it can be concluded that PRRS eradication in Germany with its intensive pig production and remarkably high pig density in several regions may only be possible through a national eradication program. The lack of potent marker vaccines that reduce the virus spread significantly, combined with the lack of differentiating diagnostic tests for routine laboratory use leads to the recommendation not to launch a national eradication program under the given circumstances. For the future it should be taken into account that the situation after reintroduction of PRRSV in a free region could only be managed by stamping-out which is generally poorly accepted by the majority of pig producers.

  8. Certification of polio eradication: process and lessons learned.

    PubMed Central

    Smith, Joseph; Leke, Rose; Adams, Anthony; Tangermann, Rudolf H.

    2004-01-01

    Since the 1988 World Health Assembly resolution to eradicate poliomyelitis, considerable progress has been made towards interrupting the transmission of wild poliovirus globally. A formal process for the certification of polio eradication was established on the basis of experience gained during smallpox eradication. Independent groups of experts were designated at the global, regional, and country levels to conduct the process. The main requirements for the global certification of the eradication of wild poliovirus are the absence of wild poliovirus, isolated from suspect polio cases, healthy individuals, or environmental samples, in all WHO regions for a period of at least three years in the presence of high-quality, certification-standard surveillance and the containment of all wild poliovirus stocks in laboratories. Three WHO regions--the Region of the Americas (1994), Western Pacific Region (2000), and European Region (2002)--have already been certified free of indigenous wild poliovirus. Eradication and certification activities are progressing well in the three endemic regions (African, Eastern Mediterranean, and South-East Asia). Several challenges remain for the certification of polio eradication: the need for even closer coordination of certification activities between WHO regions, the verification of laboratory containment, the development of an appropriate mechanism to verify the absence of circulating vaccine-derived polioviruses in the future, and the maintenance of polio-free status in certified regions until global certification. PMID:15106297

  9. Mathematical Modeling of Programmatic Requirements for Yaws Eradication.

    PubMed

    Marks, Michael; Mitjà, Oriol; Fitzpatrick, Christopher; Asiedu, Kingsley; Solomon, Anthony W; Mabey, David C W; Funk, Sebastian

    2017-01-01

    Yaws is targeted for eradication by 2020. The mainstay of the eradication strategy is mass treatment followed by case finding. Modeling has been used to inform programmatic requirements for other neglected tropical diseases and could provide insights into yaws eradication. We developed a model of yaws transmission varying the coverage and number of rounds of treatment. The estimated number of cases arising from an index case (basic reproduction number [R0]) ranged from 1.08 to 3.32. To have 80% probability of achieving eradication, 8 rounds of treatment with 80% coverage were required at low estimates of R0 (1.45). This requirement increased to 95% at high estimates of R0 (2.47). Extending the treatment interval to 12 months increased requirements at all estimates of R0. At high estimates of R0 with 12 monthly rounds of treatment, no combination of variables achieved eradication. Models should be used to guide the scale-up of yaws eradication.

  10. The final stages of the global eradication of poliomyelitis.

    PubMed

    Grassly, Nicholas C

    2013-08-05

    The global incidence of poliomyelitis has dropped by more than 99 per cent since the governments of the world committed to eradication in 1988. One of the three serotypes of wild poliovirus has been eradicated and the remaining two serotypes are limited to just a small number of endemic regions. However, the Global Polio Eradication Initiative (GPEI) has faced a number of challenges in eradicating the last 1 per cent of wild-virus transmission. The polio endgame has also been complicated by the recognition that vaccination with the oral poliovirus vaccine (OPV) must eventually cease because of the risk of outbreaks of vaccine-derived polioviruses. I describe the major challenges to wild poliovirus eradication, focusing on the poor immunogenicity of OPV in lower-income countries, the inherent limitations to the sensitivity and specificity of surveillance, the international spread of poliovirus and resulting outbreaks, and the potential significance of waning intestinal immunity induced by OPV. I then focus on the challenges to eradicating all polioviruses, the problem of vaccine-derived polioviruses and the risk of wild-type or vaccine-derived poliovirus re-emergence after the cessation of oral vaccination. I document the role of research in the GPEI's response to these challenges and ultimately the feasibility of achieving a world without poliomyelitis.

  11. Progress toward global eradication of dracunculiasis, January 2008-June 2009.

    PubMed

    2009-10-16

    Dracunculiasis is a parasitic infection caused by Dracunculus medinensis. Persons become infected by drinking water from stagnant sources (e.g., ponds) contaminated by copepods (water fleas) that contain immature forms of the parasite. In 1986, the World Health Assembly (WHA) called for the eradication of dracunculiasis (Guinea worm disease) at a time when an estimated 3.5 million cases occurred annually in 20 countries in Africa and Asia and 120 million persons were at risk for the disease. Because of slow mobilization in countries with endemic disease, the global dracunculiasis eradication program did not meet the 1995 target date for eradicating dracunculiasis set by WHA in 1991. In 2004, WHA established a new target date of 2009 ; despite considerable progress toward global eradication, that target date also will not be met. This report updates continued progress toward global eradication of dracunculiasis since January 2008. At the end of December 2008, dracunculiasis was endemic in six countries (Ethiopia, Ghana, Mali, Niger, Nigeria, and Sudan). The number of indigenous cases of dracunculiasis had decreased 52%, from 9,585 in 2007 to 4,619 in 2008. Of the 1,446 cases that occurred during January-June 2009, 1,413 (98%) were reported from Sudan and Ghana. Currently, insecurity (e.g., sporadic violence or civil unrest) in areas of Sudan and Mali where dracunculiasis is endemic poses the greatest threat to the success of the global dracunculiasis eradication program.

  12. [Acute pancreatitis due to lupus].

    PubMed

    Hani, Mohamed Aziz; Guesmi, Fethi; Ben Achour, Jamel; Zribi, Riadh; Bouasker, Ibtissem; Zoghlami, Ayoub; Najah, Nabil

    2004-02-01

    Among digestive clinical presentations of systemic lupus erythematosus, acute pancreatitis remains a serious affection with very poor prognosis. To date, pathogenesis is still unclear. We report two cases of fatal acute pancreatitis related to systemic lupus erythematosus.

  13. Metabolic pancreatitis: Etiopathogenesis and management

    PubMed Central

    Kota, Sunil Kumar; Krishna, S.V.S.; Lakhtakia, Sandeep; Modi, Kirtikumar D.

    2013-01-01

    Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis). Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson's disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis. PMID:24083160

  14. Surgery for pancreatic cancer -- discharge

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000820.htm Surgery for pancreatic cancer - discharge To use the sharing features on this ... References Claudius C, Lillemoe KD. Palliative Therapy for Pancreatic Cancer. In: Cameron JL, Cameron AM, eds. Current Surgical ...

  15. Genetics Home Reference: hereditary pancreatitis

    MedlinePlus

    ... HEREDITARY Sources for This Page Greer JB, Whitcomb DC. Inflammation and pancreatic cancer: an evidence-based review. ... J, Drumm B, Jansen J, Mountford R, Whitcomb DC, Neoptolemos JP; European Registry of Hereditary Pancreatitis and ...

  16. Complete genome sequences of pigeon adenovirus 1 and duck adenovirus 2 extend the number of species within the genus Aviadenovirus.

    PubMed

    Marek, Ana; Kaján, Győző L; Kosiol, Carolin; Harrach, Balázs; Schlötterer, Christian; Hess, Michael

    2014-08-01

    Complete genomes of the first isolates of pigeon adenovirus 1 (PiAdV-1) and Muscovy duck adenovirus (duck adenovirus 2, DAdV-2) were sequenced. The PiAdV-1 genome is 45,480bp long, and has a gene organization most similar to turkey adenovirus 1. Near the left end of the genome, it lacks ORF0, ORF1A, ORF1B and ORF1C, and possesses ORF52, whereas six novel genes were found near the right end. The DAdV-2 genome is 43,734bp long, and has a gene organization similar to that of goose adenovirus 4 (GoAdV-4). It lacks ORF51, ORF1C and ORF54, and possesses ORF55A and five other novel genes. PiAdV-1 and DAdV-2 genomes contain two and one fiber genes, respectively. Genome organization, G+C content, molecular phylogeny and host type confirm the need to establish two novel species (Pigeon aviadenovirus A and Duck aviadenovirus B) within the genus Aviadenovirus. Phylogenetic data show that DAdV-2 is most closely related to GoAdV-4.

  17. A novel monoclonal antibody targeting coxsackie virus and adenovirus receptor inhibits tumor growth in vivo

    PubMed Central

    Kawada, Manabu; Inoue, Hiroyuki; Kajikawa, Masunori; Sugiura, Masahito; Sakamoto, Shuichi; Urano, Sakiko; Karasawa, Chigusa; Usami, Ihomi; Futakuchi, Mitsuru; Masuda, Tohru

    2017-01-01

    To create a new anti-tumor antibody, we conducted signal sequence trap by retrovirus-meditated expression method and identified coxsackie virus and adenovirus receptor (CXADR) as an appropriate target. We developed monoclonal antibodies against human CXADR and found that one antibody (6G10A) significantly inhibited the growth of subcutaneous as well as orthotopic xenografts of human prostate cancer cells in vivo. Furthermore, 6G10A also inhibited other cancer xenografts expressing CXADR, such as pancreatic and colorectal cancer cells. Knockdown and overexpression of CXADR confirmed the dependence of its anti-tumor activity on CXADR expression. Our studies of its action demonstrated that 6G10A exerted its anti-tumor activity primarily through both antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Moreover, 6G10A reacted with human tumor tissues, such as prostate, lung, and brain, each of which express CXADR. Although we need further evaluation of its reactivity and safety in human tissues, our results show that a novel anti-CXADR antibody may be a feasible candidate for cancer immunotherapy. PMID:28074864

  18. Inhibition of adenovirus replication in vitro by trifluridine.

    PubMed

    Lennette, D A; Eiferman, R A

    1978-09-01

    At present, there is no effective chemotherapeutic agent available for the treatment of adenoviral keratoconjunctivitis. Recent evidence suggests that trifluridine (3FT) may effectively inhibit the replication of some adenovirus serotypes known to cause keratoconjunctivitis. The ability of 3FT to inhibit two reference strains of adenoviruses, type 8 and type 19, was examined using cell cultures. Two second-passage isolates of adenoviruses, identified as serotype 13, were also tested. Compared with untreated, virusinfected cell cultures, drug-treated cell cultures developed a lesser degree of cytopathic effect following infection with all three serotypes. Virus production was reduced in the drug-treated cell cultures: approximately tenfold for type 8, more than 1,000-fold for type 19, and 5,000-fold for the type 13 isolates.

  19. Capsid-like Arrays in Crystals of Chimpanzee Adenovirus Hexon

    SciTech Connect

    Xue,F.; Burnett, R.

    2006-01-01

    The major coat protein, hexon, from a chimpanzee adenovirus (AdC68) is of interest as a target for vaccine vector modification. AdC68 hexon has been crystallized in the orthorhombic space group C222 with unit cell dimensions of a = 90.8 Angstroms, b = 433.0 Angstroms, c = 159.3 Angstroms, and one trimer (3 x 104,942 Da) in the asymmetric unit. The crystals diffract to 2.1 Angstroms resolution. Initial studies reveal that the molecular arrangement is quite unlike that in hexon crystals for human adenovirus. In the AdC68 crystals, hexon trimers are parallel and pack closely in two-dimensional continuous arrays similar to those formed on electron microscope grids. The AdC68 crystals are the first in which adenovirus hexon has molecular interactions that mimic those used in constructing the viral capsid.

  20. Genetic Relatedness Studies with Adenovirus-associated Viruses

    PubMed Central

    Rose, James A.; Hoggan, M. David; Koczot, Frank; Shatkin, Aaron J.

    1968-01-01

    Adenovirus-associated viruses (AAV) contain double-stranded deoxyribonucleic acid (DNA). DNA from each of the four AAV serotypes was used as template for the in vitro synthesis of complementary 3H-ribonucleic acids(RNA). An estimation of genetic interrelatedness was made on the basis of hybridization reactions between synthetic AAV RNA and AAV DNA. Heterologous reactions were 27 to 37% of homologous reactions, suggesting that the AAV serotypes are related to about the same extent. AAV-1 synthetic RNA was also reacted with DNA from helper adenovirus types 2, 7, and SV15. Very low levels of RNA binding were observed, but it is not likely that these reactions represent AAV-adenovirus genetic relatedness. PMID:5739847

  1. Characterization of a novel adenovirus isolated from a skunk.

    PubMed

    Kozak, Robert A; Ackford, James G; Slaine, Patrick; Li, Aimin; Carman, Susy; Campbell, Doug; Welch, M Katherine; Kropinski, Andrew M; Nagy, Éva

    2015-11-01

    Adenoviruses are a ubiquitous group of viruses that have been found in a wide range of hosts. A novel adenovirus from a skunk suffering from acute hepatitis was isolated and its DNA genome sequenced. The analysis revealed this virus to be a new member of the genus Mastadenovirus, with a genome of 31,848 bp in length containing 30 genes predicted to encode proteins, and with a G+C content of 49.0%. Global genomic organization indicated SkAdV-1 was similar in organization to bat and canine adenoviruses, and phylogenetic comparison suggested these viruses shared a common ancestor. SkAdV-1 demonstrated an ability to replicate in several mammalian liver cell lines suggesting a potential tropism for this virus.

  2. Nutrition, Inflammation, and Acute Pancreatitis

    PubMed Central

    Petrov, Max

    2013-01-01

    Acute pancreatitis is acute inflammatory disease of the pancreas. Nutrition has a number of anti-inflammatory effects that could affect outcomes of patients with pancreatitis. Further, it is the most promising nonspecific treatment modality in acute pancreatitis to date. This paper summarizes the best available evidence regarding the use of nutrition with a view of optimising clinical management of patients with acute pancreatitis. PMID:24490104

  3. Malaria eradication: the economic, financial and institutional challenge

    PubMed Central

    Mills, Anne; Lubell, Yoel; Hanson, Kara

    2008-01-01

    Malaria eradication raises many economic, financial and institutional challenges. This paper reviews these challenges, drawing on evidence from previous efforts to eradicate malaria, with a special focus on resource-poor settings; summarizes more recent evidence on the challenges, drawing on the literature on the difficulties of scaling-up malaria control and strengthening health systems more broadly; and explores the implications of these bodies of evidence for the current call for elimination and intensified control. Economic analyses dating from the eradication era, and more recent analyses, suggest that, in general, the benefits of malaria control outweigh the costs, though few studies have looked at the relative returns to eradication versus long-term control. Estimates of financial costs are scanty and difficult to compare. In the 1960s, the consolidation phase appeared to cost less than $1 per capita and, in 1988, was estimated to be $2.31 per capita (both in 2006 prices). More recent estimates for high coverage of control measures suggest a per capita cost of several dollars. Institutional challenges faced by malaria eradication included limits to the rule of law (a major problem where malaria was concentrated in border areas with movement of people associated with illegal activities), the existence and performance of local implementing structures, and political sustainability at national and global levels. Recent analyses of the constraints to scaling-up malaria control, together with the historical evidence, are used to discuss the economic, financial and institutional challenges that face the renewed call for eradication and intensified control. The paper concludes by identifying a research agenda covering: ∘ issues of the allocative efficiency of malaria eradication, especially using macro-economic modelling to estimate the benefits and costs of malaria eradication and intensified control, and studies of the links between malaria control and economic

  4. The combination of i-leader truncation and gemcitabine improves oncolytic adenovirus efficacy in an immunocompetent model.

    PubMed

    Puig-Saus, C; Laborda, E; Rodríguez-García, A; Cascalló, M; Moreno, R; Alemany, R

    2014-02-01

    Adenovirus (Ad) i-leader protein is a small protein of unknown function. The C-terminus truncation of the i-leader protein increases Ad release from infected cells and cytotoxicity. In the current study, we use the i-leader truncation to enhance the potency of an oncolytic Ad. In vitro, an i-leader truncated oncolytic Ad is released faster to the supernatant of infected cells, generates larger plaques, and is more cytotoxic in both human and Syrian hamster cell lines. In mice bearing human tumor xenografts, the i-leader truncation enhances oncolytic efficacy. However, in a Syrian hamster pancreatic tumor model, which is immunocompetent and less permissive to human Ad, antitumor efficacy is only observed when the i-leader truncated oncolytic Ad, but not the non-truncated version, is combined with gemcitabine. This synergistic effect observed in the Syrian hamster model was not seen in vitro or in immunodeficient mice bearing the same pancreatic hamster tumors, suggesting a role of the immune system in this synergism. These results highlight the interest of the i-leader C-terminus truncation because it enhances the antitumor potency of an oncolytic Ad and provides synergistic effects with gemcitabine in the presence of an immune competent system.

  5. Effects of cold atmospheric plasmas on adenoviruses in solution

    NASA Astrophysics Data System (ADS)

    Zimmermann, J. L.; Dumler, K.; Shimizu, T.; Morfill, G. E.; Wolf, A.; Boxhammer, V.; Schlegel, J.; Gansbacher, B.; Anton, M.

    2011-12-01

    Experiments were performed with cold atmospheric plasma (CAP) to inactivate adenovirus, a non-enveloped double stranded DNA virus, in solution. The plasma source used was a surface micro-discharge technology operating in air. Various plasma diagnostic measurements and tests were performed in order to determine the efficacy of CAPs and to understand the inactivation mechanism(s). Different stages of the adenovirus ‘life cycle’ were investigated—infectivity and gene expression as well as viral replication and spread. Within 240 s of CAP treatment, inactivation of up to 6 decimal log levels can be achieved.

  6. Hepatobiliary and pancreatic ascariasis

    PubMed Central

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S

    2016-01-01

    Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease. PMID:27672273

  7. Chronic pancreatitis in dogs.

    PubMed

    Watson, Penny

    2012-08-01

    Chronic pancreatitis used to be considered uncommon in dogs, but recent pathological and clinical studies have confirmed that it is in fact a common and clinically significant disease. Clinical signs can vary from low-grade recurrent gastrointestinal signs to acute exacerbations that are indistinguishable from classical acute pancreatitis. Chronic pancreatitis is a significant cause of chronic pain in dogs, which must not be underestimated. It also results in progressive impairment of endocrine and exocrine function and the eventual development of diabetes mellitus or exocrine pancreatic insufficiency or both in some affected dogs at end stage. The etiology is unknown in most cases. Chronic pancreatitis shows an increased prevalence in certain breeds, and recent work in English Cocker Spaniels suggests it is part of a polysystemic immune-mediated disease in this breed. The histological and clinical appearance is different in different breeds, suggesting that etiologies may also be different. Diagnosis is challenging because the sensitivities of the available noninvasive tests are relatively low. However, with an increased index of suspicion, clinicians will recognize more cases that will allow them to institute supportive treatment to improve the quality of life of the patient.

  8. Hepatobiliary and pancreatic ascariasis.

    PubMed

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S

    2016-09-07

    Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease.

  9. Transport of human adenoviruses in porous media

    NASA Astrophysics Data System (ADS)

    Kokkinos, Petros; Syngouna, Vasiliki I.; Tselepi, Maria A.; Bellou, Maria; Chrysikopoulos, Constantinos V.; Vantarakis, Apostolos

    2015-04-01

    Groundwater may be contaminated with infective human enteric viruses from various wastewater discharges, sanitary landfills, septic tanks, agricultural practices, and artificial groundwater recharge. Coliphages have been widely used as surrogates of enteric viruses, because they share many fundamental properties and features. Although a large number of studies focusing on various factors (i.e. pore water solution chemistry, fluid velocity, moisture content, temperature, and grain size) that affect biocolloid (bacteria, viruses) transport have been published over the past two decades, little attention has been given toward human adenoviruses (hAdVs). The main objective of this study was to evaluate the effect of pore water velocity on hAdV transport in water saturated laboratory-scale columns packed with glass beads. The effects of pore water velocity on virus transport and retention in porous media was examined at three pore water velocities (0.39, 0.75, and 1.22 cm/min). The results indicated that all estimated average mass recovery values for hAdV were lower than those of coliphages, which were previously reported in the literature by others for experiments conducted under similar experimental conditions. However, no obvious relationship between hAdV mass recovery and water velocity could be established from the experimental results. The collision efficiencies were quantified using the classical colloid filtration theory. Average collision efficiency, α, values decreased with decreasing flow rate, Q, and pore water velocity, U, but no significant effect of U on α was observed. Furthermore, the surface properties of viruses and glass beads were used to construct classical DLVO potential energy profiles. The results revealed that the experimental conditions of this study were unfavorable to deposition and that no aggregation between virus particles is expected to occur. A thorough understanding of the key processes governing virus transport is pivotal for public

  10. Adenovirus Respiratory Tract Infections in Peru

    PubMed Central

    Ampuero, Julia S.; Ocaña, Víctor; Gómez, Jorge; Gamero, María E.; Garcia, Josefina; Halsey, Eric S.; Laguna-Torres, V. Alberto

    2012-01-01

    Background Currently, there is a paucity of data regarding human adenovirus (HAdv) circulation in Andean regions of South America. To address this shortcoming, we report the clinical, phylogenetic, and epidemiologic characteristics of HAdv respiratory tract infection from a large sentinel surveillance study conducted among adults and children in Peru. Methods/Principal Findings Oropharyngeal swabs were collected from participants visiting any of 38 participating health centers, and viral pathogens were identified by immunofluorescence assay in cell culture. In addition, molecular characterization was performed on 226 randomly selected HAdv samples. Between 2000 and 2010, a total of 26,375 participants with influenza-like illness (ILI) or severe acute respiratory infection (SARI) were enrolled in the study. HAdv infection was identified in 2.5% of cases and represented 6.2% of all viral pathogens. Co-infection with a heterologous virus was found in 15.5% of HAdv cases. HAdv infection was largely confined to children under the age of 15, representing 88.6% of HAdv cases identified. No clinical characteristics were found to significantly distinguish HAdv infection from other respiratory viruses. Geographically, HAdv infections were more common in sites from the arid coastal regions than in the jungle or highland regions. Co-circulation of subgroups B and C was observed each year between 2006 and 2010, but no clear seasonal patterns of transmission were detected. Conclusions/Significance HAdv accounted for a significant fraction of those presenting with ILI and SARI in Peru and tended to affect the younger population disproportionately. Longitudinal studies will help better characterize the clinical course of patients with HAdv in Peru, as well as determine the role of co-infections in the evolution of illness. PMID:23056519

  11. Adenovirus infection stimulates the Raf/MAPK signaling pathway and induces interleukin-8 expression.

    PubMed Central

    Bruder, J T; Kovesdi, I

    1997-01-01

    Previous studies have shown that airway administration of adenovirus or adenovirus vectors results in a dose-dependent inflammatory response which limits the duration of transgene expression. We explored the possibility that adenovirus infection triggers signal transduction pathways that induce the synthesis of cytokines and thus contribute to the early inflammatory response. Since stimulation of the Raf/mitogen-activated protein kinase (MAPK) pathway activates transcription factors that control the expression of inflammatory cytokines, we examined the activation of this pathway following adenovirus infection. Adenovirus infection induced the rapid activation of Raf-1 and a transient increase in the tyrosine phosphorylation and activation of p42mapk at early times postinfection. Activation of the Raf/MAPK pathway by adenovirus is likely triggered by the infection process, since it occurred rapidly and with various mutant adenoviruses and adenovirus vectors. Moreover, interleukin-8 (IL-8) mRNA accumulation was evident at 20 min postinfection and was induced even in the presence of cycloheximide. Both MAPK activation and IL-8 production were inhibited by forskolin, a potent inhibitor of Raf-1. These results suggest that adenovirus-induced Raf/MAPK activation contributes to IL-8 production. Adenovirus-induced activation of the Raf/MAPK signaling pathway and IL-8 production may play critical roles in the inflammation observed following in vivo administration of adenovirus vectors for gene therapy. PMID:8985363

  12. Identification and characterization of a novel adenovirus in the cloacal bursa of gulls

    SciTech Connect

    Bodewes, R.; Bildt, M.W.G. van de; Schapendonk, C.M.E.; Leeuwen, M. van; Boheemen, S. van; Jong, A.A.W. de; Osterhaus, A.D.M.E.; Smits, S.L.; Kuiken, T.

    2013-05-25

    Several viruses of the family of Adenoviridae are associated with disease in birds. Here we report the detection of a novel adenovirus in the cloacal bursa of herring gulls (Larus argentatus) and lesser black-backed gulls (Larus fuscus) that were found dead in the Netherlands in 2001. Histopathological analysis of the cloacal bursa revealed cytomegaly and karyomegaly with basophilic intranuclear inclusions typical for adenovirus infection. The presence of an adenovirus was confirmed by electron microscopy. By random PCR in combination with deep sequencing, sequences were detected that had the best hit with known adenoviruses. Phylogenetic analysis of complete coding sequences of the hexon, penton and polymerase genes indicates that this novel virus, tentatively named Gull adenovirus, belongs to the genus Aviadenovirus. The present study demonstrates that birds of the Laridae family are infected by family-specific adenoviruses that differ from known adenoviruses in other bird species. - Highlights: ► Lesions typical for adenovirus infection detected in cloacal bursa of dead gulls. ► Confirmation of adenovirus infection by electron microscopy and deep sequencing. ► Sequence analysis indicates that it is a novel adenovirus in the genus Aviadenovirus. ► The novel (Gull) adenovirus was detected in multiple organs of two species of gulls.

  13. Phylogenetic and pathogenic characterization of novel adenoviruses isolated from long-tailed ducks (Clangula hyemalis).

    PubMed

    Counihan, Katrina L; Skerratt, Lee F; Franson, J Christian; Hollmén, Tuula E

    2015-11-01

    Novel adenoviruses were isolated from a long-tailed duck (Clangula hyemalis) mortality event near Prudhoe Bay, Alaska in 2000. The long-tailed duck adenovirus genome was approximately 27 kb. A 907 bp hexon gene segment was used to design primers specific for the long-tailed duck adenovirus. Nineteen isolates were phylogenetically characterized based on portions of their hexon gene and 12 were most closely related to Goose adenovirus A. The remaining 7 shared no hexon sequences with any known adenoviruses. Experimental infections of mallards with a long-tailed duck reference adenovirus caused mild lymphoid infiltration of the intestine and paint brush hemorrhages of the mucosa and dilation of the intestine. This study shows novel adenoviruses from long-tailed ducks are diverse and provides further evidence that they should be considered in cases of morbidity and mortality in sea ducks. Conserved and specific primers have been developed that will help screen sea ducks for adenoviral infections.

  14. Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis

    PubMed Central

    Xue, Jing; Sharma, Vishal; Hsieh, Michael H.; Chawla, Ajay; Murali, Ramachandran; Pandol, Stephen J.; Habtezion, Aida

    2015-01-01

    Chronic pancreatitis (CP) is a progressive and irreversible inflammatory and fibrotic disease with no cure. Unlike acute pancreatitis, we find that alternatively activated macrophages (AAMs) are dominant in mouse and human CP. AAMs are dependent on IL-4 and IL-13 signaling and we show that mice lacking IL-4Rα, myeloid specific IL-4Rα, and IL-4/IL-13 were less susceptible to pancreatic fibrosis. Furthermore, we demonstrate that mouse and human pancreatic stellate cells (PSCs) are a source of IL-4/IL-13. Notably, we show that pharmacologic inhibition of IL-4/IL-13 in human ex-vivo studies as well as in established mouse CP decreases pancreatic AAMs and fibrosis. We identify a critical role for macrophages in pancreatic fibrosis and in turn PSCs as important inducers of macrophage alternative activation. Our study challenges and identifies pathways involved in cross talk between macrophages and PSCs that can be targeted to reverse or halt pancreatic fibrosis progression. PMID:25981357

  15. Incidental isolated pancreatic hydatid cyst.

    PubMed

    Kısaoğlu, Abdullah; Özoğul, Bünyami; Atamanalp, Sabri Selçuk; Pirimoğlu, Berhan; Aydınlı, Bülent; Korkut, Ercan

    2015-03-01

    Isolated pancreatic hydatid cysts are a rare parasitic disease even in endemic areas. It is difficult to discriminate primary pancreatic hydatid cysts from other cystic and solid lesions of the pancreas. This is a case report of an incidental isolated pancreatic hydatid cyst. A heterogeneous cystic lesion in the body of the pancreas was identified on magnetic resonance imaging of a patient previously diagnosed patient with cholelithiasis, and because of the malignant possibility of the lesion, splenectomy with distal pancreatectomy and cholecystectomy was performed. The histopathologic diagnosis was reported as a hydatid cyst. Pancreatic hydatid cysts should be kept in mind in the differential diagnosis of pancreatic pseudocysts and cystic malignancies.

  16. Eradication of poliomyelitis in countries affected by conflict.

    PubMed

    Tangermann, R H; Hull, H F; Jafari, H; Nkowane, B; Everts, H; Aylward, R B

    2000-01-01

    The global initiative to eradicate poliomyelitis is focusing on a small number of countries in Africa (Angola, Democratic Republic of the Congo, Liberia, Sierra Leone, Somalia, Sudan) and Asia (Afghanistan, Tajikistan), where progress has been hindered by armed conflict. In these countries the disintegration of health systems and difficulties of access are major obstacles to the immunization and surveillance strategies necessary for polio eradication. In such circumstances, eradication requires special endeavours, such as the negotiation of ceasefires and truces and the winning of increased direct involvement by communities. Transmission of poliovirus was interrupted during conflicts in Cambodia, Colombia, El Salvador, Peru, the Philippines, and Sri Lanka. Efforts to achieve eradication in areas of conflict have led to extra health benefits: equity in access to immunization, brought about because every child has to be reached; the revitalization and strengthening of routine immunization services through additional externally provided resources; and the establishment of disease surveillance systems. The goal of polio eradication by the end of 2000 remains attainable if supplementary immunization and surveillance can be accelerated in countries affected by conflict.

  17. Eradication of poliomyelitis in countries affected by conflict.

    PubMed Central

    Tangermann, R. H.; Hull, H. F.; Jafari, H.; Nkowane, B.; Everts, H.; Aylward, R. B.

    2000-01-01

    The global initiative to eradicate poliomyelitis is focusing on a small number of countries in Africa (Angola, Democratic Republic of the Congo, Liberia, Sierra Leone, Somalia, Sudan) and Asia (Afghanistan, Tajikistan), where progress has been hindered by armed conflict. In these countries the disintegration of health systems and difficulties of access are major obstacles to the immunization and surveillance strategies necessary for polio eradication. In such circumstances, eradication requires special endeavours, such as the negotiation of ceasefires and truces and the winning of increased direct involvement by communities. Transmission of poliovirus was interrupted during conflicts in Cambodia, Colombia, El Salvador, Peru, the Philippines, and Sri Lanka. Efforts to achieve eradication in areas of conflict have led to extra health benefits: equity in access to immunization, brought about because every child has to be reached; the revitalization and strengthening of routine immunization services through additional externally provided resources; and the establishment of disease surveillance systems. The goal of polio eradication by the end of 2000 remains attainable if supplementary immunization and surveillance can be accelerated in countries affected by conflict. PMID:10812729

  18. Surface proteins, ERAD and antigenic variation in Trypanosoma brucei.

    PubMed

    Tiengwe, Calvin; Muratore, Katherine A; Bangs, James D

    2016-11-01

    Variant surface glycoprotein (VSG) is central to antigenic variation in African trypanosomes. Although much prior work documents that VSG is efficiently synthesized and exported to the cell surface, it was recently claimed that 2-3 fold more is synthesized than required, the excess being eliminated by ER-Associated Degradation (ERAD) (Field et al., ). We now reinvestigate VSG turnover and find no evidence for rapid degradation, consistent with a model whereby VSG synthesis is precisely regulated to match requirements for a functional surface coat on each daughter cell. However, using a mutated version of the ESAG7 subunit of the transferrin receptor (E7:Ty) we confirm functional ERAD in trypanosomes. E7:Ty fails to assemble into transferrin receptors and accumulates in the ER, consistent with retention of misfolded protein, and its turnover is selectively rescued by the proteasomal inhibitor MG132. We also show that ER accumulation of E7:Ty does not induce an unfolded protein response. These data, along with the presence of ERAD orthologues in the Trypanosoma brucei genome, confirm ERAD in trypanosomes. We discuss scenarios in which ERAD could be critical to bloodstream parasites, and how these may have contributed to the evolution of antigenic variation in trypanosomes.

  19. [The lost decade of global polio eradication and moving forward].

    PubMed

    Shimizu, Hiroyuki

    2010-06-01

    The Global Polio Eradication Initiative was aimed to eradicate poliomyelitis by the year 2000, however, polio eradication is still not in sight even in 2010, over 10 years after the initial target date. In 2010, indigenous transmission of wild polioviruses has been interrupted throughout the world except four countries, Afghanistan, Pakistan, India, and Nigeria. Despite the intense use of monovalent oral polio vaccines, type 1 and type 3 wild polioviruses still circulate in the four remaining polio-endemic countries, and multiple importations of wild polioviruses have also occurred extensively from Nigeria and India to a number of previously polio-free countries in Africa, Asia, and Europe. Furthermore, the emergence of type 2 vaccine-derived polioviruses has raised concerns about low level of immunity against type 2 poliovirus in some polio-endemic areas like Nigeria and India. On the other hand, operational improvements in 2009 were reported in high-risk states in northern Nigeria and transmission of type 1 and type 3 polioviruses in Nigeria is markedly declining from 2009 to 2010. Moreover, bivalent oral polio vaccine containing Sabin 1 and Sabin 3 strains has been introduced in 2010 as a promising tool to improve and simplify the supplemental immunization activities in high-risk areas. Although there was no apparent decline in the annual number of polio cases in 2000-2009 globally, it would be critical to review our experience during "the lost decade of global polio eradication" to move forward into the final stage of global polio eradication.

  20. Progress toward global eradication of dracunculiasis, January 2009-June 2010.

    PubMed

    2010-10-01

    In 1986, the World Health Assembly (WHA) called for the elimination of dracunculiasis (Guinea worm disease), a parasitic infection in humans caused by Dracunculus medinensis. At the time, an estimated 3.5 million cases were occurring annually in 20 countries in Africa and Asia, and 120 million persons were at risk for the disease. Because of slow mobilization in countries with endemic disease, the 1991 WHA goal to eradicate dracunculiasis globally by 1995 was not achieved. In 2004, WHA established a new target date of 2009 for global eradication; despite considerable progress, that target date also was not met. This report updates both published and previously unpublished data and updates progress toward global eradication of dracunculiasis since January 2009. At the end of December 2009, dracunculiasis remained endemic in four countries (Ethiopia, Ghana, Mali, and Sudan). The number of indigenous cases of dracunculiasis worldwide had decreased 31%, from 4,613 in 2008 to 3,185 in 2009. Of the 766 cases that occurred during January--June 2010, a total of 745 (97%) were reported from 380 villages in Sudan. Ghana, Ethiopia, and Mali each are close to interrupting transmission, as indicated by the small and declining number of cases. The current target is to complete eradication in all four countries as quickly as possible. Insecurity (e.g., sporadic violence or civil unrest) in areas of Sudan and Mali where dracunculiasis is endemic poses the greatest threat to the success of the global dracunculiasis eradication program.

  1. Helicobacter pylori eradication therapy: A review of current trends.

    PubMed

    Olokoba, A B; Obateru, O A; Bojuwoye, M O

    2013-01-01

    Helicobacter pylori has been implicated in the formation of chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma and gastric cancer. Eradication of H. Pylori has been recommended as treatment and prevention for these complications. This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. Subject heading and key words used include H. Pylori, current treatment and emerging therapy. Only articles in English were included. There has been a substantial decline in the H. pylori eradication rates over the years, despite the use of proton pump inhibitor and bismuth salts for triple and quadruple therapies respectively. The reasons for eradication failure are diverse, among them, antibiotic resistance is an important factor in the treatment failure. Primary resistance to clarithromycin or metronidazole significantly affects the efficacy of eradication therapy. This has led to the introduction of second line, third line "rescue," and sequential therapies for resistant cases. Subsequently, new antibiotic combinations with proton-pump inhibitors and bismuth salts are being studied in the last decade, to find out the antibiotics that are capable of increasing the eradication rates. Some of these antibiotics include Levofloxacin, Doxycycline, Rifaximin, Rifampicin, Furazolidone based therapies. Studies are ongoing to determine the efficacy of Lactoferrin based therapy.

  2. Hypertriglyceridaemia-induced pancreatitis.

    PubMed

    Weston, Natasha; Fernando, Upul; Baskar, Varadarajan

    2013-02-27

    Hypertriglyceridaemia is the third most common cause of acute pancreatitis but is relatively rare and therefore requires a high level of clinical suspicion to be diagnosed. We discuss the case of a 46-year-old man who initially presented to the accident and emergency department with suspected first presentation of diabetic ketoacidosis (DKA) and a normal amylase but who did not respond to DKA treatment. Further history revealed significant cardiovascular risk factors, examination showed an evidence of hyperlipidaemia and investigations revealed acute pancreatitis secondary to hypertriglyceridaemia. We discuss the causes of hypertriglyceridaemia, the difficulty in differentiating primary versus secondary hypertriglyceridaemia, possible pathogenesis and current evidence-based treatments.

  3. Enzymatic Debridement in Necrotizing Pancreatitis

    PubMed Central

    Cakir, Murat; Tekin, Ahmet; Kucukkartallar, Tevfik; Vatansev, Husamettin; Kartal, Adil

    2015-01-01

    Multiple organ failure and pancreatic necrosis are the factors that determine prognosis in acute pancreatitis attacks. We investigated the effects of collagenase on the debridement of experimental pancreatic necrosis. The study covered 4 groups; each group had 10 rats. Group I was the necrotizing pancreatitis group. Group II was the collagenase group with pancreatic loge by isotonic irrigation following necrotizing pancreatitis. Group III was the collagenase group with pancreatic loge following necrotizing pancreatitis. Group IV was the intraperitoneal collagenase group following necrotizing pancreatitis. The progress of the groups was compared hematologically and histopathologically. There was no difference among the groups regarding the levels of leukocyte, hemogram, and urea. The differences in AST levels between Group I and II; and differences in glucose, calcium, LDH, AST, and amylase between Group II and III; between Group II and IV; between Group I and III; and between Group I and IV were statistically significant (P < 0.05). There were statistically significant differences between Group II and III, and Group II and IV regarding edema, acinar necrosis, inflammatory cell infiltration, hemorrhage, and fat necrosis (P < 0.05). In conclusion, the collagenase preparation used in this experimental pancreatitis model was found to be effective in the debridement of pancreatic necrosis. PMID:26011212

  4. Pancreatic disorders in inflammatory bowel disease

    PubMed Central

    Antonini, Filippo; Pezzilli, Raffaele; Angelelli, Lucia; Macarri, Giampiero

    2016-01-01

    An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn’s disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD. PMID:27574565

  5. Live pancreatic acinar imaging of exocytosis using syncollin-pHluorin.

    PubMed

    Fernandez, Nestor A; Liang, Tao; Gaisano, Herbert Y

    2011-06-01

    In this report, a novel live acinar exocytosis imaging technique is described. An adenovirus was engineered, encoding for an endogenous zymogen granule (ZG) protein (syncollin) fused to pHluorin, a pH-dependent green fluorescent protein (GFP). Short-term culture of mouse acini infected with this virus permits exogenous adenoviral protein expression while retaining acinar secretory competence and cell polarity. The syncollin-pHluorin fusion protein was shown to be correctly localized to ZGs, and the pH-dependent fluorescence of pHluorin was retained. Coupled with the use of a spinning disk confocal microscope, the syncollin-pHluorin fusion protein exploits the ZG luminal pH changes that occur during exocytosis to visualize exocytic events of live acinar cells in real-time with high spatial resolution in three dimensions. Apical and basolateral exocytic events were observed on stimulation of acinar cells with maximal and supramaximal cholecystokinin concentrations, respectively. Sequential exocytic events were also observed. Coupled with the use of transgenic mice and/or adenovirus-mediated protein expression, this syncollin-pHluorin imaging method offers a superior approach to studying pancreatic acinar exocytosis. This assay can also be applied to acinar disease models to elucidate the mechanisms implicated in pancreatitis.

  6. 21 CFR 866.3020 - Adenovirus serological reagents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Adenovirus serological reagents. 866.3020 Section 866.3020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3020...

  7. 21 CFR 866.3020 - Adenovirus serological reagents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Adenovirus serological reagents. 866.3020 Section 866.3020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3020...

  8. 21 CFR 866.3020 - Adenovirus serological reagents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Adenovirus serological reagents. 866.3020 Section 866.3020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3020...

  9. 21 CFR 866.3020 - Adenovirus serological reagents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Adenovirus serological reagents. 866.3020 Section 866.3020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3020...

  10. Mechanics of Viral Chromatin Reveals the Pressurization of Human Adenovirus.

    PubMed

    Ortega-Esteban, Alvaro; Condezo, Gabriela N; Pérez-Berná, Ana J; Chillón, Miguel; Flint, S Jane; Reguera, David; San Martín, Carmen; de Pablo, Pedro J

    2015-11-24

    Tight confinement of naked genomes within some viruses results in high internal pressure that facilitates their translocation into the host. Adenovirus, however, encodes histone-like proteins that associate with its genome resulting in a confined DNA-protein condensate (core). Cleavage of these proteins during maturation decreases core condensation and primes the virion for proper uncoating via unidentified mechanisms. Here we open individual, mature and immature adenovirus cages to directly probe the mechanics of their chromatin-like cores. We find that immature cores are more rigid than the mature ones, unveiling a mechanical signature of their condensation level. Conversely, intact mature particles demonstrate more rigidity than immature or empty ones. DNA-condensing polyamines revert the mechanics of mature capsid and cores to near-immature values. The combination of these experiments reveals the pressurization of adenovirus particles induced by maturation. We estimate a pressure of ∼30 atm by continuous elasticity, which is corroborated by modeling the adenovirus mini-chromosome as a confined compact polymer. We propose this pressurization as a mechanism that facilitates initiating the stepwise disassembly of the mature particle, enabling its escape from the endosome and final genome release at the nuclear pore.

  11. Bioaccumulation of animal adenoviruses in the pink shrimp.

    PubMed

    Luz, Roger B; Staggemeier, Rodrigo; Fabres, Rafael B; Soliman, Mayra C; Souza, Fernanda G; Gonçalves, Raoni; Fausto, Ivone V; Rigotto, Caroline; Heinzelmann, Larissa S; Henzel, Andréia; Fleck, Juliane D; Spilki, Fernando R

    2015-01-01

    Adenoviruses are among the most promising viral markers of fecal contamination. They are frequently found in the water, sediment and soil of regions impacted by human activity. Studies of the bioaccumulation of enteric viruses in shrimp are scarce. The cities located in the northern coast of the lake systems in Southern Brazil have high urbanization and intensive farming rates, and poor sewage collection and treatment. One hundred (n = 100) Farfantepenaeus paulensis pink-shrimp specimens and 48 water samples were collected from coastal lagoons between June 2012 and May 2013. Water samples were concentrated and the shrimp, mashed. After DNA extraction, samples were analyzed by real time polymerase chain reaction (qPCR) in order to detect and quantify viral genomes. Thirty-five percent of shrimp samples were positive for contamination, predominantly by avian adenoviruses. A total of 91.7% of water samples contained adenoviruses DNA, with the human form being the most frequent. Our results provided evidence of significant bioaccumulation of adenoviruses in shrimp, showing the extent of the impact of fecal pollution on aquatic ecosystems.

  12. Serologic and hexon phylogenetic analysis of ruminant adenoviruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objectives of this study were to determine the antigenic relationship among ruminant adenoviruses and determine their phylogenetic relationship based on the deduced hexon gene amino acid sequence. Results of reciprocal cross-neutralization tests demonstrated antigenic relationships in either on...

  13. Transcription activation by the adenovirus E1a protein

    NASA Astrophysics Data System (ADS)

    Lillie, James W.; Green, Michael R.

    1989-03-01

    The adenovirus Ela protein stimulates transcription of a wide variety of viral and cellular genes. It is shown here that Ela has the two functions characteristic of a typical cellular activator: one direct Ela to the promoter, perhaps by interacting with a DMA-bound protein, and the other, an activating region, enables the bound activator to stimulate transcription.

  14. Acute respiratory infection with mouse adenovirus type 1

    PubMed Central

    Weinberg, Jason B.; Stempfle, Gregory S.; Wilkinson, John E.; Younger, John G.; Spindler, Katherine R.

    2005-01-01

    Studies of the pathogenesis of adenovirus respiratory disease are limited by the strict species-specificity of the adenoviruses. Following intranasal inoculation of adult C57BL/6 mice with mouse adenovirus type 1 (MAV-1), we detected MAV-1 early region 3 (E3) and hexon gene expression in the lungs at 7 days post-infection (dpi). We detected MAV-1 E3 protein in the respiratory epithelium 7 dpi. We did not detect viral mRNA or protein at 14 dpi, but MAV-1 DNA was detected by PCR at 21 dpi. Chemokine transcript levels increased between 7 and 14 dpi in the lungs of infected mice. MAV-1 infection induced a patchy cellular infiltrate in lungs at 7 and 14 dpi. This is the first report demonstrating the presence of MAV-1 in the respiratory epithelium of infected mice and describing chemokine responses in the lung induced by MAV-1 respiratory infection. MAV-1 infection of mice has the potential to serve as a model for inflammatory changes seen in human adenovirus respiratory disease. PMID:16054189

  15. Adenovirus infection reverses the antiviral state induced by human interferon.

    PubMed

    Feduchi, E; Carrasco, L

    1987-04-06

    HeLa cells treated with human lymphoblastoid interferon do not synthesize poliovirus proteins. The antiviral state against poliovirus is reversed if cells are previously infected with adenovirus type 5. A late gene product seems to be involved in this reversion, since no effect is observed at early stages of infection or in the presence of aphidicolin.

  16. Bioaccumulation of animal adenoviruses in the pink shrimp

    PubMed Central

    Luz, Roger B.; Staggemeier, Rodrigo; Fabres, Rafael B.; Soliman, Mayra C.; Souza, Fernanda G.; Gonçalves, Raoni; Fausto, Ivone V.; Rigotto, Caroline; Heinzelmann, Larissa S.; Henzel, Andréia; Fleck, Juliane D.; Spilki, Fernando R.

    2015-01-01

    Adenoviruses are among the most promising viral markers of fecal contamination. They are frequently found in the water, sediment and soil of regions impacted by human activity. Studies of the bioaccumulation of enteric viruses in shrimp are scarce. The cities located in the northern coast of the lake systems in Southern Brazil have high urbanization and intensive farming rates, and poor sewage collection and treatment. One hundred (n = 100) Farfantepenaeus paulensis pink-shrimp specimens and 48 water samples were collected from coastal lagoons between June 2012 and May 2013. Water samples were concentrated and the shrimp, mashed. After DNA extraction, samples were analyzed by real time polymerase chain reaction (qPCR) in order to detect and quantify viral genomes. Thirty-five percent of shrimp samples were positive for contamination, predominantly by avian adenoviruses. A total of 91.7% of water samples contained adenoviruses DNA, with the human form being the most frequent. Our results provided evidence of significant bioaccumulation of adenoviruses in shrimp, showing the extent of the impact of fecal pollution on aquatic ecosystems. PMID:26413052

  17. Site-specific nicking within the adenovirus inverted terminal repetition.

    PubMed Central

    Chow, K C; Pearson, G D

    1984-01-01

    Site-specific nicking occurs on the l-strand, but not on the r-strand, of the adenovirus left inverted terminal repeat. Nicks are presumably introduced into double- or single-stranded DNA by a cellular endonuclease in an ATP-independent reaction. The consensus nick site has the sequence: (sequence in text). Images PMID:6322107

  18. Immune responses against hepatitis C virus genotype 3a virus-like particles in mice: A novel VLP prime-adenovirus boost strategy.

    PubMed

    Kumar, Anuj; Das, Soma; Mullick, Ranajoy; Lahiri, Priyanka; Tatineni, Ranjitha; Goswami, Debashree; Bhat, Prasanna; Torresi, Joseph; Gowans, Eric James; Karande, Anjali Anoop; Das, Saumitra

    2016-02-17

    Chronic hepatitis C virus (HCV) infection represents a major health threat to global population. In India, approximately 15-20% of cases of chronic liver diseases are caused by HCV infection. Although, new drug treatments hold great promise for HCV eradication in infected individuals, the treatments are highly expensive. A vaccine for preventing or treating HCV infection would be of great value, particularly in developing countries. Several preclinical trials of virus-like particle (VLP) based vaccine strategies are in progress throughout the world. Previously, using baculovirus based system, we have reported the production of hepatitis C virus-like particles (HCV-LPs) encoding structural proteins for genotype 3a, which is prevalent in India. In the present study, we have generated HCV-LPs using adenovirus based system and tried different immunization strategies by using combinations of both kinds of HCV-LPs with other genotype 3a-based immunogens. HCV-LPs and peptides based ELISAs were used to evaluate antibody responses generated by these combinations. Cell-mediated immune responses were measured by using T-cell proliferation assay and intracellular cytokine staining. We observed that administration of recombinant adenoviruses expressing HCV structural proteins as final booster enhances both antibody as well as T-cell responses. Additionally, reduction of binding of VLP and JFH1 virus to human hepatocellular carcinoma cells demonstrated the presence of neutralizing antibodies in immunized sera. Taken together, our results suggest that the combined regimen of VLP followed by recombinant adenovirus could more effectively inhibit HCV infection, endorsing the novel vaccine strategy.

  19. Population movements and problems of malaria eradication in Africa*

    PubMed Central

    Prothero, R. Mansell

    1961-01-01

    Population movements of various kinds are among the outstanding demographic features of the African continent and entail serious difficulties for malaria eradication. The majority of these movements are free and uncontrolled and are frequently inter-territorial in nature, hampering nation-wide or more limited malaria eradication projects and resulting in much reinfection. The author examines in some detail the types of population movements and their relationship to malaria problems in the Republic of Sudan, Ethiopia, Somalia, East Africa, Zanzibar, the Federation of Rhodesia and Nyasaland, Nigeria and Ghana. He concludes that these movements cannot be stopped and must be taken into account in planning malaria eradication programmes. More information on them and on the complex relationships between parasites, vectors and human beings is required, and inter-territorial co-operation is essential in obtaining this information and in planning. PMID:13738245

  20. Challenges and key research questions for yaws eradication

    PubMed Central

    Marks, Michael; Mitjà, Oriol; Vestergaard, Lasse S; Pillay, Allan; Knauf, Sascha; Chen, Cheng-Yen; Bassat, Quique; Martin, Diana L.; Fegan, David; Taleo, Fasihah; Kool, Jacob; Lukehart, Sheila; Emerson, Paul M; Solomon, Anthony W; Ye, Tun; Ballard, Ronald C; Mabey, David CW; Asiedu, Kingsley B

    2015-01-01

    Yaws is endemic in West Africa, Southeast Asia and the Pacific. The WHO has launched a campaign based on mass treatment with azithromycin, to eradicate yaws by 2020. Progress has been made towards achieving this ambitious goal, including the validation of point-of-care and molecular diagnostic tests and piloting of the strategy in a number of countries including Ghana, Vanuatu and Papua New Guinea. There is a need to address gaps in knowledge to allow refinement of the eradication strategy. Studies exploring determinants of the spatial distribution of yaws are needed to facilitate completion of baseline mapping. The finding that Haemophilus ducreyi causes lesions similar to yaws is particularly important and further work is required to assess the impact of azithromycin on these lesions. The integration of diagnostic tests in to different stages of the eradication campaign requires evaluation. Finally studies to inform the optimum mass treatment strategy for sustainably interrupting transmission must be conducted. PMID:26362174

  1. Challenges and key research questions for yaws eradication.

    PubMed

    Marks, Michael; Mitjà, Oriol; Vestergaard, Lasse S; Pillay, Allan; Knauf, Sascha; Chen, Cheng-Yen; Bassat, Quique; Martin, Diana L; Fegan, David; Taleo, Fasihah; Kool, Jacob; Lukehart, Sheila; Emerson, Paul M; Solomon, Anthony W; Ye, Tun; Ballard, Ronald C; Mabey, David C W; Asiedu, Kingsley B

    2015-10-01

    Yaws is endemic in west Africa, southeast Asia, and the Pacific region. To eradicate yaws by 2020, WHO has launched a campaign of mass treatment with azithromycin. Progress has been made towards achievement of this ambitious goal, including the validation of point-of-care and molecular diagnostic tests and piloting of the strategy in several countries, including Ghana, Vanuatu, and Papua New Guinea. Gaps in knowledge need to be addressed to allow refinement of the eradication strategy. Studies exploring determinants of the spatial distribution of yaws are needed to help with the completion of baseline mapping. The finding that Haemophilus ducreyi causes lesions similar to yaws is particularly important and further work is needed to assess the effect of azithromycin on these lesions. The integration of diagnostic tests into different stages of the eradication campaign needs investigation. Finally, studies must be done to inform the optimum mass-treatment strategy for sustainable interruption of transmission.

  2. Community participation in the eradication of guinea worm disease.

    PubMed

    Cairncross, S; Braide, E I; Bugri, S Z

    1996-04-01

    As Guinea worm eradication programmes have got under way in endemic countries over the last decade, there has been a shift towards more participatory methods. The approach to surveillance has changed from periodic cross-sectional surveys to monthly village-based reporting of cases by a volunteer village health worker. At the same time, the emphasis regarding control interventions has moved from the provision of safe water supplies to health education. The new approach has proved very effective. The village health volunteers who carry out both surveillance and health education seem to be motivated largely by the social status of their role; still more commitment will be required of them in the final stages of eradication. It is to be hoped that the networks of village health workers established for Guinea worm eradication will find a useful role in health promotion after the worms have gone.

  3. Staphylococcus aureus in Antarctica: carriage and attempted eradication.

    PubMed Central

    Krikler, S. J.

    1986-01-01

    The carriage of Staphylococcus aureus was studied in a group of 28 men living in a totally isolated environment for a year. Initially, nasal, axillary and perineal swabs were taken at weekly intervals, but from week 24 throat swabs were taken from known nasal carriers. Several attempts were made during the study to eradicate S. aureus. Eight subjects consistently carried their own phage type throughout the study, despite the application of antibacterial agents. In three subjects strains were isolated late in the study of a phage type which had either not been isolated before in this study, or had not been found for a prolonged period. Nine of the 12 nasal carriers also yielded S. aureus from the throat. It is apparent that following attempted eradication, S. aureus may seem to disappear, only to reappear some time later; 'eradication' in this case would be an erroneous appellation. PMID:3794322

  4. Some epidemiological aspects of the eradication of yaws

    PubMed Central

    Hackett, C. J.

    1960-01-01

    Much has been learnt of the epidemiology of yaws during eradication campaigns in populations in which the prevalence of active yaws was high, but not all has been published. The recognition of the importance of latent cases in the maintenance of yaws has contributed to the effectiveness of these campaigns. Yaws eradication activities are extending into populations where at present active yaws is often not high. Planning of effective and economical eradication measures, especially in such populations, needs as complete a picture of the disease as possible, from its transmission and the factors that favour this until the death of the infected person, before or after cure of the infection either after chemotherapy or spontaneously. By revealing the many gaps that still remain in our knowledge of yaws, this summary may encourage those who have gathered valuable material during field work to study and prepare it for publication. PMID:13710280

  5. Helicobacter pylori eradication as a preventive tool against gastric cancer.

    PubMed

    Hamajima, Nobuyuki; Goto, Yasuyuki; Nishio, Kazuko; Tanaka, Daisuke; Kawai, Sayo; Sakakibara, Hisataka; Kondo, Takaaki

    2004-01-01

    Helicobacter pylori (H. pylori), which increases the risk of gastric diseases, including digestive ulcers and gastric cancer, is highly prevalent in Asian countries. There is no doubt that eradication of the bacterium is effective as a treatment of digestive ulcer, but eradication aiming to reduce the gastric cancer risk is still controversial. Observational studies in Japan demonstrated that the eradication decreased the gastric cancer risk among 132 stomach cancer patients undergoing endoscopical resection (65 treated with omeprazol and antibiotics and 67 untreated). In Columbia, 976 participants were randomized into eight groups in a three-treatment factorial design including H. pylori eradication, resulting in significant regression in the H. pylori eradication group. A recent randomized study in China also showed a significant reduction of gastric cancer risk among those without any gastric atrophy, intestinal metaplasia, and dysplasia. Efficacy of eradication may vary in extent among countries with different incidence rates of gastric cancer. Since the lifetime cumulative risk (0 to 84 years old) of gastric cancer in Japan is reported to be 12.7% for males and 4.8% for females (Inoue and Tominaga, 2003), the corresponding values for H. pylori infected Japanese can be estimated at 21.2% in males and 8.0% in females under the assumptions that the relative risk for infected relative to uninfected is 5 and the proportion of those infected is 0.5. Both the fact that not all individuals are infected among those exposed and the knowledge that only a small percentage of individuals infected with the bacterium develop gastric cancer, indicate the importance of gene-environment interactions. Studies on such interactions should provide useful information for anti-H. pylori preventive strategies.

  6. Diabetes and pancreatic cancer.

    PubMed

    Burney, Saira; Irfan, Khadija; Saif, Muhammad Wasif; Masud, Faisal

    2014-07-28

    Research suggests a possible link between type 2 diabetes and several malignancies. Animal models have shown that hyperinsulinemic state underlying diabetes promotes tumor formation through stimulation of insulin-IGF-1 pathway; a possible role of inflammation is also proposed. One such link which has been under considerable study for years is that between diabetes and pancreatic cancer. Although epidemiological evidence points towards a reciprocal link between the two, the cause-effect relationship still remains unclear. This link was the subject of a large German epidemiological study presented at the American Society of Clinical Oncology Annual Meeting 2014 (Abstract #1604), which underscored the link between diabetes and some cancers. Schmidt et al. performed a retrospective database analysis over a 12 year period and reported an increased risk of certain types of cancer in diabetic patients. The most significant association (HR 2.17) was found for pancreatic cancer. Given the high mortality of pancreatic cancer, prevention through timely screening could play an important role in improving prognosis. Older subjects with recent-onset diabetes represent a high-risk group and hence are potential targets for pancreatic cancer screening thereby enabling its early diagnosis at a curable stage.

  7. Pancreatic Cancer Stage 4

    MedlinePlus

    ... lung, liver, and peritoneal cavity. An inset shows cancer cells spreading from the pancreas, through the blood and lymph system, to another ... abdomen that contains the intestines, stomach, and liver). Cancer may also have spread to ... pancreas or to lymph nodes. Stage IV pancreatic cancer. ...

  8. What Are the Key Statistics about Pancreatic Cancer?

    MedlinePlus

    ... Cancer Research? Pancreatic Cancer About Pancreatic Cancer Key Statistics for Pancreatic Cancer How common is pancreatic cancer? ... can be affected by certain risk factors . For statistics related to survival, see Pancreatic Cancer Survival Rates ...

  9. Eradication of typhus exanthematicus in Bosnia and Herzegovina.

    PubMed

    Puvacić, Zlatko; Beslagić, Edina; Zvizdić, Sukrija; Puvacić, Sandra; Ravlija, Jelena; Hamzić, Sadeta

    2006-02-01

    Typhus exanthematicus in Bosnia and Herzegovina held in endemic areas from which especially quickly began spread after 1945. That year, in 1945, one hundred epidemics of typhus fever appeared, with the highest incidence rate in Europe of 215.04 per 1,000. Directions of unique program in the world were to eradicate lice of the body, but also establish monitoring of the recidivism, Brill-Zinsser disease. Since 1971, typhus exanthematicus (classical typhus) hasn't appeared in Bosnia and Herzegovina, so epidemic typhus can considered as an eradicated communicable disease.

  10. India's poliomyelitis eradication: a milestone in public health.

    PubMed

    Grover, Manoj; Bhatnagar, Nidhi; Sinha, Smita; Kaur, Ravneet

    2013-12-01

    India has recently completed 2 years without single case of poliomyelitis on 13 January 2013. This has brought South East Asian Region closer to eradication. Recently, India is being regarded as a role model for polio eradication efforts in other low-income endemic countries-Pakistan, Nigeria and Afghanistan. However, the near elimination of wild polio virus in India has set forth newer challenges. Stricter surveillance measures are now needed to check for importations spread of virus in migratory populations and rapid containment of newly found virus. India's battle against polio will soon be cited as biggest public health achievement or most expensive public health failure.

  11. Does Helicobacter pylori eradication play a role in immune thrombocytopenia?

    PubMed

    Llovet, Valentina; Rada, Gabriel

    2016-09-05

    Helicobacter pylori infection has been implicated as trigger or disease modifier in immune thrombocytopenia (ITP). So, eradication treatment for this agent could have clinical benefits. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews comprising 40 studies addressing the question of this article overall, including one randomized controlled trial. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded Helicobacter eradication might decrease risk of bleeding in patients with immune thrombocytopenia but the certainty of the evidence is low.

  12. Transformation Potentials of the Noninfectious (Defective) Component in Pools of Adenoviruses Type 12 and Simian Adenovirus 7

    PubMed Central

    Schaller, J. P.; Yohn, D. S.

    1974-01-01

    Pools of adenovirus 12 and simian adenovirus 7 were separated into four or five fractions by density gradient centrifugation in cesium chloride. Each fraction was analyzed for total in vitro infectivity units, total transformation activity, and for total virus particle (VP) content. Two major subpopulations were separated with mean densities of 1.30 ± 0.02 and 1.34 ± 0.02 g/ml, respectively. Virions in the 1.34 g/ml range were highly infectious (102 to 103 VP per infectivity unit) in contrast to virions at 1.30 g/ml density (104 to 105 VP per infectivity units). Transformation capacity was evenly distributed throughout fractions of both viruses, indicating that genetically incomplete or defective virus particles were not deficient in their ability to induce transformation. The average VP per transformation unit for adenovirus 12 (2.85 × 106) and for simian adenovirus 7 (4.00 × 106) did not vary significantly from fraction to fraction. These values were obtained with optimal input multiplicities of 16 to 64 VP per cell. At higher multiplicities the apparent increase in VP per transformation unit was attributable to the viral cytocidal effect on hamster cells. These studies revealed that quantitation of in vitro transformation based on VP multiplicities was more reliable than on the basis of infectious units. These estimates were independent of method of virus production, extraction, and purification. Images PMID:4211167

  13. In vitro reprogramming of pancreatic alpha cells towards a beta cell phenotype following ectopic HNF4α expression.

    PubMed

    Sangan, Caroline B; Jover, Ramiro; Heimberg, Harry; Tosh, David

    2015-01-05

    There is currently a shortage of organ donors available for pancreatic beta cell transplantation into diabetic patients. An alternative source of beta cells is pre-existing pancreatic cells. While we know that beta cells can arise directly from alpha cells during pancreatic regeneration we do not understand the molecular basis for the switch in phenotype. The aim of the present study was to investigate if hepatocyte nuclear factor 4 alpha (HNF4α), a transcription factor essential for a normal beta cell phenotype, could induce the reprogramming of alpha cells towards potential beta cells. We utilised an in vitro model of pancreatic alpha cells, the murine αTC1-9 cell line. We initially characterised the αTC1-9 cell line before and following adenovirus-mediated ectopic expression of HNF4α. We analysed the phenotype at transcript and protein level and assessed its glucose-responsiveness. Ectopic HNF4α expression in the αTC1-9 cell line induced a change in morphology (1.7-fold increase in size), suppressed glucagon expression, induced key beta cell-specific markers (insulin, C-peptide, glucokinase, GLUT2 and Pax4) and pancreatic polypeptide (PP) and enabled the cells to secrete insulin in a glucose-regulated manner. In conclusion, HNF4α reprograms alpha cells to beta-like cells.

  14. Delayed internal pancreatic fistula with pancreatic pleural effusion postsplenectomy

    PubMed Central

    Jin, Shu-Guang; Chen, Zhe-Yu; Yan, Lu-Nan; Zeng, Yong

    2010-01-01

    The occurrence of pancreatic pleural effusion, secondary to an internal pancreatic fistula, is a rare clinical syndrome and diagnosis is often missed. The key to the diagnosis is a dramatically elevated pleural fluid amylase. This pancreatic pleural effusion is also called a pancreatic pleural fistula. It is characterized by profuse pleural fluid and has a tendency to recur. Here we report a case of delayed internal pancreatic fistula with pancreatic pleural effusion emerging after splenectomy. From the treatment of this case, we conclude that the symptoms and signs of a subphrenic effusion are often obscure; abdominal computed tomography may be required to look for occult, intra-abdominal infection; and active conservative treatment should be carried out in the early period of this complication to reduce the need for endoscopy or surgery. PMID:20845520

  15. Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis

    PubMed Central

    Leppkes, Moritz; Maueröder, Christian; Hirth, Sebastian; Nowecki, Stefanie; Günther, Claudia; Billmeier, Ulrike; Paulus, Susanne; Biermann, Mona; Munoz, Luis E.; Hoffmann, Markus; Wildner, Dane; Croxford, Andrew L.; Waisman, Ari; Mowen, Kerri; Jenne, Dieter E.; Krenn, Veit; Mayerle, Julia; Lerch, Markus M.; Schett, Georg; Wirtz, Stefan; Neurath, Markus F.; Herrmann, Martin; Becker, Christoph

    2016-01-01

    Ductal occlusion has been postulated to precipitate focal pancreatic inflammation, while the nature of the primary occluding agents has remained elusive. Neutrophils make use of histone citrullination by peptidyl arginine deiminase-4 (PADI4) in contact to particulate agents to extrude decondensed chromatin as neutrophil extracellular traps (NETs). In high cellular density, NETs form macroscopically visible aggregates. Here we show that such aggregates form inside pancreatic ducts in humans and mice occluding pancreatic ducts and thereby driving pancreatic inflammation. Experimental models indicate that PADI4 is critical for intraductal aggregate formation and that PADI4-deficiency abrogates disease progression. Mechanistically, we identify the pancreatic juice as a strong instigator of neutrophil chromatin extrusion. Characteristic single components of pancreatic juice, such as bicarbonate ions and calcium carbonate crystals, induce aggregated NET formation. Ductal occlusion by aggregated NETs emerges as a pathomechanism with relevance in a plethora of inflammatory conditions involving secretory ducts. PMID:26964500

  16. Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis.

    PubMed

    Leppkes, Moritz; Maueröder, Christian; Hirth, Sebastian; Nowecki, Stefanie; Günther, Claudia; Billmeier, Ulrike; Paulus, Susanne; Biermann, Mona; Munoz, Luis E; Hoffmann, Markus; Wildner, Dane; Croxford, Andrew L; Waisman, Ari; Mowen, Kerri; Jenne, Dieter E; Krenn, Veit; Mayerle, Julia; Lerch, Markus M; Schett, Georg; Wirtz, Stefan; Neurath, Markus F; Herrmann, Martin; Becker, Christoph

    2016-03-11

    Ductal occlusion has been postulated to precipitate focal pancreatic inflammation, while the nature of the primary occluding agents has remained elusive. Neutrophils make use of histone citrullination by peptidyl arginine deiminase-4 (PADI4) in contact to particulate agents to extrude decondensed chromatin as neutrophil extracellular traps (NETs). In high cellular density, NETs form macroscopically visible aggregates. Here we show that such aggregates form inside pancreatic ducts in humans and mice occluding pancreatic ducts and thereby driving pancreatic inflammation. Experimental models indicate that PADI4 is critical for intraductal aggregate formation and that PADI4-deficiency abrogates disease progression. Mechanistically, we identify the pancreatic juice as a strong instigator of neutrophil chromatin extrusion. Characteristic single components of pancreatic juice, such as bicarbonate ions and calcium carbonate crystals, induce aggregated NET formation. Ductal occlusion by aggregated NETs emerges as a pathomechanism with relevance in a plethora of inflammatory conditions involving secretory ducts.

  17. Patient Derived Cancer Cell Lines in Identifying Molecular Changes in Patients With Previously Untreated Pancreatic Cancer Receiving Gemcitabine Hydrochloride-Based Chemotherapy

    ClinicalTrials.gov

    2016-10-18

    Pancreatic Ductal Adenocarcinoma; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  18. E2F-1 gene therapy induces apoptosis and increases chemosensitivity in human pancreatic carcinoma cells.

    PubMed

    Elliott, Mary Jane; Farmer, Michael R; Atienza, Cesar; Stilwell, Ariel; Dong, Yan Bin; Yang, Hai Liang; Wong, Sandra L; McMasters, Kelly M

    2002-01-01

    Pancreatic cancer is often resistant to conventional chemotherapy. In this study, we examined the role of adenovirus-mediated overexpression of E2F-1 in inducing apoptosis and increasing the sensitivity of pancreatic cancer cells to chemotherapeutic agents. MIA PaCa-2 pancreatic head exocrine adenocarcinoma cells (mutant p53) were treated by mock infection or adenoviruses expressing beta-galactosidase or E2F-1 (Ad-E2F-1) alone or in combination with sublethal concentrations of each chemotherapeutic drug. Cell growth and viability were assessed at selected time points. Apoptosis was evaluated by flow cytometry, characteristic changes in cell morphology and poly (ADP-ribose) polymerase (PARP) cleavage. Western blot analysis was used to examine the expression of E2F-1 and Bcl-2 family member proteins and PARP cleavage. Western blot analysis revealed marked overexpression of E2F-1 at a multiplicity of infection (MOI) of 20 and 70. By 3 days after infection, Ad-E2F-1 treatment at an MOI of 70 resulted in approximately a 20-fold reduction in cell growth and 60% reduction in cell viability as compared to mock-infected cells. Cell cycle analysis, PARP cleavage and changes in cell morphology supported apoptosis as the mechanism of cell death in response to E2F-1. In order to test the efficacy of treatment with a combination of gene therapy and chemotherapy, we utilized concentrations of Ad-E2F-1 which reduced viability to 50% in combination with each chemotherapeutic agent. Cotreatment of the cells with E2F-1 virus and roscovitine (ROS) or etoposide resulted in an additive effect on cell growth inhibition and induction of apoptosis. Interestingly, 5-fluorouracil did not cooperate with Ad-E2F-1 in the mediation of tumor death or inhibition of cell growth. Immunoblotting for Bcl-2 family members revealed no significant changes in the expression levels of Bcl-2, Bcl X(L), Bax or Bak following gene or 'chemogene' therapy with E2F-1. However, a Bax cleavage product was noted

  19. Comparison of the Eradication Rate between 1- and 2-Week Bismuth-Containing Quadruple Rescue Therapies for Helicobacter pylori Eradication

    PubMed Central

    Yoon, Jai Hoon; Kim, Yeon Soo; Suk, Ki Tae; Shin, Woon Geon; Kim, Kyung Ho; Kim, Kyoung Oh; Park, Cheol Hee; Baik, Il Hyun; Jang, Hyun Joo; Kim, Jin Bong; Kae, Sea Hyub; Kim, Dong Joon; Kim, Hak Yang

    2012-01-01

    Background/Aims First-line therapies against Helicobacter pylori, including proton pump inhibitors (PPIs) plus two antibiotics, may fail in up to 20% of patients. 'Rescue' therapy is usually needed for patients who failed the first-line treatment. This study evaluated the eradication rate of bismuth-containing quadruple rescue therapy over a 1- or 2-week period. Methods We prospectively investigated 169 patients with a persistent H. pylori infection after the first-line triple therapy, which was administered from October 2008 to March 2010. The patients were randomized to receive a 1- or 2-week quadruple rescue therapy (pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d.). After the 'rescue' therapy, the eradication rate, compliance, and adverse events were evaluated. Results The 1-week group achieved 83.5% (71/85) and 87.7% (71/81) eradication rates in the intention to treat (ITT) and per-protocol (PP) analyses, respectively. The 2-week group obtained 87.7% (72/84) and 88.9% (72/81) eradication rate in the ITT and PP analyses, respectively. There was no significant difference in the eradication rate, patient compliance or rate of adverse events between the two groups. Conclusions One-week bismuth-containing quadruple therapy can be as effective as a 2-week therapy after the failure of the first-line eradication therapy. PMID:23170146

  20. Inflammatory pancreatic masses: problems in differentiating focal pancreatitis from carcinoma

    SciTech Connect

    Neff, C.C.; Simeone, J.F.; Wittenberg, J.; Mueller, P.R.; Ferrucci, J.T. Jr.

    1984-01-01

    The authors studied 19 patients with focal inflammatory masses of the pancreas over an 18-month period. In 13 cases, transhepatic cholangiography and/or endoscopic retrograde cholangiopancreatography were unsuccessful in differentiating pancreatitis from carcinoma. Eighteen patients had a history of alcohol abuse, and 12 had had pancreatitis previously. Pre-existing glandular injury appears to be a prerequisite to formation of focal inflammatory pancreatic masses.

  1. Follicular Pancreatitis: A Distinct Form of Chronic Pancreatitis - An Additional Mimic of Pancreatic Neoplasms

    PubMed Central

    Gupta, Rajib K; Xie, Bill H; Patton, Kurt T; Lisovsky, Mikhail; Burks, Eric; Behrman, Stephen W; Klimstra, David; Deshpande, Vikram

    2016-01-01

    Follicular pancreatitis is a recently described variant of chronic pancreatitis characterized clinically by the formation of a discrete pancreatic mass and histologically by the presence of florid lymphoid aggregates with reactive germinal centers. Our aim was to study the clinical and histologic features of follicular pancreatitis, as well as to critically examine potential overlap with autoimmune pancreatitis. Immunohistochemistry for Bcl-2, CD21, kappa and lambda light chains as well as IgG4 and IgG were performed. We found a total of six patients (male:female = 2:1, mean age = 57 years) who fulfilled the diagnosis of follicular pancreatitis in our institutions. Four had an incidental diagnosis while two presented with abdominal pain, fatigue and elevated liver enzymes. On imaging, three patients had a discrete solid mass while 2 cases showed a dilated main pancreatic duct, mimicking an intraductal pancreatic mucinous neoplasm on imaging. One patient had a lesion in the intra-pancreatic portion of the common bile duct. On histopathology, all cases showed numerous lymphoid follicles with Bcl-2 negative germinal centers either in a periductal or in a more diffuse (periductal and intra-parenchymal) fashion, but without attendant storiform fibrosis, obliterative phlebitis or granulocytic epithelial lesions. IgG4/IgG ratio was <40% in all 6 cases. A comparison cohort revealed germinal centers in 25% of type 1 autoimmune pancreatitis and 2% of type 2 autoimmune pancreatitis cases, but none were periductal in location. In conclusion, follicular pancreatitis, an under-recognized mimic of pancreatic neoplasms is characterized by intrapancreatic lymphoid follicles with reactive germinal centers. PMID:26563969

  2. miR-1181 inhibits invasion and proliferation via STAT3 in pancreatic cancer

    PubMed Central

    Wang, Jie; Guo, Xing-Jun; Ding, You-Ming; Jiang, Jian-Xin

    2017-01-01

    AIM To examine the role of microRNA 1181 (miR-1181) in invasion and proliferation in pancreatic cancer. METHODS We analyzed the expression of miR-1181 in several pancreatic cancer cell lines and generated stable MIA-PaCa-2 and PANC-1 cell lines with up-regulated miR-1181 expression using an adenovirus delivery system. We then investigated miR-1181's effect on invasion and proliferation of pancreatic cancer cells by transwell assay, wound healing assay, cell counting kit-8 assay and colony-forming assay, and explored any underlying mechanisms by western bolt. Beyond that, we observed the change of the PANC-1 cell's cytoskeleton by immunofluorescence staining. RESULTS Our data showed that miR-1181 was relatively down-regulated in pancreatic cancer cell lines compared with normal pancreatic ductal epithelial cells. And miR-1181 inhibited the migration, invasion and proliferation activities of MIA-PaCa-2 and PANC-1 cells. Notably, after over-expressing of miR-1181 in PANC-1 cells, F-actin depolymerized. Immunofluorescence staining shows decreased F-actin and β-tubulin expression in PANC-1 cells over-expressing miR-1181 compared with the control cells. Furthermore, we found that over-expressing miR-1181 inhibited the expression of signal transducer and activator of transcription 3 (STAT3) while knocking-down miR-1181 up-regulated the expression of STAT3. Knocking-down miR-1181 promoted the invasion and proliferation of pancreatic cancer cells. And inhibition of STAT3 blocked the promotion effects of knocking-down miR-1181 on proliferation and invasion in pancreatic cancer. CONCLUSION Together our findings suggest that miR-1181 may be involved in pancreatic cancer cell invasion and proliferation by targeting STAT3 and indicate that miR-1181 may be a potential therapeutic agent for pancreatic cancer. PMID:28321160

  3. Acute Pancreatitis after Kidney Transplantation

    PubMed Central

    Tabakovic, Mithat; Salkic, Nermin N.; Bosnjic, Jasmina; Alibegovic, Ervin

    2012-01-01

    Acute pancreatitis is a rare but life-threatening complication in patients with transplanted kidney. The incidence of acute pancreatitis after kidney transplantation ranges from 2% to 7%, with mortality rate between 50 and 100%. We report a case of a female patient aged 46 years, developing an interstitial acute pancreatitis 8 years following a renal transplantation. The specific aethiological factor was not clearly established, although possibility of biliary pancreatitis with spontaneous stone elimination and/or medication-induced pancreatitis remains the strongest. Every patient after renal transplantation with an acute onset of abdominal pain should be promptly evaluated for presence of pancreatitis with a careful application of the most appropriate diagnostic procedure for each individual patient. PMID:23259142

  4. Global polio eradication initiative: lessons learned and legacy.

    PubMed

    Cochi, Stephen L; Freeman, Andrew; Guirguis, Sherine; Jafari, Hamid; Aylward, Bruce

    2014-11-01

    The world is on the verge of achieving global polio eradication. During >25 years of operations, the Global Polio Eradication Initiative (GPEI) has mobilized and trained millions of volunteers, social mobilizers, and health workers; accessed households untouched by other health initiatives; mapped and brought health interventions to chronically neglected and underserved communities; and established a standardized, real-time global surveillance and response capacity. It is important to document the lessons learned from polio eradication, especially because it is one of the largest ever global health initiatives. The health community has an obligation to ensure that these lessons and the knowledge generated are shared and contribute to real, sustained changes in our approach to global health. We have summarized what we believe are 10 leading lessons learned from the polio eradication initiative. We have the opportunity and obligation to build a better future by applying the lessons learned from GPEI and its infrastructure and unique functions to other global health priorities and initiatives. In so doing, we can extend the global public good gained by ending for all time one of the world's most devastating diseases by also ensuring that these investments provide public health dividends and benefits for years to come.

  5. Distinguishing between retention signals and degrons acting in ERAD.

    PubMed

    Shapira, Ilana; Charuvi, Dana; Elkabetz, Yechiel; Hirschberg, Koret; Bar-Nun, Shoshana

    2007-12-15

    Endoplasmic reticulum-associated degradation (ERAD) eliminates aberrant proteins from the secretory pathway. Such proteins are retained in the endoplasmic reticulum and targeted for degradation by the ubiquitin-proteasome system. Cis-acting motifs can function in ERAD as retention signals, preventing vesicular export from the endoplasmic reticulum, or as degrons, targeting proteins for degradation. Here, we show that microstp, the C-terminal 20-residue tailpiece of the secretory IgM mus heavy chain, functions both as a portable retention signal and as an ERAD degron. Retention of microstp fusions of secreted versions of thyroid peroxidase and yellow fluorescent protein in the endoplasmic reticulum requires the presence of the penultimate cysteine of microstp. In its role as a portable degron, the microstp targets the retained proteins for ERAD but does not serve as an obligatory ubiquitin-conjugation site. Abolishing microstp glycosylation accelerates the degradation of both microstpCys-fused substrates, yet absence of the N-glycan eliminates the requirement for the penultimate cysteine in the retention and degradation of the unglycosylated yellow fluorescent protein. Hence, the dual role played by the microstpCys motif as a retention signal and as a degron can be attributed to distinct elements within this sequence.

  6. Modeling disease transmission near eradication: An equation free approach

    NASA Astrophysics Data System (ADS)

    Williams, Matthew O.; Proctor, Joshua L.; Kutz, J. Nathan

    2015-01-01

    Although disease transmission in the near eradication regime is inherently stochastic, deterministic quantities such as the probability of eradication are of interest to policy makers and researchers. Rather than running large ensembles of discrete stochastic simulations over long intervals in time to compute these deterministic quantities, we create a data-driven and deterministic "coarse" model for them using the Equation Free (EF) framework. In lieu of deriving an explicit coarse model, the EF framework approximates any needed information, such as coarse time derivatives, by running short computational experiments. However, the choice of the coarse variables (i.e., the state of the coarse system) is critical if the resulting model is to be accurate. In this manuscript, we propose a set of coarse variables that result in an accurate model in the endemic and near eradication regimes, and demonstrate this on a compartmental model representing the spread of Poliomyelitis. When combined with adaptive time-stepping coarse projective integrators, this approach can yield over a factor of two speedup compared to direct simulation, and due to its lower dimensionality, could be beneficial when conducting systems level tasks such as designing eradication or monitoring campaigns.

  7. Effects of Helicobacter Pylori Eradication Among Adults with Intellectual Disability

    ERIC Educational Resources Information Center

    Wallace, R. A.; Schluter, P. J.; Webb, P. M.

    2004-01-01

    Compared to the general population, Helicobacter pylori infection is more common among adults with intellectual disability (ID) and is associated with greater levels of disability, maladaptive behaviour, and institutionalization. Little information exists about the effects of eradication therapy in this group, so we aimed to evaluate: (1) success…

  8. [First line therapy for Helicobacter pylori eradication in France].

    PubMed

    Dupas, Jean-Louis

    2003-03-01

    The available results of triple therapy for the eradication of Helicobacter pylori (H. pylori), as recommended in European countries--i.e. combination of proton pump inhibitor (PPI) and two antibiotics among amoxicillin, clarithromycin, metronidazole for 7 days--lead to rates of failure of about 30%. Several clinical studies have been recently conducted to distinguish factors influencing effectiveness of therapy and to evaluate results of new regimens. Comparative trials have demonstrated the equivalence of omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, rabeprazole 20 mg and esomeprazole 20 mg, twice daily in these 7-days triple therapies. Efficacy of treatment is not affected by metronidazole resistance (44% in France) when amoxicillin-clarithromycin-based triple therapy is prescribed. The impact of clarithromycin resistance (14%) is much more important with failure of eradication in all cases treated by clarithromycin-based triple therapy. The eradication rate could be slightly improved by increasing the dose of clarithromycin but with more frequent side effects. To prolong the duration treatment improve also slightly the cure rate with a gain of less than 10%, but with an increasing rate of side effects. To date, the PPI-based triple therapies, as recommended in France, have not to be modified. The treatment of H. pylori infection has to be globally considered, with a first-line treatment leading to eradication in 70% of patients and a second-line treatment needed for the resting 30% of patients.

  9. Macroeconomics, (Adult) Education, and Poverty Eradication in Southern Africa

    ERIC Educational Resources Information Center

    Nhamo, Senia; Nhamo, Godwell

    2006-01-01

    The Millennium Summit held in New York in September 2000 outlined the Millennium Development Goals (MDGs). The first of these involves the eradication of extreme poverty and hunger, setting two targets: halving by 2015 the percentage of the world's populace in 1990 with income less than US-$1 a day (i.e., cutting this percentage from 27.9 to 14%);…

  10. A new challenge for the world: the eradication of polio.

    PubMed

    Gentile, Ángela; Abate, Héctor

    2016-12-01

    Poliovirus infects 100% of susceptible individuals and causes acute flaccid paralysis in one out of200 infections. Type 1 causes epidemic poliomyelitis; type 2 has been eradicated worldwide; and type 3 is close to being eradicated. In this region, the last case of wild poliovirus occurred in Peru in 1991. There are still two endemic countries: Afghanistan and Pakistan, but countries where there is no circulation of the wild poliovirus have also reported imported cases of polio. In May 2012, the World Health Assembly declared the polio eradication a programmatic emergency for global public health and, as a result, developed the Polio Eradication and Endgame Strategic Plan 2013-2018. The Plan has four objectives: 1) Detect and interrupt all poliovirus transmission and maintain surveillance of acute flaccid paralysis in children < 15 years. 2) Strengthen immunization systems and withdraw oral polio vaccine by the first trimester of 2016. Replace the trivalent oral polio vaccine with the bivalent oral vaccine, containing serotypes 1 and 3, and introduce the inactivated polio vaccine in all immunization schedules to maintain immunity against poliovirus type 2. 3) Contain poliovirus and certify interruption of transmission. 4) Plan the exploitation of the fight against polio and its impact on public health. The plan is expected to reach its goals by 2018; all use of the oral polio vaccine will be interrupted thereafter. Change in immunization schedules will require pediatricians to provide advice and guidance to families depending on the varied situations of everyday practice.

  11. From emergence to eradication: the epidemiology of poliomyelitis deconstructed.

    PubMed

    Nathanson, Neal; Kew, Olen M

    2010-12-01

    Poliomyelitis has appeared in epidemic form, become endemic on a global scale, and been reduced to near-elimination, all within the span of documented medical history. Epidemics of the disease appeared in the late 19th century in many European countries and North America, following which polio became a global disease with annual epidemics. During the period of its epidemicity, 1900-1950, the age distribution of poliomyelitis cases increased gradually. Beginning in 1955, the creation of poliovirus vaccines led to a stepwise reduction in poliomyelitis, culminating in the unpredicted elimination of wild polioviruses in the United States by 1972. Global expansion of polio immunization resulted in a reduction of paralytic disease from an estimated annual prevaccine level of at least 600,000 cases to fewer than 1,000 cases in 2000. Indigenous wild type 2 poliovirus was eradicated in 1999, but unbroken localized circulation of poliovirus types 1 and 3 continues in 4 countries in Asia and Africa. Current challenges to the final eradication of paralytic poliomyelitis include the continued transmission of wild polioviruses in endemic reservoirs, reinfection of polio-free areas, outbreaks due to circulating vaccine-derived polioviruses, and persistent excretion of vaccine-derived poliovirus by a few vaccinees with B-cell immunodeficiencies. Beyond the current efforts to eradicate the last remaining wild polioviruses, global eradication efforts must safely navigate through an unprecedented series of endgame challenges to assure the permanent cessation of all human poliovirus infections.

  12. Progress toward poliomyelitis eradication--Nigeria, 2005-2006.

    PubMed

    2007-03-30

    Only four countries (Afghanistan, India, Nigeria, and Pakistan) have never experienced interruption of poliovirus transmission. Nigeria had the largest number of cases in 2006, accounting for 1,129 (56%) of the 2,002 cases reported globally. However, major innovations to the national polio-eradication program in Nigeria were initiated in 2006. These innovations, if sustained, should advance the Global Polio Eradication Initiative. Nigeria (2006 population: 140 million) experienced a resurgence in wild poliovirus (WPV) transmission during 2003-2004 after a loss of public confidence in oral polio vaccine (OPV) and suspension of supplementary immunization activities (SIAs) in certain northern states. Subsequently, WPV spread within Nigeria and into 19 polio-free countries. Even after national SIAs recommenced, limited acceptance and ongoing operational problems resulted in low vaccination coverage and continued poliovirus transmission. The number of confirmed polio cases in Nigeria attributed to both WPV type 1 (WPV1) and type 3 (WPV3) increased from 782 in 2004 to 830 in 2005 and to 1,129 in 2006 (as of March 23, 2007). To increase the effectiveness of polio-eradication measures and community acceptance of vaccination, in 2006, health authorities in Nigeria introduced monovalent type 1 OPV (mOPV1) vaccine and changed the way SIAs were implemented. This report summarizes these new approaches and overall progress toward polio eradication in Nigeria during 2005-2006.

  13. "Endgame" issues for the global polio eradication initiative.

    PubMed

    2002-01-01

    The polio eradication initiative, created after the World Health Assembly resolved, in 1988, to eradicate poliomyelitis globally by 2000, has made remarkable progress. From 1988 through 2000, the number of countries where polio was endemic decreased from >125 to 20, and the estimated number of polio cases decreased from 350,000 to <3500, for a percentage decrease of >99%. Wild-type 2 poliovirus has not been detected worldwide since October 1999, despite improving surveillance. The major focus of the eradication effort is to complete the task of stopping wild-type poliovirus transmission. Given the rapid progress made toward this goal, planning for the posteradication era has begun in earnest (1) to minimize the risk of reintroduction of virus into the population from laboratory stocks or long-term carriers, and (2) to prevent vaccine-derived polioviruses from circulating and causing outbreaks. This report summarizes the current thinking about these "endgame" issues, as put forth by the World Health Organization's technical advisory body for the initiative, the Technical Consultative Group on the Global Eradication of Poliomyelitis.

  14. Screwworm Eradication Data System (SEDS) preprocessor program documentation, part 1

    NASA Technical Reports Server (NTRS)

    1976-01-01

    To achieve the capability required by the Screwworm Eradication Data System (SEDS) and to process the 14-track analog tapes supplied by the National Oceanic and Atmospheric Administration, the existing Earth Resources Preprocessor Software Subsystem (ERPSS) was enhanced. A brief overview of the ERPSS is given along with descriptions of only those computer program components that were modified to meet the SEDS requirements.

  15. Human papillomavirus E6E7-mediated adenovirus cell killing: selectivity of mutant adenovirus replication in organotypic cultures of human keratinocytes.

    PubMed

    Balagué, C; Noya, F; Alemany, R; Chow, L T; Curiel, D T

    2001-08-01

    Replication-competent adenoviruses are being investigated as potential anticancer agents. Exclusive virus replication in cancer cells has been proposed as a safety trait to be considered in the design of oncolytic adenoviruses. From this perspective, we have investigated several adenovirus mutants for their potential to conditionally replicate and promote the killing of cells expressing human papillomavirus (HPV) E6 and E7 oncoproteins, which are present in a high percentage of anogenital cancers. For this purpose, we have employed an organotypic model of human stratified squamous epithelium derived from primary keratinocytes that have been engineered to express HPV-18 oncoproteins stably. We show that, whereas wild-type adenovirus promotes a widespread cytopathic effect in all infected cells, E1A- and E1A/E1B-deleted adenoviruses cause no deleterious effect regardless of the coexpression of HPV18 E6E7. An adenovirus deleted in the CR2 domain of E1A, necessary for binding to the pRB family of pocket proteins, shows no selectivity of replication as it efficiently kills all normal and E6E7-expressing keratinocytes. Finally, an adenovirus mutant deleted in the CR1 and CR2 domains of E1A exhibits preferential replication and cell killing in HPV E6E7-expressing cultures. We conclude that the organotypic keratinocyte culture represents a distinct model to evaluate adenovirus selectivity and that, based on this model, further modifications of the adenovirus genome are required to restrict adenovirus replication to tumor cells.

  16. Human Papillomavirus E6E7-Mediated Adenovirus Cell Killing: Selectivity of Mutant Adenovirus Replication in Organotypic Cultures of Human Keratinocytes

    PubMed Central

    Balagué, Cristina; Noya, Francisco; Alemany, Ramon; Chow, Louise T.; Curiel, David T.

    2001-01-01

    Replication-competent adenoviruses are being investigated as potential anticancer agents. Exclusive virus replication in cancer cells has been proposed as a safety trait to be considered in the design of oncolytic adenoviruses. From this perspective, we have investigated several adenovirus mutants for their potential to conditionally replicate and promote the killing of cells expressing human papillomavirus (HPV) E6 and E7 oncoproteins, which are present in a high percentage of anogenital cancers. For this purpose, we have employed an organotypic model of human stratified squamous epithelium derived from primary keratinocytes that have been engineered to express HPV-18 oncoproteins stably. We show that, whereas wild-type adenovirus promotes a widespread cytopathic effect in all infected cells, E1A- and E1A/E1B-deleted adenoviruses cause no deleterious effect regardless of the coexpression of HPV18 E6E7. An adenovirus deleted in the CR2 domain of E1A, necessary for binding to the pRB family of pocket proteins, shows no selectivity of replication as it efficiently kills all normal and E6E7-expressing keratinocytes. Finally, an adenovirus mutant deleted in the CR1 and CR2 domains of E1A exhibits preferential replication and cell killing in HPV E6E7-expressing cultures. We conclude that the organotypic keratinocyte culture represents a distinct model to evaluate adenovirus selectivity and that, based on this model, further modifications of the adenovirus genome are required to restrict adenovirus replication to tumor cells. PMID:11462032

  17. Routine monitoring of adenovirus and norovirus within the health care environment.

    PubMed

    Pankhurst, Louise; Cloutman-Green, Elaine; Canales, Melisa; D'Arcy, Nikki; Hartley, John C

    2014-11-01

    This study investigated the presence of adenovirus and norovirus on ward surfaces using real-time polymerase chain reaction (PCR) to assist in the development of evidence-based infection control policy. Screening was carried out weekly for 6 months in the common areas of 2 pediatric wards. Additionally, a one-off screening was undertaken for adenovirus and norovirus on a day unit and for adenovirus only in patient cubicles while occupied. Over the 6-month screening of common areas, 2.4% of samples were positive for adenovirus or norovirus. In rooms occupied with adenovirus-infected children, all cubicle screening sites and almost all swabs were contaminated with adenovirus. In the day unit, 13% of samples were positive. Cleaning and environmental interaction strategies must therefore be designed to control nosocomial transmission of viruses outside of outbreak scenarios.

  18. Effect of adenovirus infection on expression of human histone genes.

    PubMed Central

    Flint, S J; Plumb, M A; Yang, U C; Stein, G S; Stein, J L

    1984-01-01

    The influence of adenovirus type 2 infection of HeLa cells upon expression of human histone genes was examined as a function of the period of infection. Histone RNA synthesis was assayed after run-off transcription in nuclei isolated from mock-infected cells and after various periods of adenovirus infection. Histone protein synthesis was measured by [3H]leucine labeling of intact cells and fluorography of electrophoretically fractionated nuclear and cytoplasmic proteins. The cellular representation of RNA species complementary to more than 13 different human histone genes was determined by RNA blot analysis of total cellular, nuclear or cytoplasmic RNA by using a series of 32P-labeled cloned human histone genes as hybridization probes and also by analysis of 3H-labeled histone mRNA species synthesized in intact cells. By 18 h after infection, HeLa cell DNA synthesis and all parameters of histone gene expression, including transcription and the nuclear and cytoplasmic concentrations of core and H1 mRNA species, were reduced to less than 5 to 10% of the control values. By contrast, transcription and processing of other cellular mRNA sequences have been shown to continue throughout this period of infection. The early period of adenovirus infection was marked by an inhibition of transcription of histone genes that accompanied the reduction in rate of HeLa cell DNA synthesis. These results suggest that the adenovirus-induced inhibition of histone gene expression is mediated in part at the transcriptional level. However, the persistence of histone mRNA species at concentrations comparable to those of mock-infected control cells during the early phase of the infection, despite a reduction in histone gene transcription and histone protein synthesis, implies that histone gene expression is also regulated post-transcriptionally in adenovirus-infected cells. These results suggest that the tight coupling between histone mRNA concentrations and the rate of cellular DNA

  19. Recombinant adenovirus expressing the haemagglutinin of peste des petits ruminants virus (PPRV) protects goats against challenge with pathogenic virus; a DIVA vaccine for PPR

    PubMed Central

    2014-01-01

    Peste des petits ruminants virus (PPRV) is a morbillivirus that can cause severe disease in sheep and goats, characterised by pyrexia, pneumo-enteritis, and gastritis. The socio-economic burden of the disease is increasing in underdeveloped countries, with poor livestock keepers being affected the most. Current vaccines consist of cell-culture attenuated strains of PPRV, which induce a similar antibody profile to that induced by natural infection. Generation of a vaccine that enables differentiation of infected from vaccinated animals (DIVA) would benefit PPR control and eradication programmes, particularly in the later stages of an eradication campaign and for countries where the disease is not endemic. In order to create a vaccine that would enable infected animals to be distinguished from vaccinated ones (DIVA vaccine), we have evaluated the immunogenicity of recombinant fowlpox (FP) and replication-defective recombinant human adenovirus 5 (Ad), expressing PPRV F and H proteins, in goats. The Ad constructs induced higher levels of virus-specific and neutralising antibodies, and primed greater numbers of CD8+ T cells than the FP-vectored vaccines. Importantly, a single dose of Ad-H, with or without the addition of Ad expressing ovine granulocyte macrophage colony-stimulating factor and/or ovine interleukin-2, not only induced strong antibody and cell-mediated immunity but also completely protected goats against challenge with virulent PPRV, 4 months after vaccination. Replication-defective Ad-H therefore offers the possibility of an effective DIVA vaccine. PMID:24568545

  20. Progress Toward Polio Eradication - Worldwide, 2015-2016.

    PubMed

    Morales, Michelle; Tangermann, Rudolf H; Wassilak, Steven G F

    2016-05-13

    In 1988, the World Health Assembly resolved to eradicate poliomyelitis. Wild poliovirus (WPV) transmission persists in only two countries (Afghanistan and Pakistan) after the removal of Nigeria from the list of countries with endemic polio in September 2015.* Indigenous WPV type 2 has not been detected since 1999 and was declared eradicated by the Global Commission for the Certification of Poliomyelitis Eradication in September 2015.(†) Since November 2012, when the last case of WPV type 3 was detected in Nigeria, WPV type 1 has been the sole circulating type of WPV (1). This report summarizes global progress toward polio eradication during 2015-2016 and updates previous reports (2). In 2015, 74 WPV cases were reported in two countries (Afghanistan and Pakistan), a decrease of 79% from the 359 WPV cases reported in 2014 in nine countries; 12 WPV cases have been reported in 2016 (to date), compared with 23 during the same period in 2015 (3). Paralytic polio caused by circulating vaccine-derived poliovirus (cVDPV) remains a risk in areas with low oral poliovirus vaccine (OPV) coverage. Seven countries, including Pakistan, reported 32 cVDPV cases in 2015 (4). In four of these countries, ≥6 months have passed since the most recent case or isolate. One country (Laos) with VDPV transmission in 2015 has reported three additional cVDPV cases in 2016 to date. Encouraging progress toward polio eradication has been made over the last year; however, interruption of WPV transmission will require focus on reaching and vaccinating every missed child through high quality supplementary immunization activities (SIAs) and cross-border coordination between Afghanistan and Pakistan (5,6).

  1. Metabolic consequences of Helicobacter pylori infection and eradication

    PubMed Central

    Buzás, György Miklós

    2014-01-01

    Helicobacter pylori (H. pylori) is still the most prevalent infection of the world. Colonization of the stomach by this agent will invariably induce chronic gastritis which is a low-grade inflammatory state leading to local complications (peptic ulcer, gastric cancer, lymphoma) and remote manifestations. While H. pylori does not enter circulation, these extragastric manifestations are probably mediated by the cytokines and acute phase proteins produced by the inflammed mucosa. The epidemiologic link between the H. pylori infection and metabolic changes is inconstant and controversial. Growth delay was described mainly in low-income regions with high prevalence of the infection, where probably other nutritional and social factors contribute to it. The timely eradication of the infection will lead to a more healthy development of the young population, along with preventing peptic ulcers and gastric cancer An increase of total, low density lipoprotein and high density liporotein cholesterol levels in some infected people creates an atherogenic lipid profile which could promote atherosclerosis with its complications, myocardial infarction, stroke and peripheral vascular disease. Well designed and adequately powered long-term studies are required to see whether eradication of the infection will prevent these conditions. In case of glucose metabolism, the most consistent association was found between H. pylori and insulin resistance: again, proof that eradication prevents this common metabolic disturbance is expected. The results of eradication with standard regimens in diabetics are significantly worse than in non-diabetic patients, thus, more active regimens must be found to obtain better results. Successful eradication itself led to an increase of body mass index and cholesterol levels in some populations, while in others no such changes were encountered. Uncertainities of the metabolic consequences of H. pylori infection must be clarified in the future. PMID:24833852

  2. Progress toward poliomyelitis eradication - Nigeria, January 2011-September 2012.

    PubMed

    2012-11-09

    In 1988, the World Health Assembly launched the Global Polio Eradication Initiative (GPEI) and, in 2012, declared the completion of polio eradication a programmatic emergency for global public health. To date, wild poliovirus (WPV) cases reported worldwide in 2012 are at historically low levels. Nigeria is one of only three countries with uninterrupted WPV transmission (in addition to Pakistan and Afghanistan) and has been the origin of WPV imported into 25 previously polio-free countries since 2003. This report updates previous reports and describes polio eradication activities and progress in Nigeria during January 2011-September 2012, as of October 30, 2012. The number of reported WPV cases increased from 21 in 2010 to 62 in 2011. During January-September 2012, a total of 99 WPV cases were reported, more than doubling from the 42 cases reported during the same period in 2011. During 2011, a total of 32 circulating vaccine-derived polio virus type 2 (cVDPV2) cases were confirmed; six cVDPV2 cases were confirmed during January-September 2012, compared with 18 cVDPV2 cases during the same period in 2011. Nigeria's 2012 Polio Eradication Emergency Plan includes senior government leadership oversight, new program management and strategic initiatives, an accountability framework, and a surge in human resources to address chronically missed children during supplemental immunization activities (SIAs).* In 2012, indicators of immunization campaign quality show modest improvements; available data indicate gaps in surveillance. Continuing WPV transmission in Nigeria poses an ongoing risk for WPV reintroduction and outbreaks in polio-free countries and is a major obstacle to achieving global eradication.

  3. [Latest advances in acute pancreatitis].

    PubMed

    de-Madaria, Enrique

    2015-09-01

    The present article analyses the main presentations on acute pancreatitis at Digestive Disease Week 2015. Arterial pseudoaneurysm is an uncommon complication of acute pancreatitis (incidence 0.7%) and mortality from this cause is currently anecdotal. Diabetes mellitus has little impact on the clinical course of acute pancreatitis, unlike cirrhosis, which doubles the risk of mortality. Intake of unsaturated fat could be associated with an increased severity of acute pancreatitis and is a confounding factor in studies evaluating the relationship between obesity and morbidity and mortality. PET-CT (positron emission tomography-computed tomography) could be a non-invasive tool to detect infection of collections in acute pancreatitis. Peripancreatic fat necrosis is less frequent than pancreatic fat necrosis and is associated with a better clinical course. If the clinical course is poor, increasing the calibre of the percutaneous drains used in the treatment of infected necrosis can avoid surgery in 20% of patients. The use of low molecular-weight heparin in moderate or severe pancreatitis could be associated with a better clinical course, specifically with a lower incidence of necrosis. In acute recurrent pancreatitis, simvastatin is a promising drug for prophylaxis of new episodes of acute pancreatitis. Nutritional support through a nasogastric tube does not improve clinical course compared with oral nutrition.

  4. [Exocrine pancreatic insufficiency (author's transl)].

    PubMed

    Götze, H

    1980-12-01

    Exocrine pancreatic insufficiency usually does not develop before reduction of enzyme output by more than 90%. Patients with pancreatic insufficiency have a ravenous appetite but fail to thrive from malnutrition. The caloric deprivation is primarily due to fat malabsorption, recognized by the passage of bulky foul smelling greasy stools. Several isolated enzyme deficiencies can be separated from diseases with generalised pancreatic insufficiency. Under replacement therapy with pancreatic enzyme supplements most patients improve and gain weight, although fat and bile acid malabsorption are not abolished.

  5. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez-Muñoz, J Enrique

    2013-10-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern knowledge of the etiopathogenesis of the disease, the pharmacological treatment of pain, and knowledge of the natural history of autoimmune pancreatitis. New evidence supports the relatively low prevalence of chronic alcoholic pancreatitis, and the role of tobacco in triggering the etiopathogenic mechanisms of chronic pancreatitis is better understood. Some studies have identified certain factors that are associated with having a positive genetic test in adults with chronic idiopathic pancreatitis, which should help to select those patients who should undergo genetic studies. Antioxidant therapy has been shown to be effective in reducing pain secondary to chronic pancreatitis, although the type and optimal dose of antioxidants remains to be elucidated. Finally, the development of exocrine and endocrine pancreatic insufficiency is a very common finding during the long-term follow-up of patients with autoimmune pancreatitis. Smoking also seems to play a role in this type of pancreatitis.

  6. Acute pancreatitis: The stress factor

    PubMed Central

    Binker, Marcelo G; Cosen-Binker, Laura I

    2014-01-01

    Acute pancreatitis is an inflammatory disorder of the pancreas that may cause life-threatening complications. Etiologies of pancreatitis vary, with gallstones accounting for the majority of all cases, followed by alcohol. Other causes of pancreatitis include trauma, ischemia, mechanical obstruction, infections, autoimmune, hereditary, and drugs. The main events occurring in the pancreatic acinar cell that initiate and propagate acute pancreatitis include inhibition of secretion, intracellular activation of proteases, and generation of inflammatory mediators. Small cytokines known as chemokines are released from damaged pancreatic cells and attract inflammatory cells, whose systemic action ultimately determined the severity of the disease. Indeed, severe forms of pancreatitis may result in systemic inflammatory response syndrome and multiorgan dysfunction syndrome, characterized by a progressive physiologic failure of several interdependent organ systems. Stress occurs when homeostasis is threatened, and stressors can include physical or mental forces, or combinations of both. Depending on the timing and duration, stress can result in beneficial or harmful consequences. While it is well established that a previous acute-short-term stress decreases the severity of experimentally-induced pancreatitis, the worsening effects of chronic stress on the exocrine pancreas have received relatively little attention. This review will focus on the influence of both prior acute-short-term and chronic stress in acute pancreatitis. PMID:24914340

  7. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez-Muñoz, J Enrique

    2014-09-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the prediction of the fibrosis degree of the gland, the evaluation of patients with asymptomatic hyperenzimemia, the medical and surgical treatment of abdominal pain and the knowledge of the natural history of the autoimmune pancreatitis. In patients with indetermined EUS findings of chronic pancreatitis, a new endoscopic ultrasound examination in the follow-up is of help to confirm or to exclude the disease. Smoking, number of relapses, results of pancreatic function tests and EUS findings allow predicting the degree of pancreatic fibrosis in patients with chronic pancreatitis. Antioxidant therapy has shown to be effective in reducing pain secondary to chronic pancreatitis, although the type and optimal dose of antioxidants remains to be elucidated. Development of intestinal bacterial overgrowth is frequent in patients with chronic pancreatitis, but its impact on symptoms is unknown and deserves further investigations. Finally, autoimmune pancreatitis relapses in about half of the patients with either type 1 or type 2 disease; relapses frequently occur within the first two years of follow-up.

  8. Province-wide adenovirus type 3 outbreak with severe cases in New Brunswick

    PubMed Central

    Girouard, Gabriel; Garceau, Richard; Thibault, Louise; Bourque, Christine; Bastien, Nathalie; Li, Yan

    2011-01-01

    Adenovirus is a commonly isolated virus in clinical samples. Life-threatening infections, although rare, are described worldwide. An epidemic spread of an adenovirus type 3 strain occurred in the province of New Brunswick during the fall of 2008 to the winter of 2009; it resulted in three severely ill patients, with one fatality. Adenovirus should be considered as a cause of severe community-acquired viral pneumonia, especially when the influenza test is negative. PMID:22379488

  9. Large Epidemic of Respiratory Illness Due to Adenovirus Types 7 and 3 in Healthy Young Adults

    DTIC Science & Technology

    2008-02-15

    Epidemic of Respiratory fliness Due to Adenovirus Types 7 and 3 in Healthy Young Adults Margaret A. K. Ryan, Gregory C. Gray," Besa Smith, Jamie A...immunization, respiratory infections due to adenoviruses have reemerged to threaten the health of young adults in the military. Shortly after the loss...challenges for young adults in the military in the postvaccine era. The US military has long had concern about the impact adenovirus serotypes 4 and 7

  10. Dramatic Decline of Respiratory Illness Among US Military Recruits After the Renewed Use of Adenovirus Vaccines

    DTIC Science & Technology

    2014-10-01

    Naval Health Research Center Dramatic Decline of Respiratory Illness Among US Military Recruits After the Renewed Use of Adenovirus Vaccines ...Renewed Use of Adenovirus Vaccines Jennifer M. Radin,1,2 Anthony W. Hawksworth,1 Patrick J. Blair,1 Dennis J. Faix,3 Rema Raman,4 Kevin L. Russell,5...hiatus, oral vaccines against adenovirus types 4 (Ad4) and 7 (Ad7) were again produced and administered to US military recruits. This study examined the

  11. Adenovirus urethritis and concurrent conjunctivitis: a case series and review of the literature.

    PubMed

    Liddle, Olivia Louise; Samuel, Mannampallil Itty; Sudhanva, Malur; Ellis, Joanna; Taylor, Chris

    2015-03-01

    We present eight cases and review the literature of concurrent urethritis and conjunctivitis where adenovirus was identified as the causative pathogen. The focus of this review concerns the identification of specific sexual practices, symptoms, signs and any serotypes that seem more commonly associated with such adenovirus infections. We discuss the seasonality of adenovirus infection and provide practical advice for clinicians to give to the patient.

  12. Overcoming pre-existing adenovirus immunity by genetic engineering of adenovirus-based vectors.

    PubMed

    Seregin, Sergey S; Amalfitano, Andrea

    2009-12-01

    Adenovirus (Ad)-based vectors offer several benefits showing their potential for use in a variety of vaccine applications. Recombinant Ad-based vaccines possess potent immunogenic potential, capable of generating humoral and cellular immune responses to a variety of pathogen-specific antigens expressed by the vectors. Ad5 vectors can be readily produced, allowing for usage in thousands of clinical trial subjects. This is now coupled with a history of safe clinical use in the vaccine setting. However, traditional Ad5-based vaccines may not be generating optimal antigen-specific immune responses, and generate diminished antigen-specific immune responses when pre-existing Ad5 immunity is present. These limitations have driven initiation of several approaches to improve the efficacy of Ad-based vaccines, and/or allow modified vaccines to overcome pre-existing Ad immunity. These include: generation of chemically modified Ad5 capsids; generation of chimeric Ads; complete replacement of Ad5-based vaccine platforms with alternative (human and non-human origin) Ad serotypes, and Ad5 genome modification approaches that attempt to retain the native Ad5 capsid, while simultaneously improving the efficacy of the platform as well as minimizing the effect of pre-existing Ad immunity. Here we discuss recent advances in- and limitations of each of these approaches, relative to their abilities to overcome pre-existing Ad immunity.

  13. Combinatorial treatment with oncolytic adenovirus and helper-dependent adenovirus augments adenoviral cancer gene therapy

    PubMed Central

    Farzad, Lisa; Cerullo, Vincenzo; Yagyu, Shigeki; Bertin, Terry; Hemminki, Akseli; Rooney, Cliona; Lee, Brendan; Suzuki, Masataka

    2014-01-01

    Oncolytic adenoviruses (Onc.Ads) produce significant antitumor effects but as single agents they rarely eliminate tumors. Investigators have therefore incorporated sequences into these vectors that encode immunomodulatory molecules to enhance antitumor immunity. Successful implementation of this strategy requires multiple tumor immune inhibitory mechanisms to be overcome, and insertion of the corresponding multiple functional genes reduces the titer and replication of Onc.Ads, compromising their direct ant-tumor effects. By contrast, helper-dependent (HD) Ads are devoid of viral coding sequences, allowing inclusion of multiple transgenes. HDAds, however, lack replicative capacity. Since HDAds encode the adenoviral packaging signal, we hypothesized that the coadministration of Onc.Ad with HDAd would allow to be amplified and packaged during replication of Onc.Ad in transduced cancer cells. This combination could provide immunostimulation without losing oncolytic activity. We now show that coinfection of Onc.Ad with HDAd subsequently replicates HDAd vector DNA in trans in human cancer cell lines in vitro and in vivo, amplifying the transgenes the HDAd encode. This combinatorial treatment significantly suppresses the tumor growth compared to treatment with a single agent in an immunocompetent mouse model. Hence, combinatorial treatment of Onc.Ad with HDAd should overcome the inherent limitations of each agent and provide a highly immunogenic oncolytic therapy. PMID:27119096

  14. Thromboembolism and pancreatic cancer.

    PubMed

    De Souza, Andre Luiz; Saif, Muhammad Wasif

    2014-07-28

    Venous thromboembolism (VTE) is a frequent event in the clinical course of patients with exocrine pancreatic cancer; studies have been designed to evaluate the role of prophylactic anticoagulation in this ominous disease. Searching for the molecular basis of thrombosis in cancer, Bozkurt et al. present in the Abstract #e22049 the result of their investigation on the frequency of inherited and carcinogenesis-acquired proteins in oncologic patients with and without venous thromboembolism. From the bedside, Muñoz Martin et al. present in the Abstract #e15187 their work on the incidence of venous thromboembolism in patients with exocrine pancreatic cancer and the role of the established Khorana score in predicting symptomatic and incidental venous thromboembolism. At last, Cella et al. in the Abstract #e20625 expand the predictor landscape from the Khorana score to other risk factors for venous thromboembolism, refining the selection of oncologic patients who can benefit from prophylactic anticoagulation.

  15. Pancreatic neuroendocrine tumors

    PubMed Central

    Sun, Jian

    2017-01-01

    Summary Pancreatic neuroendocrine neoplasms (pNENs) are a heterogeneous group of tumors including well differentiated pancreatic neuroendocrine tumors (pNETs) and neuroendocrine carcinomas (pNECs). The incidence of pNENs has increased over the past few decades. Although, the understanding and interest for this tumor have also increased significantly, the debate about classification and diagnosis continues. Although the primary treatment for pNENs is surgical resection, there is still a lack of effective therapeutic options for patients with advanced unresectable pNENs. Although many therapeutic methods have proven effective, the choice of treatment and specific programs are still unclear. Our article presents an overview of pNENs, with a focus on their diagnostic work-up, clinical presentation and treatment options. PMID:28357177

  16. Strengthening the partnership between routine immunization and the global polio eradication initiative to achieve eradication and assure sustainability.

    PubMed

    Abdelwahab, Jalaa; Dietz, Vance; Eggers, Rudolf; Maher, Christopher; Olaniran, Marianne; Sandhu, Hardeep; Vandelaer, Jos

    2014-11-01

    Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988, the number of polio endemic countries has declined from 125 to 3 in 2013. Despite this remarkable achievement, ongoing circulation of wild poliovirus in polio-endemic countries and the increase in the number of circulating vaccine-derived poliovirus cases, especially those caused by type 2, is a cause for concern. The Polio Eradication and Endgame Strategic Plan 2013-2018 (PEESP) was developed and includes 4 objectives: detection and interruption of poliovirus transmission, containment and certification, legacy planning, and a renewed emphasis on strengthening routine immunization (RI) programs. This is critical for the phased withdrawal of oral poliovirus vaccine, beginning with the type 2 component, and the introduction of a single dose of inactivated polio vaccine into RI programs. This objective has inspired renewed consideration of how the GPEI and RI programs can mutually benefit one another, how the infrastructure from the GPEI can be used to strengthen RI, and how a strengthened RI can facilitate polio eradication. The PEESP is the first GPEI strategic plan that places strong and clear emphasis on the necessity of improving RI to achieve and sustain global polio eradication.

  17. Phylogenetic analyses of novel squamate adenovirus sequences in wild-caught Anolis lizards.

    PubMed

    Ascher, Jill M; Geneva, Anthony J; Ng, Julienne; Wyatt, Jeffrey D; Glor, Richard E

    2013-01-01

    Adenovirus infection has emerged as a serious threat to the health of captive snakes and lizards (i.e., squamates), but we know relatively little about this virus' range of possible hosts, pathogenicity, modes of transmission, and sources from nature. We report the first case of adenovirus infection in the Iguanidae, a diverse family of lizards that is widely-studied and popular in captivity. We report adenovirus infections from two closely-related species of Anolis lizards (anoles) that were recently imported from wild populations in the Dominican Republic to a laboratory colony in the United States. We investigate the evolution of adenoviruses in anoles and other squamates using phylogenetic analyses of adenovirus polymerase gene sequences sampled from Anolis and a range of other vertebrate taxa. These phylogenetic analyses reveal that (1) the sequences detected from each species of Anolis are novel, and (2) adenoviruses are not necessarily host-specific and do not always follow a co-speciation model under which host and virus phylogenies are perfectly concordant. Together with the fact that the Anolis adenovirus sequences reported in our study were detected in animals that became ill and subsequently died shortly after importation while exhibiting clinical signs consistent with acute adenovirus infection, our discoveries suggest the need for renewed attention to biosecurity measures intended to prevent the spread of adenovirus both within and among species of snakes and lizards housed in captivity.

  18. Addition of Polyadenylate Sequences to Virus-Specific RNA during Adenovirus Replication

    PubMed Central

    Philipson, L.; Wall, R.; Glickman, G.; Darnell, J. E.

    1971-01-01

    Adenovirus-specific nuclear and polysomal RNA, both early and late in the infectious cycle, contain a covalently linked region of polyadenylic acid 150-250 nucleotides long. A large proportion of the adenovirus-specific messenger RNA contains poly(A). As revealed by hybridization experiments, the poly(A) is not transcribed from adenovirus DNA. Furthermore, an adenosine analogue, cordycepin, blocks the synthesis of poly(A) and also inhibits the accumulation of adenovirus messenger RNA on polysomes. Addition of poly(A) to viral RNA may involve a host-controlled mechanism that regulates the processing and transport of messenger RNA. PMID:5315962

  19. Inhibitory effect of interferon-gamma on adenovirus replication and late transcription.

    PubMed

    Mistchenko, A S; Diez, R A; Falcoff, R

    1989-06-15

    We have previously shown that human interferon-gamma inhibited adenovirus multiplication in vitro in a dose-dependent fashion. This action was previous to capsid proteins synthesis and did not involve virus adsorption nor penetration. In this report we have analysed viral mRNA levels at early (7 hr post infection (p.i.)) or late (20 hr p.i.) times, as well as DNA replication in Wish cells pretreated with interferon-gamma and infected with adenovirus 5. Controls included untreated cells as well as cells treated with interferon-alpha, to which adenovirus are reported to be resistant. Transcription of adenovirus regions E1, E4, L1 and L2 has been analysed by Northern blot. Adenovirus DNA replication was determined by DNA-DNA hybridization with total adenovirus 2 DNA. We have also searched for adenovirus E1A proteins by immunoblot with a specific monoclonal antibody. Although pretreatment of cells with either interferon-alpha or interferon-gamma resulted in reduced amounts of E1 and E4 mRNA in the early phase of infection (7 hr p.i.), the near complete inhibition of viral DNA and late transcription was only achieved by interferon-gamma. Immunoblot has shown the absence of the 48-kD E1A protein in cells pretreated with interferon-gamma. The lack of this regulatory adenovirus protein may be involved in the inhibitory mechanism of interferon-gamma on adenovirus.

  20. Addition of polyadenylate sequences to virus-specific RNA during adenovirus replication.

    PubMed

    Philipson, L; Wall, R; Glickman, G; Darnell, J E

    1971-11-01

    Adenovirus-specific nuclear and polysomal RNA, both early and late in the infectious cycle, contain a covalently linked region of polyadenylic acid 150-250 nucleotides long. A large proportion of the adenovirus-specific messenger RNA contains poly(A). As revealed by hybridization experiments, the poly(A) is not transcribed from adenovirus DNA. Furthermore, an adenosine analogue, cordycepin, blocks the synthesis of poly(A) and also inhibits the accumulation of adenovirus messenger RNA on polysomes. Addition of poly(A) to viral RNA may involve a host-controlled mechanism that regulates the processing and transport of messenger RNA.

  1. Antiviral antibodies target adenovirus to phagolysosomes and amplify the innate immune response.

    PubMed

    Zaiss, Anne K; Vilaysane, Akosua; Cotter, Matthew J; Clark, Sharon A; Meijndert, H Christopher; Colarusso, Pina; Yates, Robin M; Petrilli, Virginie; Tschopp, Jurg; Muruve, Daniel A

    2009-06-01

    Adenovirus is a nonenveloped dsDNA virus that activates intracellular innate immune pathways. In vivo, adenovirus-immunized mice displayed an enhanced innate immune response and diminished virus-mediated gene delivery following challenge with the adenovirus vector AdLacZ suggesting that antiviral Abs modulate viral interactions with innate immune cells. Under naive serum conditions in vitro, adenovirus binding and internalization in macrophages and the subsequent activation of innate immune mechanisms were inefficient. In contrast to the neutralizing effect observed in nonhematopoietic cells, adenovirus infection in the presence of antiviral Abs significantly increased FcR-dependent viral internalization in macrophages. In direct correlation with the increased viral internalization, antiviral Abs amplified the innate immune response to adenovirus as determined by the expression of NF-kappaB-dependent genes, type I IFNs, and caspase-dependent IL-1beta maturation. Immune serum amplified TLR9-independent type I IFN expression and enhanced NLRP3-dependent IL-1beta maturation in response to adenovirus, confirming that antiviral Abs specifically amplify intracellular innate pathways. In the presence of Abs, confocal microscopy demonstrated increased targeting of adenovirus to LAMP1-positive phagolysosomes in macrophages but not epithelial cells. These data show that antiviral Abs subvert natural viral tropism and target the adenovirus to phagolysosomes and the intracellular innate immune system in macrophages. Furthermore, these results illustrate a cross-talk where the adaptive immune system positively regulates the innate immune system and the antiviral state.

  2. Phylogenetic Analyses of Novel Squamate Adenovirus Sequences in Wild-Caught Anolis Lizards

    PubMed Central

    Ascher, Jill M.; Geneva, Anthony J.; Ng, Julienne; Wyatt, Jeffrey D.; Glor, Richard E.

    2013-01-01

    Adenovirus infection has emerged as a serious threat to the health of captive snakes and lizards (i.e., squamates), but we know relatively little about this virus' range of possible hosts, pathogenicity, modes of transmission, and sources from nature. We report the first case of adenovirus infection in the Iguanidae, a diverse family of lizards that is widely-studied and popular in captivity. We report adenovirus infections from two closely-related species of Anolis lizards (anoles) that were recently imported from wild populations in the Dominican Republic to a laboratory colony in the United States. We investigate the evolution of adenoviruses in anoles and other squamates using phylogenetic analyses of adenovirus polymerase gene sequences sampled from Anolis and a range of other vertebrate taxa. These phylogenetic analyses reveal that (1) the sequences detected from each species of Anolis are novel, and (2) adenoviruses are not necessarily host-specific and do not always follow a co-speciation model under which host and virus phylogenies are perfectly concordant. Together with the fact that the Anolis adenovirus sequences reported in our study were detected in animals that became ill and subsequently died shortly after importation while exhibiting clinical signs consistent with acute adenovirus infection, our discoveries suggest the need for renewed attention to biosecurity measures intended to prevent the spread of adenovirus both within and among species of snakes and lizards housed in captivity. PMID:23593364

  3. First detection of adenovirus in the vampire bat (Desmodus rotundus) in Brazil.

    PubMed

    Lima, Francisco Esmaile de Sales; Cibulski, Samuel Paulo; Elesbao, Felipe; Carnieli Junior, Pedro; Batista, Helena Beatriz de Carvalho Ruthner; Roehe, Paulo Michel; Franco, Ana Cláudia

    2013-10-01

    This paper describes the first detection of adenovirus in a Brazilian Desmodus rotundus bat, the common vampire bat. As part of a continuous rabies surveillance program, three bat specimens were captured in Southern Brazil. Total DNA was extracted from pooled organs and submitted to a nested PCR designed to amplify a 280 bp long portion of the DNA polymerase gene of adenoviruses. One positive sample was subjected to nucleotide sequencing, confirming that this DNA fragment belongs to a member of the genus Mastadenovirus. This sequence is approximately 25 % divergent at the nucleotide level from equine adenovirus 1 and two other recently characterized bat adenoviruses.

  4. Adenovirus vector delivery stimulates natural killer cell recognition

    PubMed Central

    Tomasec, Peter; Wang, Eddie C. Y.; Groh, Veronika; Spies, Thomas; McSharry, Brian P.; Aicheler, Rebecca J.; Stanton, Richard J.; Wilkinson, Gavin W. G.

    2007-01-01

    We report that delivery of first-generation replication-deficient adenovirus (RDAd) vectors into primary human fibroblasts is associated with the induction of natural killer (NK) cell-mediated cytolysis in vitro. RDAd vector delivery induced cytolysis by a range of NK cell populations including the NK cell clone NKL, primary polyclonal NK lines and a proportion of NK clones (36 %) in autologous HLA-matched assays. Adenovirus-induced cytolysis was inhibited by antibody blocking of the NK-activating receptor NKG2D, implicating this receptor in this function. NKG2D is ubiquitously expressed on NK cells and CD8+ T cells. Significantly, γ-irradiation of the vector eliminated the effect, suggesting that breakthrough expression from the vector induces at least some of the pro-inflammatory responses of unknown aetiology following the application of RDAd vectors during in vivo gene delivery. PMID:17374753

  5. Adenovirus-derived vectors for prostate cancer gene therapy.

    PubMed

    de Vrij, Jeroen; Willemsen, Ralph A; Lindholm, Leif; Hoeben, Rob C; Bangma, Chris H; Barber, Chris; Behr, Jean-Paul; Briggs, Simon; Carlisle, Robert; Cheng, Wing-Shing; Dautzenberg, Iris J C; de Ridder, Corrina; Dzojic, Helena; Erbacher, Patrick; Essand, Magnus; Fisher, Kerry; Frazier, April; Georgopoulos, Lindsay J; Jennings, Ian; Kochanek, Stefan; Koppers-Lalic, Daniela; Kraaij, Robert; Kreppel, Florian; Magnusson, Maria; Maitland, Norman; Neuberg, Patrick; Nugent, Regina; Ogris, Manfred; Remy, Jean-Serge; Scaife, Michelle; Schenk-Braat, Ellen; Schooten, Erik; Seymour, Len; Slade, Michael; Szyjanowicz, Pio; Totterman, Thomas; Uil, Taco G; Ulbrich, Karel; van der Weel, Laura; van Weerden, Wytske; Wagner, Ernst; Zuber, Guy

    2010-07-01

    Prostate cancer is a leading cause of death among men in Western countries. Whereas the survival rate approaches 100% for patients with localized cancer, the results of treatment in patients with metastasized prostate cancer at diagnosis are much less successful. The patients are usually presented with a variety of treatment options, but therapeutic interventions in prostate cancer are associated with frequent adverse side effects. Gene therapy and oncolytic virus therapy may constitute new strategies. Already a wide variety of preclinical studies has demonstrated the therapeutic potential of such approaches, with oncolytic prostate-specific adenoviruses as the most prominent vector. The state of the art and future prospects of gene therapy in prostate cancer are reviewed, with a focus on adenoviral vectors. We summarize advances in adenovirus technology for prostate cancer treatment and highlight areas where further developments are necessary.

  6. Dielectrophoresis and dielectrophoretic impedance detection of adenovirus and rotavirus

    NASA Astrophysics Data System (ADS)

    Nakano, Michihiko; Ding, Zhenhao; Suehiro, Junya

    2016-01-01

    The aim of this study is the electrical detection of pathogenic viruses, namely, adenovirus and rotavirus, using dielectrophoretic impedance measurement (DEPIM). DEPIM consists of two simultaneous processes: dielectrophoretic trapping of the target and measurement of the impedance change and increase in conductance with the number of trapped targets. This is the first study of applying DEPIM, which was originally developed to detect bacteria suspended in aqueous solutions, to virus detection. The dielectric properties of the viruses were also investigated in terms of their dielectrophoretic behavior. Although their estimated dielectric properties were different from those of bacteria, the trapped viruses increased the conductance of the microelectrode in a manner similar to that in bacteria detection. We demonstrated the electrical detection of viruses within 60 s at concentrations as low as 70 ng/ml for adenovirus and 50 ng/ml for rotavirus.

  7. Critical Role for Arginine Methylation in Adenovirus-Infected Cells▿

    PubMed Central

    Iacovides, Demetris C.; O'Shea, Clodagh C.; Oses-Prieto, Juan; Burlingame, Alma; McCormick, Frank

    2007-01-01

    During the late stages of adenovirus infection, the 100K protein (100K) inhibits the translation of cellular messages in the cytoplasm and regulates hexon trimerization and assembly in the nucleus. However, it is not known how it switches between these two functions. Here we show that 100K is methylated on arginine residues at its C terminus during infection and that this region is necessary for binding PRMT1 methylase. Methylated 100K is exclusively nuclear. Mutation of the third RGG motif (amino acids 741 to 743) prevents localization to the nucleus during infection, suggesting that methylation of that sequence is important for 100K shuttling. Treatment of infected cells with methylation inhibitors inhibits expression of late structural proteins. These data suggest that arginine methylation of 100K is necessary for its localization to the nucleus and is a critical cellular function necessary for productive adenovirus infection. PMID:17686851

  8. An Analysis of Adenovirus Genomes Using Whole Genome Software Tools

    PubMed Central

    Mahadevan, Padmanabhan

    2016-01-01

    The evolution of sequencing technology has lead to an enormous increase in the number of genomes that have been sequenced. This is especially true in the field of virus genomics. In order to extract meaningful biological information from these genomes, whole genome data mining software tools must be utilized. Hundreds of tools have been developed to analyze biological sequence data. However, only some of these tools are user-friendly to biologists. Several of these tools that have been successfully used to analyze adenovirus genomes are described here. These include Artemis, EMBOSS, pDRAW, zPicture, CoreGenes, GeneOrder, and PipMaker. These tools provide functionalities such as visualization, restriction enzyme analysis, alignment, and proteome comparisons that are extremely useful in the bioinformatics analysis of adenovirus genomes. PMID:28293072

  9. Traumatic pancreatic pseudocysts.

    PubMed

    Popoola, D; Lou, M A; Sims, E H

    1983-05-01

    At the Martin Luther King, Jr, General Hospital in Los Angeles, during the period from June 1972 to April 1981, seven patients underwent surgery for traumatic pancreatic pseudocysts. The overall average age was 28 and the average hospital stay was 31 days. Ultrasound was the most useful test for diagnosis and follow-up. Preoperatively, serum amylases were not consistently elevated. Overall recurrences and complications totaled 57 percent. There were no deaths. The authors consider a large cystogastrostomy the treatment of choice for mature cysts that are satisfactorily adherent to the stomach. The second preference is a Roux-en-Y cystojejunostomy. External drainage was employed for acute cysts that required drainage. A distal pancreatectomy was performed for patients with small pancreatic tail pseudocysts. Patients who underwent acute drainage were usually drained externally and had a poorer outcome than patients who were operated on later with internal drainage. When compared with another group of 15 alcoholic patients who were operated on for pancreatic pseudocysts, patients with traumatic pseudocysts had a poorer outcome.

  10. Transplantable pancreatic acinar carcinoma

    SciTech Connect

    Warren, J.R.; Reddy, J.K.

    1981-03-15

    Fragments of the nafenopin-induced pancreatic acinar cell carcinoma of rat have been examined in vitro for patterns of intracellular protein transport and carbamylcholine-induced protein discharge. Continuous incubation of the fragments with (3H)-leucine for 60 minutes resulted in labeling of rough endoplasmic reticulum, Golgi cisternae, and mature zymogen granules, revealed by electron microscope autoradiography. This result indicates transport of newly synthesized protein from the rough endoplasmic reticulum to mature zymogen granules in approximately 60 minutes. The secretagogue carbamylcholine induced the discharge of radioactive protein by carcinoma fragments pulse-chase labeled with (3H)-leucine. A maximal effective carbamylcholine concentration of 10(-5) M was determined. The acinar carcinoma resembles normal exocrine pancreas in the observed rate of intracellular protein transport and effective secretagogue concentration. However, the acinar carcinoma fragments demonstrated an apparent low rate of carbamylcholine-induced radioactive protein discharge as compared with normal pancreatic lobules or acinar cells. It is suggested that the apparent low rate of radioactive protein discharge reflects functional immaturity of the acinar carcinoma. Possible relationships of functional differentiation to the heterogeneous cytodifferentiation of the pancreatic acinar carcinoma are discussed.

  11. Lessons for Implementation from the World's Most Successful Programme: The Global Eradication of Smallpox.

    ERIC Educational Resources Information Center

    Pratt, David

    1999-01-01

    Focuses on lessons educators might learn from the Intensified Campaign for the Global Eradication of Smallpox. Outlines the history of smallpox eradication. Discusses the eradication effort's obstacles, campaign, and costs and benefits. Considers five factors relevant to the successful implementation of educational programs. (CMK)

  12. 76 FR 20706 - South Farallon Islands Nonnative Mouse Eradication Project; Farallon National Wildlife Refuge...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... Fish and Wildlife Service South Farallon Islands Nonnative Mouse Eradication Project; Farallon National... project to eradicate nonnative mice from the South Farallon Islands, part of the Farallon National... the eradication of the house mouse and the prevention of future human introduction of mice. We...

  13. Therapy of Breast Cancers Using Conditionally Replicating Adenovirus

    DTIC Science & Technology

    2005-08-01

    virotherapy on breast cancer cells in vitro. We have developed a CRAd using the fit-I promoter element for specific EIA gene expression (CRAdflt), RGD...replicating adenoviruses (CRAd) and investigate effects of CRAd virotherapy on endothelial cells and breast cancer cells in vitro. Vascular targeting...determined the capacity of CRAdRGDflt-mda-7 virotherapy to induce breast cancer cell death. To verify the levels of MDA-7/IL-24 protein expression in vitro

  14. Oncolytic adenovirus-mediated therapy for prostate cancer

    PubMed Central

    Sweeney, Katrina; Halldén, Gunnel

    2016-01-01

    Prostate cancer is a leading cause of cancer-related death and morbidity in men in the Western world. Tumor progression is dependent on functioning androgen receptor signaling, and initial administration of antiandrogens and hormone therapy (androgen-deprivation therapy) prevent growth and spread. Tumors frequently develop escape mechanisms to androgen-deprivation therapy and progress to castration-resistant late-stage metastatic disease that, in turn, inevitably leads to resistance to all current therapeutics, including chemotherapy. In spite of the recent development of more effective inhibitors of androgen–androgen receptor signaling such as enzalutamide and abiraterone, patient survival benefits are still limited. Oncolytic adenoviruses have proven efficacy in prostate cancer cells and cause regression of tumors in preclinical models of numerous drug-resistant cancers. Data from clinical trials demonstrate that adenoviral mutants have limited toxicity to normal tissues and are safe when administered to patients with various solid cancers, including prostate cancer. While efficacy in response to adenovirus administration alone is marginal, findings from early-phase trials targeting local-ized and metastatic prostate cancer suggest improved efficacy in combination with cytotoxic drugs and radiation therapy. Here, we review recent progress in the development of multimodal oncolytic adenoviruses as biological therapeutics to improve on tumor elimination in prostate cancer patients. These optimized mutants target cancer cells by several mechanisms including viral lysis and by expression of cytotoxic transgenes and immune-stimulatory factors that activate the host immune system to destroy both infected and noninfected prostate cancer cells. Additional modifications of the viral capsid proteins may support future systemic delivery of oncolytic adenoviruses. PMID:27579296

  15. [Adenovirus vectors and their clinical application in gene therapy].

    PubMed

    Adám, E; Nász, I

    2001-09-23

    The potential therapeutic application of the gene transfer technology with adenovirus vectors seems to be enormous. Adenovirus vectors offer several advantages over other vectors, but several important limitations of adenovirus mediated gene transfer are also known. Great number of studies in inherited diseases and in different cancer therapy clinical trials have provided information of critical importance for design of efficient clinical protocols. Clinical trials have been extended to the treatment of many other diseases, too. There are about thirty currently active gene therapy protocols for the treatment only of HIV-1 infection in the USA. These programs aim to confer protective immunity against HIV-1 transmission to individuals who are in risk of infection, to develop preventive or therapeutic vaccines for patients with AIDS and other infectious diseases. Gene therapy represents one of the most important developments in oncology, however, before this can be realised as standard treatment the technical problems of gene delivery and higher safety must be overcome. The early--first and second generation--adenovirus vectors are now likely to be phased out for most diseases, and further experiments seem to be necessary. It might be change to the third generation or other, more modern vector application in clinical trials, as the helper dependent vectors. Almost all transcriptional unit is removed from the DNA of these vectors ("gutless vectors"), therefore they cannot reproduce, give higher gene expression and far less inflammatory. Despite the latest achievement reported in vector design it is not possible to predict yet to what extent and when gene therapy will be effective.

  16. An outbreak of lethal adenovirus infection among different otariid species.

    PubMed

    Inoshima, Yasuo; Murakami, Tomoaki; Ishiguro, Naotaka; Hasegawa, Kazuhiro; Kasamatsu, Masahiko

    2013-08-30

    An outbreak of fatal fulminant hepatitis at a Japanese aquarium involved 3 otariids: a California sea lion (Zalophus californianus), a South African fur seal (Arctocephalus pusillus) and a South American sea lion (Otaria flavescens). In a span of about a week in February 2012, 3 otariids showed diarrhea and were acutely low-spirited; subsequently, all three animals died within a period of 3 days. Markedly increased aspartate amino transferase and alanine amino transferase activities were observed. Necrotic hepatitis and eosinophilic intranuclear inclusion bodies in liver hepatocytes and intestinal epithelial cells were observed in the South American sea lion on histological examination. Otarine adenovirus DNA was detected from the livers of all three animals by polymerase chain reaction and determination of the sequences showed that all were identical. These results suggest that a single otarine adenovirus strain may have been the etiological agent of this outbreak of fatal fulminant hepatitis among the different otariid species, and it may be a lethal threat to wild and captive otariids. This is the first evidence of an outbreak of lethal adenovirus infection among different otariid species.

  17. Effect of CD4 gene expression on adenovirus replication.

    PubMed Central

    Hotta, J; Shi, L; Ginsberg, H S

    1994-01-01

    The gene encoding the CD4 receptor was introduced into KB cells to establish the KBT4 cell line, a cell line susceptible to infection with human immunodeficiency virus type 1. Adenovirus replication was found to be significantly less in these cells than in the parental KB cells. Similar decreased adenovirus type 5 (Ad5) replication occurred in HeLaT4 cells compared with the original HeLa cells. The presence of CD4 did not alter the cell surface population of KB cell adenovirus receptors, since viral adsorption was similar in the two cell lines. Moreover, addition of soluble CD4 did not reduce viral replication in either KB or KBT4 infected cells. Uncoating of viral DNA was also unchanged in KBT4 cells compared with the parental KB cells. In contrast, migration to or entrance of viral DNA into nuclei and synthesis of early viral RNAs was delayed and reduced in KBT4 cells. These effects were more pronounced for Ad7 than for Ad5. The yields of infectious viruses were the same in both cell lines, however, after transfection of naked viral DNAs to initiate infection. These results imply that the expression of the CD4 gene in KBT4 cells interfered with passage of uncoated virus across endosomal vesicles and/or transfer of uncoated core viral DNA into the nucleus. Images PMID:7933112

  18. Effect of CD4 gene expression on adenovirus replication.

    PubMed

    Hotta, J; Shi, L; Ginsberg, H S

    1994-11-01

    The gene encoding the CD4 receptor was introduced into KB cells to establish the KBT4 cell line, a cell line susceptible to infection with human immunodeficiency virus type 1. Adenovirus replication was found to be significantly less in these cells than in the parental KB cells. Similar decreased adenovirus type 5 (Ad5) replication occurred in HeLaT4 cells compared with the original HeLa cells. The presence of CD4 did not alter the cell surface population of KB cell adenovirus receptors, since viral adsorption was similar in the two cell lines. Moreover, addition of soluble CD4 did not reduce viral replication in either KB or KBT4 infected cells. Uncoating of viral DNA was also unchanged in KBT4 cells compared with the parental KB cells. In contrast, migration to or entrance of viral DNA into nuclei and synthesis of early viral RNAs was delayed and reduced in KBT4 cells. These effects were more pronounced for Ad7 than for Ad5. The yields of infectious viruses were the same in both cell lines, however, after transfection of naked viral DNAs to initiate infection. These results imply that the expression of the CD4 gene in KBT4 cells interfered with passage of uncoated virus across endosomal vesicles and/or transfer of uncoated core viral DNA into the nucleus.

  19. Ion etching of human adenovirus 2: structure of the core

    SciTech Connect

    Newcomb, W.W.; Boring, J.W.; Brown, J.C.

    1984-07-01

    The surface of human adenovirus 2 was etched by irradiating intact virions with low-energy (1-keV) Ar/sup +/ ions in a Technics Hummer V sputter coater. Viral structures exposed by the etching process were shadowed and then examined in the electron microscope. Periods of etching that were sufficient to reduce the viral diameter by 20 to 30 nm revealed distinct substructural elements in the virion core. Cores were found to consist of a cluster of 12 large, uniformly sized spheres which abutted one another in the intact virion. The spheres, for which we suggest the name adenosomes, had a diameter of 23.0 +/- 2.3 nm, and they were related to each other by two-, three-, and fivefold axes of rotational symmetry. The results support the view, originally suggested by Brown et al. that the adenovirus 2 core is composed of 12 large spheres packed tightly together in such a way that each is directed toward the vertex of an icosahedron. Such a structure, constructed of 23.0-nm-diameter spheres, would have an outside diameter (vertex-to-vertex distance) of 67.0 nm and a face-to-face distance of 58.2 nm. It could be accommodated inside the icosahedral adenovirus capsid if each large sphere were located beneath a capsid vertex.

  20. Progress on adenovirus-vectored universal influenza vaccines.

    PubMed

    Xiang, Kui; Ying, Guan; Yan, Zhou; Shanshan, Yan; Lei, Zhang; Hongjun, Li; Maosheng, Sun

    2015-01-01

    Influenza virus (IFV) infection causes serious health problems and heavy financial burdens each year worldwide. The classical inactivated influenza virus vaccine (IIVV) and live attenuated influenza vaccine (LAIV) must be updated regularly to match the new strains that evolve due to antigenic drift and antigenic shift. However, with the discovery of broadly neutralizing antibodies that recognize conserved antigens, and the CD8(+) T cell responses targeting viral internal proteins nucleoprotein (NP), matrix protein 1 (M1) and polymerase basic 1 (PB1), it is possible to develop a universal influenza vaccine based on the conserved hemagglutinin (HA) stem, NP, and matrix proteins. Recombinant adenovirus (rAd) is an ideal influenza vaccine vector because it has an ideal stability and safety profile, induces balanced humoral and cell-mediated immune responses due to activation of innate immunity, provides 'self-adjuvanting' activity, can mimic natural IFV infection, and confers seamless protection against mucosal pathogens. Moreover, this vector can be developed as a low-cost, rapid-response vaccine that can be quickly manufactured. Therefore, an adenovirus vector encoding conserved influenza antigens holds promise in the development of a universal influenza vaccine. This review will summarize the progress in adenovirus-vectored universal flu vaccines and discuss future novel approaches.

  1. Progress on adenovirus-vectored universal influenza vaccines

    PubMed Central

    Xiang, Kui; Ying, Guan; Yan, Zhou; Shanshan, Yan; Lei, Zhang; Hongjun, Li; Maosheng, Sun

    2015-01-01

    Influenza virus (IFV) infection causes serious health problems and heavy financial burdens each year worldwide. The classical inactivated influenza virus vaccine (IIVV) and live attenuated influenza vaccine (LAIV) must be updated regularly to match the new strains that evolve due to antigenic drift and antigenic shift. However, with the discovery of broadly neutralizing antibodies that recognize conserved antigens, and the CD8+ T cell responses targeting viral internal proteins nucleoprotein (NP), matrix protein 1 (M1) and polymerase basic 1 (PB1), it is possible to develop a universal influenza vaccine based on the conserved hemagglutinin (HA) stem, NP, and matrix proteins. Recombinant adenovirus (rAd) is an ideal influenza vaccine vector because it has an ideal stability and safety profile, induces balanced humoral and cell-mediated immune responses due to activation of innate immunity, provides ‘self-adjuvanting’ activity, can mimic natural IFV infection, and confers seamless protection against mucosal pathogens. Moreover, this vector can be developed as a low-cost, rapid-response vaccine that can be quickly manufactured. Therefore, an adenovirus vector encoding conserved influenza antigens holds promise in the development of a universal influenza vaccine. This review will summarize the progress in adenovirus-vectored universal flu vaccines and discuss future novel approaches. PMID:25876176

  2. Structural organization and polypeptide composition of the avian adenovirus core.

    PubMed Central

    Li, P; Bellett, A J; Parish, C R

    1984-01-01

    CELO virus (fowl adenovirus 1) contained three core polypeptides of molecular weights 20,000, 12,000, and 9,500. The core was similar to that of human adenoviruses, with some evidence of compact subcore domains. Micrococcal nuclease digestion of CELO virus cores produced a smear of DNA fragments of gradually decreasing size, with no nucleosome subunit or repeat pattern. Moreover, when digested cores were analyzed without protease treatment, there was again no evidence of a nucleosome substructure; neither DNA fragments nor core proteins entered a 4% polyacrylamide gel. The organization of the core is thus quite unlike that of chromatin. Restriction endonuclease analysis of the DNA from digested cores showed that the right end was on the outside of the core. We suggest that adenovirus DNA is condensed into the core by cross-linking and neutralization by the core proteins, beginning with the packaging sequence at the center of the core and ending with the right end of the DNA on the outside. Images PMID:6092686

  3. Template requirements for the initiation of adenovirus DNA replication.

    PubMed Central

    Challberg, M D; Rawlins, D R

    1984-01-01

    The first step in the replication of the adenovirus genome is the covalent attachment of the 5'-terminal nucleotide, dCMP, to the virus-encoded terminal protein precursor (pTP). This reaction can be observed in vitro and has been previously shown to be dependent upon either viral DNA or linearized plasmid DNA containing viral terminal sequences. Plasmids containing deletions or point mutations within the viral terminal sequence were constructed by site-directed mutagenesis. In the case of linear double-stranded templates, pTP-dCMP formation required sequences located within the first 18 base pairs of the viral genome. This sequence contains a segment of 10 base pairs that is conserved in all human adenovirus serotypes. Point mutations within the conserved segment greatly reduced the efficiency of initiation, while a point mutation at a nonconserved position within the first 18 base pairs had little effect. Single-stranded DNAs can also support pTP-dCMP formation in vitro. In contrast to the results obtained with duplex templates, experiments with a variety of single-stranded templates, including phage M13-adenovirus recombinants, denatured plasmids, and synthetic oligodeoxynucleotides, failed to reveal any requirements for specific nucleotide sequences. With single-stranded templates containing no dG residues, the specific deoxynucleoside triphosphate requirements of the initiation reaction were altered. Images PMID:6320160

  4. Adenovirus infection elevates levels of cellular topoisomerase I.

    PubMed Central

    Chow, K C; Pearson, G D

    1985-01-01

    We have developed a specific, sensitive, and quantitative assay for topoisomerase I, which is based on the formation of a covalent enzyme-DNA intermediate. Our assay measures the quantitative transfer of 32P radioactivity from 32P-labeled DNA to topoisomerase I. Since 32P-labeled topoisomerase molecules are resolved by NaDodSO4/PAGE, HeLa topoisomerase I (100 kDa) and calf thymus topoisomerase I (82 kDa) can be quantitatively assayed in the same reaction mixture. The assay can detect at least 0.3 ng (3 fmol) of topoisomerase I. We have used our assay to measure the levels of topoisomerase I activity in crude extracts of nuclei prepared from uninfected, adenovirus-infected, and adenovirus-transformed human cells. The evidence suggests that an adenovirus early gene product, presumably a protein encoded in early region 1A (E1A), increases cellular topoisomerase I activity at least 10-fold. Immunoblotting analysis with antiserum against calf thymus topoisomerase I shows that the increase in activity is due to an increase in the amount of enzyme. Images PMID:2986107

  5. Prevalence of human adenoviruses in raw and treated water.

    PubMed

    van Heerden, J; Ehlers, M M; van Zyl, W B; Grabow, W O K

    2004-01-01

    Human adenoviruses (HAds), of which there are 51 antigenic types, are associated aetiologically with gastrointestinal, respiratory, urinary tract and eye infections. The clinical importance of HAds and the potential health risks constituted by HAds in water environments are widely recognised. This study was conducted to assess the use of an optimised integrated cell culture molecular-based technique to determine the prevalence of HAds in raw and treated drinking-water supplies in South Africa. Selected supplies were monitored weekly for the presence of adenoviruses over a one-year period (July 2001 to June 2002). Drinking-water supplies were derived from acceptable quality surface water sources using treatment processes that conformed to international standards for the production of safe drinking water. Adenoviruses were detected by amplification in cell cultures, followed by amplifying the extracted nucleic acids using molecular techniques (nested PCR). HAds were detected in 29.8% (59/198) of the treated drinking water, 16% (8/50) of dam water and 44% (22/50) of river-water samples tested. The results of this study confirmed the presence of HAds in some raw and treated drinking water supplies in South Africa.

  6. An Update on Canine Adenovirus Type 2 and Its Vectors

    PubMed Central

    Bru, Thierry; Salinas, Sara; Kremer, Eric J.

    2010-01-01

    Adenovirus vectors have significant potential for long- or short-term gene transfer. Preclinical and clinical studies using human derived adenoviruses (HAd) have demonstrated the feasibility of flexible hybrid vector designs, robust expression and induction of protective immunity. However, clinical use of HAd vectors can, under some conditions, be limited by pre-existing vector immunity. Pre-existing humoral and cellular anti-capsid immunity limits the efficacy and duration of transgene expression and is poorly circumvented by injections of larger doses and immuno-suppressing drugs. This review updates canine adenovirus serotype 2 (CAV-2, also known as CAdV-2) biology and gives an overview of the generation of early region 1 (E1)-deleted to helper-dependent (HD) CAV-2 vectors. We also summarize the essential characteristics concerning their interaction with the anti-HAd memory immune responses in humans, the preferential transduction of neurons, and its high level of retrograde axonal transport in the central and peripheral nervous system. CAV-2 vectors are particularly interesting tools to study the pathophysiology and potential treatment of neurodegenerative diseases, as anti-tumoral and anti-viral vaccines, tracer of synaptic junctions, oncolytic virus and as a platform to generate chimeric vectors. PMID:21994722

  7. History of the restoration of adenovirus type 4 and type 7 vaccine, live oral (Adenovirus Vaccine) in the context of the Department of Defense acquisition system.

    PubMed

    Hoke, Charles H; Snyder, Clifford E

    2013-03-15

    Respiratory pathogens cause morbidity and mortality in US military basic trainees. Following the influenza pandemic of 1918, and stimulated by WWII, the need to protect military personnel against epidemic respiratory disease was evident. Over several decades, the US military elucidated etiologies of acute respiratory diseases and invented and deployed vaccines to prevent disease caused by influenza, meningococcus, and adenoviruses. In 1994, the Adenovirus Vaccine manufacturer stopped its production. By 1999, supplies were exhausted and adenovirus-associated disease, especially serotype 4-associated febrile respiratory illness, returned to basic training installations. Advisory bodies persuaded Department of Defense leaders to initiate restoration of Adenovirus Vaccine. In 2011, after 10 years of effort by government and contractor personnel and at a cost of about $100 million, the Adenovirus Vaccine was restored to use at all military basic training installations. Disease and adenovirus serotype 4 isolation rates have fallen dramatically since vaccinations resumed in October 2011 and remain very low. Mindful of the adage that "The more successful a vaccine is, the more quickly the need for it will be forgotten.", sustainment of the supply of the Adenovirus Vaccine may be a challenge, and careful management will be required for such sustainment.

  8. Groove Pancreatitis: A Rare form of Chronic Pancreatitis

    PubMed Central

    Jani, Bharivi; Rzouq, Fadi; Saligram, Shreyas; Nawabi, Atta; Nicola, Marian; Dennis, Katie; Ernst, Carly; Abbaszadeh, Ali; Bonino, John; Olyaee, Mojtaba

    2015-01-01

    Context: Groove pancreatitis is a rare form of chronic pancreatitis affecting the “groove” of the pancreas among the pancreatic head, duodenum, and common bile duct. The exact cause is unknown, although there are associations with long-term alcohol abuse, smoking, peptic ulcer disease, heterotopic pancreas, gastric resection, biliary disease, and anatomical or functional obstruction of the minor papilla. The diagnosis can be challenging. Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography are the preferred imaging modalities. The treatment of choice is conservative although surgical intervention can sometimes be required. Case Report: A 57-year-old male with a history of human immunodeficiency virus and hepatitis B presented with 4 days of epigastric pain. Abdominal exam revealed absent bowel sounds and epigastric tenderness. He had a creatinine of 1.72 mg/dL, potassium of 2.9 mmol/L, and a normal lipase level of 86 U/L. Liver enzymes and total bilirubin were normal. Computed tomography abdomen showed high-grade obstruction of the second portion of the duodenum without any obvious mass. An esophagogastroduodenoscopy showed a mass at the duodenal bulb causing luminal narrowing, with biopsies negative for malignancy. Magnetic resonance imaging revealed a mass in the region of the pancreatic head and descending duodenum. EUS revealed a 3 cm mass in the region of pancreatic head with irregular borders and no vascular invasion. Fine needle aspiration (FNA) was nondiagnostic. The patient then underwent a Whipple's procedure. Pathology of these specimens was negative for malignancy but was consistent with para-duodenal or groove pancreatitis. Conclusion: The low incidence of groove pancreatitis is partly due to lack of familiarity with the disease. Groove pancreatitis should be considered in the differential for patients presenting with pancreatic head lesions and no cholestatic jaundice, especially when a duodenal obstruction is present, and

  9. Acute pancreatitis in patients with pancreatic cancer

    PubMed Central

    Li, Shaojun; Tian, Bole

    2017-01-01

    Abstract Acute pancreatitis (AP) is a rare manifestation of pancreatic cancer (PC). The relationship between AP and PC remains less distinct. From January 2009 to November 2015, 47consecutive patients with PC who presented with AP were reviewed for this study. Clinical features, clinicopathologic variables, postoperative complications, and follow-up evaluations of patients were documented in detail from our database. In order to identify cutoff threshold time for surgery, receiver operating curve (ROC) was built according to patients with or without postoperative complications. Cumulative rate of survival was calculated by using the Kaplan–Meier method. The study was conducted in accordance with the principles of the Declaration of Helsinki and the guidelines of West China Hospital. This study included 35 men (74.5%) and 12 women (25.5%) (mean age: 52 years), with a median follow-up of 40 months. AP was clinically mild in 45 (95.7%) and severe in 2 (4.3%). The diagnosis of PC was delayed by 2 to 660 days (median 101 days). Thirty-nine (83.0%) cases underwent surgery. Eight (17.0%) cases performed biopsies only. Of 39 patients, radical surgery was performed in 32 (82.1%) cases and palliative in 7 (19.9%) cases. Two (8.0%) patients were needed for vascular resection and reconstruction. Postoperative complications occurred in 12 (30.8%) patients. About 24.5 days was the best cutoff point, with an area under curve (AUC) of 0.727 (P = 0.025, 95% confidence interval: 0.555–0.8999). The survival rate of patients at 1 year was 23.4%. The median survival in patients with vascular resection and reconstruction was 18 months, compared with 10 months in patients without vascular resection (P = 0.042). For the primary stage (T), Tix was identified in 3 patients, the survival of whom were 5, 28, 50 months, respectively. And 2 of them were still alive at the follow-up period. The severity of AP was mainly mild. Surgical intervention after 24.5 days may benefit for

  10. Tropism modification of adenovirus vectors by peptide ligand insertion into various positions of the adenovirus serotype 41 short-fiber knob domain.

    PubMed

    Hesse, Andrea; Kosmides, Daniela; Kontermann, Roland E; Nettelbeck, Dirk M

    2007-03-01

    Recombinant adenoviruses have emerged as promising agents in therapeutic gene transfer, genetic vaccination, and viral oncolysis. Therapeutic applications of adenoviruses, however, would benefit substantially from targeted virus cell entry, for example, into cancer or immune cells, as opposed to the broad tropism that adenoviruses naturally possess. Such tropism modification of adenoviruses requires the deletion of their natural cell binding properties and the incorporation of cell binding ligands. The short fibers of subgroup F adenoviruses have recently been suggested as a tool for genetic adenovirus detargeting based on the reduced infectivity of corresponding adenovectors with chimeric fibers in vitro and in vivo. The goal of our study was to determine functional insertion sites for peptide ligands in the adenovirus serotype 41 (Ad41) short fiber knob. With a model peptide, CDCRGDCFC, we could demonstrate that ligand incorporation into three of five analyzed loops of the knob, namely, EG, HI, and IJ, is feasible without a loss of fiber trimerization. The resulting adenovectors showed enhanced infectivity for various cell types, which was superior to that of viruses with the same peptide fused to the fiber C terminus. Strategies to further augment gene transfer efficacy by extension of the fiber shaft, insertion of tandem copies of the ligand peptide, or extension of the ligand-flanking linkers failed, indicating that precise ligand positioning is pivotal. Our study establishes that internal ligand incorporation into a short-shafted adenovirus fiber is feasible and suggests the Ad41 short fiber with ligand insertion into the top (IJ loop) or side (EG and HI loops) of the knob domain as a novel platform for genetic targeting of therapeutic adenoviruses.

  11. Beer and its Non-Alcoholic Compounds: Role in Pancreatic Exocrine Secretion, Alcoholic Pancreatitis and Pancreatic Carcinoma

    PubMed Central

    Gerloff, Andreas; Singer, Manfred V; Feick, Peter

    2010-01-01

    In this article we provide an overview of the newest data concerning the effect of non-alcoholic constituents of alcoholic beverages, especially of beer, on pancreatic secretion, and their possible role in alcoholic pancreatitis and pancreatic carcinoma. The data indicate that non-alcoholic constituents of beer stimulate pancreatic enzyme secretion in humans and rats, at least in part, by direct action on pancreatic acinar cells. Some non-alcoholic compounds of beer, such as quercetin, resveratrol, ellagic acid or catechins, have been shown to be protective against experimentally induced pancreatitis by inhibiting pancreatic secretion, stellate cell activation or by reducing oxidative stress. Quercetin, ellagic acid and resveratrol also show anti-carcinogenic potential in vitro and in vivo. However, beer contains many more non-alcoholic ingredients. Their relevance in beer-induced functional alterations of pancreatic cells leading to pancreatitis and pancreatic cancer in humans needs to be further evaluated. PMID:20617020

  12. Canagliflozin-Associated Acute Pancreatitis.

    PubMed

    Verma, Rajanshu

    2016-01-01

    Canagliflozin is a new drug in class of sodium-glucose cotransporter 2 inhibitors used for treatment of type 2 diabetes mellitus. We describe a patient who developed moderately severe acute pancreatitis as an untoward consequence after being initiated on this drug. To the best of our knowledge, this is the first reported case of canagliflozin-associated acute pancreatitis in clinical literature.

  13. Treatment with near-infrared radiation promotes apoptosis in pancreatic cancer cells

    PubMed Central

    OBAYASHI, TOMOHIKO; FUNASAKA, KOHEI; OHNO, EIZABURO; MIYAHARA, RYOJI; HIROOKA, YOSHIKI; HAMAGUCHI, MICHINARI; GOTO, HIDEMI; SENGA, TAKESHI

    2015-01-01

    Cancer remains one of the leading causes of human mortality worldwide. Radiation and chemotherapy are commonly used for cancer treatment; however, the combination of these therapies and surgery do not completely eradicate cancer cells. Near-infrared radiation (NIR) is a low-energy form of radiation that exerts multiple effects on mammalian cells. Previous studies have reported that NIR induces DNA double-strand breaks and apoptosis of cancer cells. In the present study, a 915-nm laser was used to examine the effects of NIR on pancreatic cancer cells. Irradiation of pancreatic cancer cells using a 915-nm laser significantly induced caspase-3 activation and apoptosis. In addition, the combination of gemcitabine treatment and a 915-nm laser synergistically increased the number of apoptotic cells. The results of the present study indicate the use of infrared irradiation and chemotherapy may be a possible therapy for the treatment of cancer. PMID:26622761

  14. The Evaluation of Polyhexamethylene Biguanide (PHMB) as a Disinfectant for Adenovirus

    PubMed Central

    Romanowski, Eric G.; Yates, Kathleen A.; O’Connor, Katherine E.; Mah, Francis S.; Shanks, Robert M. Q.; Kowalski, Regis P.

    2013-01-01

    Purpose Swimming pools can be a vector for transmission of adenovirus ocular infections. Polyhexamethylene biguanide (PHMB) is a disinfectant used in swimming pools and hot tubs. The current study determined whether PHMB is an effective disinfectant against ocular adenovirus serotypes at a concentration used to disinfect swimming pools and hot tubs. Methods The direct disinfecting activity of PHMB was determined in triplicate assays by incubating nine human adenovirus types (1, 2, 3, 4, 5, 7a, 8, 19, and 37) with 50 and 0 PPM (µg/ml) of PHMB for 24 hours at room temperature, to simulate swimming pool temperatures, or 40°C, to simulate hot tub temperatures. Plaque assays determined adenovirus titers after incubation. Titers were Log10 converted and mean ± standard deviation Log10 reductions from controls were calculated. Virucidal (greater than 99.9%) decreases in mean adenovirus titers after PHMB treatment were determined for each adenovirus type and temperature tested. Results At room temperature, 50 PPM of PHMB produced mean reductions in titers less than 1 Log10 for all adenovirus types tested. At 40°C, 50 PPM of PHMB produced mean reductions in titers less than 1 Log10 for two adenovirus types and greater than 1 Log10, but less than 3 Log10, for seven of nine adenovirus types. Conclusions 50 PPM of PHMB was not virucidal against adenovirus at temperatures consistent with swimming pools or hot tubs. Clinical Relevance Recreational water maintained and sanitized with PHMB has the potential to serve as a vector for the transmission of ocular adenovirus infections. PMID:23450376

  15. Somatostatin therapy of acute experimental pancreatitis.

    PubMed Central

    Lankisch, P G; Koop, H; Winckler, K; Fölsch, U R; Creutzfeldt, W

    1977-01-01

    Because somatostatin (SRIF) reduces exocrine pancreatic secretion, its effect on acute pancreatitis was investigated in rats. Linear SRIF reduced serum amylase and lipase but had no effect on pancreatic necrosis, oedema, leucocyte infiltration, and enzyme content. The mortality rate was not reduced. These results do not recommend the use of SRIF in the treatment of acute pancreatitis. PMID:604191

  16. [Therapeutic attitude in acute necrotizing pancreatitis].

    PubMed

    Leşe, Mihaela; Pop, C; Naghi, Ildiko; Mureşan, Lavinia

    2002-01-01

    The necrosectomy, celiostomy and pancreatic drainage represent the surgical treatment of choice in necrotizing pancreatitis. We present the clinical observation of a patient 59 years old operated in surgical service of Baia Mare for acute necrotizing pancreatitis, discussing the moment of operation, tips of operations, postoperative complications as well as our experience in acute grave pancreatitis treatment.

  17. [Biological aspects of pancreatic cancer].

    PubMed

    Tonel, E; Carbone, A; Scirelli, T; Bellone, G; Emanuelli, G

    2005-04-01

    Pancreatic ductal carcinoma still is an aggressive disease with a fatal prognosis due to late diagnosis and resistance to pharmacological and surgical treatments. Molecular investigations of pancreatic cancer are complicated by the restricted accessibility of the organ for biopsies. However, recent studies have indicated that pancreatic cancer is a multi-stage process resulting from the accumulation of genetic changes in the somatic DNA of normal cells. These molecular alterations, including overexpression of receptor-ligand systems, oncogene activation and loss of tumour suppressor genes, leads to a profound disturbance in cell cycle regulation and continuous growth. The molecular findings are now integrated in a pancreatic tumour progression model, with genetically and morphological defined precursor lesions. However, it remains unclear whether the initial target cells of this cancer develop from ductal or acinar cells. This review will present recent emerging questions on the biology of pancreatic cancer with particular emphasis on the cell origin and tumour microenvironment.

  18. Proteomics studies of pancreatic cancer

    PubMed Central

    Chen, Ru; Pan, Sheng; Aebersold, Ruedi; Brentnall, Teresa A.

    2008-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in the United States, with 4% survival 5 years after diagnosis. Biomarkers are desperately needed to improve earlier, more curable cancer diagnosis and to develop new effective therapeutic targets. The development of quantitative proteomics technologies in recent years offers great promise for understanding the complex molecular events of tumorigenesis at the protein level, and has stimulated great interest in applying the technology for pancreatic cancer studies. Proteomic studies of pancreatic tissues, juice, serum/plasma, and cell lines have recently attempted to identify differentially expressed proteins in pancreatic cancer to dissect the abnormal signaling pathways underlying oncogenesis, and to detect new biomarkers. It can be expected that the continuing evolution of proteomics technology with better resolution and sensitivity will greatly enhance our capability in combating pancreatic cancer. PMID:18633454

  19. Autoimmune pancreatitis: a surgical dilemma.

    PubMed

    Saavedra-Perez, David; Vaquero, Eva C; Ayuso, Juan R; Fernandez-Cruz, Laureano

    2014-12-01

    Autoimmune pancreatitis (AIP) is defined as a particular form of pancreatitis that often manifests as obstructive jaundice associated with a pancreatic mass or an obstructive bile duct lesion, and that has an excellent response to corticosteroid treatment. The prevalence of AIP worldwide is unknown, and it is considered as a rare entity. The clinical and radiological presentation of AIP can mimic bilio-pancreatic cancer, presenting difficulties for diagnosis and obliging the surgeon to balance decision-making between the potential risk presented by the misdiagnosis of a deadly disease against the desire to avoid unnecessary major surgery for a disease that responds effectively to corticosteroid treatment. In this review we detail the current and critical points for the diagnosis, classification and treatment for AIP, with a special emphasis on surgical series and the methods to differentiate between this pathology and bilio-pancreatic cancer.

  20. [Surgical management of chronic pancreatitis].

    PubMed

    Regimbeau, Jean-Marc; Dumont, Frédéric; Yzet, Thierry; Chatelain, Denis; Bartoli, Eacute Ric; Brazier, Franck; Bréhant, Olivier; Dupas, Jean-Louis; Mauvais, François; Delcenserie, Richard

    2007-01-01

    Surgical indications for chronic pancreatitis can be schematically separated into five main groups: pain, effects of fibrosis on adjacent organs, the consequences of main pancreatic duct rupture above an obstruction, and suspected cancer. Finally surgery is also indicated in patients who cannot undergo endoscopic procedures (no accessible papilla) or who have too recently undergone this procedure. Surgical procedures include derivation (pancreatic, cystic, biliary) or mixed procedures combining derivation/resection or pancreatic resection. Finally splanchnicectomy can be discussed. Whatever the indication, surgical treatment must meet several goals: the approach to surgery must be multidisciplinary, surgery must be associated with low morbidity and mortality, preserve as much endocrine function as possible, improve quality of life, and be evaluated in the long term, as well as prospectively if possible. We clarify some important points about the management of patients with chronic pancreatitis before discussing the various treatments in detail.

  1. [Diabetes mellitus in acute pancreatitis].

    PubMed

    Díaz-Rubio, José Luis; Torre-Delgadillo, Aldo; Robles-Díaz, Guillermo

    2002-01-01

    Exocrine and endocrine components of pancreas are interrelated anatomically and functionally. Exocrine pancreatic dysfunction often accompanies endocrine pancreatic impairment and vice versa. Diabetes mellitus resulting from alterations of exocrine pancreas, such as acute or chronic pancreatitis, is known as pancreatic diabetes. Hyperglycemia during acute pancreatitis (AP) can be due to abnormalities in insulin secretion, increase in counterregulatory hormones release, or decrease in glucose utilization by peripheral tissues. Causal association is suggested between diabetic ketoacidosis and AP and is attributed to alternation in metabolism of triglycerides. High blood glucose levels are associated with severe AP and constitute factor of worst prognosis. Some patients are discharged with diabetes after AP episode, while others develop diabetes during first year of follow-up. Origin and frequency of glycemic abnormalities associated with AP have not been settled yet accurately. Also, predictive factors for diabetes development and persistence after AP have not been recognized to date.

  2. Blood tests for acute pancreatitis

    PubMed Central

    Basnayake, Chamara; Ratnam, Dilip

    2015-01-01

    Summary The diagnosis of acute pancreatitis requires the presence of at least two of the three diagnostic criteria – characteristic abdominal pain, elevated serum amylase or lipase, and radiological evidence of pancreatitis. Serum concentrations of amylase and lipase rise within hours of the pancreatic injury. A threshold concentration 2–4 times the upper limit of normal is recommended for diagnosis. Serum lipase is now the preferred test due to its improved sensitivity, particularly in alcohol-induced pancreatitis. Its prolonged elevation creates a wider diagnostic window than amylase. Neither enzyme is useful in monitoring or predicting the severity of an episode of pancreatitis in adults. New biomarkers including trypsinogen and elastase have no significant advantage over amylase or lipase. PMID:26648641

  3. New developments in pancreatic cancer.

    PubMed

    Greer, Julia B; Brand, Randall E

    2011-04-01

    Pancreatic adenocarcinoma presents in an advanced stage and has a dismal prognosis. Extensive recent research efforts have provided us with greater insight into the etiology of pancreatic cancer and have also improved our means of prognostication. Molecular analysis demonstrated that specific pathways involved in pancreatic carcinogenesis are perhaps more valuable to study than single genetic aberrations. Previous risk factors, including family history, body mass index, and current cigarette smoking, were validated and novel risks, such as ABO blood group alleles, were identified. Similar to other illnesses, combinations of healthful habits, such as not smoking, adhering to a Mediterranean dietary pattern, and engaging in physical activity, may decrease pancreatic cancer risk. Finally, CA 19-9 levels, the presence of diabetes mellitus, and a six-gene signature provided critical information regarding survival that could help guide treatment of individuals diagnosed with pancreatic adenocarcinoma.

  4. [Helicobacter pylori eradication therapy with omeprazole and amoxicillin: current status].

    PubMed

    Bayerdörffer, E; Miehlke, S; Mannes, G A

    1994-11-01

    Combined therapy with the proton pump inhibitor omeprazole and amoxicillin has become an important alternative in the treatment of ulcer disease associated with Helicobacter pylori infection. Due to the high efficacy in eradicating H.pylori, missing resistance of H.pylori against amoxicillin and high tolerability and digestibility this regimen may be recommended for widespread routine use. In a randomized, double-blind multicenter trial an H.pylori eradication rate of over 90% has been achieved for the first time by dual therapy using a daily omeprazole dose of 120 mg (3x40 mg) in combination with 3 x 750 mg amoxicillin for 14 days, which is comparable with classical triple therapy containing bismuth and two antibiotics. On the basis of an "intention-to-treat-analysis" dual therapy of omeprazole 3x40 mg + 3x750 mg amoxicillin is considered at present to be the most effective regimen for the treatment of H.pylori-associated diseases.

  5. The new polio eradication end game: rationale and supporting evidence.

    PubMed

    Sutter, Roland W; Platt, Lauren; Mach, Ondrej; Jafari, Hamid; Aylward, R Bruce

    2014-11-01

    Polio eradication requires the removal of all polioviruses from human populations, whether wild poliovirus or those emanating from the oral poliovirus vaccine (OPV). The Polio Eradication & Endgame Strategic Plan 2013-2018 provides a framework for interruption of wild poliovirus transmission in remaining endemic foci and lays out a plan for the new polio end game, which includes the withdrawal of Sabin strains, starting with type 2, and the introduction of inactivated poliovirus vaccine, for risk mitigation purposes. This report summarizes the rationale and evidence that supports the policy decision to switch from trivalent OPV to bivalent OPV and to introduce 1 dose of inactivated poliovirus vaccine into routine immunization schedules, and it describes the proposed implementation of this policy in countries using trivalent OPV.

  6. Logistics of Guinea worm disease eradication in South Sudan.

    PubMed

    Jones, Alexander H; Becknell, Steven; Withers, P Craig; Ruiz-Tiben, Ernesto; Hopkins, Donald R; Stobbelaar, David; Makoy, Samuel Yibi

    2014-03-01

    From 2006 to 2012, the South Sudan Guinea Worm Eradication Program reduced new Guinea worm disease (dracunculiasis) cases by over 90%, despite substantial programmatic challenges. Program logistics have played a key role in program achievements to date. The program uses disease surveillance and program performance data and integrated technical-logistical staffing to maintain flexible and effective logistical support for active community-based surveillance and intervention delivery in thousands of remote communities. Lessons learned from logistical design and management can resonate across similar complex surveillance and public health intervention delivery programs, such as mass drug administration for the control of neglected tropical diseases and other disease eradication programs. Logistical challenges in various public health scenarios and the pivotal contribution of logistics to Guinea worm case reductions in South Sudan underscore the need for additional inquiry into the role of logistics in public health programming in low-income countries.

  7. Logistics of Guinea Worm Disease Eradication in South Sudan

    PubMed Central

    Jones, Alexander H.; Becknell, Steven; Withers, P. Craig; Ruiz-Tiben, Ernesto; Hopkins, Donald R.; Stobbelaar, David; Makoy, Samuel Yibi

    2014-01-01

    From 2006 to 2012, the South Sudan Guinea Worm Eradication Program reduced new Guinea worm disease (dracunculiasis) cases by over 90%, despite substantial programmatic challenges. Program logistics have played a key role in program achievements to date. The program uses disease surveillance and program performance data and integrated technical–logistical staffing to maintain flexible and effective logistical support for active community-based surveillance and intervention delivery in thousands of remote communities. Lessons learned from logistical design and management can resonate across similar complex surveillance and public health intervention delivery programs, such as mass drug administration for the control of neglected tropical diseases and other disease eradication programs. Logistical challenges in various public health scenarios and the pivotal contribution of logistics to Guinea worm case reductions in South Sudan underscore the need for additional inquiry into the role of logistics in public health programming in low-income countries. PMID:24445199

  8. Eradication of HIV and Cure of AIDS, Now and How?

    PubMed

    Zhang, Jielin; Crumpacker, Clyde

    2013-10-18

    Recent studies have highlighted the importance of eradication of human immunodeficiency virus (HIV) and cure of acquired immunodeficiency syndrome (AIDS). However, a pivotal point that the patient immunity controls HIV reactivation after highly active anti-retroviral therapy [HAART or combination anti-retroviral therapy (cART)] remains less well addressed. In spite of the fact that both innate and adaptive immunities are indispensable and numerous cells participate in the anti-HIV immunity, memory CD4 T-cells are indisputably the key cells organizing all immune actions against HIV while being the targets of HIV. Here we present a view and multidisciplinary approaches to HIV/AIDS eradication and cure. We aim at memory CD4 T-cells, utilizing the stem cell properties of these cells to reprogram an anti-HIV memory repertoire to eliminate the viral reservoir, toward achieving an AIDS-free world.

  9. Eradication of HIV and Cure of AIDS, Now and How?

    PubMed Central

    Zhang, Jielin; Crumpacker, Clyde

    2013-01-01

    Recent studies have highlighted the importance of eradication of human immunodeficiency virus (HIV) and cure of acquired immunodeficiency syndrome (AIDS). However, a pivotal point that the patient immunity controls HIV reactivation after highly active anti-retroviral therapy [HAART or combination anti-retroviral therapy (cART)] remains less well addressed. In spite of the fact that both innate and adaptive immunities are indispensable and numerous cells participate in the anti-HIV immunity, memory CD4 T-cells are indisputably the key cells organizing all immune actions against HIV while being the targets of HIV. Here we present a view and multidisciplinary approaches to HIV/AIDS eradication and cure. We aim at memory CD4 T-cells, utilizing the stem cell properties of these cells to reprogram an anti-HIV memory repertoire to eliminate the viral reservoir, toward achieving an AIDS-free world. PMID:24151495

  10. Eradication of poliomyelitis in Cuba: a historical perspective.

    PubMed Central

    Más Lago, P.

    1999-01-01

    The eradication of poliomyelitis in Cuba, for which effective vaccines had to be acquired, is reviewed in this article. The strategy for eradication was based on mass immunization campaigns for the annual delivery of two doses of trivalent Sabin oral poliovirus vaccine (OPV). Except during the first campaign in 1962, the ages of the children for immunization were determined through national serological surveys of the entire country, including rural and urban areas. The interruption of wild virus transmission had been suspected since 1967 in Cuba, and since 1970 no studies have detected any wild virus. The important role of political and social organizations in the success of the programme and in the execution of the mass immunization campaigns is underscored. Countries that have successfully interrupted poliovirus circulation should maintain high immunization coverage for as long as there are other countries in the world where poliovirus still exists. PMID:10516790

  11. Control and eradication of animal diseases in New Zealand.

    PubMed

    Davidson, R M

    2002-01-01

    New Zealand is free from all the major epidemic (Office International des Epizooties List A) diseases of animals and other important diseases, such as rabies and the transmissible spongiform encephalopathies. The once endemic conditions of sheep scab (Psoroptes ovis), bovine brucellosis (Brucella abortus), hydatids (Echinococcus granulosus) and Aujeszky's disease have been eradicated. Anthrax (Bacillus anthracis) is no longer considered endemic and Pullorum disease (Salmonella Pullorum) has effectively been eradicated from commercial poultry flocks. There are current control programmes for bovine tuberculosis (Mycobacterium bovis), enzootic bovine leucosis in dairy cattle, infectious bursal disease, ovine epididymitis (Brucella ovis), and caprine arthritis encephalitis. Historically, incursions by three important non-endemic diseases, contagious bovine pleuropneumonia, classical swine fever and scrapie, have been successfully eliminated. Any new occurrence of a serious exotic disease would be dealt with swiftly using powerful legislative authorities available for the purpose.

  12. Macroeconomics, (Adult) Education, and Poverty Eradication in Southern Africa

    NASA Astrophysics Data System (ADS)

    Nhamo, Senia; Nhamo, Godwell

    2006-05-01

    The Millennium Summit held in New York in September 2000 outlined the Millennium Development Goals (MDGs). The first of these involves the eradication of extreme poverty and hunger, setting two targets: halving by 2015 the percentage of the world's populace in 1990 with income less than US-1 a day (i.e., cutting this percentage from 27.9 to 14%); and halving the share of people who suffer from hunger. As for education, the MDGs seek to ensure that all children can complete primary schooling by 2015. Drawing on examples from selected southern African countries, the present study examines the need to strengthen economic support for (adult) education as an instrument of poverty eradication. It argues that human capital is one of the fundamental determinants of economic growth, and that this economic resource is essentially determined in both qualitative and quantitative regards by education.

  13. Guinea worm (Dracunculiasis) eradication: update on progress and endgame challenges.

    PubMed

    Al-Awadi, Abdul R; Al-Kuhlani, Abdulhakim; Breman, Joel G; Doumbo, Ogobara; Eberhard, Mark L; Guiguemde, Robert T; Magnussen, Pascal; Molyneux, David H; Nadim, Abolhassan

    2014-05-01

    The International Commission for the Certification of Dracunculiasis Eradication (ICCDE) met in December to review progress towards eradication. The status of the programme was presented by WHO and The Carter Center, Atlanta. The Commission received reports from international certification teams that Cote d'Ivoire, Niger and Nigeria were free of transmission and should be certified, while four countries, namely Chad, Ethiopia, Mali and South Sudan, remained endemic. The Commission certified that Somalia and South Africa were free of transmission. During 2013, there was a decline of about 78% in the numbers of cases reported in South Sudan. A report of the perplexing dracunculiasis epidemiology in Chad was also discussed, where dogs have been found to be infected with Dracunculus medinensis.

  14. How Polyomaviruses Exploit the ERAD Machinery to Cause Infection

    PubMed Central

    Dupzyk, Allison; Tsai, Billy

    2016-01-01

    To infect cells, polyomavirus (PyV) traffics from the cell surface to the endoplasmic reticulum (ER) where it hijacks elements of the ER-associated degradation (ERAD) machinery to penetrate the ER membrane and reach the cytosol. From the cytosol, the virus transports to the nucleus, enabling transcription and replication of the viral genome that leads to lytic infection or cellular transformation. How PyV exploits the ERAD machinery to cross the ER membrane and access the cytosol, a decisive infection step, remains enigmatic. However, recent studies have slowly unraveled many aspects of this process. These emerging insights should advance our efforts to develop more effective therapies against PyV-induced human diseases. PMID:27589785

  15. The Effect of Probiotics Supplementation on Helicobacter pylori Eradication Rates and Side Effects during Eradication Therapy: A Meta-Analysis

    PubMed Central

    Dang, Yini; Reinhardt, Jan D.; Zhou, Xiaoying; Zhang, Guoxin

    2014-01-01

    Background Previous meta-analyses reported that probiotics improve the effectiveness of Helicobacter pylori (H. pylori) eradication during antibiotic therapy, while results regarding a possible reduction of side effects remained inconclusive. Moreover, the effectiveness of different strains of probiotics has not been studied so far. It is further conceivable that probiotics will produce additional effects only if antibiotics are relatively ineffective. Methods This meta-analysis includes eligible randomized controlled trials examining effects of probiotics supplementation on eradication rates (ER) and side effects, published up to May 2014. Sub-group analysis was performed to compare different probiotic strains and antibiotic therapies with different effectiveness in controls (ER <80% vs.>80%). Publication bias was assessed with funnel plots and Harbord's test. The quality of the trials was assessed with the Cochrane risk of bias tool. Results Thirty-three RCTs involving a total of 4459 patients met the inclusion criteria in case of eradication rates of which 20 assessed total side effects in addition. Overall, the pooled eradication rate in probiotics supplementation groups was significantly higher than in controls (ITT analysis: RR 1.122, 95% CI 1.086–1.159, PP analysis: RR 1.114, 95% CI 1.070–1.159). Sub group-analysis could, however, confirm this finding only for four individual strains (Lactobacillus acidophilus, Lactobacillus casei DN-114001, Lactobacillus gasseri, and Bifidobacterium infantis 2036) and for relatively ineffective antibiotic therapies. There was a significant difference between groups in the overall incidence of side effects (RR 0.735, 95% CI 0.598–0.902). This result was, however, only confirmed for non-blinded trials. Conclusions The pooled data suggest that supplementation with specific strains of probiotics compared with eradication therapy may be considered an option for increasing eradication rates, particularly when antibiotic

  16. Alcohol consumption on pancreatic diseases.

    PubMed

    Herreros-Villanueva, Marta; Hijona, Elizabeth; Bañales, Jesus Maria; Cosme, Angel; Bujanda, Luis

    2013-02-07

    Although the association between alcohol and pancreatic diseases has been recognized for a long time, the impact of alcohol consumption on pancreatitis and pancreatic cancer (PC) remains poorly defined. Nowadays there is not consensus about the epidemiology and the beverage type, dose and duration of alcohol consumption causing these diseases. The objective of this study was to review the epidemiology described in the literature for pancreatic diseases as a consequence of alcoholic behavior trying to understand the association between dose, type and frequency of alcohol consumption and risk of pancreatitis and PC. The majority of the studies conclude that high alcohol intake was associated with a higher risk of pancreatitis (around 2.5%-3% between heavy drinkers and 1.3% between non drinkers). About 70% of pancreatitis are due to chronic heavy alcohol consumption. Although this incidence rate differs between countries, it is clear that the risk of developing pancreatitis increases with increasing doses of alcohol and the average of alcohol consumption vary since 80 to 150 g/d for 10-15 years. With regard to PC, the role of alcohol consumption remains less clear, and low to moderate alcohol consumption do not appear to be associated with PC risk, and only chronic heavy drinking increase the risk compared with lightly drinkers. In a population of 10%-15% of heavy drinkers, 2%-5% of all PC cases could be attributed to alcohol consumption. However, as only a minority (less than 10% for pancreatitis and 5% for PC) of heavily drinkers develops these pancreatic diseases, there are other predisposing factors besides alcohol involved. Genetic variability and environmental exposures such as smoking and diet modify the risk and should be considered for further investigations.

  17. Progress Toward Poliomyelitis Eradication--Nigeria, January 2014-July 2015.

    PubMed

    Etsano, Andrew; Gunnala, Rajni; Shuaib, Faisal; Damisa, Eunice; Mkanda, Pascal; Ticha, Johnson M; Banda, Richard; Korir, Charles; Chevez, Ana Elena; Enemaku, Ogu; Corkum, Melissa; Davis, Lora B; Nganda, Gatei-Wa; Burns, Cara C; Wassilak, Steven G F; Vertefeuille, John F

    2015-08-21

    Since the 1988 launch of global poliomyelitis eradication efforts, four of the six World Health Organization (WHO) regions have been certified polio-free. Nigeria is one of only three countries, along with Afghanistan and Pakistan, where transmission of wild poliovirus (WPV) has never been interrupted. During 2003-2013, northern Nigeria served as a reservoir for WPV reintroduction into 26 previously polio-free countries. In 2012, the Nigerian government launched a national polio eradication emergency plan to intensify efforts to interrupt WPV transmission. This report describes polio eradication activities and progress in Nigeria during January 2014-July 2015 and updates previous reports. No WPV cases have been reported to date in 2015, compared with a total of six cases reported during 2014. Onset of paralysis in the latest reported WPV type 1 (WPV1) case was July 24, 2014. Only one case of circulating vaccine-derived poliovirus type 2 (cVDPV2) has been reported to date in 2015, compared with 20 cVDPV2 cases during the same period in 2014. Pending final laboratory testing of 218 remaining specimens of 16,617 specimens collected since January 2015, Nigeria could be removed from the WHO list of polio-endemic countries in September 2015. Major remaining challenges to the national polio eradication program include sustaining political support and program funding in the absence of active WPV transmission, maintaining high levels of population immunity in hard-to-reach areas, and accessing children in security-compromised areas of the northeastern states.

  18. Smallpox: can we still learn from the journey to eradication?

    PubMed Central

    Smith, Kendall A.

    2013-01-01

    One of the most celebrated achievements of immunology and modern medicine is the eradication of the dreaded plague smallpox. From the introduction of smallpox vaccination by Edward Jenner, to its popularization by Louis Pasteur, to the eradication effort led by Donald Henderson, this story has many lessons for us today, including the characteristics of the disease and vaccine that permitted its eradication, and the obviousness of the vaccine as a vector for other intractable Infectious diseases. The disease itself, interpreted in the light of modern molecular immunology, is an obvious immunopathological disease, which occurs after a latent interval of 1-2 weeks, and manifests as a systemic cell-mediated delayed type hypersensitivity (DTH) syndrome. The vaccine that slayed this dragon was given the name vaccinia, and was thought to have evolved from cowpox virus, but is now known to be most closely related to a poxvirus isolated from a horse. Of interest is the fact that of the various isolates of orthopox viruses, only variola, vaccinia and monkeypox viruses can infect humans. In contrast to the systemic disease of variola, vaccinia only replicates locally at the site of inoculation, and causes a localized DTH response that usually peaks after 7-10 days. This difference in the pathogenicity of variola vs. vaccinia is thought to be due to the capacity of variola to circumvent innate immunity, which allows it to disseminate widely before the adaptive immune response occurs. Thus, the fact that vaccinia virus is attenuated compared to variola, but is still replication competent, makes for its remarkable efficacy as a vaccine, as the localized infection activates all of the cells and molecules of both innate and adaptive immunity. Accordingly vaccinia itself, and not modified replication incompetent vaccina, is the hope for use as a vector in the eradication of additional pathogenic microbes from the globe. PMID:23760373

  19. Smallpox: can we still learn from the journey to eradication?

    PubMed

    Smith, Kendall A

    2013-05-01

    One of the most celebrated achievements of immunology and modern medicine is the eradication of the dreaded plague smallpox. From the introduction of smallpox vaccination by Edward Jenner, to its popularization by Louis Pasteur, to the eradication effort led by Donald Henderson, this story has many lessons for us today, including the characteristics of the disease and vaccine that permitted its eradication, and the obviousness of the vaccine as a vector for other intractable Infectious diseases. The disease itself, interpreted in the light of modern molecular immunology, is an obvious immunopathological disease, which occurs after a latent interval of 1-2 weeks, and manifests as a systemic cell-mediated delayed type hypersensitivity (DTH) syndrome. The vaccine that slayed this dragon was given the name vaccinia, and was thought to have evolved from cowpox virus, but is now known to be most closely related to a poxvirus isolated from a horse. Of interest is the fact that of the various isolates of orthopox viruses, only variola, vaccinia and monkeypox viruses can infect humans. In contrast to the systemic disease of variola, vaccinia only replicates locally at the site of inoculation, and causes a localized DTH response that usually peaks after 7-10 days. This difference in the pathogenicity of variola vs. vaccinia is thought to be due to the capacity of variola to circumvent innate immunity, which allows it to disseminate widely before the adaptive immune response occurs. Thus, the fact that vaccinia virus is attenuated compared to variola, but is still replication competent, makes for its remarkable efficacy as a vaccine, as the localized infection activates all of the cells and molecules of both innate and adaptive immunity. Accordingly vaccinia itself, and not modified replication incompetent vaccina, is the hope for use as a vector in the eradication of additional pathogenic microbes from the globe.

  20. Cryotherapy of shoot tips: novel pathogen eradication method.

    PubMed

    Wang, Qiaochun; Valkonen, Jari P T

    2009-03-01

    Cryotherapy is a novel application of plant cryopreservation techniques that allows pathogen eradication at a high frequency. It eliminates plant pathogens such as viruses, phytoplasmas and bacteria by briefly treating shoot tips in liquid nitrogen using cryopreservation protocols. Healthy plants are regenerated from the surviving pathogen-free meristematic tissue. The method facilitates treatment of large numbers of samples and is independent of shoot tip size. It has the potential to replace more traditional methods like meristem culture.

  1. Dracunculiasis eradication--finishing the job before surprises arise.

    PubMed

    Visser, Benjamin Jelle

    2012-07-01

    Dracunculiasis (Guinea worm disease) is a preventable waterborne parasitic disease that affects the poorest people living in remote rural areas in sub-Saharan African countries, who do not have access to safe drinking water. The Guinea Worm Eradication Program, a 25-year old campaign to rid the world of Guinea Worm disease has now reached its final stage accelerating to zero cases in all endemic countries. During the 19th and 20th centuries, dracunculiasis was common in much of Southern Asia and the African continent. The overall number of cases has been reduced tremendously by ≥99%, from the 3.32 million cases estimated to have occurred in 1986 in Africa to only 1,797 cases reported in 2010 reported in only five countries (Sudan, Mali, Ethiopia, Chad and Ghana) and Asia free of the disease. This achievement is unique in its kind--the only previously eradicated disease is smallpox, a viral infection for which vaccination was possible--and it has been achieved through primary community-based prevention and health education programs. Most efforts need to be taken in two countries, South Sudan (comprising 94% or 1,698 out of 1,797 of the cases reported world-wide in 2010) and Mali because of frequent movements of nomads in a vast area inside and outside Mali's borders. All factors favourable to dracunculiasis eradication are available including adequate financial resources, community and political support and high levels of advocacy. Thus there is no reason that this disabling parasitic disease cannot be eradicated soon before surprises arise such as new civil conflicts in currently endemic countries.

  2. Progress Toward Poliomyelitis Eradication--Pakistan, January 2014-September 2015.

    PubMed

    Farag, Noha H; Wadood, Mufti Zubair; Safdar, Rana Muhammad; Ahmed, Nabil; Hamdi, Sabrine; Tangermann, Rudolph H; Ehrhardt, Derek

    2015-11-20

    Since Nigeria reported its last case of wild poliovirus type 1 (WPV1) in July 2014, Pakistan and Afghanistan remain the only two countries where WPV transmission has never been interrupted. This report describes actions taken and progress achieved toward polio eradication in Pakistan during January 2014-September 2015 and updates previous reports. A total of 38 WPV1 cases were reported in Pakistan during January-September 2015, compared with 243 during the same period in 2014 (an 84% decline). Among WPV1 cases reported in 2015, 32 (84%) occurred in children aged <36 months, nine (32%) of whom had never received oral poliovirus vaccine (OPV). Twenty-six (68%) of the 38 reported cases occurred in the Federally Administered Tribal Areas (FATA) and Khyber Pakhtunkhwa (KPK) Province. During January-September 2015, WPV1 was detected in 20% (64 of 325) of environmental samples collected, compared with 34% (98 of 294) of samples collected during the same period in 2014. The quality and scope of polio eradication activities improved considerably following the establishment of a national Emergency Operations Center, which coordinated polio eradication partners' activities. All activities are following a National Polio Eradication Emergency Action Plan that includes a rigorous action plan for the polio low transmission season (January-April). The presence of WPV1 in environmental samples in areas where no polio cases are detected highlights the need to improve surveillance for acute flaccid paralysis (AFP). Focused efforts to close remaining immunity gaps by locating, tracking, and vaccinating continually missed children and improving coverage with OPV through the routine vaccination program are needed to stop WPV transmission in Pakistan.

  3. Progress toward global eradication of dracunculiasis, January 2010-June 2011.

    PubMed

    2011-10-28

    In 1986, the World Health Assembly (WHA) called for the elimination of dracunculiasis (Guinea worm disease), a parasitic infection in humans caused by Dracunculus medinensis. At the time, an estimated 3.5 million cases were occurring annually in 20 countries in Africa and Asia, and 120 million persons were at risk for the disease. Because of slow mobilization in countries with endemic disease, the 1991 WHA goal to eradicate dracunculiasis globally by 1995 was not achieved. In 2004, WHA established a new target date of 2009 for global eradication; despite considerable progress, that target date also was not met. This report updates published and previously unpublished data and describes progress towards global eradication of dracunculiasis since January 2010. The number of indigenous cases of dracunculiasis worldwide decreased 44%, from 3,185 cases in 2009 to 1,793 in 2010. As of June 2011, dracunculiasis remained endemic in three countries (Ethiopia, Mali, and South Sudan). Of the 814 cases that occurred during January-June 2011, a total of 801 (98%) were reported from 358 villages in South Sudan. By October 2010, Ghana had gone 12 months without an indigenous case, thereby interrupting transmission; Ethiopia and Mali are close to interrupting transmission, as indicated by the small and declining numbers of cases in these two countries. An outbreak of 10 cases was discovered in Chad in 2010. The current target is to interrupt transmission in the remaining countries as soon as possible. Insecurity (e.g., sporadic violence or civil unrest) in areas of South Sudan and Mali, where dracunculiasis is endemic, poses the greatest threat to the success of the global dracunculiasis eradication campaign.

  4. The clinical significance of pancreatic steatosis.

    PubMed

    Smits, Mark M; van Geenen, Erwin J M

    2011-03-01

    More research is now focused on pancreatic steatosis. Multiple definitions, clinical associations and synonyms for pancreatic steatosis are described in the literature and can be confusing. The integration and comparison of several studies concerning this topic is therefore challenging. In the past, pancreatic steatosis was considered an innocuous condition, a bystander of many underlying diseases (such as congenital syndromes, hemochromatosis and viral infection). However, evidence that pancreatic steatosis (strongly associated with obesity and the metabolic syndrome) has a role in type 2 diabetes mellitus, pancreatic exocrine dysfunction, acute pancreatitis, pancreatic cancer and the formation of pancreatic fistula after pancreatic surgery is emerging. This Review focuses on the different etiological factors and the clinical consequences of pancreatic steatosis.

  5. Hereditary pancreatic cancer: a clinical perspective.

    PubMed

    Greer, Julia B; Lynch, Henry T; Brand, Randall E

    2009-01-01

    Pancreatic cancer is an extraordinarily deadly disease and is responsible for over 220,000 deaths worldwide each year. One of the greatest risk factors for developing pancreatic cancer is a positive family history. Hereditary pancreatitis patients have a greatly elevated pancreatic cancer risk and individuals with cystic fibrosis may rarely develop this cancer, but often at very young ages. Various genetically linked cancer syndromes have been associated with pancreatic cancer in mutation-positive family members. Finally, familial pancreatic cancer-defined as families with two or more first-degree relatives who have pancreatic cancer but do not have a known cancer syndrome-is a known entity whose disease-causing mutation remains unidentified. This article describes research to date on hereditary pancreatic cancer, addresses how best clinicians should recognise hereditary forms of pancreatic cancer and explains the emotional burden of discovering a potentially lethal mutation. Many controversies and unanswered questions in hereditary pancreatic cancer remain.

  6. India's Research Contributions Towards Polio Eradication (1965-2015).

    PubMed

    John, T Jacob

    2016-08-07

    Pioneering research has been conducted in India during the past five decades, comprehensively covering epidemiology of poliovirus infection and of polio, efficacy and effectiveness of oral and inactivated polio vaccines (OPV, IPV) as well as pathogenesis of wild and vaccine polioviruses. It was estimated, based on epidemiology data, that India had a very heavy burden of polio, with average 500-1000 cases per day. Prevention was an urgent need, but OPV showed unacceptably low vaccine efficacy (VE) for poliovirus types 1 and 3. Having learned that response to sequential doses followed arithmetic pattern and not prime-boost principle, multiple doses were tested and found to be a simple intervention to increase VE. Eventually this knowledge became critical for polio eradication. Indian research demonstrated that monovalent OPV (mOPV) had nearly three timed higher VE than trivalent OPV (tOPV). Eventually, mOPV type 1 became essential to interrupt wild type 1 infection in many locations where the VE of tOPV was very low. Indian research pointed to the epidemiologic importance of direct person-to-person spread of wild polio viruses and the need and potential of IPV to prevent and control polio. Research on vaccine responses led to the understanding that OPV would become wild-like through back mutations and to the definition of eradication as interrupting transmission of both wild and vaccine-derived polioviruses. By asking and answering the right questions insequence, Indian polio research presaged and guided polio eradication.

  7. Progress toward polio eradication--Somalia, 1998-2013.

    PubMed

    Mbaeyi, Chukwuma; Kamadjeu, Raoul; Mahamud, Abdirahman; Webeck, Jenna; Ehrhardt, Derek; Mulugeta, Abraham

    2014-11-01

    Since the 1988 resolution of the World Health Assembly to eradicate polio, significant progress has been made toward achieving this goal, with the result that only Afghanistan, Nigeria, and Pakistan have never successfully interrupted endemic transmission of wild poliovirus. However, one of the greatest challenges of the Global Polio Eradication Initiative has been that of maintaining the polio-free status of countries in unstable regions with weak healthcare infrastructure, a challenge exemplified by Somalia, a country in the Horn of Africa region. Somalia interrupted indigenous transmission of wild poliovirus in 2002, 4 years after the country established its national polio eradication program. But political instability and protracted armed conflict, with significant disruption of the healthcare system, have left Somalia vulnerable to 2 imported outbreaks of wild poliovirus. The first occurred during 2005-2007, resulting in >200 cases of paralytic polio, whereas the second, which began in 2013, is currently ongoing. Despite immense challenges, the country has a sensitive surveillance system that has facilitated prompt detection of outbreaks, but its weak routine immunization system means that supplementary immunization activities constitute the primary strategy for reaching children with polio vaccines. Conducting vaccination campaigns in a setting of conflict has been at times hazardous, but the country's polio program has demonstrated resilience in overcoming many obstacles to ensure that children receive lifesaving polio vaccines. Regaining and maintaining Somalia's polio-free status will depend on finding innovative and lasting solutions to the challenge of administering vaccines in a setting of ongoing conflict and instability.

  8. Polio Eradication and Endgame Plan - Victory within Grasp.

    PubMed

    Patel, Manish; Menning, Lisa; Bhatnagar, Pankaj

    2016-08-07

    Since the launch of the Global Polio Eradication Initiative (GPEI) by the World Health Assembly (WHA) in 1988, the number of polio-endemic countries has decreased from 125 to 2 (Afghanistan and Pakistan). To secure the gains and to address the remaining challenges, the GPEI developed the Polio Eradication and Endgame Strategic Plan, 2013-2018 (the Plan), endorsed by all Member States at the WHA in May 2013. One of the major elements that distinguishes this Plan from previous GPEI strategies is the approach to ending all polioviruses, both wild and vaccine-derived. Overall, the Plan outlines four main objectives: (1) to stop all wild poliovirus (WPV) transmission; (2) to introduce inactivated polio vaccine (IPV), withdraw all oral polio vaccines (OPV), and strengthen immunization systems in countries with weak immunization systems and strong polio infrastructure; (3) to certify all regions as polio-free and safely contain all poliovirus stocks; (4) and to mainstream the investment in polio eradication to benefit other priority public health initiatives for years to come. Implementing the Plan and meeting the milestones in a timely manner will help to ensure that that the world remains permanently polio-free.

  9. [POLIOMYELITIS ERADICATION--ONE STEP TO ACHIEVE THE GOAL].

    PubMed

    Ljubin-Sternak, Sunčanica; Kaić, Bernard; Vilibić-Čavlek, Tatjana; Mlinarić-Galinović, Gordana

    2014-12-01

    Poliomyelitis is a very old disease of humans, caused by poliovirus. With appearance of the epidemics in the 20th century, poliomyelitis became a global public health issue. In 1988, the World Health Organization started a campaign for global eradication of poliomyelitis and till now poliomyelitis cases have been reduced by more than 99%. In Croatia, the introduction of vaccination in 1961 resulted in dramatic reduction of paralytic disease. The European region, including Croatia was certified polio free in 2002. However, the final goal of the "polio-free world" has not yet been reached. To reinforce the campaign, the global polio eradication initiative has come up with the Polio Eradication & Endgame Strategic Plan 2013-2018 with detailed program how to resolve the main challenges: (a) continued transmission of wild polioviruses in endemic reservoirs; (b) reinfection of polio-free areas; and (c) outbreaks due to the circulating vaccine-derived polioviruses (cVDPV). Global oral polio vaccine cessation will follow, with the introduction of universal use of inactivated polio vaccine.

  10. Progress toward polio eradication - worldwide, 2014-2015.

    PubMed

    Hagan, José E; Wassilak, Steven G F; Craig, Allen S; Tangermann, Rudolf H; Diop, Ousmane M; Burns, Cara C; Quddus, Arshad

    2015-05-22

    In 1988, the World Health Assembly of the World Health Organization (WHO) resolved to eradicate polio worldwide. Wild poliovirus (WPV) transmission has been interrupted in all but three countries (Afghanistan, Nigeria, and Pakistan). No WPV type 2 cases have been detected worldwide since 1999, and the last WPV type 3 case was detected in Nigeria in November 2012; since 2012, only WPV type 1 has been detected. Circulating vaccine-derived poliovirus (cVDPV), usually type 2, continues to cause cases of paralytic polio in communities with low population immunity. In 2012, the World Health Assembly declared global polio eradication "a programmatic emergency for global public health", and in 2014, WHO declared the international spread of WPV to previously polio-free countries to be "a public health emergency of international concern". This report summarizes global progress toward polio eradication during 2014-2015 and updates previous reports. In 2014, a total of 359 WPV cases were reported in nine countries worldwide. Although reported WPV cases increased in Pakistan and Afghanistan, cases in Nigeria decreased substantially in 2014, and encouraging progress toward global WPV transmission interruption has occurred. Overcoming ongoing challenges to interruption of WPV transmission globally will require sustained programmatic enhancements, including improving the quality of supplementary immunization activities (SIAs) to interrupt transmission in Afghanistan and Pakistan and to prevent WPV exportation to polio-free countries.

  11. Usefulness of antimicrobial susceptibility in the eradication of Helicobacter pylori.

    PubMed

    Cosme, A; Montes, M; Martos, M; Gil, I; Mendarte, U; Salicio, Y; Piñeiro, L; Recasens, M T; Ibarra, B; Sarasqueta, C; Bujanda, L

    2013-04-01

    The rate of eradication of Helicobacter pylori with standard triple therapy using omeprazole, amoxicillin and clarithromycin (OAC) is unacceptable in populations with high rates of clarithromycin resistance (15-20%). The aim of this study was to compare the efficacy of 10-day OAC therapy as the first-line treatment in patients diagnosed by culture with antimicrobial susceptibility or diagnosed by a (13) C-labelled urea breath test (UBT) without antimicrobial susceptibility in an area where the clarithromycin resistance rate was 15-20%. This was a retrospective cohort study of 266 patients, recruited consecutively throughout 2008. A total of 247 H. pylori-infected patients received antibiotic therapy (221 received the 10-day OAC therapy and 26 received other regimens) of which 134 patients were diagnosed by culture of gastric samples followed by antimicrobial susceptibility testing and 113 were diagnosed by UBT. In all patients, the eradication of H. pylori was checked by UBT. The cost of eradication by 10-day OAC treatment was assessed in each patient. The success rate of 10-day OAC therapy in patients diagnosed by culture and by UBT was 88% (103/117) and 49% (51/104), respectively (p <0.0005). The treatment was also more cost-effective in the former of these two groups (€571 versus €666). To perform culture and antimicrobial susceptibility of the H. pylori isolates was a more successful and cost effective strategy than empirical 10-day OAC treatment in populations with high rates of resistance to clarithromycin.

  12. Polio eradication: mobilizing and managing the human resources.

    PubMed Central

    Aylward, R. Bruce; Linkins, Jennifer

    2005-01-01

    Between 1988 and 2004, the Global Polio Eradication Initiative grew to become the largest international health effort in history, operating in every country of the world. An estimated 10 million health workers and volunteers have been engaged in implementing the necessary polio supplementary immunization activities (SIAs) on a recurring basis, and at least 35,000 well-trained workers have been conducting polio surveillance. A combination of task simplification, technological innovations and adaptation of strategies to fit local circumstances has allowed the Initiative to use a wide range of workers and volunteers, from both inside and outside the health sector, to deliver the polio vaccine during SIAs and to monitor progress in virtually every area of every country, regardless of the health infrastructure, conflict, geography and/or culture. This approach has required sustained political advocacy and mass community mobilization, together with strong management and supervisory processes. Non-monetary incentives, reimbursement of costs and substantial technical assistance have been essential. Given the unique features of eradication programmes in general, and polio eradication in particular, the implications of this approach for the broader health system must continue to be studied if it is to be replicated for the delivery and monitoring of other interventions. PMID:15868017

  13. Role of gastritis pattern on Helicobacter pylori eradication.

    PubMed

    Zullo, Angelo; Severi, Carola; Vannella, Lucy; Hassan, Cesare; Sbrozzi-Vanni, Andrea; Annibale, Bruno

    2012-12-01

    Helicobacter pylori eradication rate following standard triple therapy is decreasing. Identification of predictive factors of therapy success would be useful for H. pylori management in clinical practice. This study aimed to evaluate the role of different gastritis patterns on the efficacy of the currently suggested 14-day triple therapy regimen. One-hundred and seventeen, consecutive, non-ulcer dyspeptic patients, with H. pylori infection diagnosed at endoscopy, were enrolled. All patients received a 14-day, triple therapy with lansoprazole 30 mg, clarithromycin 500 mg and amoxicillin 1 g, all given twice daily. Bacterial eradication was assessed with (13)C-urea breath test 4-6 weeks after completion of therapy. H. pylori infection was cured in 70.1% at ITT analysis and 83.7% at PP analysis. The eradication rate tended to be lower in patients with corpus-predominant gastritis as compared to those with antral-predominant gastritis at both ITT (66.1 vs 74.5%) and PP (80.4 vs 87.2%) analyses. The multivariate analysis failed to identify factors associated with therapy success. However, 14-day triple therapy does not achieve acceptable H. pylori cure rate in Italy, and should be not recommended in clinical practice.

  14. CYP2C19 polymorphism influences Helicobacter pylori eradication

    PubMed Central

    Kuo, Chao-Hung; Lu, Chien-Yu; Shih, Hsiang-Yao; Liu, Chung-Jung; Wu, Meng-Chieh; Hu, Huang-Ming; Hsu, Wen-Hung; Yu, Fang-Jung; Wu, Deng-Chyang; Kuo, Fu-Chen

    2014-01-01

    The known factors that have contributed to the decline of Helicobacter pylori (H. pylori) eradication rate include antibiotic resistance, poor compliance, high gastric acidity, high bacterial load, and cytochrome P450 2C19 (CYP2C19) polymorphism. Proton pump inhibitor (PPI) is important in the eradication regimen. The principal enzyme implicated in the metabolism of PPIs is CYP2C19. The effects of PPI depend on metabolic enzyme, cytochrome P450 enzymes, and CYP2C19 with genetic differences in the activity of this enzyme (the homozygous EM, heterozygous EM (HetEM), and poor metabolizer). The frequency of the CYP2C19 polymorphism is highly varied among different ethnic populations. The CYP2C19 genotype is a cardinal factor of H. pylori eradication in patients taking omeprazole- based or lansoprazole-based triple therapies. In contrast, the CYP2C19 polymorphism has no significant effect on the rabeprazole-based or esomeprazole-based triple therapies. The efficacy of levofloxacin-based rescue triple therapy might be also affected by the CYP2C19 polymorphism, but CYP2C19 genotypes did not show obvious impact on other levofloxacin-based rescue therapies. Choice of different PPIs and/or increasing doses of PPIs should be individualized based on the pharmacogenetics background of each patient and pharmacological profile of each drug. Other possible factors influencing gastric acid secretion (e.g., IL-1β- 511 polymorphism) would be also under consideration. PMID:25473155

  15. Effect of copper and silver ionization on Legionella pneumophila eradication

    SciTech Connect

    Lin, Y.E.; Vidic, R.D.; Stout, J.E.; Yu, V.L.

    1995-11-01

    The presence of Legionella pneumophila in water distribution systems has been epidemiologically linked to hospital-acquired Legionnaires` disease. The objective of this study was to evaluate the efficiency of copper and silver ions for inactivation of Legionella pneumophila. Experimental results showed that L. pneumophila was completely inactivated at copper concentration of 0.1 mg/L within the period of 2.5 hours while 6-log reduction requires a Ct value of 0.8 mg/L*hour. On the other hand, more than 24 hours was required to completely eradicate L. pneumophila at the highest silver ion concentration (0.08 mg/L) tested and only 4-log reduction is observed for Ct value of 0.8 mg/L*hour. The effective synergism of these ions in eradicating L. pneumophila was observed for copper concentrations of 0.05 and silver concentration of 0.04 mg/L. One approach for the control of L. pneumophila in water distribution systems is to initiate copper/silver ion concentrations at 0.4/0.04 mg/L to achieve complete eradication of L. pneumophila already present in the water distribution system (as established in previous studies) followed by a lower residual (0.05/0.04 mg/L) protection against L. pneumophila in the incoming water.

  16. Progress toward poliomyelitis eradication--Pakistan and Afghanistan, 2007.

    PubMed

    2008-03-28

    Of the four countries worldwide where wild poliovirus (WPV) transmission has never been interrupted, Pakistan and Afghanistan are considered a single epidemiologic block. Use of intense poliomyelitis eradication measures, including close coordination between the two countries and increased use of monovalent oral poliovirus vaccines (mOPVs) against type 1 WPV (WPV1) and type 3 WPV (WPV3), has reduced WPV transmission to historically low levels. However, despite these efforts, in 2007 both types of WPV continued to circulate in areas of Pakistan and Afghanistan. Ongoing conflicts and security concerns in remote areas with rugged terrain limit access to children and decrease vaccination coverage from routine and supplementary immunization activities (SIAs) in border areas of both countries where WPV transmission is endemic. In other WPV-endemic areas of Pakistan, where security and access concerns do not exist, operational problems in implementing SIAs resulted in inadequate vaccination of children, which failed to interrupt WPV transmission. This report updates previous reports and describes polio eradication activities in Pakistan and Afghanistan during January-December 2007 (data as of March 22, 2008). Further progress toward polio eradication will require continued measures to address security concerns in portions of both countries and problems with implementing SIAs in secure areas of Pakistan.

  17. Minimally invasive treatment of infected pancreatic necrosis

    PubMed Central

    Cebulski, Włodzimierz; Słodkowski, Maciej; Krasnodębski, Ireneusz W.

    2014-01-01

    Infected pancreatic necrosis is a challenging complication that worsens prognosis in acute pancreatitis. For years, open necrosectomy has been the mainstay treatment option in infected pancreatic necrosis, although surgical debridement still results in high morbidity and mortality rates. Recently, many reports on minimally invasive treatment in infected pancreatic necrosis have been published. This paper presents a review of minimally invasive techniques and attempts to define their role in the management of infected pancreatic necrosis. PMID:25653725

  18. Venous complications of pancreatitis: a review.

    PubMed

    Aswani, Yashant; Hira, Priya

    2015-01-31

    Pancreatitis is notorious to cause vascular complications. While arterial complications include pseudoaneurysm formation with a propensity to bleed, venous complications can be quite myriad. Venous involvement in pancreatitis often presents with thrombosis. From time to time case reports and series of unusual venous complications associated with pancreatitis have, however, been described. In this article, we review multitudinous venous complications in the setting of pancreatitis and propose a system to classify pancreatitis associated venous complications.

  19. [Ultrasonography of pancreatic neoplasms].

    PubMed

    Innocenti, P; Falchini, M; Stecco, A

    1999-01-01

    Pancreatic tumors are the fourth cause of death in Occident: the 5-year-survival rate is less than 5% because of diagnostic difficulties, low clinical expression at early stage, and complexity of the surgical treatment. The role of ultrasound (US) is in early diagnosis, because also in early cancer there could be lymphatic spread or peritoneal involvement. There are multiple modalities to study the pancreas with US: abdominal US, "contact" US (endosonography and intra-operative or laparoscopic US). The first is not invasive, cheap but limited by extrinsic and intrinsic factors, the latter are respectively characterized by high cost, and need of endoscopic specialists for endosonography, the complementarity to laparoscopy or surgery for the laparoscopic/intraoperative US. Abdominal US is the first diagnostic step for the pancreas, but it is not affordable in 15-25% of patients, because of meteorism. In all the other cases, it represents the pancreas with a good contrast between the normal parenchyma and tumoral tissues. Abdominal US, together with biopsy, can define the resectability. Ecoendoscopy is actually dedicated to small tumors staging, but recent studies demonstrate the same results achieved by spiral TC. Laparoscopic US is a second step imaging in patients already selected for surgery. The first finality in US evaluation of tumor masses is early diagnosis of pancreatic cancer; it can give to some of these patients the opportunity of undergoing to surgical treatment. This could be achieved by a proper use of the moititude of ultrasonic abdominal explorations that are requested in daily practice. US, together with CT and MR, can define the resectability of the tumor, with further supplementar evaluation by mean of laparoscopic US. Intraoperative US is now indicated for planning and guiding the surgeon in resection of the pancreatic cancer.

  20. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  1. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  2. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  3. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  4. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  5. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  6. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  7. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  8. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Type 2 Vaccine, Killed Virus. 113.202 Section 113.202 Animals and Animal Products ANIMAL AND PLANT...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  9. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Type 2 Vaccine. 113.305 Section 113.305 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  10. Recruitment of wild-type and recombinant adeno-associated virus into adenovirus replication centers.

    PubMed Central

    Weitzman, M D; Fisher, K J; Wilson, J M

    1996-01-01

    Replication of a human parvovirus, adeno-associated virus (AAV), is facilitated by coinfection with adeno-virus to provide essential helper functions. We have used the techniques of in situ hybridization and immunocytochemistry to characterize the localization of AAV replication within infected cells, Previous studies have shown that adenovirus establishes foci called replication centers within the nucleus, where adenoviral replication and transcription occur. Our studies indicate that AAV is colocalized with the adenovirus replication centers, where it may utilize adenovirus and cellular proteins for its own replication. Expression of the AAV Rep protein inhibits the normal maturation of the adenovirus centers. Similar experiments were performed with recombinant AAV (rAAV) to establish a relationship between intranuclear localization and rAAV transduction. rAAV efficiently entered the cell, and its genome was faintly detectable in a perinuclear distribution and was mobilized to replication centers when the cell was infected with adenovirus. The recruitment of the replication-defective genome into the intranuclear adenovirus domains resulted in enhanced transduction. These studies illustrate the importance of intracellular compartmentalization for such complex interactions as the relationship between AAV and adenovirus. PMID:8627709

  11. Recruitment of wild-type and recombinant adeno-associated virus into adenovirus replication centers.

    PubMed

    Weitzman, M D; Fisher, K J; Wilson, J M

    1996-03-01

    Replication of a human parvovirus, adeno-associated virus (AAV), is facilitated by coinfection with adeno-virus to provide essential helper functions. We have used the techniques of in situ hybridization and immunocytochemistry to characterize the localization of AAV replication within infected cells, Previous studies have shown that adenovirus establishes foci called replication centers within the nucleus, where adenoviral replication and transcription occur. Our studies indicate that AAV is colocalized with the adenovirus replication centers, where it may utilize adenovirus and cellular proteins for its own replication. Expression of the AAV Rep protein inhibits the normal maturation of the adenovirus centers. Similar experiments were performed with recombinant AAV (rAAV) to establish a relationship between intranuclear localization and rAAV transduction. rAAV efficiently entered the cell, and its genome was faintly detectable in a perinuclear distribution and was mobilized to replication centers when the cell was infected with adenovirus. The recruitment of the replication-defective genome into the intranuclear adenovirus domains resulted in enhanced transduction. These studies illustrate the importance of intracellular compartmentalization for such complex interactions as the relationship between AAV and adenovirus.

  12. Avian influenza mucosal vaccination in chickens with replication-defective recombinant adenovirus vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We evaluated protection conferred by mucosal vaccination with replication competent adenovirus (RCA)-free recombinant adenovirus expressing a codon-optimized avian influenza (AI) H5 gene (AdTW68.H5ck). Commercial layer-type chicken groups were singly vaccinated ocularly at 5 days of age, or singly v...

  13. Protection of chickens against avian influenza with non-replicating adenovirus-vectored vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Protective immunity against avian influenza (AI) virus was elicited in chickens by single-dose vaccination with a replication competent adenovirus (RCA) -free human adenovirus (Ad) vector encoding a H7 hemagglutinin gene from a low pathogenic North American isolate (AdChNY94.H7). Chickens vaccinate...

  14. Immunocompetent syngeneic cotton rat tumor models for the assessment of replication-competent oncolytic adenovirus

    SciTech Connect

    Steel, Jason C.; Morrison, Brian J.; Mannan, Poonam; Abu-Asab, Mones S.; Wildner, Oliver; Miles, Brian K.; Yim, Kevin C.; Ramanan, Vijay; Prince, Gregory A.; Morris, John C.

    2007-12-05

    Oncolytic adenoviruses as a treatment for cancer have demonstrated limited clinical activity. Contributing to this may be the relevance of preclinical animal models used to study these agents. Syngeneic mouse tumor models are generally non-permissive for adenoviral replication, whereas human tumor xenograft models exhibit attenuated immune responses to the vector. The cotton rat (Sigmodon hispidus) is susceptible to human adenovirus infection, permissive for viral replication and exhibits similar inflammatory pathology to humans with adenovirus replicating in the lungs, respiratory passages and cornea. We evaluated three transplantable tumorigenic cotton rat cell lines, CCRT, LCRT and VCRT as models for the study of oncolytic adenoviruses. All three cells lines were readily infected with adenovirus type-5-based vectors and exhibited high levels of transgene expression. The cell lines supported viral replication demonstrated by the induction of cytopathogenic effect (CPE) in tissue culture, increase in virus particle numbers and assembly of virions seen on transmission electron microscopy. In vivo, LCRT and VCRT tumors demonstrated delayed growth after injection with replicating adenovirus. No in vivo antitumor activity was seen in CCRT tumors despite in vitro oncolysis. Adenovirus was also rapidly cleared from the CCRT tumors compared to LCRT and VCRT tumors. The effect observed with the different cotton rat tumor cell lines mimics the variable results of human clinical trials highlighting the potential relevance of this model for assessing the activity and toxicity of oncolytic adenoviruses.

  15. Adenovirus-based vaccines against avian-origin H5N1 influenza viruses.

    PubMed

    He, Biao; Zheng, Bo-jian; Wang, Qian; Du, Lanying; Jiang, Shibo; Lu, Lu

    2015-02-01

    Since 1997, human infection with avian H5N1, having about 60% mortality, has posed a threat to public health. In this review, we describe the epidemiology of H5N1 transmission, advantages and disadvantages of different influenza vaccine types, and characteristics of adenovirus, finally summarizing advances in adenovirus-based H5N1 systemic and mucosal vaccines.

  16. Comparison of throat swab and nasopharyngeal aspirate specimens for rapid detection of adenovirus.

    PubMed

    Hara, Michimaru; Takao, Shinichi; Shimazu, Yukie

    2015-06-01

    Nasopharyngeal aspirate (NPA) and throat swab (TS) specimens from individual patients were compared with regard to usefulness for adenovirus detection. In 153 adenovirus-infected patients, rapid test sensitivities with NPAs (90.8%) were nearly equivalent to those with TSs (91.5%) based on real-time polymerase chain reaction standards, indicating that NPAs are equally useful.

  17. Adenovirus Type 7 Pneumonia in Children Who Died from Measles-Associated Pneumonia, Hanoi, Vietnam, 2014.

    PubMed

    Hai, Le Thanh; Thach, Hoang Ngoc; Tuan, Ta Anh; Nam, Dao Huu; Dien, Tran Minh; Sato, Yuko; Kumasaka, Toshio; Suzuki, Tadaki; Hanaoka, Nozomu; Fujimoto, Tsuguto; Katano, Harutaka; Hasegawa, Hideki; Kawachi, Shoji; Nakajima, Noriko

    2016-04-01

    During a 2014 measles outbreak in Vietnam, postmortem pathologic examination of hospitalized children who died showed that adenovirus type 7 pneumonia was a contributory cause of death in children with measles-associated immune suppression. Adenovirus type 7 pneumonia should be recognized as a major cause of secondary infection after measles.

  18. Location of the Origin of DNA Replication in Adenovirus Type 2

    PubMed Central

    Horwitz, Marshall S.

    1974-01-01

    Utilizing the isolated left and right halves of both adenovirus type 2 and the nondefective adenovirus simian virus 40 hybrid (Ad2+ND1), studies were undertaken to find the site on the DNA molecules at which replication begins. The data are consistent with several models which include an initiation event at both ends and bidirectional growth. PMID:4363250

  19. Subgenomic viral DNA species synthesized in simian cells by human and simian adenoviruses.

    PubMed Central

    Daniell, E

    1981-01-01

    DNA synthesized after infection of simian tissue culture cells (BSC-1 or CV-1) with human adenovirus type 2 or 5 or with simian adenovirus 7 was characterized. It was demonstrated that as much as 40% of the virus-specific DNA in nuclei of infected monkey cells consists of subgenomic pieces. No subgenomic viral DNA species were detected in the nuclei of human (HeLa) cells infected with these adenovirus types. Restriction analysis showed that these short viral DNA molecules contain normal amounts of the sequences from the ends of the viral genome, whereas internal regions are underrepresented. The production of subgenomic DNAs is not correlated with semipermissive infection. Although adenovirus types 2 and 5 are restricted in monkey cells, these cells are fully permissive for simian adenovirus 7. HR404, an adenovirus type 5 mutant which is not restricted in monkey cells, produced the same percentage of subgenomic DNAs as did its wild type (restricted) parent, and coinfection of monkey cells with adenovirus type 5 DNAs. The array of predominant size classes among the heterogeneously sized short DNAs is serotype specific. Extensive plaque purification and comparison of wild-type adenovirus type 5 with several viral mutants indicated that the distribution of aberrant sizes of DNA is characteristic of the virus and not a result of random replicative errors and then enrichment of particular species. Images PMID:6261009

  20. Optimization and evaluation of a method to detect adenoviruses in river water

    EPA Pesticide Factsheets

    This dataset includes the recoveries of spiked adenovirus through various stages of experimental optimization procedures. This dataset is associated with the following publication:McMinn , B., A. Korajkic, and A. Grimm. Optimization and evaluation of a method to detect adenoviruses in river water. JOURNAL OF VIROLOGICAL METHODS. Elsevier Science Ltd, New York, NY, USA, 231(1): 8-13, (2016).

  1. Combination Chemotherapy With or Without Oregovomab Followed by Stereotactic Body Radiation Therapy and Nelfinavir Mesylate in Treating Patients With Locally Advanced Pancreatic Cancer

    ClinicalTrials.gov

    2017-02-28

    Pancreatic Adenocarcinoma; Resectable Pancreatic Carcinoma; Stage I Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

  2. Screening for Pancreatic Cancer.

    PubMed

    Ngamruengphong, Saowanee; Canto, Marcia Irene

    2016-12-01

    Pancreatic cancer (PC) is a highly fatal disease that can only be cured by complete surgical resection. However, most patients with PC have unresectable disease at the time of diagnosis, highlighting the need to detect PC and its precursor lesions earlier in asymptomatic patients. Screening is not cost-effective for population-based screening of PC. Individuals with genetic risk factors for PC based on family history or known PC-associated genetic syndromes, however, can be a potential target for PC screening programs. This article provides an overview of the epidemiology and genetic background of familial PC and discusses diagnostic and management approaches.

  3. Studies on the Interaction of Tumor-Derived HD5 Alpha Defensins with Adenoviruses and Implications for Oncolytic Adenovirus Therapy.

    PubMed

    Vragniau, Charles; Hübner, Jens-Martin; Beidler, Peter; Gil, Sucheol; Saydaminova, Kamola; Lu, Zhuo-Zhuang; Yumul, Roma; Wang, Hongjie; Richter, Maximilian; Sova, Pavel; Drescher, Charles; Fender, Pascal; Lieber, André

    2017-03-15

    Defensins are small antimicrobial peptides capable of neutralizing human adenovirus (HAdV) in vitro by binding capsid proteins and blocking endosomal escape of virus. In humans, the alpha defensin HD5 is produced by specialized epithelial cells of the gastrointestinal and genito-urinary tracts. Here, we demonstrate, using patient biopsy specimens, that HD5 is also expressed as an active, secreted peptide by epithelial ovarian and lung cancer cells in situ This finding prompted us to study the role of HD5 in infection and spread of replication-competent, oncolytic HAdV type 3 (HAdV3). HAdV3 produces large amounts of penton-dodecahedra (PtDd), virus-like particles, during replication. We have previously shown that PtDd are involved in opening epithelial junctions, thus facilitating lateral spread of de novo-produced virions. Here, we describe a second function of PtDd, namely, the blocking of HD5. A central tool to prove that viral PtDd neutralize HD5 and support spread of progeny virus was an HAdV3 mutant virus in which formation of PtDd was disabled (mut-Ad3GFP, where GFP is green fluorescent protein). We demonstrated that viral spread of mut-Ad3GFP was blocked by synthetic HD5 whereas that of the wild-type (wt) form (wt-Ad3GFP) was only minimally impacted. In human colon cancer Caco-2 cells, induction of cellular HD5 expression by fibroblast growth factor 9 (FGF9) significantly inhibited viral spread and progeny virus production of mut-Ad3GFP but not of wt-Ad3GFP. Finally, the ectopic expression of HD5 in tumor cells diminished the in vivo oncolytic activity of mut-Ad3GFP but not of wt-Ad3GFP. These data suggest a new mechanism of HAdV3 to overcome innate antiviral host responses. Our study has implications for oncolytic adenovirus therapy.IMPORTANCE Previously, it has been reported that human defensin HD5 inactivates specific human adenoviruses by binding to capsid proteins and blocking endosomal escape of virus. The central new findings described in our

  4. Segmental pancreatic autotransplantation for chronic pancreatitis. A preliminary report

    SciTech Connect

    Rossi, R.L.; Braasch, J.W.; O'Bryan, E.M.; Watkins, E. Jr.

    1983-03-01

    A patient who underwent 95% pancreatectomy with autotransplantation of the body and tail of the gland to the femoral area for chronic pancreatitis is presented. The pain resolved, and the patient's blood glucose level remained within normal limits. High levels of insulin were found in the iliac vein on the transplanted side. Patency of the graft was demonstrated by technetium scan and arteriography and followed by a color-coded Doppler imaging system. Segmental pancreatic autotransplantation offers a method of relieving pain with preservation of endocrine function in selected patients with chronic pancreatitis.

  5. Omeprazole enhances efficacy of triple therapy in eradicating Helicobacter pylori.

    PubMed Central

    Borody, T J; Andrews, P; Fracchia, G; Brandl, S; Shortis, N P; Bae, H

    1995-01-01

    Triple therapy has been recommended as the most effective treatment for Helicobacter pylori eradication. Despite achieving a comparatively high eradication result, however, around 10% of patients still fail to be cured. Omeprazole can enhance efficacy of single and double antibiotic protocols and is particularly effective when combined with clarithromycin and a nitroimidazole. This study examined the effect of combining triple therapy with omeprazole. A prospective, randomised, unblinded, single centre trial was carried out on consecutive patients with symptoms of dyspepsia and H pylori infection confirmed by rapid urease test, microbiological culture, and histological assessment. Patients were given a five times/day, 12 day course of colloidal bismuth subcitrate chewable tablets (108 mg), tetracycline HCl (250 mg), and metronidazole (200 mg) with either 20 mg omeprazole twice daily (triple therapy+omeprazole) or 40 mg famotidine (triple therapy+famotidine) at night. Compliance and side effects were determined using a standard questionnaire form. One hundred and twenty five of 165 triple therapy+omeprazole patients and 124 of 171 triple therapy+famotidine patients returned for rebiopsy four weeks after completion of treatment. Significantly more triple therapy+omeprazole patients achieved eradication 122 of 125 (97.6%) as assessed by negative urease test, culture, and histological assessment, when compared with 110 of 124 (89%) triple therapy+famotidine patients (p = 0.006; chi 2). There were 30 triple therapy+omeprazole (24%) and 26 triple therapy+famotidine (21%) patients with de novo metronidazole resistant H pylori included in the study. Side effects were mild and infrequent and were comparable in both groups, although pain in duodenal ulcer, gastric ulcer, and oesophagitis patients seemed to subside earlier in those taking omeprazole. Compliance (>95% of drugs taken) was achieved by 98% of patients of both groups. A 12 days regimen of triple therapy with

  6. Helicobacter pylori eradication: Sequential therapy and Lactobacillus reuteri supplementation

    PubMed Central

    Efrati, Cesare; Nicolini, Giorgia; Cannaviello, Claudio; O’Sed, Nicole Piazza; Valabrega, Stefano

    2012-01-01

    AIM: To evaluate the role of sequential therapy and Lactobacillus reuteri (L. reuteri) supplementation, in the eradication treatment of Helicobacter pylori (H. pylori). METHODS: H. pylori infection was diagnosed in 90 adult dyspeptic patients. Patients were excluded if previously treated for H. pylori infection or if they were taking a proton pump inhibitor (PPI), H2-receptor antagonist or antibiotics. Patients were assigned to receive one of the following therapies: (1) 7-d triple therapy (PPI plus clarithromycin and amoxicillin or metronidazole) plus L. reuteri supplementation during antibiotic treatment; (2) 7-d triple therapy plus L. reuteri supplementation after antibiotic treatment; (3) sequential regimen (5-d PPI plus amoxicillin therapy followed by a 5-d PPI, clarithromycin and tinidazole) plus L. reuteri supplementation during antibiotic treatment; and (4) sequential regimen plus L. reuteri supplementation after antibiotic treatment. Successful eradication therapy was defined as a negative urea breath test at least 4 wk following treatment. RESULTS: Ninety adult dyspeptic patients were enrolled, and 83 (30 male, 53 female; mean age 57 ± 13 years) completed the study. Nineteen patients were administered a 7-d triple treatment: 11 with L. reuteri supplementation during and 8 after therapy. Sixty-four patients were administered a sequential regimen: 32 with L. reuteri supplementation during and 32 after therapy. The eradication rate was significantly higher in the sequential group compared with the 7-d triple regimen (88% vs 63%, P = 0.01). No difference was found between two types of PPI. No difference in eradication rates was observed between patients submitted to L. reuteri supplementation during or after antibiotic treatment. Compliance with therapy was excellent in all patients. No difference in adverse effects was observed between the different antibiotic treatments and between patients submitted to L. reuteri supplementation during and after

  7. Welfare effects of a disease eradication programme for dairy goats.

    PubMed

    Muri, K; Leine, N; Valle, P S

    2016-02-01

    The Norwegian dairy goat industry has largely succeeded in controlling caprine arthritis encephalitis (CAE), caseous lymphadenitis (CLA) and paratuberculosis through a voluntary disease eradication programme called Healthier Goats (HG). The aim of this study was to apply an on-farm welfare assessment protocol to assess the effects of HG on goat welfare. A total of 30 dairy goat farms were visited, of which 15 had completed disease eradication and 15 had not yet started. Three trained observers assessed the welfare on 10 farms each. The welfare assessment protocol comprised both resource-based and animal-based welfare measures, including a preliminary version of qualitative behavioural assessments with five prefixed terms. A total of 20 goats in each herd were randomly selected for observations of human-animal interactions and physical health. The latter included registering abnormalities of eyes, nostrils, ears, skin, lymph nodes, joints, udder, claws and body condition score. For individual-level data, robust clustered logistic regression analyses with farm as cluster variable were conducted to assess the association with disease eradication. Wilcoxon rank-sum tests were used for comparisons of herd-level data between the two groups. Goats with swollen joints (indicative of CAE) and enlarged lymph nodes (indicative of CLA) were registered on 53% and 93% of the non-HG farms, respectively, but on none of the HG farms. The only other health variables with significantly lower levels in HG herds were skin lesions (P=0.008) and damaged ears due to torn out ear tags (P<0.001). Goats on HG farms showed less fear of unknown humans (P=0.013), and the qualitative behavioural assessments indicated that the animals in these herds were calmer than in non-HG herds. Significantly more space and lower gas concentrations reflected the upgrading of buildings usually done on HG farms. In conclusion, HG has resulted in some welfare improvements beyond the elimination of infectious

  8. Human adenoviruses in water: occurrence and health implications: a critical review.

    PubMed

    Jiang, Sunny C

    2006-12-01

    Adenoviruses are important human pathogens that are responsible for both enteric illnesses and respiratory and eye infections. Recently, these viruses have been found to be prevalent in rivers, coastal waters, swimming pool waters, and drinking water supplies worldwide. United Sates Environmental Protection Agency (USEPA) listed adenovirus as one of nine microorganisms on the Contamination Candidate List for drinking water because their survival characteristic during water treatment is not yet fully understood. Adenoviruses have been found to be significantly more stable than fecal indicator bacteria and other enteric viruses during UV treatment. Adenovirus infection may be caused by consumption of contaminated water or inhalation of aerosolized droplets during water recreation. The goal of this review is to summarize the state of technology for adenovirus detection in natural and drinking waters and the human health risk imposed by this emerging pathogen. The occurrence of these viruses in natural and treated waters is summarized from worldwide reports.

  9. Rotavirus and adenovirus prevalence at Tepecik education and research hospital (Turkey).

    PubMed

    Ece, Gulfem; Samlioglu, Pinar; Ulker, Temel; Kose, Sukran; Ersan, Gursel

    2012-06-01

    Diarrhoea affects many people globally. Rotaviruses and enteric adenovirus types 40 and 41 are the most common viruses causing childhood gastroenteritis. The aim of this study was to determine the prevalence of rotavirus and adenovirus from the faecal samples obtained at the Infectious Diseases and Clinical Microbiology Laboratory of Tepecik Education and Research Hospital. The faecal samples were screened for rotavirus, and adenovirus by commercially available immunochromatographic EIA kit (Rotavirus/Adenovirus Combo Rapid Test Device) (San Diego, CA, USA). A total of 1112 stool samples were collected from May 23rd 2008 to May 25th 2010. Of these faecal samples, 201(18.07%) were positive for rotavirus and 14 (1.2 %) for adenovirus antigen. In our study the most common agent detected was rotavirus. Viral antigen analysis in stool specimens is important for diagnosis. Detection of the viral aetiology in gastroenteritis cases will prevent unnecessary antibiotic consumption.

  10. Redox signaling in acute pancreatitis

    PubMed Central

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-01-01

    Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis. PMID:25778551

  11. Redox signaling in acute pancreatitis.

    PubMed

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-08-01

    Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF-VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.

  12. Immunotherapy of pancreatic carcinoma.

    PubMed

    Märten, Angela

    2008-05-01

    Patients with carcinoma of the exocrine pancreas have especially poor prognosis with a five-year survival rate of <1% and a median survival of 4-6 months. Pancreatic carcinoma is a systemic disease, insensitive to radiotherapy and mostly to chemotherapy. Accordingly, new treatment modalities are worth being investigated. One of the promising approaches is immunotherapy. Several phase I/II trials that have been published show interesting results, whereupon antibody-based strategies seem to fail and unspecific stimulation or vaccination with peptides look encouraging. Furthermore, phase II trials dealing with combination therapies are highly promising. One of them, a combination of chemoradiotherapy plus interferon-alpha is currently tested in a randomized phase III trial. As most of the trials had enrolled only limited numbers of patients and most of the trials were not conducted and/or reported according to the new standards it is difficult to draw final conclusions from the discussed trials. Immuno-monitoring was performed only in 40% of the discussed publications. In all cases immune responses were observed and correlation with the clinical outcome is discussed. Immunotherapy of pancreatic adenocarcinoma and especially combination therapies including immunotherapy is an up-and-coming approach and needs to be investigated in well conducted phase III randomized controlled trials accompanied by appropriate immuno-monitoring.

  13. Necrotizing pancreatitis: challenges and solutions

    PubMed Central

    Bendersky, Victoria A; Mallipeddi, Mohan K; Perez, Alexander; Pappas, Theodore N

    2016-01-01

    Acute pancreatitis is a common disease that can progress to gland necrosis, which imposes significant risk of morbidity and mortality. In general, the treatment for pancreatitis is a supportive therapy. However, there are several reasons to escalate to surgery or another intervention. This review discusses the pathophysiology as well as medical and interventional management of necrotizing pancreatitis. Current evidence suggests that patients are best served by delaying interventions for at least 4 weeks, draining as a first resort, and debriding recalcitrant tissue using minimally invasive techniques to promote or enhance postoperative recovery while reducing wound-related complications. PMID:27826206

  14. Recent Progress in Pancreatic Cancer

    PubMed Central

    Wolfgang, Christopher L.; Herman, Joseph M.; Laheru, Daniel A.; Klein, Alison P.; Erdek, Michael A.; Fishman, Elliot K.; Hruban, Ralph H.

    2013-01-01

    Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in our understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer. PMID:23856911

  15. Pancreatic infection with Candida parapsilosis.

    PubMed

    Ibáñez, R; Serrano-Heranz, R

    1999-01-01

    Candida species other than C. albicans have been implicated as pathogens in intravascular (bloodstream, intravascular devices, endocarditis) and extravascular (arthritis, osteomielitis, endophtalmitis) infections. C. parapsilosis, however, is rarely implicated in intra-abdominal infections (peritonitis during peritoneal dialysis, complicating surgery or solid-organ transplantation). We describe a case of a 48-y-old male with acute pancreatitis who had a pancreatic abscess produced by primary C. parapsilosis infection. Although he received adequate treatment with antifungal medication and surgical drainage, the outcome was fatal. Because the clinical findings are indistinguishable from bacterial abscesses, Candida species should be considered in cases of complicated pancreatitis, in order to establish a prompt adequate treatment.

  16. Online Registry for Nationwide Database of Current Trend of Helicobacter pylori Eradication in Korea: Interim Analysis

    PubMed Central

    2016-01-01

    Eradication of Helicobacter pylori using first-line therapy is becoming less effective. Subjects who had been treated for H. pylori infection were prospectively enrolled through an on-line database registry from October 2010 to December 2012. Demographic data, detection methods, treatment indication, regimens, durations, compliance, adverse events, and eradication results for H. pylori infection were collected. Data of 3,700 patients from 34 hospitals were analyzed. The overall eradication rate of the first-line therapy was 73.0%. Eradication failure was significantly associated with old age, concomitant medication, and comorbidity. Regional differences in eradication rates were observed. The most common first-line therapy was proton pump inhibitor-based triple therapy (standard triple therapy, STT) for 7 days (86.8%). The eradication rates varied with regimens, being 73% in STT, 81.8% in bismuth-based quadruple therapy, 100% in sequential therapy, and 90.3% in concomitant therapy. The eradication rate in treatment-naïve patients was higher than that in patients previously treated for H. pylori infection (73.8% vs. 58.5%, P < 0.001). The overall eradication rate for second-line therapy was 84.3%. There was no statistical difference in eradication rates among various regimens. H. pylori eradication rate using STT is decreasing in Korea and has become sub-optimal, suggesting the need for alternative regimens to improve the efficacy of first-line therapy for H. pylori infection. PMID:27478335

  17. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection

    PubMed Central

    Gilliland, Taylor M.; Villafane-Ferriol, Nicole; Shah, Kevin P.; Shah, Rohan M.; Tran Cao, Hop S.; Massarweh, Nader N.; Silberfein, Eric J.; Choi, Eugene A.; Hsu, Cary; McElhany, Amy L.; Barakat, Omar; Fisher, William; Van Buren, George

    2017-01-01

    Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL). The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI) manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995–2016) addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC). We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1) patients with albumin < 2.5 mg/dL or weight loss > 10% should postpone surgery and begin aggressive nutrition supplementation; (2) patients with albumin < 3 mg/dL or weight loss between 5% and 10% should have nutrition supplementation prior to surgery; (3) enteral nutrition (EN) should be preferred as a nutritional intervention over total parenteral nutrition (TPN) postoperatively; and, (4) a multidisciplinary approach should be used to allow for early detection of symptoms of endocrine and exocrine pancreatic insufficiency alongside implementation of appropriate

  18. Estramustine phosphate reversibly inhibits an early stage during adenovirus replication.

    PubMed

    Everitt, E; Ekstrand, H; Boberg, B; Hartley-Asp, B

    1990-01-01

    Estramustine phosphate, an estradiol-mustard conjugate, was shown to reversibly inhibit a stage during the first hour of productive adenovirus 2 infection of HeLa cells. This drug, employed in the therapy of advanced prostatic cancer, specifically interacts with microtubule-associated proteins (MAPs) of the cytoskeleton. The results obtained under physiological conditions in vivo suggest a MAPs-interference with the microtubule-mediated vectorial migration of the virus inoculum to the nucleus. Virus attachment, uncoating kinetics and the appearance of established uncoating intermediates were not affected.

  19. Boosting oncolytic adenovirus potency with magnetic nanoparticles and magnetic force.

    PubMed

    Tresilwised, Nittaya; Pithayanukul, Pimolpan; Mykhaylyk, Olga; Holm, Per Sonne; Holzmüller, Regina; Anton, Martina; Thalhammer, Stefan; Adigüzel, Denis; Döblinger, Markus; Plank, Christian

    2010-08-02

    Oncolytic adenoviruses rank among the most promising innovative agents in cancer therapy. We examined the potential of boosting the efficacy of the oncolytic adenovirus dl520 by associating it with magnetic nanoparticles and magnetic-field-guided infection in multidrug-resistant (MDR) cancer cells in vitro and upon intratumoral injection in vivo. The virus was complexed by self-assembly with core-shell nanoparticles having a magnetite core of about 10 nm and stabilized by a shell containing 68 mass % lithium 3-[2-(perfluoroalkyl)ethylthio]propionate) and 32 mass % 25 kDa branched polyethylenimine. Optimized virus binding, sufficiently stable in 50% fetal calf serum, was found at nanoparticle-to-virus ratios of 5 fg of Fe per physical virus particle (VP) and above. As estimated from magnetophoretic mobility measurements, 3,600 to 4,500 magnetite nanocrystallites were associated per virus particle. Ultrastructural analysis by electron and atomic force microscopy showed structurally intact viruses surrounded by magnetic particles that occasionally bridged several virus particles. Viral uptake into cells at a given virus dose was enhanced 10-fold compared to nonmagnetic virus when infections were carried out under the influence of a magnetic field. Increased virus internalization resulted in a 10-fold enhancement of the oncolytic potency in terms of the dose required for killing 50% of the target cells (IC(50) value) and an enhancement of 4 orders of magnitude in virus progeny formation at equal input virus doses compared to nonmagnetic viruses. Furthermore, the full oncolytic effect developed within two days postinfection compared with six days in a nonmagnetic virus as a reference. Plotting target cell viability versus internalized virus particles for magnetic and nonmagnetic virus showed that the inherent oncolytic productivity of the virus remained unchanged upon association with magnetic nanoparticles. Hence, we conclude that the mechanism of boosting the

  20. Novel adenovirus detected in kowari (Dasyuroides byrnei) with pneumonia.

    PubMed

    Gál, János; Mándoki, Míra; Sós, Endre; Kertész, Péter; Koroknai, Viktória; Bányai, Krisztián; Farkas, Szilvia L

    2017-02-15

    A male kowari (Dasyuroides byrnei) originating from a zoo facility was delivered for post mortem evaluation in Hungary. Acute lobar pneumonia with histopathologic changes resembling an adenovirus (AdV) infection was detected by light microscopic examination. The presence of an AdV was confirmed by obtaining partial sequence data from the adenoviral DNA-dependent DNA-polymerase. Although the exact taxonomic position of this novel marsupial origin virus could not be determined, pairwise identity analyses and phylogenetic calculations revealed that it is distantly related to other members in the family Adenoviridae.

  1. Packaging capacity and stability of human adenovirus type 5 vectors.

    PubMed Central

    Bett, A J; Prevec, L; Graham, F L

    1993-01-01

    Adenovirus vectors are extensively used for high-level expression of proteins in mammalian cells and are receiving increasing attention for their potential use as live recombinant vaccines and as transducing viruses for use in gene therapy. Although it is commonly argued that one of the chief advantages of adenovirus vectors is their relative stability, this has not been thoroughly investigated. To examine the genetic stability of adenovirus type 5 vectors and in particular to examine the relationship between genetic stability and genome size, adenovirus vectors were constructed with inserts of 4.88 (herpes simplex virus type 1 gB), 4.10 (herpes simplex virus type 1 gB), or 3.82 (LacZ) kb combined with a 1.88-kb E3 deletion or with a newly generated 2.69-kb E3 deletion. The net excess of DNA over the wild-type (wt) genome size ranged from 1.13 to 3.00 kb or 3.1 to 8.3%. Analysis of these vectors during serial passage in tissue culture revealed that when the size exceeded 105% of the wt genome length by approximately 1.2 kb (4.88-kb insert combined with a 1.88-kb deletion), the resulting vector grew very poorly and underwent rapid rearrangement, resulting in loss of the insert after only a few passages. In contrast, vectors with inserts resulting in viral DNA close to or less than a net genome size of 105% of that of the wt grew well and were relatively stable. In general, viruses with genomes only slightly above 105% of that of the wt were unstable and the rapidity with which rearrangement occurred correlated with the size of the insert. These findings suggest that there is a relatively tight constraint on the amount of DNA which can be packaged into virions and that exceeding the limit results in a sharply decreased rate of virus growth. The resultant strong selection for variants which have undergone rearrangement, generating smaller genomes, is manifested as genetic instability of the virus population. Images PMID:8371349

  2. Canine adenovirus type 1 in a fennec fox (Vulpes zerda).

    PubMed

    Choi, Jeong-Won; Lee, Hyun-Kyoung; Kim, Seong-Hee; Kim, Yeon-Hee; Lee, Kyoung-Ki; Lee, Myoung-Heon; Oem, Jae-Ku

    2014-12-01

    A 10-mo-old female fennec fox (Vulpes zerda) with drooling suddenly died and was examined postmortem. Histologic examination of different tissue samples was performed. Vacuolar degeneration and diffuse fatty change were observed in the liver. Several diagnostic methods were used to screen for canine parvovirus, canine distemper virus, canine influenza virus, canine coronavirus, canine parainfluenza virus, and canine adenovirus (CAdV). Only CAdV type 1 (CAdV-1) was detected in several organs (liver, lung, brain, kidney, spleen, and heart), and other viruses were not found. CAdV-1 was confirmed by virus isolation and nucleotide sequencing.

  3. The Length of the Terminal Repetition in Adenovirus-2 DNA

    PubMed Central

    Roberts, Richard J.; Arrand, John R.; Keller, Walter

    1974-01-01

    Adenovirus-2 DNA was end-labeled by partial digestion with Escherichia coli exonuclease III and resynthesis with the DNA polymerase from avian myeloblastosis virus and α-32P-labeled deoxyribonucleoside triphosphates. This end-labeled DNA was cleaved with several specific endonucleases and the terminal fragments were characterized by gel electrophoresis and pyrimidine tract analysis. Two endonucleases gave identical fragments from both ends, presumably from cleavage within the inverted terminal repetition, while all other endonucleases gave dissimilar fragments from the two ends. From the sizes of these fragments it is estimated that the inverted terminal repetition is between 100 and 140 nucleotide pairs long. Images PMID:4139703

  4. Magnetic resonance imaging of pancreatitis: An update

    PubMed Central

    Manikkavasakar, Sriluxayini; AlObaidy, Mamdoh; Busireddy, Kiran K; Ramalho, Miguel; Nilmini, Viragi; Alagiyawanna, Madhavi; Semelka, Richard C

    2014-01-01

    Magnetic resonance (MR) imaging plays an important role in the diagnosis and staging of acute and chronic pancreatitis and may represent the best imaging technique in the setting of pancreatitis due to its unmatched soft tissue contrast resolution as well as non-ionizing nature and higher safety profile of intravascular contrast media, making it particularly valuable in radiosensitive populations such as pregnant patients, and patients with recurrent pancreatitis requiring multiple follow-up examinations. Additional advantages include the ability to detect early forms of chronic pancreatitis and to better differentiate adenocarcinoma from focal chronic pancreatitis. This review addresses new trends in clinical pancreatic MR imaging emphasizing its role in imaging all types of acute and chronic pancreatitis, pancreatitis complications and other important differential diagnoses that mimic pancreatitis. PMID:25356038

  5. Simultaneous occurrence of autoimmune pancreatitis and pancreatic cancer in patients resected for focal pancreatic mass

    PubMed Central

    Macinga, Peter; Pulkertova, Adela; Bajer, Lukas; Maluskova, Jana; Oliverius, Martin; Smejkal, Martin; Heczkova, Maria; Spicak, Julius; Hucl, Tomas

    2017-01-01

    AIM To assess the occurrence of autoimmune pancreatitis (AIP) in pancreatic resections performed for focal pancreatic enlargement. METHODS We performed a retrospective analysis of medical records of all patients who underwent pancreatic resection for a focal pancreatic enlargement at our tertiary center from January 2000 to July 2013. The indication for surgery was suspicion of a tumor based on clinical presentation, imaging findings and laboratory evaluations. The diagnosis of AIP was based on histology findings. An experienced pathologist specialized in pancreatic disease reviewed all the cases and confirmed the diagnosis in pancreatic resection specimens suggestive of AIP. The histological diagnosis of AIP was set according to the international consensus diagnostic criteria. RESULTS Two hundred ninety-five pancreatic resections were performed in 201 men and 94 women. AIP was diagnosed in 15 patients (5.1%, 12 men and 3 women) based on histology of the resected specimen. Six of them had AIP type 1, nine were diagnosed with AIP type 2. Pancreatic adenocarcinoma (PC) was also present in six patients with AIP (40%), all six were men. Patients with AIP + PC were significantly older (60.5 vs 49 years of age, P = 0.045), more likely to have been recently diagnosed with diabetes (67% vs 11%, P = 0.09), and had experienced greater weight loss (15.5 kg vs 8.5 kg, P = 0.03) than AIP patients without PC. AIP was not diagnosed in any patients prior to surgery; however, the diagnostic algorithm was not fully completed in every case. CONCLUSION The possible co-occurrence of PC and AIP suggests that preoperative diagnosis of AIP does not rule out simultaneous presence of PC.

  6. Pancreatic stellate cell: Pandora's box for pancreatic disease biology

    PubMed Central

    Bynigeri, Ratnakar R; Jakkampudi, Aparna; Jangala, Ramaiah; Subramanyam, Chivukula; Sasikala, Mitnala; Rao, G Venkat; Reddy, D Nageshwar; Talukdar, Rupjyoti

    2017-01-01

    Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin. PSCs maintain their activated phenotype via an autocrine loop involving different cytokines and contribute to progressive fibrosis in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC). Several pathways (e.g., JAK-STAT, Smad, Wnt signaling, Hedgehog etc.), transcription factors and miRNAs have been implicated in the inflammatory and profibrogenic function of PSCs. The role of PSCs goes much beyond fibrosis/desmoplasia in PDAC. It is now shown that PSCs are involved in significant crosstalk between the pancreatic cancer cells and the cancer stroma. These interactions result in tumour progression, metastasis, tumour hypoxia, immune evasion and drug resistance. This is the rationale for therapeutic preclinical and clinical trials that have targeted PSCs and the cancer stroma. PMID:28210075

  7. SPOC1-Mediated Antiviral Host Cell Response Is Antagonized Early in Human Adenovirus Type 5 Infection

    PubMed Central

    Schreiner, Sabrina; Kinkley, Sarah; Bürck, Carolin; Mund, Andreas; Wimmer, Peter; Schubert, Tobias; Groitl, Peter; Will, Hans; Dobner, Thomas

    2013-01-01

    Little is known about immediate phases after viral infection and how an incoming viral genome complex counteracts host cell defenses, before the start of viral gene expression. Adenovirus (Ad) serves as an ideal model, since entry and onset of gene expression are rapid and highly efficient, and mechanisms used 24–48 hours post infection to counteract host antiviral and DNA repair factors (e.g. p53, Mre11, Daxx) are well studied. Here, we identify an even earlier host cell target for Ad, the chromatin-associated factor and epigenetic reader, SPOC1, recently found recruited to double strand breaks, and playing a role in DNA damage response. SPOC1 co-localized with viral replication centers in the host cell nucleus, interacted with Ad DNA, and repressed viral gene expression at the transcriptional level. We discovered that this SPOC1-mediated restriction imposed upon Ad growth is relieved by its functional association with the Ad major core protein pVII that enters with the viral genome, followed by E1B-55K/E4orf6-dependent proteasomal degradation of SPOC1. Mimicking removal of SPOC1 in the cell, knock down of this cellular restriction factor using RNAi techniques resulted in significantly increased Ad replication, including enhanced viral gene expression. However, depletion of SPOC1 also reduced the efficiency of E1B-55K transcriptional repression of cellular promoters, with possible implications for viral transformation. Intriguingly, not exclusive to Ad infection, other human pathogenic viruses (HSV-1, HSV-2, HIV-1, and HCV) also depleted SPOC1 in infected cells. Our findings provide a general model for how pathogenic human viruses antagonize intrinsic SPOC1-mediated antiviral responses in their host cells. A better understanding of viral entry and early restrictive functions in host cells should provide new perspectives for developing antiviral agents and therapies. Conversely, for Ad vectors used in gene therapy, counteracting mechanisms eradicating incoming

  8. Erlotinib Hydrochloride in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery

    ClinicalTrials.gov

    2014-10-07

    Intraductal Papillary Mucinous Neoplasm of the Pancreas; Recurrent Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

  9. Drugs Approved for Pancreatic Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for pancreatic cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  10. Evaluating steatosis in pancreatic transplant.

    PubMed

    Verma, Aneesha Ratan; Papalois, Vassilios

    2011-06-01

    Pancreatic transplant remains the only treatment that cures insulin-dependent diabetes mellitus. It is recognized by transplant surgeons that donor pancreases with excessive fat infiltration have a poorer clinical outcome, resulting in significant recipient morbidity and mortality. However, no objective measure of pancreatic fat infiltration exists, and no study has been done that correlates the level of fat infiltration with clinical outcome. There have been significant radiologic advances that allow assessment of fat content of organs, and these could be used to accurately quantify the extent of pancreatic fat infiltration. We reviewed the literature regarding pancreatic steatosis, and examined ways in which the level of steatosis could be objectively measured before transplant, thereby improving clinical outcome.

  11. Chronic pancreatitis and cystic fibrosis

    PubMed Central

    Witt, H

    2003-01-01

    Recent discoveries of trypsinogen and trypsin inhibitor mutations in patients with chronic pancreatitis (CP) support the hypothesis that an inappropriate activation of pancreatic zymogens to active enzymes within the pancreatic parenchyma starts the inflammatory process. Current data suggest that CP may be inherited dominant, recessive, or complex as a result of mutations in the above mentioned or yet unidentified genes. Evaluation of patients with CP should include genetic testing. Cystic fibrosis (CF) is an autosomal recessive inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene and is characterised by pancreatic insufficiency and chronic bronchopulmonary infection. The progression and severity of pulmonary disease differs considerably between people with identical CFTR mutations and does not seem to correlate with the type or class of the CFTR mutation. The identification of further disease modifying genetic factors will increase the pathophysiological understanding and may help to identify new therapeutic targets. PMID:12651880

  12. Progress toward polio eradication--Worldwide, 2013-2014.

    PubMed

    Moturi, Edna K; Porter, Kimberly A; Wassilak, Steven G F; Tangermann, Rudolf H; Diop, Ousmane M; Burns, Cara C; Jafari, Hamid

    2014-05-30

    In 1988, the World Health Assembly of the World Health Organization (WHO) resolved to interrupt wild poliovirus (WPV) transmission worldwide, and in 2012, the World Health Assembly declared the completion of global polio eradication a programmatic emergency for public health. By 2013, the annual number of WPV cases had decreased by >99% since 1988, and only three countries remained that had never interrupted WPV transmission: Afghanistan, Nigeria, and Pakistan. This report summarizes global progress toward polio eradication during 2013-2014 and updates previous reports. In 2013, a total of 416 WPV cases were reported globally from eight countries, an 86% increase from the 223 WPV cases reported from five countries in 2012. This upsurge in 2013 was caused by a 60% increase in WPV cases detected in Pakistan, and by outbreaks in five previously polio-free countries resulting from international spread of WPV. In 2014, as of May 20, a total of 82 WPV cases had been reported worldwide, compared with 34 cases during the same period in 2013. Polio cases caused by circulating vaccine-derived poliovirus (cVDPV) were detected in eight countries in 2013 and in two countries so far in 2014. To achieve polio eradication in the near future, further efforts are needed to 1) address health worker safety concerns in areas of armed conflict in priority countries, 2) to prevent further spread of WPV and new outbreaks after importation into polio-free countries, and 3) to strengthen surveillance globally. Based on the international spread of WPV to date in 2014, the WHO Director General has issued temporary recommendations to reduce further international exportation of WPV through vaccination of persons traveling from currently polio-affected countries.

  13. Progress toward poliomyelitis eradication--Nigeria, January 2013-September 2014.

    PubMed

    Etsano, Andrew; Gunnala, Rajni; Shuaib, Faisal; Damisa, Eunice; Mkanda, Pascal; Banda, Richard; Korir, Charles; Enemaku, Ogu; Corkum, Melissa; Usman, Samuel; Davis, Lora B; Nganda, Gatei wa; Burns, Cara C; Mahoney, Frank; Vertefeuille, John F

    2014-11-21

    In 1988, the World Health Assembly resolved to interrupt wild poliovirus (WPV) transmission worldwide. By 2013, only three countries remained that had never interrupted WPV transmission: Afghanistan, Nigeria, and Pakistan. Since 2003, northern Nigeria has been a reservoir for WPV reintroduction into 26 previously polio-free countries. In May 2014, the World Health Organization declared the international spread of polio a Public Health Emergency of International Concern. Nigeria's main strategic goal is to interrupt WPV type 1 (WPV1) transmission by the end of 2014, which is also a main objective of the Global Polio Eradication Initiative's Polio Eradication and Endgame Strategic Plan for 2013-2018. This report updates previous reports (4-6) and describes polio eradication activities and progress in Nigeria during January 2013-September 30, 2014. Only six WPV cases had been reported in 2014 through September 30 compared with 49 reported cases during the same period in 2013. The quality of supplemental immunization activities (SIAs) improved during this period; the proportion of local government areas (LGAs) within 11 high-risk states with estimated oral poliovirus vaccine (OPV) campaign coverage at or above the 90% threshold increased from 36% to 67%. However, the number of reported circulating vaccine-derived poliovirus type 2 (cVDPV2) cases increased from four in 2013 to 21 to date in 2014, and surveillance gaps are suggested by genomic sequence analysis and continued detection of WPV1 by environmental surveillance. Interrupting all poliovirus circulation in Nigeria is achievable with continued attention to stopping cVDPV2 transmission, improving the quality of acute flaccid paralysis (AFP) surveillance, increasing vaccination coverage by strengthened routine immunization services, continuing support from all levels of government, and undertaking special initiatives to provide vaccination to children in conflict-affected areas in northeastern Nigeria.

  14. [Eradication therapy of antibiotic-resistant strains of Helicobacter pylori].

    PubMed

    Shcherbakov, P L; Belousova, N L; Shcherbakova, M Iu; Kashnikov, V S

    2010-01-01

    Treatment of inflammatory diseases of the upper digestive tract, associated with Helicobacter pylori has recently greatly complicated by the presence of significant number of resistant strains of this microorganism to traditionally used drugs for eradication therapy. Average resistance to metronidazole and clarithromycin in Russia is about 30 and 25% respectively. The article presents the experience of treating patients with metronidazole resistant strains of H. pylori with using triple therapy, which included a drug used nitrofurans--nifuroxazide in suspension, proton pump inhibitors and clarithromycin.

  15. Cimex lectularius ("Bed Bugs"): Recognition, Management, and Eradication.

    PubMed

    McMenaman, Kathryn S; Gausche-Hill, Marianne

    2016-11-01

    Reports of bed bug infestations in major cities in the United States and abroad have been in the public press. Physicians and other clinicians who care for children need to be able to recognize bed bug bites and understand the social, psychological, and medical implications that this diagnosis will have on patients and their families. In this article, a case presentation serves to guide discussion regarding establishing the diagnosis, differential diagnosis, and the management of bed bug bites and their complications. Integrated pest management programs involving housing managers, residents, and professional pest exterminators provide both chemical and nonchemical solutions for eradication of bed bug infestations.

  16. Listeria Vaccines for Pancreatic Cancer

    DTIC Science & Technology

    2013-10-01

    AD_________________ Award Number: W81XWH-12-1-0411 TITLE: Listeria vaccines for pancreatic cancer...29September2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Listeria vaccines for pancreatic cancer 5b. GRANT NUMBER W81XWH-12-1-0411 5c...explored the capacity of Listeria vaccines to induce anti-tumor T cell immunity in the KPC model. We have found that Listeria vaccines produce

  17. High antibiotic resistance rate: A difficult issue for Helicobacter pylori eradication treatment.

    PubMed

    Zhang, Mei

    2015-12-28

    Helicobacter pylori (H. pylori) infection is associated with a variety of upper gastrointestinal diseases, including gastric cancer. With the wide application of antibiotics in H. pylori eradication treatment, drug-resistant strains of H. pylori are increasing. H. pylori eradication treatment failure affects the outcome of a variety of diseases of the upper gastrointestinal tract. Therefore, antibiotic resistance that affects H. pylori eradication treatment is a challenging situation for clinicians. The ideal H. pylori eradication therapy should be safe, effective, simple, and economical. The eradication rate of triple antibiotic therapy is currently less than 80% in most parts of the world. Antibiotic resistance is the main reason for treatment failure, therefore the standard triple regimen is no longer suitable as a first-line treatment in most regions. H. pylori eradication treatment may fail for a number of reasons, including H. pylori strain factors, host factors, environmental factors, and inappropriate treatment.

  18. Investing in Justice: Ethics, Evidence, and the Eradication Investment Cases for Lymphatic Filariasis and Onchocerciasis

    PubMed Central

    Merritt, Maria W.; Tediosi, Fabrizio

    2015-01-01

    It has been suggested that initiatives to eradicate specific communicable diseases need to be informed by eradication investment cases to assess the feasibility, costs, and consequences of eradication compared with elimination or control. A methodological challenge of eradication investment cases is how to account for the ethical importance of the benefits, burdens, and distributions thereof that are salient in people’s experiences of the diseases and related interventions but are not assessed in traditional approaches to health and economic evaluation. We have offered a method of ethical analysis grounded in theories of social justice. We have described the method and its philosophical rationale and illustrated its use in application to eradication investment cases for lymphatic filariasis and onchocerciasis, 2 neglected tropical diseases that are candidates for eradication. PMID:25713967

  19. Investing in justice: ethics, evidence, and the eradication investment cases for lymphatic filariasis and onchocerciasis.

    PubMed

    Bailey, Theodore C; Merritt, Maria W; Tediosi, Fabrizio

    2015-04-01

    It has been suggested that initiatives to eradicate specific communicable diseases need to be informed by eradication investment cases to assess the feasibility, costs, and consequences of eradication compared with elimination or control. A methodological challenge of eradication investment cases is how to account for the ethical importance of the benefits, burdens, and distributions thereof that are salient in people's experiences of the diseases and related interventions but are not assessed in traditional approaches to health and economic evaluation. We have offered a method of ethical analysis grounded in theories of social justice. We have described the method and its philosophical rationale and illustrated its use in application to eradication investment cases for lymphatic filariasis and onchocerciasis, 2 neglected tropical diseases that are candidates for eradication.

  20. Pancreatic carcinogenesis: apoptosis and angiogenesis.

    PubMed

    Onizuka, Shinya; Kawakami, Shunsuke; Taniguchi, Ken; Fujioka, Hikaru; Miyashita, Kosei

    2004-04-01

    Apoptosis and angiogenesis are critical biologic processes that are altered during carcinogenesis. Both apoptosis and angiogenesis may play an important role in pancreatic carcinogenesis. Despite numerous advances in the diagnosis and treatment of pancreatic cancer, its prognosis remains dismal and a new therapeutic approach is much needed. Recent research has revealed that apoptosis and angiogenesis are closely interrelated. Several reports show that a tumor suppresser gene that is expressed in pancreatic carcinoma and related to malignant potential can induce apoptosis and also inhibit angiogenesis. At present, it is generally accepted that tumor growth in cancers, including pancreatic cancer, depends on angiogenesis. We have identified 2 new angiogenesis inhibitors from a conditioned medium of human pancreatic carcinoma cell line (BxPC-3): antiangiogenic antithrombin III (aaAT-III) and vitamin D binding protein-macrophage activating factor (DBP-maf). These molecules were able to regress tumors in severe combined immunodeficiency disease (SCID) mice, demonstrating potent inhibition of endothelial cell proliferation. Moreover, the angiogenesis inhibitors induced tumor dormancy in the animal model. These results suggest that antiangiogenic therapy using angiogenesis inhibitors may become a new strategy for treatment of pancreatic cancer in the near future.