Gene/Protein Disease Symptom Drug Enzyme Compound
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 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A combined meeting of the American Society of Microbiology and the Infectious Diseases Society of America was held recently in Washington, DC, USA, which gathered worldwide experts in the fields of infectious diseases, microbiology and the pharmaceutical industry, among others. Owing to its huge attendance and being among the largest conferences in the world during the year for infectious disease specialists, we focus only in the most relevant issues related to pediatric vaccines. Among others, we mention dengue, rotavirus, HIV, influenza virus, Streptococcus pneumoniae, Neisseria meningitidis, pertussis, measles and mumps. The case with mumps and measles illustrates the negative impact that vaccine refusal, fears and low coverage rates have on the resurgence of outbreaks produced by these two viruses. However, even with full vaccination schedules, other factors, such as waning immunity, influence the resurgence of these old diseases: pertussis, measles and mumps. This illustrates the importance of continuous surveillance in the epidemiology of vaccine-preventable diseases once a vaccine is licensed and introduced in a given population.
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PMID:48th ICAAC/46th IDSA Annual Meeting: a pediatric perspective. 1919 93

A spectrum of blood-borne infectious agents is transmitted through transfusion of infected blood donated by apparently healthy and asymptomatic blood donors. The diversity of infectious agents includes hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency viruses (HIV-1/2), human T-cell lymphotropic viruses (HTLV-I/II), Cytomegalovirus (CMV), Parvovirus B19, West Nile Virus (WNV), Dengue virus, trypanosomiasis, malaria, and variant CJD. Several strategies are implemented to reduce the risk of transmitting these infectious agents by donor exclusion for clinical history of risk factors, screening for the serological markers of infections, and nucleic acid testing (NAT) by viral gene amplification for direct and sensitive detection of the known infectious agents. Consequently, transfusions are safer now than ever before and we have learnt how to mitigate risks of emerging infectious diseases such as West Nile, Chikungunya, and Dengue viruses.
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PMID:Transfusion-transmitted infectious diseases. 1923 Dec 36

Many infectious diseases are transmissible by blood transfusion but the overall risk of transfusion transmitted infections is very low through the combination of restrictive donor selection and increasingly sensitive screening. The noninfectious risks (hemolytic transfusion reactions, circulatory overload, transfusion related lung injury) are higher than the current infectious risks. Bacterial contamination of blood components remains the most frequent infectious risk from transfusion but are constantly declining. The estimated residual risk for transfusion transmitted HIV and hepatitis are lower 1/2 600 000 for HIV, 1/6 500 000 for HCV, 1/1 700 000 for HBV. For the future, the concerns are the risks of emerging or reemerging infections transmitted by blood as dengue, Chickungunya, West Nile Virus... Four transfusion transmissions of vCJD have been reported in UK, uncertainties about the incubation periods, the number of infected donors and the lack of sensitive assays for screening blood aggravate concerns about the transfusion transmission risks for vCJD. The ultimate strategy against infectious disease (all but vCJD) could be to develop inactivation methods. Pathogen inactivation have been implemented for plasma, are expected to become available for platelets, but for red blood cells are only in development.
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PMID:[Update on infectious risks associated with blood products]. 1925 89

A genetic contribution to infectious disease in human populations has long been suspected and is now supported by more than 50 years of epidemiological evidence showing, for example, infection rates to be much higher than disease rates. In successful family studies of high-penetrance effects, single gene mutations have been identified that reveal a molecular mechanism leading to increased risk of a specific infectious disease. However, in population-based studies, genetic variants conferring host susceptibility to various infectious diseases have been difficult to uncover. Although mutations such as that in the CCR5 gene, which confers protection against HIV infection, have been reliably discovered, polymorphisms affecting larger proportions of a population have been hard to prove definitively. The recent arrival of the genome-wide association study format, currently being applied to Kawasaki disease, tuberculosis, malaria, HIV, dengue and others, gives us hope that these challenges can finally be met, with implications for population-based treatment and prognosis strategies.
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PMID:Genome-wide association studies are coming for human infectious diseases. 1934 90

We evaluated the incidence of anti-Dengue virus (DENV) antibodies and dengue viremia in a region of Mexico with a high prevalence of dengue. DENV is the most important arthropod-borne virus in terms of human morbidity and mortality in America We tested 800 blood donors from a tertiary care teaching hospital that provides care in Northeast Mexico, to identify anti-DENV IgM and IgG antibodies by enzyme-linked immunosorbent assay (ELISA) and DENV genome by reverse transcription polymerase chain reaction (RT-PCR). In addition, routine tests for donors including Brucella, Hepatitis C virus (HCV), Venereal Disease Research Laboratory (VDRL), HIV-1 and HBsAg identification were performed. We found that 59% of donors were reactive for anti-DENV IgG and none of them had reported recent DENV infection; however, 16 (2%) were reactive for anti-DENV IgM antibodies. None of them were viremic at the time of donation. Routine tests showed that the prevalence of anti-Brucella was 0.71%, anti-HCV 0.71%, anti-HIV-1-2 0.14%, HBsAg 0.14% and VDRL test 0.57%. Although DENV transmission by blood transfusion had not been confirmed in Mexico, the finding of a high prevalence of anti-DENV IgM-positive donors with asymptomatic manifestations and the recent viremia reported in blood donors suggests that this route of transmission might be possible.
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PMID:Dengue virus antibodies in blood donors from an endemic area. 1956 69

This review article presents the fourth part (part D) in the series of stories on antiviral drug discovery. The stories told in part D focus on: (i) the cyclotriazadisulfonamide compounds; (ii) the {5-[(4-bromophenylmethyl]-2-phenyl-5H-imidazo[4,5-c]pyridine} compounds; (iii) (1H,3H-thiazolo[3,4-a]benzimidazole) derivatives; (iv) T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) and (v) its structurally closely related analogue pyrazine 2-carboxamide (pyrazinamide); (vi) new strategies for the treatment of hemorrhagic fever virus infections, including, as the most imminent, (vii) dengue fever, (viii) the veterinary use of acyclic nucleoside phosphonates; (ix) the potential (off-label) use of cidofovir in the treatment of papillomatosis, particularly RRP (recurrent respiratory papillomatosis); and (x) finally, the prophylactic use of tenofovir to prevent HIV infections.
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PMID:Yet another ten stories on antiviral drug discovery (part D): paradigms, paradoxes, and paraductions. 1962 94

Dengue viruses belong to the Flavivirus family and are responsible for hemorrhagic fever in Human. Dengue virus infection triggers apoptosis especially through the expression of the small membrane (M) protein. Using isolated mitochondria, we found that synthetic peptides containing the C-terminus part of the M ectodomain caused apoptosis-related mitochondrial membrane permeabilization (MMP) events. These events include matrix swelling and the dissipation of the mitochondrial transmembrane potential (DeltaPsi(m)). Protein M Flavivirus sequence alignments and helical wheel projections reveal a conserved distribution of charged residues. Moreover, when combined to the cell penetrating HIV-1 Tat peptide transduction domain (Tat-PTD), this sequence triggers a caspase-dependent cell death associated with DeltaPsi(m) loss and cytochrome c release. Mutational approaches coupled to functional screening on isolated mitochondria resulted in the selection of a protein M derived sequence containing nine residues with potent MMP-inducing properties on isolated mitochondria. A chimeric peptide composed of a Tat-PTD linked to the 9-mer entity triggers MMP and cell death. Finally, local administration of this chimeric peptide induces growth inhibition of xenograft prostate PC3 tumors in immuno-compromised mice, and significantly enhances animal survival. Together, these findings support the notion of using viral genomes as valuable sources to discover mitochondria-targeted sequences that may lead to the development of new anticancer compounds.
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PMID:A flavivirus protein M-derived peptide directly permeabilizes mitochondrial membranes, triggers cell death and reduces human tumor growth in nude mice. 1969 74

Horizontal gene transfer and recombination play a major role in microbial evolution and have been detected in diverse groups, including many of medical relevance such as HIV and dengue virus. In the absence of mechanistic barriers, the evolutionary success of a particular recombination event is determined by whether the recombinant genotype suffers a fitness cost through the disruption of favorable epistatic interactions within the genome, and if so, the extent to which this fitness cost might be mitigated by subsequent compensatory evolution. To investigate the importance of epistatic interactions between genes and the evolutionary viability of a homologous recombination event between diverged ancestral genotypes, we constructed two recombinant microvirid bacteriophages by exchanging their alleles of the gene encoding the coat protein. The coding sequences for this gene differ by approximately 8% at the amino acid level and were interchanged between two ancestral phages related to varphiX174 and well adapted to their culture conditions. Because the recombinant phages showed drastically reduced fitnesses, we further explored their evolutionary viability by subjecting replicate lines of each of them to selection. We found that all four lineages achieved fitnesses commensurate with ancestral fitnesses in as few as 60 generations, and on average, the first substitution accounted for more than half of the total fitness recovery. Fitness recovery required three to five substitutions in each lineage, and overall eight of the nine essential phage genes were involved, suggesting extensive epistatic interactions throughout the genome. Interestingly, the proteins with the most extensive and apparent physical interactions with the exchanged protein in the viral capsid did not appear to have much of a role in fitness recovery. This result appears to be a consequence of the conservation of the amino acid residues involved in the interactions. It suggests that strong epistatic interactions are less important than weaker, transient ones in producing genic incompatibilities because they preclude variability in the interacting regions of the proteins.
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PMID:Genic incompatibilities in two hybrid bacteriophages. 1972 36

Although dengue virus (DEN) endemic regions overlap with human immunodeficiency virus 1 (HIV) high incidence areas, little has been documented on HIV and DEN mixed infection. Here we report DEN/HIV concurrent infections recorded during the DEN-3 epidemic in 2001-2002 in Havana. Serologic-confirmed DEN is described in two HIV-infected subjects with dengue fever symptoms. Although patients had dengue disease, the CD4+ cells remained within normal levels and no accelerated progression of HIV disease was observed. To our knowledge, DEN cases caused by DEN-3 in HIV-infected individuals have not been reported previously. Further research is needed to diagnose this likely underreported mixed viral infection in DEN endemic areas.
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PMID:Dual infection with dengue virus 3 and human immunodeficiency virus 1 in Havana, Cuba. 1975 97

Global warming, globalisation, and constantly increasing number of people involved in long-distance tourism and travel to exotic destinations are likely to increase the number of cases of exotic diseases "imported" to nonendemic countries. One of the often forgotten and neglected diseases has been visceral leishmaniasis (VL or kala-azar). The disease is endemic to 62 countries, with India and Sudan accounting for the majority of the cases. It is typically fatal if left untreated. Each year about 500 000 new cases are reported worldwide, and 50 000 die as a result of the disease. Kala-azar is present in the Mediterranean Europe and 70% of cases are imported to non-endemic countries of European Union from that area. Immunocompromised status of patients, like HIV carriers are the principal prospective target for kala-azar. HIV/VL-coinfected patients have significantly higher relapse rates and decreased life expectancy. There is no formal system of reporting imported cases in Europe, except from Germany. In non-endemic countries, including Poland, there is usually the substantial delay between the onset of symptoms and the final diagnosis, with an average exceeding 3 months. This fact suggests that physicians are not familiar with leishmania infections. Despite progress in vaccine development, the only way to prevent the infection is avoiding sandfly bites. Mosquito nets, wearing appropriate clothes and repellents containing DEET (diethyl toluamide) can reduce number of bites and protect also from the other vector-borne diseases like malaria or dengue. Education concerning kala-azar risk and ways of the disease prevention is a needed for tourists and the other travelers.
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PMID:[Visceral leishmaniasis as a threat for non-endemic countries]. 1985 34


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