Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

International trade and travel have rendered political and geographic boundaries irrelevant when it comes to diseases. HIV and SARS are among the more recent examples of deadly viruses that spread swiftly from one continent to the next before international health experts can identify them, much less begin to search for a cure. This snapshot of global health issues looks at payer systems from a cross section of nations, lists the world's eight most infectious diseases and their rate of incidence by region, and pays special attention to the shortage of health care workers, which has reached crisis proportions in many areas and is pitting nation against nation in the competition for qualified staff.
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PMID:Global health report. A snapshot of the payer systems, major diseases and workforce trends from around the world. 1290 94

A remarkable collaborative effort coordinated by the severe acute respiratory syndrome (SARS) team at WHO resulted in discovery of the etiologic agent of severe acute respiratory syndrome less than 2 months after the announcement of global alert. The development of a vaccine to prevent SARS should be pursued with the same urgency and cooperative spirit, as SARS is highly lethal and, if not controlled during the first few generations of transmission, is likely to become endemic in regions of the world where health-care infrastructure is underdeveloped and epidemiological control measures are weak. The scientific community already learned many important lessons from HIV vaccine development; these should be heeded. For example, consideration should be given to the development of a vaccine that will protect across regional strains of SARS, as the newly emergent coronavirus SARS-coronavirus (SARS-CoV) is proving to be variable and may be mutating in response to immune pressure. SARS-specific research reagents should also be collected and shared. These would include SARS peptides, adjuvants, DNA vaccine vectors and clinical grade viral vectors. Rapidly developing a collaborative approach to developing a SARS vaccine that will be both effective and safe is the only way to go. This article reviews parallels between HIV and SARS and proposes an approach that would accelerate the development of a SARS vaccine.
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PMID:How the SARS vaccine effort can learn from HIV-speeding towards the future, learning from the past. 1450 86

Over 15 years ago, the Benner group noticed that the DNA alphabet need not be limited to the four standard nucleotides known in natural DNA. Rather, twelve nucleobases forming six base pairs joined by mutually exclusive hydrogen bonding patterns are possible within the geometry of the Watson-Crick pair (Fig. 1). Synthesis and studies on these compounds have brought us to the threshold of a synthetic biology, an artificial chemical system that does basic processes needed for life (in particular, Darwinian evolution), but with unnatural chemical structures. At the same time, the artificial genetic information systems (AEGIS) that we have developed have been used in FDA-approved commercial tests for managing HIV and hepatitis C infections in individual patients, and in a tool that seeks the virus for severe acute respiratory syndrome (SARS). AEGIS also supports the next generation of robotic probes to search for genetic molecules on Mars, Europa, and elsewhere where NASA probes will travel.
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PMID:Synthetic biology with artificially expanded genetic information systems. From personalized medicine to extraterrestrial life. 1451 Apr 12

The synthesis of the structurally unusual heterotricyclic compound 1-[3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridinyl]-2,8,9-trioxaadamantane-3,5,7-triol (trivially named bananin, BN) from pyridoxylidenephloroglucinol and a theoretical prospect on possible biological activities of BN are presented in this report. Pyridoxylidenephloroglucinol is synthesized by Knoevenagel condensation of the vitamin B6 aldehyde pyridoxal with phloroglucinol. Pyridoxylidenephloroglucinol rearranges to light-yellow (4'RS)-1',4'-dihydrobananin by refluxing in 5M hydrochloric acid. Air oxidation subsequently forms BN in the heat which immediately yields orange-yellow (4'RS)-4'-chloro-1',4'-dihydrobananin by 1,4-addition of hydrogen chloride. This intermediate could be isolated but, interestingly, not a BN hydrochloride. Brown BN is finally achieved by base-catalyzed elimination of hydrogen chloride from (4'RS)-4'-chloro-1',4'-dihydrobananin. Regarding possible biological activities, it was demonstrated that BN acts as zinc (Zn2+) chelator. Therefore, a target of interest could be the human immunodeficiency virus type 1 (HIV-1) zinc finger HIV-1 RNA-binding nucleocapsid protein p7 (NCp7). Through suggested zinc ejection from HIV-1 genomic RNA psi-element-binding and HIV-1-RNA-duplex packaging NCp7 by BN, thus rendering NCp7 functionally obsolete, it is deduced that HIV-1 replication and effective infectious virion encapsidation could be inhibited by BN. Furthermore, theoretical and structural considerations propose that BN is converted into bananin 5'-monophosphate (BNP) by the cell type-ubiquitous human enzyme pyridoxal kinase (EC 2.7.1.35). Together with the putative antilentiviral retinoid vitamin A-vitamin B6 conjugate analogue B6RA (Kesel, A. J. Biochem. Biophys. Res. Comm. 2003, 300, 793), BNP is postulated to serve as effector in a system of protein target sequences RX(D/E) of RNA virus components. Human immunodeficiency Retroviridae (HIVs) could possibly be influenced by B6RA and BNP. In addition, candidate targets of B6RA and BNP could be adsorption, transcription and/or viral RNA replication of an interestingly wide RNA virus selection including Picornaviridae (poliovirus, human coxsackievirus, hepatitis A virus), Flaviviridae (yellow fever virus, Dengue virus, West Nile virus, Kunjin virus, St. Louis encephalitis virus, hepatitis C virus), Togaviridae (rubella virus), Coronaviridae (human coronavirus, human SARS-associated coronavirus), Rhabdoviridae (rabies virus), Paramyxoviridae (human parainfluenza virus, measles virus, human respiratory syncytial virus), Filoviridae (Marburg virus, Ebola virus), Bornaviridae (Borna disease virus), Bunyaviridae (Hantaan virus), Arenaviridae (Lassa virus), and Reoviridae (human rotavirus). The postulated scope of 'metabolically trapped' BNP might resemble the antiviral spectrum of the RNA-viral virustatic ribavirin.
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PMID:A system of protein target sequences for anti-RNA-viral chemotherapy by a vitamin B6-derived zinc-chelating trioxa-adamantane-triol. 1452 57

Chloroquine is a 9-aminoquinoline known since 1934. Apart from its well-known antimalarial effects, the drug has interesting biochemical properties that might be applied against some viral infections. Chloroquine exerts direct antiviral effects, inhibiting pH-dependent steps of the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses. Its best-studied effects are those against HIV replication, which are being tested in clinical trials. Moreover, chloroquine has immunomodulatory effects, suppressing the production/release of tumour necrosis factor alpha and interleukin 6, which mediate the inflammatory complications of several viral diseases. We review the available information on the effects of chloroquine on viral infections, raising the question of whether this old drug may experience a revival in the clinical management of viral diseases such as AIDS and severe acute respiratory syndrome, which afflict mankind in the era of globalisation.
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PMID:Effects of chloroquine on viral infections: an old drug against today's diseases? 1459 3

The outstanding issue regarding recent trends in the epidemiology of infectious diseases is the epidemic occurrence of severe acute respiratory syndrome (SARS) in 2003. SARS is caused by a novel coronavirus, presumably originating from wild cats. This new agent was rapidly identified and characterized, the outbreak was terminated in early summer 2003 after implementation of strict infectious control measures. Especially the high rate of complications and nosocomial infections has caused severe public health problems in China and Canada. The number of persons infected with HIV is still rising rapidly globally. New regions with rapid spread include the countries of the former Soviet Union in East Europe and Central Asia. The introduction of modern antiretroviral therapy in countries with high prevalence is making slow progress, with no visible impact on transmission dynamics so far. The WHO has implemented a number of programs to eradicate or eliminate targeted infectious diseases. Polio eradication and elimination of neonatal tetanus are making slow progress, obstacles to the control of these diseases are ongoing armed conflicts in regions with high prevalence and under financing of programs. Lack of funding is especially obvious regarding programs for the control and therapy of malarial infections. The numbers of patients newly identified with new variant Creutzfeldt-Jakob disease are not rising, but rather constant or even declining, making a large epidemic of vCJD unlikely.
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PMID:[Infectious diseases-part I: epidemiology]. 1471 83

In April 2003, the Ontario Legislature amended the province's public health legislation as part of a package of amendments related to the recent outbreak of Severe Acute Respiratory Syndrome (SARS). Although the amendments to the Health Protection and Promotion Act (HPPA) were clearly designed to address emergency situations like SARS, they may have unintended and negative consequences for people living with HIV/AIDS.
Can HIV AIDS Policy Law Rev 2003 Aug
PMID:Class orders now possible under Ontario's public health legislation. 1474 97

We have expressed a series of truncated spike (S) glycoproteins of SARS-CoV and found that the N-terminus 14-502 residuals were sufficient to bind to SARS-CoV susceptible Vero E6 cells. With this soluble S protein fragment as an affinity ligand, we screened HeLa cells transduced with retroviral cDNA library from Vero E6 cells and obtained a HeLa cell clone which could bind with the S protein. This cell clone was susceptible to HIV/SARS pseudovirus infection and the presence of a functional receptor for S protein in this cell clone was confirmed by the cell-cell fusion assay. Further studies showed the susceptibility of this cell was due to the expression of endogenous angiotensin-converting enzyme 2 (ACE2) which was activated by inserted LTR from retroviral vector used for expression cloning. When human ACE2 cDNA was transduced into NIH3T3 cells, the ACE2 expressing NIH3T3 cells could be infected with HIV/SARS pseudovirus. These data clearly demonstrated that ACE2 was the functional receptor for SARS-CoV.
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PMID:Expression cloning of functional receptor used by SARS coronavirus. 1476 27

Chloroquine and related anti-malarial drugs appear to promote apoptosis in T-cells by suppressing NF-kappa-B, which enhances the expression of anti-apoptotic proteins (e.g., Bcl-2). Thus, chloroquine has found applications in autoimmune diseases where it apparently facilitates apoptosis of abnormally persistent T-cell clones. The mode of action of chloroquine in prevention of malaria is not known, but it may be to minimize replication of the parasite in the liver cells, which occurs before invasion of the erythrocytes, by facilitating premature apoptosis of the infected host cells. After introduction of chloroquine in the 1950s world-wide for prophylactic use, chloroquine-resistant malaria emerged. Here it is hypothesized that concurrent with emergence of chloroquine-resistant malaria (presumably with enhanced anti-apoptotic capabilities), other intracellular parasites have evolved to enhance their ability to prevent apoptosis in host cells. Two examples of viral diseases that have emerged from areas of high incidence of chloroquine-resistant malaria are AIDS from HIV and SARS from coronavirus. The hypothesis holds that prophylactic exposure to pro-apoptotic chloroquine drugs caused natural selection for strains of viruses and other parasites that have enhanced anti-apoptotic abilities. When transmitted to host organisms that are not under the influence of the pro-apoptotic drug, the new "anti-apoptotic" strains may cause unexpected diseases. In the case of SARS, the coronavirus appears to have accessed a new niche where it proves to be lethal to its host. In the case of AIDS, the HIV (which has had a long-term symbiotic relationship with primates) has run amuck because the infected cells are now substantially more tolerant to the toxins (i.e., resistant to apoptosis) that they secrete than the uninfected bystander cells, which are not unusually resistant to apoptosis. A corollary to the hypothesis is that if the level of resistance to apoptosis in the infected cells were no higher than the level of resistance in the bystander cells, then the infected cells would preferentially kill themselves through apoptosis. It appears that in the case of HIV, the increased resistance to apoptosis is provided by expression of Bcl-2 and suppression of p53. Hence, drugs that suppresses Bcl-2 or restore p53 function might be effective in restoring the parity of resistance to apoptosis between infected and uninfected cells. Currently, an antisense drug targeting Bcl-2 (G3139/Genasense(TM), Genta, Inc.) is in late-stage cancer trials and may be on the market for those indications in months. It would be interesting to try these drugs against various intracellular parasites including HIV. This approach to prevent or eliminate active infections might be particularly attractive against a range of parasites (virus, bacteria, protozoa, fungus) when safe and effective vaccines are not available.
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PMID:Hypothesis links emergence of chloroquine-resistant malaria and other intracellular pathogens and suggests a new strategy for treatment of diseases caused by intracellular parasites. 1497 2

The outbreak of severe acute respiratory syndrome (SARS) has drawn enormous attention and caused fear worldwide since early 2003. The disease appears to be under control now; however, the possible return of SARS must be emphasized. Although many clinical experiments have been reported, the treatment of SARS is largely anecdotal, and so far no treatment consensus has been reached. We summarize 14 clinical reports and attempt to assess the effectiveness of various treatment regimens. A combination treatment of steroids and ribavirin was widely used empirically from the outset of the epidemic. In general, the use of steroids for SARS seemed beneficial, but the optimal timing, dosage, and duration of treatment have not yet been determined. On the other hand, ribavirin administration apparently reduced neither the rate of intratracheal intubation nor that of mortality. Moreover, significant toxicity, such as hemolytic anemia, has been attributed to ribavirin. A few preliminary trials and in vitro data suggest the possibility of treating SARS with interferon. Other agents, including the HIV protease inhibitor glycyrrhizin and convalescent plasma, remain to be evaluated.
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PMID:Current concepts in SARS treatment. 1499 10


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