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)

The article focuses on the Indian initiative of making kits for diagnosis of various infectious and non-infectious diseases as well as reproductive hormones and hormones in various other endocrine disorders. Indigenous diagnostic kits for the detection of various infections such as filariasis, typhoid, amebiasis, Japanese encephalitis, hepatitis, HIV, dengue, leishmaniasis, malaria, rabies, toxoplasmosis, rotavirus, and group A streptococci have been developed. Agreements to transfer the know-how of some of these leads to industries have been signed. The know-how of enzyme-linked immunosorbent assay (ELISA) for detection of hepatitis C has been successfully transferred to industry and is being commercially produced. For detection of HIV-1 and HIV-2, indigenous diagnostic kits based on three different formats, namely ELISA, Western blot and rapid test have been developed and are being commercially produced by Indian industries. The factors influencing the successful transfer of laboratory-scale diagnostic assays from academia to industry and their commercial exploitation have been discussed. Indian scientists have made seminal contributions in exploring the possibility to develop an effective and safe contraceptive vaccine to control the increasing human population of India. Achieving contraception by means of vaccine is a novel approach, which entails generation of a specific antibody response against antigens critically involved in the process of mammalian reproduction. In India, three major programs on contraceptive vaccines based on the beta-subunit of human chorionic gonadotrophin ((beta)hCG) for women, ovine follicle stimulating hormone (oFSH) for men, and riboflavin carrier protein for both males and females have been initiated. The work at the National Institute of Immunology, New Delhi on contraceptive vaccine for women, based on (beta)hCG, has demonstrated, for the first time, that it is feasible to regulate fertility by such an approach. Basic research being carried out to achieve immunocontraception by interfering at sperm-oocyte interaction level has been briefly discussed. These developments are still at the research stage. In addition to advances in the area of contraceptive vaccines, a non-steroidal contraceptive oral pill has been developed by Central Drug Research Institute, Lucknow, commercially produced by two Indian pharmaceutical companies and has been incorporated in the National Family Welfare Program. Another interesting approach for fertility regulation in male has been developed in India, which involves vas occlusion with styrene maleic anhydride (SMA) and is currently undergoing clinical trials in human subjects.
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PMID:Status of immunodiagnosis and immunocontraceptive vaccines in India. 1293 96

Health problems of gold miners who worked underground include decreased life expectancy; increased frequency of cancer of the trachea, bronchus, lung, stomach, and liver; increased frequency of pulmonary tuberculosis (PTB), silicosis, and pleural diseases; increased frequency of insect-borne diseases, such as malaria and dengue fever; noise-induced hearing loss; increased prevalence of certain bacterial and viral diseases; and diseases of the blood, skin, and musculoskeletal system. These problems are briefly documented in gold miners from Australia, North America, South America, and Africa. In general, HIV infection or excessive alcohol and tobacco consumption tended to exacerbate existing health problems. Miners who used elemental mercury to amalgamate and extract gold were heavily contaminated with mercury. Among individuals exposed occupationally, concentrations of mercury in their air, fish diet, hair, urine, blood, and other tissues significantly exceeded all criteria proposed by various national and international regulatory agencies for protection of human health. However, large-scale epidemiological evidence of severe mercury-associated health problems in this cohort was not demonstrable.
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PMID:Health risks of gold miners: a synoptic review. 1297 Dec 53

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

Viruses, especially those with RNA genomes, represent ideal organisms to study the dynamics of microevolutionary change. In particular, their rapid rate of nucleotide substitution means that the epidemiological processes that shape their diversity act on the same time-scale as mutations are fixed in viral populations. Consequently, the branching structure of virus phylogenies provides a unique insight into spatial and temporal dynamics. Herein, I describe the key processes in virus phylogeography. These are generally associated with the relative rates of dispersal among populations and virus-host codivergence (vicariance), and the division between acute (short-term) and persistent (long-term) infections. These processes will be illustrated by important human viruses - HIV, dengue, rabies, polyomavirus JC and human papillomavirus - which display varying spatial and temporal structures and virus-host relationships. Key research questions for the future will also be established.
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PMID:The phylogeography of human viruses. 1501 53

Although the development of antimicrobial drugs has advanced rapidly in the past several years, such agents act against only certain groups of microbes and are associated with increasing rates of resistance. These limitations of treatment force physicians to continue to rely on prevention, which is more effective and cost-effective than therapy. From the use of the smallpox vaccine by Jenner in the 1700s to the current concerns about biologic warfare, the technology for vaccine development has seen numerous advances. The currently available vaccines for viral illnesses include Dryvax for smallpox; the combination measles, mumps, and rubella vaccine; inactivated vaccine for hepatitis A; plasma-derived vaccine for hepatitis B; and the live attenuated Oka strain vaccine for varicella zoster. Vaccines available against bacterial illnesses include those for anthrax, Haemophilus influenzae, and Neisseria meningitidis. Currently in development for both prophylactic and therapeutic purposes are vaccines for HIV, herpes simplex virus, and human papillomavirus. Other vaccines being investigated for prevention are those for cytomegalovirus, respiratory syncytial virus, parainfluenza virus, hepatitis C, and dengue fever, among many others. Fungal and protozoan diseases are also subjects of vaccine research. Among immunoglobulins approved for prophylactic and therapeutic use are those against cytomegalovirus, hepatitis A and B, measles, rabies, and tetanus. With this progress, it is hoped that effective vaccines soon will be developed for many more infectious diseases with cutaneous manifestations.
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PMID:Vaccines and immunotherapies for the prevention of infectious diseases having cutaneous manifestations. 1503 1

Some emerging infectious diseases have recently become endemic in Germany. Others remain confined to specific regions in the world. Physicians notice them only when travelers after infection in endemic areas present themselves with symptoms. Several of these emerging infections will be explained. HIV is an example for an imported pathogen which has become endemic in Germany. SARS and avian influenza are zoonoses with the potential to spread from person to person. Avian influenza in humans provides a possibility for the reassortment of a potential new pandemic strain. Outbreaks of dengue fever in endemic areas are reflected in increased infections in travelers returning from these areas. Currently, West-Nile-virus infections are only imported into Germany. The timely implementation of diagnostic, therapeutic and infection control measures requires physicians to include these diseases in their differential diagnosis. To achieve this goal, good cooperation between physicians, laboratories and the public health service is essential.
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PMID:["Emerging infectious diseases". Dengue-fever, West-Nile-fever, SARS, avian influenza, HIV]. 1510 83

Ampligen [polyI:polyC12U] is a mismatched double-stranded RNA that acts by inducing interferon production (immunomodulator) and by activating an intracellular enzyme (RNase-L) against viral RNA transcripts (antiviral). Ampligen, currently under development by Hemispherx Biopharma in the US, acts on the immunological system through T-lymphocyte stimulation and is indicated for the treatment of chronic fatigue syndrome and acquired immunodeficiency deficiency syndrome (AIDS), as part of the combined therapy. Ampligen is available for licensing worldwide. In February 2004, Fujisawa Deutschland GmbH, a subsidiary of Fujisawa Pharmaceutical Co., entered into an option agreement with Hemispherx Biopharma with the intent of becoming a distributor for Ampligen for the potential treatment of chronic fatigue syndrome in Germany, Switzerland and Austria. An option fee of 400,000 euros was paid pursuant to the terms of the option agreement and upon execution of the Distribution Agreement, Fujisawa will pay Hemispherx fees and milestone payments with a potential worth of several millions of dollars. In September 2003, Hemispherx Biopharma Inc. entered into an agreement with Guangdong Medicine Group Corporation to organise clinical trials, marketing, sales and distribution for both of its lead compounds, Ampligen and Alferon N in the People's Republic of China. The agreement stipulates that the Guangdong Medicine Group Corporation (GMC) will conduct clinical trials with Ampligen for the treatment of HIV. All costs related to the trials are to be covered by GMC. Additionally, GMC has to develop and implement marketing and promotional programmes. In May 2003, Hemispherx Biopharma and the Center for Cell and Gene Therapy entered into a research project agreement that will see Ampligen implemented in a protocol used in patients with relapsed EBV-positive Hodgkin's Lymphoma. In March 2002, Esteve and Hemispherx Biopharma entered into a collaborative agreement under which Esteve will be the sole distributor of Ampligen in Spain, Portugal and Andorra for the treatment of chronic fatigue syndrome. Under this agreement, in addition to other terms, Esteve will also collaborate in the drug product development by conducting clinical studies in Spain in patients coinfected with HIV/HCV. In July 2001 Hemispherx Biopharma announced that it had formed a strategic alliance with Empire Health Resources for clinical trials of Ampligen in the treatment of HIV and hepatitis C virus infections. Empire Health Resources, a healthcare management firm, will be responsible for accrual and retention of patients for HIV trials, and protocols for trials in patients with hepatitis C or both HIV and hepatitis C infections. Hemispherx has entered into a collaboration with RED Laboratories, and RED Laboratories NV expects that this will facilitate the continued development of Ampligen. Hemispherx has also entered into an agreement with Schering Plough to use a Schering facility as its principal manufacturing platform in the US. This agreement may be expanded to include other territories. Hemispherx and AOP Orphan Pharmaceuticals have signed a marketing agreement for Ampligen for the treatment of chronic fatigue syndrome for Austria, the Czech Republic, Poland and Hungary. In an arrangement between Hemispherx and Bioclones, Bioclones has certain marketing rights for Ampligen in the Southern Hemisphere, UK and Ireland. In the US, Ampligen has been granted orphan drug status for the treatment of AIDS, renal cell carcinoma (phase II, completed), chronic fatigue syndrome (phase III) and invasive/metastatic malignant melanoma (phase II). In August 2004, Hemispherx announced that it intends to use the proceeds from the private placement of company stock to complete the clinical work for its immunotherapeutics/ antivirals Ampligen and Oragens. Previously, Hemispherx submitted an application to the EMEA for the approval of Ampligen for the treatment of chronic fatigue syndrome; the first stage of th;) for the treatment of chronic fatigue syndrome; the first stage of the regulatory review has been cleared. In 2000, Hemispherx Europe (Hemispherx) obtained orphan drug status for Ampligen for the treatment of chronic fatigue syndrome in the EU, providing Hemispherx with 10 years of marketing exclusivity following the launch of the drug, as well as potential financial research benefits for the agent. In February 2000, Crystaal Corporation (now Biovail Pharmaceuticals Canada) acquired exclusive marketing rights to Ampligen in Canada, where it submitted an NDA for the agent for the treatment of chronic fatigue syndrome. In the meantime, Ampligen has been available since May 1996 under the Canadian Emergency Drug Release Programme for the treatment of chronic fatigue syndrome and immune dysfunction syndrome by Rivex Pharma (Helix BioPharma). Bioclones has initiated clinical studies with Ampligen for the treatment of chronic fatigue syndrome in Australia. The active substance for Ampligen is manufactured by F.H. Faulding Ltd. Clinical treatment programmes for chronic fatigue syndrome in other Pacific Rim countries are planned. Ampligen is available for severe chronic fatigue syndrome on a named patient, cost-recovery basis in South Africa. Hemispherx has developed a 'ready-to-use' liquid formulation of the drug and has begun treating patients with chronic fatigue syndrome in ongoing clinical trials. Hemispherx has also developed an oral version of the drug (Oragen), which is undergoing preclinical evaluation. In February 2001, Hemispherx Biopharma announced that it was initiating phase II/III trials of Ampligen in the treatment of late-stage, multidrug-resistant strains of HIV in the European Union. Patients treated in these studies will have exhausted all other treatment options. In July 2001, Hemispherx stated that Ampligen was being evaluated in a phase IIb trial in patients with HIV in the US. The trial, comprising two studies, REARMI and REARMII (Research/Evaluation of Ampligen for Retroviral Mutations I and II), will evaluate the ability of Ampligen to prevent the emergence of mutated, drug-resistant strains of the virus. 'Several hundred' patients currently on antiretroviral therapy and at risk of viral relapse will be enrolled at centres in Connecticut, New York, Florida and California. A second phase IIb study evaluating the effect of Ampligen on structured treatment interruptions (STI) is also underway. Final results from this study were reported in December 2002. NIH sponsored studies of potential therapies for SARS have identified Ampligen as having unusually high and consistent antiviral activity against human coronavirus, the pathogen implicated as the causative agent of the disease. Ampligen demonstrated very high potency at very low concentrations (0.4 microg/mL) and had a favourable safety profile. In October 2003, Hemispherx announced that, based on these promising new results, the company will stockpile injectible and/or oral formats of Ampligen and Alferon N. Independent researchers have demonstrated the antiviral activity of Ampligen against flaviviruses (West Nile virus, Equine Encephalitis virus, Dengue fever virus and Japanese Encephalitis virus) as well as virus classes associated with bioterrorism. In an animal study, Ampligen was shown to prevent destruction of nerve cells, reduce virus concentrations in the brain and blood stream and increase survival rates. Researchers at the Rega Institute in Belgium have published results from an animal study demonstrating that Ampligen was superior at protecting mice against coxsackie B3 virus-induced myocarditis compared with pegylated interferon. In May 2004 Hemispherx announced that it had filed an expanded US patent application covering the use of Ampligen for the potential treatment and prevention of severe acute respiratory syndrome (SARS) and dreaded emerging viruses.
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PMID:Mismatched double-stranded RNA: polyI:polyC12U. 1535 29

Lymphocytic choriomeningitis virus (LCMV) represents a useful experimental model of murine infection with a non-cytopathic virus, bearing resemblance to HIV and hepatitis C virus (HCV) infections in humans. Recent data from the LCMV model indicate that the humoral immune response that is induced by non-cytopathic viruses is far more complex than previously appreciated. LCMV-induced IgG production is largely polyclonal, with more than 90% of the antibody repertoire constituting non-relevant specificities. A delayed virus-neutralizing antibody response is induced, including specificities directed not only against the parental LCMV-strain present in the host but also cross-specifically against LCMV-variants isolated from other hosts. These findings provide novel insights to aid our understanding of clinically relevant observations that are recorded following human infection with HIV, HCV and dengue viruses.
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PMID:Public, private and non-specific antibodies induced by non-cytopathic viral infections. 1535 63

In 2003 the first virus entry inhibitor, the anti-HIV peptide T20 (Fuzeon, enfuvirtide), was approved for treatment of advanced Human Immunodeficiency Virus Type 1 infection. T20 is an unconventional antiviral drug, as it does not target a viral replicase or protease but a conformational transition within the HIV1 fusion protein gp41 required for virus-cell membrane fusion. Beyond membrane fusion, numerous early drug targets have been identified that will allow for large scale screening or structure-based drug design. The first encounter of the virus with the host might be through binding to attachment receptors, such as the C-type lectins DC- and L-SIGN, which might play an important role of infection for a large number of enveloped viruses by capturing, concentrating and transmitting infectious virions. Once a virus reaches its target cell, a cascade of events generally starting with the interaction of viral envelope glycoproteins with specific entry receptors and co-receptors is necessary in order to trigger the virus-cell membrane fusion. The present review will highlight recent advances in the identification of new drugs and targets at the level of virus entry for three major human pathogens accounting for several hundred million infections worldwide: HIV, Dengue Virus and Hepatitis C virus.
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PMID:Virus attachment and entry offer numerous targets for antiviral therapy. 1557 65

In order to competently advise people who are planning to travel abroad the doctor needs information both about the planned journey (the mode of travel, the itinerary, the time of the trip) and about possible preexisting health problems. The area where the traveller intends to stay determines the specific risk of endemic diseases such as malaria, dengue-fever, yellow-fever etc. The recommendations for prophylaxis of malaria and for the different vaccinations are constantly modified and can be attained from the internet. Pre-existing health hazards such as cardiovascular diseases, diabetes mellitus, HIV-infection need to be assessed. Special consideration should be taken for pregnant women. The traveller returning from an endemic malarious area who feels ill or is febrile is a medical emergency and must be assessed for the possibility of having malaria since nontreated malaria in non-immune people has a very high mortality rate. Diarrhea is a common problem but is rarely dangerous. Long standing or bloody diarrhea, however, calls for a thorough search for the responsible pathogen. Healthy return travellers do not need a check-up examination because there are virtually no consequences for treatment.
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PMID:[Travellers in medical practice]. 1577 39


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