UMLS:C0021051 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
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Human immunoglobulins are plasma derivatives with a low risk of transmitting viral infections. To the present, no proven case of human immunoglobulins transmitting human immunodeficiency viruses has been reported. However, there have been a few reports on the transmission of hepatitis C virus by these plasma proteins. To improve further the safety of both 5s iv human immunoglobulins and 7s im immunoglobulins, we introduced a 10-hour heat treatment of the aqueous solutions at 60 degrees C (i.e., pasteurization) into the manufacturing procedure. This treatment was not added to the manufacturing procedure of 7s iv immunoglobulin that already contained the S-sulfonation as a virus inactivating method. We now report on experimental data that show that the whole manufacturing procedures of the above immunoglobulins inactivate efficiently hepatitis C virus and that the specific virus inactivation methods alone, namely, pasteurization or S-sulfonation, also inactivate completely viruses of the flavivirus family, to which the hepatitis C virus belongs. The inactivation of the Flaviviridae bovine viral diarrhea virus, tick-borne encephalitis virus, and yellow fever virus by pasteurization or S-sulfonation was at least 10(5). The clearance of HCV achieved by the entire manufacturing process of each of these immunoglobulins was also at least 10(5). The experiments therefore show that pasteurization or S-sulfonation provides a high margin of safety to human immunoglobulins regarding the transmission of hepatitis C virus.
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PMID:Virus safety of human immunoglobulins: efficient inactivation of hepatitis C and other human pathogenic viruses by the manufacturing procedure. 131 86

A series of 23 Amaryllidaceae isoquinoline alkaloids and related synthetic analogues were isolated or synthesized and subsequently evaluated in cell culture against the RNA-containing flaviviruses (Japanese encephalitis, yellow fever, and dengue viruses), bunyaviruses (Punta Toro, sandfly fever, and Rift Valley fever viruses), alphavirus (Venezuelan equine encephalomyelitis virus), lentivirus (human immunodeficiency virus-type 1) and the DNA-containing vaccinia virus. Narciclasine [1], lycoricidine [2], pancratistatin [4], 7-deoxypancratistatin [5], and acetates 6-8, isonarciclasine [13a], cis-dihydronarciclasine [14a], trans-dihydronarciclasine [15a], their 7-deoxy analogues 13b-15b, lycorines 16 and 17, and pretazettine [18] exhibited consistent in vitro activity against all three flaviviruses and against the bunyaviruses, Punta Toro and Rift Valley fever virus. Activity against sandfly fever virus was only observed with 7-deoxy analogues. In most cases, however, selectivity of the active compounds was low, with toxicity in uninfected cells (TC50) occurring at concentrations within 10-fold that of the viral inhibitory concentrations (IC50). No activity was observed against human immunodeficiency virus-type 1, Venezuelan equine encephalomyelitis virus, or vaccinia viruses. Pancratistatin [4] and its 7-deoxy analogue 5 were evaluated in two murine Japanese encephalitis mouse models (differing in viral dose challenge, among other factors). In two experiments (low LD50 viral challenge, variant I), prophylactic administration of 4 at 4 and 6 mg/kg/day (2% EtOH/saline, sc, once daily for 7 days, day -1 to +5) increased survival of Japanese-encephalitis-virus-infected mice to 100% and 90%, respectively. In the same model, prophylactic administration of 5 at 40 mg/kg/day in hydroxypropylcellulose (sc, once daily for 7 days, day -1 to +5) increased survival of Japanese-encephalitis-virus-infected mice to 80%. In a second variant (high LD50 viral challenge), administration of 4 at 6 mg/kg/day (ip, twice daily for 9 days, day -1 to +7) resulted in a 50% survival rate. In all cases, there was no survival in the diluent-treated control mice. Thus, 4 and 5 demonstrated activity in mice infected with Japanese encephalitis virus but only at near toxic concentrations. To our knowledge, however, this represents a rare demonstration of chemotherapeutic efficacy (by a substance other than an interferon inducer) in a Japanese-encephalitis-virus-infected mouse model.
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PMID:Antiviral (RNA) activity of selected Amaryllidaceae isoquinoline constituents and synthesis of related substances. 133 40

One of the most important aspects of preparing travelers for destinations throughout the world is providing them with immunizations. Before administering any vaccines, however, a careful health and immunization history and travel itinerary should be obtained in order to determine vaccine indications and contraindications. There are three categories of immunizations for foreign travel. The first category includes immunizations which are routinely recommended whether or not the individual is traveling. Many travelers are due for primary vaccination or boosting against tetanus-diphtheria, measles-mumps-rubella, pneumococcal pneumonia, and influenza, for example, and the pre-travel visit is an ideal time to administer these. The second category are immunizations which might be required by a country as a condition for entry; these are yellow fever and cholera. The final category contains immunizations which are recommended because there is a risk of acquiring a particular disease during travel. Typhoid fever, meningococcal disease, rabies, and hepatitis are some examples. Travelers who are pregnant or who are infected with the human immunodeficiency virus require special consideration. Provision of appropriate immunizations for foreign travel is an important aspect of preventing illness in travelers.
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PMID:Immunizations for foreign travel. 133 7

Ten, hitherto unreported, analogues of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride (2a, ribamidine) and methyl carboximidate 5 have been synthesized. These include the N-cyano (2b), N-alkyl (2c-e), N-amino acid (2f-h), N,N'-disubstituted (6, 7a,b), and the N-methylated carboxamide (1f) analogues of ribavirin. In addition, a new facile synthesis of carboxamidine 2a was also developed. All compounds were evaluated for biological activity against the following RNA viruses: Punta Toro (PT) and sandfly fever (SF) viruses (bunyaviruses); Japanese encephalitis (JE), yellow fever (YF), and dengue-4 viruses (flaviviruses); parainfluenza type 3 (PIV3), respiratory syncytial virus (RSV), and measles viruses (paramyxoviruses); influenza A and influenza B viruses (orthomyxoviruses); Venezuelan equine encephalomyelitis virus (VEE, alphavirus); human immunodeficiency virus type-1 (HIV-1, lentivirus); the DNA-containing vaccinia (VV) virus (poxvirus); and adeno type 5 (Ad5) viruses. All of the compounds except for 2b and 7a,b exhibited activity against the bunyaviruses such as that observed with 2a; however, higher IC50 values were generally observed. Glycine analogue 2f showed activity in PT-virus-infected mice in terms of increased survivors and decreased markers of viral pathogenicity. Carboxamidine 2a, carboximidate 5, and dimethyl amidine 6 exhibited activity against dengue type-4 virus. Monomethyl amidine 2c demonstrated activity against RSV, PIV3, and, to a lesser extent, influenza A and B. Activity of 2c generally required higher IC50 values than unsubstituted 2a. The latter exhibited hitherto unreported activity against RSV; therapeutic indices for 2a against RSV and PIV3 were greater than 64 and greater than 21. No substantial in vitro activity was observed for any of the compounds tested against Ad5, measles, JE, YF, VEE, or HIV-1. In addition, evidence is presented which argues in favor of a distinct antiviral mechanism of action for carboxamidines, e.g. 6, in contrast to a role as a carboxamide precursor.
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PMID:Synthesis and antiviral evaluation of N-carboxamidine-substituted analogues of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride. 150 8

A lambda gt11-random-primed-cDNA clone specific for chronic hepatitis C was isolated from pooled serum presumably infected by hepatitis C virus. The translation product of the clone detect 50% of patients with chronic hepatitis C in 4 test panels but none of the patients with acute hepatitis C, other liver diseases or normal controls was positive for the peptide. The nucleotide sequence of the cDNA clone, the size of which is 66 bp, has no homology to the complete sequences of known human viruses such as adenovirus, coxsackievirus, rhinovirus, immunodeficiency virus type 1, Epstein-Barr virus, polioma virus, poliovirus, papilloma virus, parvovirus, papovavirus, varicella-zoster virus, yellow fever virus, endogenous retrovirus, T-cell lymphotropic virus types I, II, and III Japanese encephalitis virus, and hepatitis A, B, and D viruses. Probably only one or two epitopes are present on the molecule encoded by the clone as the peptide consists of only 22 amino acid residues.
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PMID:A lambda gt11-cDNA clone specific for chronic hepatitis C generated from pooled serum presumably infected by hepatitis C virus. 250 79

Large numbers of tourists visit South Africa every year. Travelers to urban areas are at little risk of contracting an infectious disease, however the adventure traveler is at increased risk. Yellow fever is not known to occur in South Africa. Malaria is endemic in Mpumalanga and KwaZula-Natal. Schistosomiasis is endemic in large parts of the country. Although rabies is found throughout the country, only a small number of human cases is reported. High risk areas are KwaZulu-Natal, the eastern Cape and Mpumalanga provinces. The incidence of human immunodeficiency virus (HIV) infection is high and counseling regarding sexually transmitted diseases is important. Sanitation of water is excellent in most large cities and towns; however travelers to rural areas should exercise caution. Arbovirus infections do occur but relatively few cases are reported. The hiker is at risk for tick bite fever and should be counseled. Since the abolition of apartheid, South Africa has been seen as an inexpensive, high quality destination by many tourists. In 1997, a total of 5,436,848 travelers from many different countries visited the country. Areas most frequently visited include Johannesburg, Cape Town, Durban, the Garden Route, Kruger National Park, KwaZulu-Natal and Pretoria. The most common reason for visiting the country was holiday (44%), followed by visiting friends and relatives (23%), business travel (27%) other (6%).1 Travelers, to the larger cities such as Johannesburg, Cape Town and Durban are at little risk of acquiring an infectious disease. The adventure traveler however is at greater risk as parts of the country are endemic for malaria, schistosomiasis, rabies, food and waterborne diseases, sexually transmitted diseases and arbovirus infections. Accidental deaths due to motor vehicle accidents and interpersonal violence are important health risks in South Africa. Travelers visiting popular attractions are at significantly lower risk. However this has never been quantified. This review aims to address the occurrence of infectious diseases and attempts to give guidelines to practitioners caring for travelers.
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PMID:Health risks of travelers in South Africa. 1046 56

Mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid (MPA), is currently used as an immunosuppressive agent in kidney transplant recipients. After oral administration, MMF is hydrolysed to MPA, the active compound, which is a potent inhibitor of inosine monophosphate dehydrogenase (IMP-DH). Inhibition of this enzyme results in a depletion of the intracellular GTP and dGTP pools. MPA has been shown to inhibit the replication of a number of viruses, including arena viruses (Junin and Tacaribe), yellow fever virus, reovirus-1, parainfluenza-3 virus, Coxsackie B4 virus, Epstein-Barr virus and human immunodeficiency virus. To examine whether MPA also has an inhibitory effect on HBV replication, experiments were performed using cultures of primary human hepatocytes and HBV-transfected, HepG2 2.2.15 cells. After in vitro infection with HBV in human hepatocytes, HBV covalently-closed-circular (ccc) DNA and HBV mRNAs were detectable in the cells during the 10 days following infection. HBV DNA and hepatitis B surface antigen (HBsAg) were also secreted into the culture medium. In the presence of 10 microg ml-1 MPA (the therapeutic serum level of MPA as an immunosuppressive agent) in culture medium, HBV ccc DNA and HBV mRNAs became undetectable 5 days after treatment was started. The secretion of HBV DNA and HBsAg into the medium was also markedly reduced. No cytotoxic effect of the drug was noted during the experiments. The effect of MPA on HBV replication was abolished by the presence of guanosine (50 microg ml-1). In HepG2 2.2.15 cells (which contain an integrated tandem dimer of the HBV genome), MPA treatment had no significant inhibitory effect on the secretion of HBV DNA and HBsAg into the culture medium. HBV ccc DNA and HBV mRNAs in HepG2 2.2.15 cells were also not affected. The observed effect of MPA on HBV replication in primary human hepatocyte cultures may involve only episomal replication and may have clinical implications, especially before integration of HBV DNA into the host genome.
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PMID:Mycophenolic acid, an immunosuppressive agent, inhibits HBV replication in vitro. 1060 35

A few million years ago, when primates moved from the east African forest to the savannah, they were already infected with endogenous viruses and occultly transmitted them to the prime Homo species. However it was much later with the building of the first large cities in Mesopotamia that interhuman viral transmission began in earnest. Spreading was further enhanced with the organization of the Egyptian, Greek, Roman, and Arab empires around the Mediterranean. Discovery of the New World in 1492 led to an unprecedented clash of civilizations and the destruction of pre-Columbian Indian civilizations. It also led to a rapid spread of viruses across the Atlantic Ocean with the emergence of yellow fever and appearance of smallpox and measles throughout the world. However the greatest opportunities for worldwide viral development have been created by our present, modern civilization. This fact is illustrated by epidemic outbreaks of human immunodeficiency virus, Venezuela hemorrhagic fever, Rift valley fever virus, and monkey pox virus. Close analysis underscores the major role of human intervention in producing these events.
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PMID:[Viruses and civilization]. 1090 42

Despite spectacular progress in the eradication of infectious diseases, malaria and tuberculosis are making a comeback in many parts of the world. After years of decline, plague, diphtheria, dengue, meningococcal meningitis, yellow fever, and cholera have reappeared as public health threats. In the last 20 years [before 1997] more than 30 new and highly infectious diseases have been identified, including Ebola-type hemorrhagic fever, HIV/AIDs, and hepatitis C. Antibiotic resistance has also emerged during this period, and fewer new antibiotics are being produced because of high development costs and licensing. Drugs no longer offer protection or cure for many infectious diseases, and consequently more people need hospitalization with higher treatment costs. The causes of the appearance of new diseases and the resurgence of old ones include the rapid increase in international travel, the growth of mega-cities with high population densities, inadequate safe water and sanitation, food-borne diseases by the globalization of trade, and human penetration into remote animal and insect habitats. Meanwhile, resources for public health are being reduced, with the result that either the appearance of new diseases or resistance to drugs go unnoticed. A recent example is the human immunodeficiency virus, which went unrecognized until a large number of people got infected. For this very reason the 1997 World Health Day featured the theme of emerging infectious diseases and global response. Such forums are held to help countries rebuild the foundations of disease surveillance and control, while the public and private sectors may be encouraged to develop better techniques for surveillance to confront a common global threat.
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PMID:Emerging infectious disease: global response, global alert. 1234 2

This report updates CDC's recommendations for using yellow fever vaccine (CDC. Yellow Fever Vaccine: Recommendations of the Advisory Committee on Immunizations Practices: MMWR 1990;39[No. RR-6]1-6). The 2002 recommendations include new or updated information regarding 1) reports of yellow fever vaccine-associated viscerotropic disease (previously reported as febrile multiple organ system failure); 2) use ofyellow fever vaccine for pregnant women and persons infected with human immunodeficiency virus (HIV); and 3) concurrent use of yellow fever vaccine with other vaccines. A link to this report and other information related to yellow fever can be accessed at the website for Travelers' Health, Division of Global Migration and Quarantine, National Center for Infectious Diseases, CDC, at http://www.cdc.gov/travel/index.htm, and through the website for the Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, CDC, at http://www.cdc.gov/ncidod/ dvbid/yellowfever/index.htm.
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PMID:Yellow fever vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2002. 1243 92

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