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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two novel alkaloids, named manadomanzamines A (1) and B (2), were isolated from an Indonesian sponge Acanthostrongylophora sp. (Haplosclerida: Petrosiidae). Their structures were elucidated and shown to be a novel organic skeleton related to the manzamine type alkaloids. Their absolute configuration and conformation were determined by CD, NOESY, and molecular modeling analysis. The microbial community analysis for the sponge that produces these unprecedented alkaloids has also been completed. Manadomanzamines A (1) and B (2) exhibited strong activity against Mycobacterium tuberculosis (Mtb) with MIC values of 1.9 and 1.5 mug/mL, respectively. Manadomanzamines A and B also exhibit activities against human immunodeficiency virus (HIV-1) and AIDS opportunistic fungal infections.
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PMID:Manadomanzamines A and B: a novel alkaloid ring system with potent activity against mycobacteria and HIV-1. 1458 33

A study of oropharyngeal candidiasis (OPC) in Indian human immunodeficiency virus (HIV)/AIDS patients was conducted over a period of 15 months. This study revealed that 75% of the HIV/AIDS patients had OPC. MIC testing revealed that 5% of the Candida isolates were fluconazole resistant. A correlation between CD4(+)-T-cell counts and development of OPC in HIV/AIDS patients was also observed. Molecular typing of C. albicans isolates showed that all were genetically unrelated.
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PMID:Susceptibility pattern and molecular type of species-specific Candida in oropharyngeal lesions of Indian human immunodeficiency virus-positive patients. 1500 88

DEVELOPEMENT OF MAC LUNG DISEASE: An increase of nodular bronchiectatic type of MAC lung disease becomes a problem among respiratory physician today. The reason is still unknown, but it seems to be globally recognized that this type of MAC disease is developing particularly in middle-aged woman. Some papers mentioned the existence of such type of MAC lung disease already early in the 70s, in Japan. Yamamoto described that 17 cases of middle lobe type lung disease out of 154 non-photochoromogen cases, and 76.5% were female, in 1970. Shimoide also pointed such type of 39 cases out of 240 MAC lung disease and 84.6% were female, in 1980. Prince reported MAC lung disease seen in old and middle age female of 21 cases including lethality example of 4 cases without a precedent disease in 1989. After his report, the international consensus of this peculiar type of MAC lung disease seems to be spread. In 1989, we compared 72 cases of nodular bronchiectatic type of MAC lung disease and 56 cases of diffuse panbronchiolitis (DPB) that was a most typical chronic airway disease at that time in Japan. The average age of disease onset of DPB group was 37.0 +/- 16.3 years old and that of MAC group was 54.5 +/- 16.3 years old. The percentage of female was 32% in DPB group and 87.5% in MAC group. It was highly possible that two groups belong different parent population. We could grasp that nodular bronchiectatic type of MAC lung disease patients is a unique group. We observed the serial films of 21 cases of nodular bronchiectatic MAC lung disease, and divide the progression of the disease to sequential 7 steps as Fig. 1. Small nodules progress to cavities in mean about 10 years. However, why is MAC which is opportunistic pathogen with weak virulence, able to form a lesion at unimpaired lung parenchyma? Is there really normal site? Why dose it start from lingula? Why is MAC seen a lot in woman? While it is extremely pathognomonic clinical picture, and, is an extremely interesting problem, most are still unidentified. STUDY OF MAC LUNG DISEASE TREATMENT: It was known that Mycobacterium kansasii lung disease is healed with a chemotherapy like analog of anti-tuberculosis chemotherapy, already in those days. However, the results of MAC lung disease chemotherapy were extremely poor. We tried to express a physicians experience quantitatively as follows, in 1987. The results of 8 weeks sputum culture on Ogawa egg medium were converted semi-quantitatively to CFU numbers based on "Japanese standard guideline of Mycobacterium tuberculosis inspection". We exhibit the ratio of post-treatment consecutive 6 months culture yield to pre-treatment culture yield as response rate, about 110 pulmonary MAC cases. Through this study, we clarify the followings. The results of chemotherapy do not correlate susceptibility test for Mycobacterium tuberculosis. Multidrug regimen is more useful. Small extent of lesion is more responsive. Combination with aminoglycoside chemotherapy is more effective. These conclusions were almost same as the ATS guideline of 1990. New drugs such as, new macrolides and new quinolones appeared for pulmonary MAC treatment through the feedback from systemic MAC complicated AIDS treatments from the latter half of 90's. We measured the sensitive strain ratio at 2 mcg/ml of OFLX, CPFX, LVFX about 990 clinical isolates and could expect availability for M. kansasii or M. fortuitum, but these new quinolones are not enough effective for MAC. Also we examined MIC for various antimycobacterial agent by 50 MAC clinical isolates, and we could expect a certain availability of SPFX, GFLX, CPFX, CAM for MAC. The availability of clarithromycin (CAM) has been established through many randomized clinical trials for disseminated MAC complicated AIDS, but for pulmonary MAC, complete cure is still difficult if we use CAM including regimen. We performed surgical treatment for relatively young patients with localized lesions. We carry out the adaptation reference such as Table, now. The localization of the lesions become a problem at surgical resection. Through the study of our 55 surgical treatment cases, 8 cases (67%) relapsed out of 12 cases which had destructive airway structure in unresected lung field. On the other, only 1 case relapsed (10%) relapsed out of 10 cases without airway destruction in unresected lung. Therefore, even if there is a little dispersal focus without airway destruction in the other pulmonary lobe except purpose focus of resection, it seems that control is possible by post operational chemotherapy. LONG SURVIVAL: As overall consequence, we calculate the survival curves of 201 pulmonary MAC patients visited Tokyo National Hospital from 1953. The survival medium value was 7332 days. The prognosis of nodular bronchiectatic type was better than that of post-tuberculosis type. Extent of disease measured by chest X-ray examination at the time of first visit may be a most affecting factor to the survival rate.
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PMID:[Clinical study on development of nontuberculous mycobacterial lung disease]. 1578 19

A series of nevirapine derivatives has been synthesized in an effort to enhance the spectrum of chemotherapeutic properties for the effective treatment of AIDS and AIDS-related opportunistic infections. The nevirapine derivative bearing isoniazid moiety (3a) was found to be the most potent compound with EC50 of<0.0636 microM, CC50 of>1000 microM and selectivity index of>15,723 which also exhibited 90% inhibition against Mycobacterium tuberculosis at 6.25 microg/ml. Compound 3c showed 100% inhibition against M. tuberculosis and also exhibited potent antibacterial activity against 24 pathogenic bacteria with MIC less than 1 microg/ml.
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PMID:Nevirapine derivatives with broad-spectrum chemotherapeutic properties for the effective treatment of HIV/AIDS. 1614 Apr 95

HIV is the most significant risk factor for many opportunistic infections like tuberculosis. In this study, we designed an isatinimino lead compound as a novel non-nucleoside reverse transcriptase inhibitor with antimycobacterial properties for the effective treatment of AIDS and AIDS-related tuberculosis. Among the compounds sythesized, 1-cyclopropyl-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-7[[N4-[3'-[(4,6-dimethylpyrimidin-2-yl)benzenesulfonamido-4-yl]imino-1'-(5-fluoroisatinyl)]methyl]-3-methyl N1-piperazinyl]-3-quinoline carboxylic acid (9) emerged as the most potent broad-spectrum chemotherapeutic agent active against HIV (EC50: 12.1 microg/ml), and Mycobacterium tuberculosis (MIC: 1.22 microg/ml).
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PMID:Synthesis, anti-HIV and antitubercular activities of isatin derivatives. 1664 36

HIV is the most significant risk factor for many opportunistic infections like tuberculosis, bacterial infections etc. In this paper, we designed aminopyrimidinimino isatin lead compound as a novel non-nucleoside reverse transcriptase inhibitor with broad-spectrum chemotherapeutic properties for the effective treatment of AIDS and AIDS-related opportunistic infections. Compound 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7[[N(4)-[3'-(4'-amino-5'-chloroben-zylpyrimidin-2'-yl)imino-1'-(5-methylisatinyl)] methyl]N(1)-piperazinyl]-3-quinoline carboxylic acid (10) emerged as the most potent broad-spectrum chemotherapeutic agent active against HIV-1 replication (EC(50): 9.4 microg /ml), M. tuberculosis (MIC: 3.13 microg /ml) and various pathogenic bacteria (MIC's: 1.22 microg /ml).
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PMID:Aminopyrimidinimino isatin analogues: design and synthesis of novel non- nucleoside HIV-1 reverse transcriptase inhibitors with broad-spectrum anti-microbial properties. 1678 23

Cryptococcus neoformans is a common cause of meningoencephalitis among AIDS patients. Several C. neoformans virulence factors have been identified, but the relative importance of particular factors is unknown. This study examined the correlation of the virulence of 18 C. neoformans var. grubii isolates from AIDS patients with the expression of several well-described virulence factors. The LD50 at 15 days after intracranial inoculation of ICR mice was <100 c.f.u. for 22 % of isolates, 100-1000 for 28 %, 1000-10,000 for 11 % and >20,000 for 39 %. Higher cryptococcal concentrations in brains were noted for isolates with lower LD50 (P = 0.002). In survival studies, no immunocompetent BALB/c mice (nu/-) infected with 3 x LD50 of three virulent isolates (LD50 = 62, 99, 1280) survived beyond 23 days, whereas 100 %, 90 % and 90 % of mice infected with 20,000 c.f.u. of three hypovirulent isolates (LD50 > 20,000) survived for 60 days (P < 0.0001). Even among BALB/c nude (nu/nu) mice, survival rates over 60 days were 100 %, 70 % and 50 %, respectively, for the hypovirulent isolates. Growth rate at 37 degrees C and capsule size within brains correlated with LD50 by univariate (P = 0.0001 and 0.028, respectively) and multivariate (P = 0.017 and 0.016, respectively) analyses. There was no correlation between LD50 and capsule size in vitro, phospholipase activity, melanin formation, proteinase activity and fluconazole MIC. In conclusion, AIDS patients are susceptible to infection by C. neoformans isolates of wide-ranging virulence, including isolates that are markedly hypovirulent. The virulence of a given isolate reflects a composite of factors rather than the contribution of a dominant factor. Growth at 37 degrees C and capsule size in vivo make particularly important contributions.
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PMID:Cryptococcus neoformans var. grubii isolates recovered from persons with AIDS demonstrate a wide range of virulence during murine meningoencephalitis that correlates with the expression of certain virulence factors. 1684 91

As part of an investigation to generate optimized drug leads from marine natural pharmacophores for the treatment of neoplastic and infectious diseases, a series of novel isoaaptamine analogs were prepared by coupling acyl halides to the C9 position of isoaaptamine (2) isolated from the Aaptos sponge. This library of new semisynthetic products was evaluated for biological activity against HIV-1, Mtb, AIDS-OI, tropical parasitic diseases, and cancer. Compound 4 showed potent activity against HIV-1 (EC(50) 0.47microg/mL), compound 19 proved to possess remarkable activity against Mycobacterium intracellulare with an IC(50) and MIC value of 0.15 and 0.31microg/mL, while compounds 4 and 17 possessed anti-leishmanial activity with IC(50) values of 0.1 and 0.4microg/mL, respectively. Compounds 16 and 17 showed antimalarial activity with EC(50) values of 230 and 240ng/mL, respectively, and compound 14 exhibited an EC(50) of 0.05microM against the Leukemia cell line K-562.
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PMID:Modification at the C9 position of the marine natural product isoaaptamine and the impact on HIV-1, mycobacterial, and tumor cell activity. 1704 80

MIC molecules are stress-inducible ligands of the activating receptor NKG2D, which is expressed on natural killer cells and subsets of T lymphocytes. In rhesus macaques (Macaca mulatta), three different MIC sequences (MIC1, MIC2, MIC3) have been described that are closely related to but, according to phylogenetic analysis, do not represent orthologues of the human MICA and MICB genes. Although a single haplotype of the rhesus macaque Mhc (Mamu) has been completely sequenced, it remained unknown so far whether these three sequences are derived from two or three Mamu-MIC genes. We genotyped a cohort of 115 rhesus macaque individuals for the presence of MIC1, MIC2, and MIC3 sequences and analysed the segregation in families. All individuals were positive for MIC2, whereas only 66.1 and 80.9 % were positive for MIC1 and MIC3, respectively. MIC1 and MIC3 sequences segregated in offspring, indicating that they behave as alleles. Thus, we conclude that two MIC genes are present in the rhesus macaque Mhc, which we propose to designate as Mamu-MICA (MIC1 and MIC3) and Mamu-MICB (MIC2). "MIC1" and "MIC3" are regarded as divergent allelic lineages of the Mamu-MICA gene. Mamu-MIC genotyping of DNA of a cohort of 68 experimentally simian immunodeficiency virus (SIV)-infected rhesus macaques revealed no significant association of either of the two Mamu-MICA allelic lineages with differences in progression to AIDS-like symptoms.
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PMID:Genotyping and segregation analyses indicate the presence of only two functional MIC genes in rhesus macaques. 1721 37

Infection caused by Mycobacterium avium complex (MAC) is common in patients with immunosuppression, such as AIDS, and deficiencies of gamma interferon and interleukin-12, as well as patients with chronic lung diseases. Treatment of MAC disease is limited since few drugs show in vivo activity. We tested a new bridged bicyclic macrolide, EDP-420, against MAC in vitro and in beige mice. EDP-420 was inhibitory in vitro at a concentration ranging from 2 to 8 microg/ml (MIC(50) of 4 microg/ml and MIC(90) of 8 microg/ml). In macrophages, EDP-420 was inhibitory at 0.5 microg/ml, suggesting that the drug concentrates intracellularly. Mice infected with macrolide-susceptible MAC strain 101 were given 100 mg of EDP-420/kg of body weight daily for 4 weeks and showed a significant reduction in the number of bacteria in both liver and spleen which was greater than the reduction observed with clarithromycin treatment at the same dose (P < 0.05). However, macrolide-resistant MAC 101 did not respond to EDP-420 treatment. A combination of EDP-420 with mefloquine was shown to be indifferent; mefloquine alone was active against macrolide-resistant MAC. The frequency of resistance to EDP-420 in MAC 101 was 10(-9), which is significantly less than the emergence of resistance to clarithromycin, approximately 10(-7) (P < 0.05). Further evaluation of EDP-420 in the treatment of MAC disease is warranted.
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PMID:EDP-420, a bicyclolide (bridged bicyclic macrolide), is active against Mycobacterium avium. 1729 42


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