Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because of the rising incidence of failures in the treatment of oropharyngeal candidosis in the case of severely immunosuppressed patients (mostly human immunodeficiency virus [HIV]-infected patients), there is need for the development of new, more effective agents and/or compounds that support the activity of the common antifungal agents. Since lactoferrin is one of the nonspecific host defense factors present in saliva that exhibit antifungal activity, we studied the antifungal effects of human, bovine, and iron-depleted lactoferrin in combination with fluconazole, amphotericin B, and 5-fluorocytosine in vitro against clinical isolates of Candida species. Distinct antifungal activities of lactoferrin were observed against clinical isolates of Candida. The MICs generally were determined to be in the range of 0.5 to 100 mg. ml(-1). Interestingly, in the combination experiments we observed pronounced cooperative activity against the growth of Candida by using lactoferrin and the three antifungals tested. Only in a limited concentration range was minor antagonism detected. The use of lactoferrin and fluconazole appeared to be the most successful combination. Significant reductions in the minimal effective concentrations of fluconazole were found when it was combined with a relatively low lactoferrin concentration (1 mg/ml). Such combinations still resulted in complete growth inhibition, while synergy of up to 50% against several Candida species was observed. It is concluded that the combined use of lactoferrin and antifungals against severe infections with Candida is an attractive therapeutic option. Since fluconazole-resistant Candida species have frequently been reported, especially in HIV-infected patients, the addition of lactoferrin to the existing fluconazole therapy could postpone the occurrence of species resistance against fluconazole. Clinical studies to further elucidate the potential utility of this combination therapy have been initiated.
 ...
PMID:Synergistic fungistatic effects of lactoferrin in combination with antifungal drugs against clinical Candida isolates. 1054 40

Humans with advanced human immunodeficiency virus (HIV) infection present some evidence suggestive of iron accumulation. Ferritin concentrations increase with HIV disease progression, and iron accumulates in several tissues. Iron excess may exert negative effects in individuals with HIV. Indeed, iron accumulation seems to be associated with shorter survival, and a number of investigations point to an iron-mediated oxidative stress in subjects with HIV infection. The observations on humans infected with HIV are in part supported by in-vitro findings. Indeed, in-vitro HIV infection is associated with changes in iron metabolism, and an iron-mediated oxidative stress is likely to contribute to viral cytopathogenicity. Furthermore, it is interesting to point out that the interaction between iron and HIV may be reciprocal, since viruses with a life-cycle involving a DNA phase require chelatable iron for optimum replication. This combined evidence suggests that iron metabolism is an important area for virus/host interaction. These observations may be relevant to both laboratory monitoring and clinical treatment of individuals with HIV.
 ...
PMID:Iron metabolism and HIV infection: reciprocal interactions with potentially harmful consequences? 1058 15

We report the results of a cross-sectional study carried out in 1995-96 on anaemia in pregnant women who were attending two antenatal clinics in Bobo-Dioulasso, Burkina Faso, as part of a research programme including a clinical trial of zidovudine (ZDV) in pregnancy (ANRS 049 Clinical Trial). For women infected with human immunodeficiency virus (HIV) in Africa, anaemia is of particular concern when considering the use of ZDV to decrease mother-to-child transmission of HIV. The objectives were to determine the prevalence of and risk factors for maternal anaemia in the study population, and the effect of HIV infection on the severity of maternal anaemia. HIV counselling and testing were offered to all women, and haemograms were determined for those women who consented to serological testing. Haemoglobin (Hb) levels were available for 2308 of the 2667 women who accepted HIV testing. The prevalence of HIV infection was 9.7% (95% confidence interval (CI): 8.6-10.8%). The overall prevalence of anaemia during pregnancy (Hb level < 11 g/dl) was 66% (95% CI: 64-68%). The prevalence of mild (10 g/dl < or = Hb < 11 g/dl), moderate (7 g/dl < or = Hb < 10 g/dl) and severe (Hb < 7 g/dl) anaemia was 30.8%, 33.5% and 1.7%, respectively. The prevalence of anaemia was 78.4% in HIV-infected women versus 64.7% in HIV-seronegative women (P < 0.001). Although the relative risk of HIV-seropositivity increased with the severity of anaemia, no significant association was found between degree of anaemia and HIV serostatus among the study women with anaemia. Logistic regression analysis showed that anaemia was significantly and independently related to HIV infection, advanced gestational age, and low socioeconomic status. This study confirms the high prevalence of anaemia during pregnancy in Burkina Faso. Antenatal care in this population must include iron supplementation. Although HIV-infected women had a higher prevalence of anaemia, severe anaemia was infrequent, possibly because few women were in the advanced stage of HIV disease. A short course regimen of ZDV should be well tolerated in this population.
 ...
PMID:Anaemia during pregnancy in Burkina Faso, west Africa, 1995-96: prevalence and associated factors. DITRAME Study Group. 1061 87

Replication of human immunodeficiency virus type 1 (HIV-1) can be influenced by iron. Hence, decreasing the availability of iron may inhibit HIV-1 replication. Deferoxamine and deferiprone, both forming catalytically inactive iron-chelator complexes, and bleomycin, by use of which iron catalyzes oxidative nucleic acid destruction, were investigated. Expression of p24 antigen in human monocyte-derived macrophages and peripheral blood lymphocytes (PBL) was reduced by all 3 iron chelators. In PBL, p24 reduction was mirrored by a decrease in proliferation after incubation with deferoxamine or deferiprone, suggesting that viral inhibition is closely linked to a decrease in cellular proliferation. In contrast, clinically relevant bleomycin concentrations reduced p24 levels by approximately 50% without affecting proliferation. When deferoxamine and the nucleoside analogue dideoxyinosine were used in combination, they acted synergistically in inhibiting HIV-1 replication. These observations suggest that iron chelators with different mechanisms of action could be of additional benefit in antiretroviral combination therapy.
 ...
PMID:Inhibition of human immunodeficiency virus type 1 replication in human mononuclear blood cells by the iron chelators deferoxamine, deferiprone, and bleomycin. 1066 30

Pseudomonas aeruginosa exotoxin A (PE) is a 67-kDa protein expressed under the selective pressure of a low iron environment. Previous studies using non-toxic PE chimeras containing a viral surface antigen, the V3 loop of MN gp120 from human immunodeficiency virus type 1 (HIV-1), resulted in not only an effective mucosal immunization but also a striking systemic immune response following epithelial application. Presently, we have examined the possibility that such a strong dual immune response was generated by the efficient targeting of critical cells of the immune system. Mice were dosed with 10 microg of toxic PE or a non-toxic mutant of PE (ntPE) by intratracheal instillation. Examination of lung, liver and spleen tissues isolated 4, 8 and 12 h following intratracheal instillation with PE demonstrated specific cell damage in these tissues which was not observed in mice dosed with ntPE. Based upon the location and characteristics of observed responses, the cells targeted by PE appear to be involved in the antigen presentation arm of the immune response. Since ntPE chimeras with inserted peptide antigen epitopes from a wide variety of pathogens are easy to prepare and administer, these results support this approach for mucosal immunization.
 ...
PMID:Epithelial application of Pseudomonas aeruginosa exotoxin A results in a selective targeting to cells in the liver, spleen and lymph node. 1069 89

The objective of this cross-sectional study was to identify risk factors for anemia among human immunodeficiency virus (HIV)-positive pregnant women in Dar es Salaam, Tanzania. Baseline data from 1064 women enrolled in a clinical trial on the effect of vitamin supplementation in HIV infection were examined to identify potential determinants of anemia. The mean hemoglobin (Hb) level was 94 g/L, and the prevalence of severe anemia (Hb < 85 g/L) was 28%; 83% of the women had Hb < 110 g/L. Iron deficiency and infectious disease appeared to be the predominant causes of anemia. Significant independent associations with severe anemia were observed for women with body mass index (BMI) < 19 kg/m(2) compared with women with BMI > 24 kg/m(2) [odds ratio (OR) 3.13, 95% confidence interval (CI): 1. 37-7.14); malaria parasite densities > 1000/mm(3) (OR 2.70, CI: 1. 58-4.61) compared with women with no parasites; eating soil during early pregnancy (OR 2.47, CI: 1.66-3.69); CD4+ cell count < 200/microL compared with CD4+ count > 500/microL (OR 2.70, CI: 1. 42-5.12); and serum retinol levels < 70 micromol/L (OR 2.45, CI: 1. 44-4.17) compared with women with retinol levels > 1.05 micromol/L. The most significant risk factors associated with severe anemia in this population are preventable. Public health recommendations include increasing the effectiveness of iron supplementation and malaria management during pregnancy, and providing health education messages that increase awareness of the potentially adverse nutritional consequences of eating soil during pregnancy.
 ...
PMID:Nutritional factors and infectious disease contribute to anemia among pregnant women with human immunodeficiency virus in Tanzania. 1091 7

A 13-year-old girl with a history of 4 months of perianal skin lesions is described. Physical examination revealed three 0.5 I 1-cm red, swollen, fleshy, skin tags extending from the perianal area to the perineum (Fig. 1). The patient reported intermittent fever, diarrhea, and abdominal pain, and her body weight was below the third percentile for her age. Laboratory studies showed an erythrocyte sedimentation rate of 101 mm/h; hematocrit of 26%; white blood cell count of 9800/mm3; serum iron of 15 mg/L (normal value (NV), 60-160 mg/L); ferritin of 43.4 microg/L (NV, 12-150 microg/L); transferrin of 203 mg/100 mL (NV, 200-400 mg/100 mL); transferrin saturation of 6% (NV, 20-50%); hypoalbuminemia; negative purified protein derivative (PPD), cytomegalovirus (CMV), human immunodeficiency virus (HIV), venereal disease research laboratory (VDRL), and antinuclear antibody tests; and Toxoplasma titers of 1/16, Van de Kamer 1.67 g/day. A barium examination revealed marked irregularity of the descending colon, and a colonoscopy showed uneven areas of mucosal edema and pseudopolyps in the transverse and descending colon, associated with irregular thickening and stenosis. Histopathologically, large intestine and skin lesions consisted of noncaseating epithelioid and giant cell granulomas (Fig. 2). Cultures for acid-fast bacilli and fungi were negative, and under polarized light no foreign bodies were seen. Treatment with metronidazole (250 mg three times a day), prednisone (0.5 mg/kg/day), and acetylsalicylic acid (75 mg/kg/day) was moderately effective. Vitamin, folic acid, and iron supplements were also added.
 ...
PMID:Perianal Crohn's disease. 1097 32

Human herpesvirus 8 (HHV-8) is involved in the pathogenesis of Kaposi's sarcoma, of B-cells lymphomas, and of Castelman's disease. However, the role of this virus is not yet well known. To investigate the relationship between HHV-8 infection and diseases correlated with human immunodeficiency virus (HIV), we studied a cohort of 67 HIV-seropositive subjects, some of them coinfected with HHV-8. An indirect immunofluorescence test was employed to detect the antibodies against this virus. Positive cases were 31 (46.3%); among the 67 patients, 14 were weakly positive, or + (20.9%); 11 were significantly positive, or ++ (16.4%); and 6 were strongly positive, or (8.9%). These last six patients were the most affected by opportunistic infections, and all were affected by neoplastic pathologies. Moreover, the HHV-8 positive subjects showed hematologic and martial alterations more severe than those in the negative subjects. HHV-8 seroprevalence in HIV-seropositive patients of our cohort was higher (46.3%) than in normal population (0-10%). The presence of disseminated Kaposi's sarcoma and other neoplasms associated with high HIV-RNA levels in HHV-8-positive patients, and particularly in those with strong positivity, corroborates the hypothesis that the virus is correlated with the progression of HIV infection and with its related diseases, especially those that are neoplastic. Last, the severe alterations of iron metabolism found in the patients coinfected with HHV-8 and the negative effect of this virus on the lymphocytic populations can contribute to the unfavorable evolution of HIV infection and also might facilitate tumor development.
 ...
PMID:Human herpesvirus 8 and associated diseases in a group of 67 human immunodeficiency virus-seropositive individuals. 1097 88

The antimicrobial activities of chloroquine (CQ) and several 4-aminoquinoline drugs were tested against Penicillium marneffei, an opportunistic fungus that invades and grows inside macrophages and causes disseminated infection in AIDS patients. Human THP1 and mouse J774 macrophages were infected in vitro with P. marneffei conidia and treated with different doses of drugs for 24 to 48 h followed by cell lysis and the counting of P. marneffei CFU. CQ and amodiaquine exerted a dose-dependent inhibition of fungal growth, whereas quinine and artemisinin were fungistatic and not fungicidal. The antifungal activity of CQ was not due to an impairment of fungal iron acquisition in that it was not reversed by the addition of iron nitrilotriacetate, FeCl3, or iron ammonium citrate. Perl's staining indicated that CQ did not alter the ability of J774 cells to acquire iron from the medium. Most likely, CQ's antifungal activity is due to an increase in the intravacuolar pH and a disruption of pH-dependent metabolic processes. Indeed, we demonstrate that (i) bafilomycin A1 and ammonium chloride, two agents known to alkalinize intracellular vesicles by different mechanisms, were inhibitory as well and (ii) a newly synthesized 4-amino-7-chloroquinoline molecule (compound 9), lacking the terminal amino side chain of CQ that assists in drug accumulation, did not inhibit P. marneffei growth. These results suggest that CQ has a potential for use in prophylaxis of P. marneffei infections in human immunodeficiency virus-infected patients in countries where P. marneffei is endemic.
 ...
PMID:Inhibition of intramacrophage growth of Penicillium marneffei by 4-aminoquinolines. 1130 9

The relationships among hemoglobin, ferritin, and transferrin receptor levels and 2 markers of human immunodeficiency virus (HIV) disease severity--HIV load and CD4(+) lymphocyte count--were characterized among 483 pregnant women in Malawi, Africa. The only significant correlation was an inverse correlation between hemoglobin level and plasma HIV load (r=-.104; P<.03). The prevalence of iron deficiency anemia was not significantly different across quartiles of HIV load or CD4(+) lymphocyte count. In contrast to previous studies, these data suggest that iron status is not related to markers of HIV disease severity in pregnant women in Africa.
 ...
PMID:Iron status and indicators of human immunodeficiency virus disease severity among pregnant women in Malawi. 1171 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>