Gene/Protein Disease Symptom Drug Enzyme Compound
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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.
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PMID:Synergistic fungistatic effects of lactoferrin in combination with antifungal drugs against clinical Candida isolates. 1054 40

A variety of milk proteins including lactoferrin, angiogenin-1, alpha-lactalbumin, beta-lactoglobulin, lactoperoxidase, casein and the novel whey proteins lactogenin and glycolactin were tested for inhibitory activity toward human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT), alpha-glucosidase, beta-glucosidase and beta-glucuronidase. Lactoferrin exerted the most potent inhibitory action with an IC50 of about 6 microM. Lactoperoxidase, lactogenin, angiogenin-1 and glycolactin inhibited HIV-1 RT activity with decreasing potencies. Beta-lactoglobulin, alpha-lactalbumin and casein displayed little or no inhibitory effect. Succinylation with succinic anhydride augmented the inhibitory effect of glycolactin, beta-lactoglobulin, alpha-lactalbumin, casein and human lactoferrin. The inhibitory effect of the various milk proteins on the activities of alpha-glucosidase, beta-glucosidase and beta-glucuronidase was meager. Succinylation tended to increase the alpha-glucosidase-inhibitory effect of milk proteins but neither their beta-glucosidase-inhibitory nor beta-glucuronidase-inhibitory effect was affected.
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PMID:First demonstration of an inhibitory activity of milk proteins against human immunodeficiency virus-1 reverse transcriptase and the effect of succinylation. 1110 90

Mastitis, an inflammation in the breast, has recently been linked with higher human immunodeficiency virus (HIV) load in breast milk and higher risk of mother-to-child transmission of HIV. Among 334 HIV-infected women in Malawi who were breastfeeding, the prevalence of mastitis, as indicated by elevated breast milk sodium, was 16.4% at six weeks and 2.8% at six months postpartum. Mastitis is associated with significantly higher concentrations of immunological and inflammatory mediators in breast milk, including lactoferrin, lysozyme, secretory leukocyte protease inhibitor, interleukin-8, and RANTES. Mastitis is potentially preventable by improving micronutrient status of breastfeeding women and can be treated with antibiotics and clinical management. These studies in Malawi suggest that mastitis may contribute to transmission of HIV through breast milk.
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PMID:Mastitis and transmission of human immunodeficiency virus through breast milk. 1113 99

A variety of innate defense factors in saliva such as lysozyme and lactoferrin contribute to mucosal protection and modulate Candida populations in the oral cavity. It is also known that in human immunodeficiency virus (HIV)-infected individuals significant variations in the concentrations of lysozyme and lactoferrin in saliva occur during disease progression. Therefore, the aim of this study was to determine the in vitro susceptibility to human lactoferrin and hen egg white lysozyme of genotypically similar oral Candida albicans isolates obtained from six HIV-infected ethnic Chinese during sequential visits over a 12-month period. The similarity of the genotypes (50 in total) was evaluated using a randomly amplified polymorphic DNA assay. A blastospore viability assay was performed to evaluate the sensitivity of the organisms to lysozyme and lactoferrin. Exposure to physiological concentrations of either lysozyme (30 microg/ml) or lactoferrin (20 microg/ml) caused a rapid loss of viability among all isolates to a varying extent. None of the sequential C. albicans isolates demonstrated significant differences in sensitivity to either protein from one visit to the next; similar results were noted when the different genotypes from the same individual were compared. On Spearman correlation analysis of two genotypes that were sequentially isolated from a single patient, a significant negative correlation between lysozyme (r = -0.88; P < 0.02) (but not lactoferrin) resistance and the duration of HIV disease was seen. These results imply that a minority of C. albicans isolates that persist intraorally in individuals with HIV disease develop progressive resistance to innate salivary antifungal defenses such as lysozyme, possibly as an adaptive response. However, the vast majority of the Candida isolates appear to succumb to these nonspecific host immune mediators abundantly present in the oral environment.
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PMID:Antifungal effects of lysozyme and lactoferrin against genetically similar, sequential Candida albicans isolates from a human immunodeficiency virus-infected southern Chinese cohort. 1152 66

Different proteins have been isolated from bovine milk including lactoferrin, lactoperoxidase, glycolactin, angiogenin-1, lactogenin, alpha-lactalbumin, lactoglobulin and casein. These proteins have been assayed for inhibitory activity against human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, protease and integrase, enzymes crucial to the HIV-1 life cycle. It was found that different milk proteins inhibited the three aforementioned HIV enzymes to different extents. Lactoferrin strongly inhibited HIV-1 reverse transcriptase but only slightly inhibited HIV-1 protease and integrase. On the other hand, alpha-lactalbumin, beta-lactoglobulin and casein inhibited HIV-1 protease and integrase to an appreciable extent but did not inhibit HIV-1 reverse transcriptase. Glycolactin and angiogenin-1 suppressed the activity of HIV-1 reverse transcriptase by a moderate extent but more powerfully inhibited HIV-1 protease and integrase. In comparison with the other milk proteins glycolactin was a strong inhibitor of HIV-1 protease and integrase and a moderate inhibitor of HIV-1 reverse transcriptase. Lactogenin was a strong inhibitor of HIV-1 integrase, a moderate inhibitor of HIV-1 reverse transcriptase and a weak inhibitor of HIV-1 protease.
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PMID:Inhibition of human immunodeficiency virus type 1 reverse transcriptase, protease and integrase by bovine milk proteins. 1166 64

There is a paradox that profound HIV-induced immunodeficiency is present systemically, whereas the majority of infections associated with HIV disease are present or initiated at mucosal surfaces. There is therefore a need to understand both specific and non-specific mechanisms of mucosal protection against HIV and its copathogens. The majority of HIV infections occur as a result of the passage of virus across mucosal membranes. Resistance to HIV infection at mucosal surfaces may be related to HIV-specific CD8+ T cell responses in some individuals and may be the basis for protective vaccine design. However, T-cells, macrophages and dendritic cells in mucosa may be a portal of entry for HIV. Transcytosis of HIV can occur from the mucosal to the submucosal surface and vice versa, and may be inhibited by mucosal immunoglobulins and neutralizing IgA within epithelial cells. HIV-induced alterations to oral epithelial cells, together with impairment of mucosal CD4+ T-cells and consequent altered cytokine secretion, may contribute to secondary infections. It also appears that HIV infection is associated with decreased salivary IgA levels, although a dichotomy between IgA concentrations in saliva and serum has been reported. Mucosal antibody responses, however, seem to be maintained. Considerable attention has been given to the possibility of mucosal immunization against HIV and there is evidence that secretory IgA antibody is neutralizing to different HIV strains. In addition to specific immune factors, it is likely that innate nonspecific factors may be significant in protecting mucosal surfaces, including lactoferrin, secretory leukocyte protease inhibitor, mucins, proline rich proteins and cystatins. These may be useful candidate virucides in topical preparations. Thus humoral, cellular and innate immune mechanisms, as well as lymphocyte-epithelial interactions, may all be impaired at mucosal surfaces as a result of HIV infection and may contribute to the susceptibility of mucosa to infective processes.
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PMID:Oral mucosal immunity and HIV infection: current status. 1216 61

The aim of this study was to explore lysozyme and lactoferrin concentrations in human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis (OPC). These proteins were measured by time-resolved immunofluorometric assay, validated in Part I of this study, in paired serum and salivary secretions of 30 patients. Eleven HIV-positive patients without OPC, eight HIV-positive patients with OPC and eleven HIV-negative healthy subjects were included in the study. The relative coefficient of excretion of salivary albumin was used to establish protein origin. In serum, the low lactoferrin concentrations in HIV-infected patients with and without OPC (0.610 mg/l (p < 0.05) and 0.896 mg/l (p < 0.01) vs. 1.439 mg/l in healthy subjects) were probably due to a decrease in nonspecific immunity, particularly the polymorphonuclear cells. In HIV-infected patients with OPC, the high salivary lysozyme and lactoferrin concentrations (170.94 mg/l and 66.48 mg/l vs. 23.35 mg/l and 10.20 mg/l in healthy subjects, respectively) and their mean relative coefficient of excretion of above 1 indicated a high local production of lysozyme and lactoferrin in saliva. The development of OPC in HIV-infected patients could be a consequence of inefficient lysozyme and lactoferrin concentrations and of decreased cooperation between innate and adaptative immune systems.
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PMID:New sensitive method for the measurement of lysozyme and lactoferrin to explore mucosal innate immunity. Part II: time-resolved immunofluorometric assay used in HIV patients with oral candidiasis. 1266 97

Milk forms a rich source of biologically interesting components. In particular, its protein fraction is known to encompass many kinds of biological functions. In this review we focus on antibacterial and antiviral properties of milk proteins and milk protein derivatives. The latter include chemically modified proteins and enzymatically induced peptides. If such peptides are released by enzymes present within the digestive tract (e.g. trypsin or pepsin), it is likely that they play a role in the health defense system. This is especially the case when the active fragments can survive the intestinal conditions long enough to arrive at the right place to exert their beneficial function. In the first part of this paper attention is paid to the antibacterial proteins lactoferrin, lactoperoxidase, and lysozyme. Furthermore, antibacterial peptides originating from caseins and whey proteins are described. The second part reports on studies of antiviral effects of milk proteins and derivatives thereof. Special focus is directed to the antiviral action towards the human immunodeficiency virus (HIV) and the human cytomegalovirus (HCMV). Unmodified milk proteins are generally not active against these viruses. An exception is lactoferrin, which shows significant antiviral activity against both HIV and HCMV. Several other milk proteins tested showed strong antiviral effects only after chemical modification, i.e. by making them polyanionic (for anti-HIV activity) or polycationic (for anti-HCMV activity). In a number of cases, conclusions are drawn concerning possible relationships between antibacterial/antiviral activity and molecular structure of the components described.
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PMID:Antibacterial and antiviral effects of milk proteins and derivatives thereof. 1276 35

Lactoferrin (Lf), a multifunctional molecule present in mammalian secretions and blood, plays important roles in host defense and cancer. Indeed, Lf has been reported to inhibit the proliferation of cancerous mammary gland epithelial cells and manifest a potent antiviral activity against human immunodeficiency virus and human cytomegalovirus. The Lf-binding sites on the cell surface appear to be proteoglycans and other as yet undefined protein(s). Here, we isolated a Lf-binding 105 kDa molecular mass protein from cell extracts and identified it as human nucleolin. Medium-affinity interactions ( approximately 240 nm) between Lf and purified nucleolin were further illustrated by surface plasmon resonance assays. The interaction of Lf with the cell surface-expressed nucleolin was then demonstrated through competitive binding studies between Lf and the anti-human immunodeficiency virus pseudopeptide, HB-19, which binds specifically surface-expressed nucleolin independently of proteoglycans. Interestingly, binding competition studies between HB-19 and various Lf derivatives in proteoglycan-deficient hamster cells suggested that the nucleolin-binding site is located in both the N- and C-terminal lobes of Lf, whereas the basic N-terminal region is dispensable. On intact cells, Lf co-localizes with surface nucleolin and together they become internalized through vesicles of the recycling/degradation pathway by an active process. Morever, a small proportion of Lf appears to translocate in the nucleus of cells. Finally, the observations that endocytosis of Lf is inhibited by the HB-19 pseudopeptide, and the lack of Lf endocytosis in proteoglycan-deficient cells despite Lf binding, point out that both nucleolin and proteoglycans are implicated in the mechanism of Lf endocytosis.
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PMID:Surface nucleolin participates in both the binding and endocytosis of lactoferrin in target cells. 1471 98

Milk forms a rich source of biologically interesting components and the protein fraction is known to facilitate many different biological functions. In this manuscript, we review the antiviral properties of the milk protein lactoferrin (LF). In particular, we will describe its antiviral activity against the human immunodeficiency virus type 1 (HIV-1).
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PMID:The antiviral activity of the milk protein lactoferrin against the human immunodeficiency virus type 1. 1522 80


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