Mycobacterium tuberculosis(M.tb) and human immunodeficiency virus(HIV) co-infection has become a public health issue worldwide. Up to now, there have been many unresolved issues either in the clinical diagnosis and tr...Mycobacterium tuberculosis(M.tb) and human immunodeficiency virus(HIV) co-infection has become a public health issue worldwide. Up to now, there have been many unresolved issues either in the clinical diagnosis and treatment of M.tb/HIV coinfection or in the basic understanding of the mechanisms for the impairments to the immune system by interactions of these two pathogens. One important reason for these unsolved issues is the lack of appropriate animal models for the study of M.tb/HIV coinfection. This paper reviews the recent development of research on the animal models of M.tb/HIV co-infection, with a focus on the non-human primate models.展开更多
Zinc (Zn) deficiencies are currently thought to cause chronic metabolic derangement leading to or exacerbating immune deficiencY, gastrointestinal problems, endocrine disorders, neurologic dysfunction, cancer, accel...Zinc (Zn) deficiencies are currently thought to cause chronic metabolic derangement leading to or exacerbating immune deficiencY, gastrointestinal problems, endocrine disorders, neurologic dysfunction, cancer, accelerated aging, degenerative disease, and more. Zn deficiency caused by malnutrition and foods with low bioavailability, aging, certain diseases, or deregulated homeostasis is a far more common risk to human health than intoxication. Higher dose of Zn should be limited to short-term use because of an increased risk of gastrointestinal adverse effects, copper deficiency, anemia, and genitourinary complications. This review has detonated the literature on the spectrum of health effects of Zn status, ranging from symptoms of Zn deficiency to excess exposure.展开更多
In order to clarify, the mechanism of inhibition of human neutrophil peptide-1 ( HNP-1 ) on hu- man immunodeficiency vires type 1 (HIV-1 ), CD4^ + cells were used as the target cells for acute infection with HIV-...In order to clarify, the mechanism of inhibition of human neutrophil peptide-1 ( HNP-1 ) on hu- man immunodeficiency vires type 1 (HIV-1 ), CD4^ + cells were used as the target cells for acute infection with HIV-1, and experiments were peffomed separately with the interaction of different concentrations of HNP-1 with free vires particles, un-infected and infected CD4^+ cells. The activity of reverse transcriptase (RT) in the supematant of cell cultures of different lots of experiments were then assayed accordingly, and the toxicity effect on human lymphocytic cells MT4 was measured by MTT assay. The experimental results showed that pre-incubation of HNP-1 with the concentrated stock of vires could block the binding of vires to target cells with EC50 of 2.49 μg/ml, while pre-treatment of CD4^+ cells with HNP- 1 prior to inoculation could reduce the ability of cells to bind vires with EC50 of 20.7 μg/ml. In addition, When culturing the infected CD4^+ cells in the continuous presence of various concentrations of HNP-1 added immediately after infection, HNP-1 exhibited modest inhibitory effect on viral replication with reduced RT activities in comparison with those of the control group ( P 〈 0.05 at 100 μg/ml of the highest concentration) . No cytotoxieity effect of HNP-1 was observed as demonstrated by MTT assay. These results indicate that HNP-1 exerts anti-HIV activity by at least two levels: direct inactivation of vires particles and effect on the ability of target cells to bind with viruses. The evaluation of two parameters, inhibitoty effect and the cytotoxicity renders HNP-1 an available candidate for anti-HIV therapeutic agent.展开更多
Abacavir is an effective nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus(HIV) infected patients.Its main side effect is hypersensitivity reaction(HSR).The incidence of the ...Abacavir is an effective nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus(HIV) infected patients.Its main side effect is hypersensitivity reaction(HSR).The incidence of the HSR is associated with ethnicity among patients exposed to abacavir,and retrospective and prospective studies show a significantly increased risk of abacavir-induced HSR in human leukocyte antigen(HLA)-B*57:01-carrying patients.Immunological studies indicated that abacavir interacts specifically with HLA-B*57:01 and changed the binding specificity between the HLA molecule and the HLA-presented endogenous peptide repertoire,leading to a systemic autoimmune reaction.HLA-B*57:01 screening,combined with patch testing,had clinically predictive value and cost-effective impact in reducing the incidence of abacavir-induced HSR regardless of the HLA-B*57:01 prevalence in the population.Therefore,the US Food and Drug Administration(FDA) and international HIV treatment guidelines recommend a routine HLA-B*57:01 screening prior to abacavir treatment to decrease false positive diagnosis and prevent abacavir-induced HSR.The studies of abacavir-induced HSR and the implementation of the HLA-B*57:01 screening in the clinic represent a successful example of the use of pharmacogenetics for personalized diagnosis and therapy.展开更多
基金supported by grants from the National Natural Sciences Foundation of China(81201261,81301428)the National Science Foundation for Post-doctoral Scientists of China(2013M5317456)the National Science and Technology Major Project of the Ministry of Science and Technology of China(2012ZX10004501-001-004)
文摘Mycobacterium tuberculosis(M.tb) and human immunodeficiency virus(HIV) co-infection has become a public health issue worldwide. Up to now, there have been many unresolved issues either in the clinical diagnosis and treatment of M.tb/HIV coinfection or in the basic understanding of the mechanisms for the impairments to the immune system by interactions of these two pathogens. One important reason for these unsolved issues is the lack of appropriate animal models for the study of M.tb/HIV coinfection. This paper reviews the recent development of research on the animal models of M.tb/HIV co-infection, with a focus on the non-human primate models.
文摘Zinc (Zn) deficiencies are currently thought to cause chronic metabolic derangement leading to or exacerbating immune deficiencY, gastrointestinal problems, endocrine disorders, neurologic dysfunction, cancer, accelerated aging, degenerative disease, and more. Zn deficiency caused by malnutrition and foods with low bioavailability, aging, certain diseases, or deregulated homeostasis is a far more common risk to human health than intoxication. Higher dose of Zn should be limited to short-term use because of an increased risk of gastrointestinal adverse effects, copper deficiency, anemia, and genitourinary complications. This review has detonated the literature on the spectrum of health effects of Zn status, ranging from symptoms of Zn deficiency to excess exposure.
文摘In order to clarify, the mechanism of inhibition of human neutrophil peptide-1 ( HNP-1 ) on hu- man immunodeficiency vires type 1 (HIV-1 ), CD4^ + cells were used as the target cells for acute infection with HIV-1, and experiments were peffomed separately with the interaction of different concentrations of HNP-1 with free vires particles, un-infected and infected CD4^+ cells. The activity of reverse transcriptase (RT) in the supematant of cell cultures of different lots of experiments were then assayed accordingly, and the toxicity effect on human lymphocytic cells MT4 was measured by MTT assay. The experimental results showed that pre-incubation of HNP-1 with the concentrated stock of vires could block the binding of vires to target cells with EC50 of 2.49 μg/ml, while pre-treatment of CD4^+ cells with HNP- 1 prior to inoculation could reduce the ability of cells to bind vires with EC50 of 20.7 μg/ml. In addition, When culturing the infected CD4^+ cells in the continuous presence of various concentrations of HNP-1 added immediately after infection, HNP-1 exhibited modest inhibitory effect on viral replication with reduced RT activities in comparison with those of the control group ( P 〈 0.05 at 100 μg/ml of the highest concentration) . No cytotoxieity effect of HNP-1 was observed as demonstrated by MTT assay. These results indicate that HNP-1 exerts anti-HIV activity by at least two levels: direct inactivation of vires particles and effect on the ability of target cells to bind with viruses. The evaluation of two parameters, inhibitoty effect and the cytotoxicity renders HNP-1 an available candidate for anti-HIV therapeutic agent.
文摘Abacavir is an effective nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus(HIV) infected patients.Its main side effect is hypersensitivity reaction(HSR).The incidence of the HSR is associated with ethnicity among patients exposed to abacavir,and retrospective and prospective studies show a significantly increased risk of abacavir-induced HSR in human leukocyte antigen(HLA)-B*57:01-carrying patients.Immunological studies indicated that abacavir interacts specifically with HLA-B*57:01 and changed the binding specificity between the HLA molecule and the HLA-presented endogenous peptide repertoire,leading to a systemic autoimmune reaction.HLA-B*57:01 screening,combined with patch testing,had clinically predictive value and cost-effective impact in reducing the incidence of abacavir-induced HSR regardless of the HLA-B*57:01 prevalence in the population.Therefore,the US Food and Drug Administration(FDA) and international HIV treatment guidelines recommend a routine HLA-B*57:01 screening prior to abacavir treatment to decrease false positive diagnosis and prevent abacavir-induced HSR.The studies of abacavir-induced HSR and the implementation of the HLA-B*57:01 screening in the clinic represent a successful example of the use of pharmacogenetics for personalized diagnosis and therapy.