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2.
Int J Epidemiol ; 44(1): 251-63, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25859596

ABSTRACT

BACKGROUND: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. METHODS: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/ml in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. RESULTS: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/ml was 529/ml [95% confidence interval (CI): 517­541] in North America, 494/ml (95% CI: 429­559) in West Africa, 515/ml (95% CI: 508­522) in Southern Africa, 503/ml (95% CI: 478­528) in Asia and 437/ml (95% CI: 425­449) in East Africa. CONCLUSIONS: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.


Subject(s)
Anti-HIV Agents/immunology , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count/statistics & numerical data , HIV Infections/drug therapy , HIV Infections/immunology , Adult , Africa/epidemiology , Alkynes , Anti-HIV Agents/administration & dosage , Asia/epidemiology , Benzoxazines/immunology , Benzoxazines/therapeutic use , Cyclopropanes , Drug Therapy, Combination , Female , Humans , Male , Nevirapine/immunology , Nevirapine/therapeutic use , North America/epidemiology , RNA, Viral , Virus Replication/drug effects , Virus Replication/immunology
3.
Mol Nutr Food Res ; 59(7): 1324-38, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25600612

ABSTRACT

Benzoxazinoids (BXs) are a group of natural chemical compounds with putative pharmacological and health-protecting properties. BXs were formerly identified in and isolated from selected dicot medicinal plants and young cereal plants. Recently, BXs were found to be present in mature cereal grains and bakery products, such that knowledge about the pharmacological properties of BXs, which until now have unknowingly been consumed through the daily bread and breakfast cereals, has come into new focus. This review discusses published results from in vitro studies and a few human and animal model studies on the health effects and pharmacological responses of various BX compounds. Many of these studies have reported antimicrobial, anticancer, reproductive system stimulatory, central nervous system stimulatory, immunoregulatory, and appetite- and weight-reducing effects of BXs and/or BX derivatives. The health benefits of wholegrain intake may be associated with the solitary and/or overlapping biological effects of fibers, lignans, phenolic acids, alkylresorcinols, BXs, and other bioactive compounds. In the context of BXs as dietary ingredients, further comprehensive investigations are required to understand their biological functions, to elucidate the underlying mechanisms, to explore their potential contribution on the health effects associated with wholegrain consumption, and to examine their potential as functional food ingredients.


Subject(s)
Anti-Infective Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Appetite Depressants/pharmacology , Benzoxazines/pharmacology , Edible Grain/chemistry , Animals , Antineoplastic Agents, Phytogenic/chemistry , Benzoxazines/adverse effects , Benzoxazines/immunology , Humans , Immune System/drug effects , Weight Loss
4.
Curr Opin Plant Biol ; 15(4): 407-14, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22445190

ABSTRACT

In plants, a host's responses to an attempted infection include activation of various secondary metabolite pathways, some of which are specific for particular plant phylogenetic clades. Phytochemicals that represent respective end products in plant immunity have been stereotypically linked to antimicrobial properties. However, in many cases, owing to the lack of unequivocal evidence for direct antibiotic action in planta, alternative functions of secondary metabolites should be considered. Correspondingly, recent findings have identified novel, and rather unexpected, functions of phytochemicals in plant immunity that mediate regulatory pathways for conserved defence responses. It also seems likely that these conserved responses can be regulated by clade-specific phytochemicals.


Subject(s)
Anti-Infective Agents/immunology , Host-Pathogen Interactions/immunology , Plant Immunity/immunology , Plants/immunology , Plants/microbiology , ATP-Binding Cassette Transporters/immunology , Bacteria/immunology , Benzoxazines/immunology , Cell Wall/immunology , Chemical Warfare Agents/metabolism , Fungi/immunology , Glucosinolates/immunology , Indoles/immunology , Isothiocyanates/immunology , Plants/metabolism , Thiazoles/immunology
5.
Plant J ; 68(5): 901-11, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21838747

ABSTRACT

In monocotyledonous plants, 1,4-benzoxazin-3-ones, also referred to as benzoxazinoids or hydroxamic acids, are one of the most important chemical barriers against herbivores. However, knowledge about their behavior after attack, mode of action and potential detoxification by specialized insects remains limited. We chose an innovative analytical approach to understand the role of maize 1,4-benzoxazin-3-ones in plant-insect interactions. By combining unbiased metabolomics screening and simultaneous measurements of living and digested plant tissue, we created a quantitative dynamic map of 1,4-benzoxazin-3-ones at the plant-insect interface. Hypotheses derived from this map were tested by specifically developed in vitro assays using purified 1,4-benzoxazin-3-ones and active extracts from mutant plants lacking 1,4-benzoxazin-3-ones. Our data show that maize plants possess a two-step defensive system that effectively fends off both the generalist Spodoptera littoralis and the specialist Spodoptera frugiperda. In the first step, upon insect attack, large quantities of 2-ß-d-glucopyranosyloxy-4,7-dimethoxy-1,4-benzoxazin-3-one (HDMBOA-Glc) are formed. In the second step, after tissue disruption by the herbivores, highly unstable 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one (HDMBOA) is released by plant-derived ß-glucosidases. HDMBOA acts as a strong deterrent to both S. littoralis and S. frugiperda. Although constitutively produced 1,4-benzoxazin-3-ones such as 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) are detoxified via glycosylation by the insects, no conjugation of HDMBOA in the insect gut was found, which may explain why even the specialist S. frugiperda has not evolved immunity against this plant defense. Taken together, our results show the benefit of using a plant-insect interface approach to elucidate plant defensive processes and unravel a potent resistance mechanism in maize.


Subject(s)
Benzoxazines/metabolism , Glucosides/metabolism , Herbivory/immunology , Spodoptera/immunology , Zea mays/immunology , Zea mays/parasitology , Animals , Benzoxazines/immunology , Benzoxazines/toxicity , Gastrointestinal Tract/immunology , Gastrointestinal Tract/metabolism , Glucosides/immunology , Glucosides/toxicity , Glycosylation , Host-Parasite Interactions , Larva/immunology , Larva/metabolism , Larva/physiology , Principal Component Analysis , Protein Stability , Species Specificity , Spodoptera/metabolism , Spodoptera/physiology , Toxicity Tests , Zea mays/metabolism , Zea mays/toxicity
6.
Mycorrhiza ; 21(8): 721-731, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21484338

ABSTRACT

Arbuscular mycorrhizas are the most important symbioses in terrestrial ecosystems and they enhance the plant defense against numerous soil-borne pathogenic fungi and nematodes. Two corn (Zea mays) varieties, Gaoyou-115 that is susceptible to sheath blight disease caused by Rhizoctonia solani and Yuenong-9 that is resistant, were used for mycorrhizal inoculation in this study. Pre-inoculation of susceptible Gaoyou-115 with arbuscular mycorrhizal fungus (AMF) Glomus mosseae significantly reduced the disease incidence and disease severity of sheath blight of corn. HPLC analysis showed that AMF inoculation led to significant increase in 2,4-dihydroxy-7-methoxy-2 H-1,4-benzoxazin-3(4 H)-one (DIMBOA) accumulation in the roots of both corn varieties and in leaves of resistant Yuenong-9. R. solani inoculation alone did not result in accumulation of DIMBOA in both roots and leaves of the two corn varieties. Our previous study showed that DIMBOA strongly inhibited mycelial growth of R. solani in vitro. Real-time PCR analysis showed that mycorrhizal inoculation itself did not affect the transcripts of most genes tested. However, pre-inoculation with G. mosseae induced strong responses of three defense-related genes PR2a, PAL, and AOS, as well as BX9, one of the key genes in DIMBOA biosynthesis pathway, in the leaves of corn plants of both Yuenong-9 and Gaoyou-115 after the pathogen attack. Induction of defense responses in pre-inoculated plants was much higher and quicker than that in non-inoculated plants upon R. solani infection. These results indicate that induction of accumulation of DIMBOA, an important phytoalexin in corn, and systemic defense responses by AMF, plays a vital role in enhanced disease resistance of mycorrhizal plants of corn against sheath blight. This study also suggests that priming is an important mechanism in mycorrhiza-induced resistance.


Subject(s)
Benzoxazines/immunology , Glomeromycota/growth & development , Mycorrhizae/growth & development , Plant Diseases/immunology , Zea mays/immunology , Disease Resistance , Gene Expression Regulation, Plant , Glomeromycota/genetics , Glomeromycota/isolation & purification , Mycorrhizae/genetics , Mycorrhizae/isolation & purification , Plant Diseases/genetics , Plant Diseases/microbiology , Rhizoctonia/physiology , Zea mays/genetics , Zea mays/microbiology
7.
J Agric Food Chem ; 57(5): 1677-96, 2009 Mar 11.
Article in English | MEDLINE | ID: mdl-19199602

ABSTRACT

Many cereals accumulate hydroxamic acids derived from 2-hydroxy-2H-1,4-benzoxazin-3(4H)-one. These benzoxazinoid hydroxamic acids are involved in defense of maize against various lepidopteran pests, most notably the European corn borer, in defense of cereals against various aphid species, and in allelopathy affecting the growth of weeds associated with rye and wheat crops. The role of benzoxazinoid hydroxamic acids in defense against fungal infection is less clear and seems to depend on the nature of the interactions at the plant-fungus interface. Efficient use of benzoxazinoid hydroxamic acids as resistance factors has been limited by the inability to selectively increase their levels at the plant growth stage and the plant tissues where they are mostly needed for a given pest. Although the biosynthesis of benzoxazinoid hydroxamic acids has been elucidated, the genes and mechanisms controlling their differential expression in different plant tissues and along plant ontogeny remain to be unraveled.


Subject(s)
Benzoxazines/metabolism , Edible Grain/immunology , Hydroxamic Acids/immunology , Plant Diseases/immunology , Animals , Aphids/physiology , Benzoxazines/immunology , Edible Grain/genetics , Edible Grain/metabolism , Edible Grain/parasitology , Gene Expression Regulation, Plant , Hydroxamic Acids/metabolism , Plant Diseases/microbiology , Plant Diseases/parasitology
8.
Lancet Infect Dis ; 7(11): 733-8, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17961859

ABSTRACT

The non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are chemically distinct, but both may cause cutaneous hypersensitivity and hepatotoxicity. We reviewed the literature to assess the evidence for cross-reactivity between nevirapine and efavirenz. All papers, abstracts, or presentations, regardless of study design, that made reference to the response of patients who were switched from one NNRTI to another as a result of an adverse drug reaction were included. Most of the studies were retrospective. Recurrent reactions occurred in 30 (12.6%) of 239 reported patients with rash who were switched from nevirapine to efavirenz, compared with eight (50%) of 16 patients switched from efavirenz to nevirapine. Hepatitis did not recur in either the 11 reported patients switched from nevirapine to efavirenz, or in the single reported patient who was switched from efavirenz to nevirapine. Substituting efavirenz for nevirapine following hepatotoxicity or cutaneous hypersensitivity appears to be reasonable, providing that the adverse reaction to nevirapine was not life-threatening. There is insufficient evidence to recommend substituting nevirapine for efavirenz following either hepatotoxicity or cutaneous hypersensitivity.


Subject(s)
Benzoxazines/therapeutic use , HIV Infections/drug therapy , Nevirapine/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , Alkynes , Benzoxazines/adverse effects , Benzoxazines/immunology , Chemical and Drug Induced Liver Injury/etiology , Cross Reactions , Cyclopropanes , Drug Eruptions/etiology , Humans , Nevirapine/adverse effects , Nevirapine/immunology , Reverse Transcriptase Inhibitors/adverse effects , Reverse Transcriptase Inhibitors/immunology
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