The effects of an exogenous emulsifier, glyceryl polyethylene glycol ricinoleate, on performance and carcass traits of broiler chickens were assessed. The emulsifier was added to the diet at dose rates of 0 (control), 1 (E1) and 2 (E2) % of added fat (saturated palm oil). Live weight gain (P < .07) and feed conversion ratio (P < .05) in 39 days were higher in the E1 dietary group. Gain: ME intake and gain: protein intake during the grower phase improved quadratically (P < .05). Gross carcass traits were not affected. Body fat content and fat accretion increased (P < .05) and liver fat content decreased (P < .05) linearly with the level of emulsifier in diet. Fat excretion decreased (P < .001) leading to increased ileal fat digestibility (P < .06) in the E1 group (quadratic response). Metabolizable intake of N (P < .1) and fat (P < .05) increased quadratically due to supplementation of emulsifier in diet. Metabolism of trace elements and serum lipid profiles were not affected. The study revealed that supplementation of exogenous emulsifiers in diets containing moderate quantities of added vegetable fats may substantially improve broiler performance.
Herpes genitalis, caused by HSV-2, is an incurable genital ulcerative disease transmitted by sexual intercourse. The virus establishes life-long latency in sacral root ganglia and reported to have synergistic relationship with HIV-1 transmission. Till date no effective vaccine is available, while the existing therapy frequently yielded drug resistance, toxicity and treatment failure. Thus, there is a pressing need for non-nucleotide antiviral agent from traditional source. Based on ethnomedicinal use we have isolated a compound 7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole (HM) from the traditional herb Ophiorrhiza nicobarica Balkr, and evaluated its efficacy on isolates of HSV-2 in vitro and in vivo. The cytotoxicity (CC50), effective concentrations (EC50) and the mode of action of HM was determined by MTT, plaque reduction, time-of-addition, immunofluorescence (IFA), Western blot, qRT-PCR, EMSA, supershift and co-immunoprecipitation assays; while the in vivo toxicity and efficacy was evaluated in BALB/c mice. The results revealed that HM possesses significant anti-HSV-2 activity with EC50 of 1.1-2.8 µg/ml, and selectivity index of >20. The time kinetics and IFA demonstrated that HM dose dependently inhibited 50-99% of HSV-2 infection at 1.5-5.0 µg/ml at 2-4 h post-infection. Further, HM was unable to inhibit viral attachment or penetration and had no synergistic interaction with acyclovir. Moreover, Western blot and qRT-PCR assays demonstrated that HM suppressed viral IE gene expression, while the EMSA and co-immunoprecipitation studies showed that HM interfered with the recruitment of LSD-1 by HCF-1. The in vivo studies revealed that HM at its virucidal concentration was nontoxic and reduced virus yield in the brain of HSV-2 infected mice in a concentration dependent manner, compared to vaginal tissues. Thus, our results suggest that HM can serve as a prototype to develop non-nucleotide antiviral lead targeting the viral IE transcription for the management of HSV-2 infections.
Acute diarrheal illness and gastroenteritis caused by Campylobacter jejuni infection remain significant public health risks in developing countries with substantial mortality and morbidity in humans, particularly in children under the age of five. Genetic diversities among Campylobacter jejuni and limited understanding of immunological correlations of host protection remain primary impediments for developing an effective measure to controlCampylobacter infection. Moreover, the lack of a reliable in vivo model to mimic natural infection against Campylobacter jejuni has substantially delayed the vaccine-development process. Given the role of bacterial outer membrane associated proteins in intestinal adherence and invasion as well as modulating dynamic interplay between host and pathogens, bacterial outer-membrane vesicles have emerged as a potential vaccine target against a number of gut pathogens, including Campylobacter jejuni. Here, we describe a mucosal vaccine strategy using chitosan-coated outer-membrane vesicles to induce specific immune responses against Campylobacter jejuni in mice. To overcome the challenges of mucosal delivery of outer membrane vesicles in terms of exposure to variable pH and risk of enzymatic degradation, we preferentially used chitosan as a nontoxic, mucoadhesive polymer. We show that intragastric delivery of chitosan-coated outer-membrane vesicles imparts significant immune protection against Campylobacter jejuni with high level local and systemic antibody production. Further, immunization with the outer membrane vesicles resulted in potent cellular responses with an increased CD4 + and CD8 + T cell population. Moreover, significant upregulation of IFN-γ and IL-6 gene expression suggests that mucosal delivery of outer membrane vesicles promotes a Th1/Th2 mixed-type immune response. Together, as an acellular and nonreplicating canonical end product of bacterial secretion, mucosal delivery of outer membrane vesicles may represent a promising platform for developing an effective vaccine against Campylobacter jejuni.
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