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111.
Akhirunnesa Mily Rokeya Sultana Rekha S. M. Mostafa Kamal Abu Saleh Mohammad Arifuzzaman Zeaur Rahim Lamia Khan Md. Ahsanul Haq Khaliqu Zaman Peter Bergman Susanna Brighenti Gudmundur H. Gudmundsson Birgitta Agerberth Rubhana Raqib 《PloS one》2015,10(9)
Background
Development of new tuberculosis (TB) drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D3 (vitD3) and 4-phenyl butyrate (PBA) are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects.Objective
To examine if oral adjunctive therapy with 5,000IU vitD3 or 2x500 mg PBA or PBA+vitD3 to standard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients.Methods
Adult TB patients (n = 288) were enrolled in a randomized, double-blind, placebo-controlled trial conducted in Bangladesh. Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8. Clinical assessments and sputum smear microscopy were performed weekly up to week 4, fortnightly up to week 12 and at week 24; TB culture was performed at week 0, 4 and 8; concentrations of LL-37 in cells, 25-hydroxyvitamin D3 (25(OH)D3) in plasma and ex vivo bactericidal function of monocyte-derived macrophages (MDM) were determined at week 0, 4, 8, 12 and additionally at week 24 for plasma 25(OH)D3.Results
At week 4, 71% (46/65) of the patients in the PBA+vitD3-group (p = 0.001) and 61.3% (38/62) in the vitD3-group (p = 0.032) were culture negative compared to 42.2% (27/64) in the placebo-group. The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD3-group (p = 0.001) and 2.2 times higher in vitD3-group (p = 0.032) compared to placebo. The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 (p = 0.034). Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo (log rank 11.38, p = 0.01).Conclusion
Adjunct therapy with PBA+vitD3 or vitD3 or PBA to standard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host-directed-therapy in the treatment of TB.Trial Registration
clinicaltrials.gov NCT01580007 相似文献112.
Ahmed Kamal Dyab Lamia Ahmed Galal Abeer El-Sayed Mahmoud Yasser Mokhtar 《The Korean journal of parasitology》2015,53(1):77-83
Wuchereria bancrofti, Dirofilaria immitis, and Dirofilaria repens are filarial nematodes transmitted by mosquitoes belonging to Culex, Aedes, and Anopheles genera. Screening by vector dissection is a tiresome technique. We aimed to screen filarial parasites in their vectors by single and multiplex PCR and evaluate the usefulness of multiplex PCR as a rapid xenomonitoring and simultaneous differentiation tool, in area where 3 filarial parasites are coexisting. Female mosquitoes were collected from 7 localities in Assiut Governorate, were microscopically identified and divided into pools according to their species and collection site. Detection of W. bancrofti, D. immitis, and D. repens using single PCR was reached followed by multiplex PCR. Usefulness of multiplex PCR was evaluated by testing mosquito pools to know which genera and species are used by filarial parasites as a vector. An overall estimated rate of infection (ERI) in mosquitoes was 0.6%; the highest was Culex spp. (0.47%). W. bancrofti, D. immitis, and D. repens could be simultaneously and differentially detected in infected vectors by using multiplex PCR. Out of 100 mosquito pools, 8 were positive for W. bancrofti (ERI of 0.33%) and 3 pools each were positive for D. immitis and D. repens (ERI 0.12%). The technique showed 100% sensitivity and 98% specificity. El-Nikhila, El-Matiaa villages, and Sahel Seleem district in Assiut Governorate, Egypt are still endemic foci for filarial parasites. Multiplex PCR offers a reliable procedure for molecular xenomonitoring of filariasis within their respective vectors in endemic areas. Therefore, it is recommended for evaluation of mosquito infection after lymphatic filariasis eradication programs. 相似文献
113.
Cruz-Garcia L Sánchez-Gurmaches J Bouraoui L Saera-Vila A Pérez-Sánchez J Gutiérrez J Navarro I 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2011,158(4):391-399
The effects of fish oil (FO) substitution by 66% vegetable oils in a diet with already 75% vegetable protein (66VO) on adipose tissue lipid metabolism of gilthead sea bream were analysed after a 14-month feeding trial. In the last 3 months of the experiment, a FO diet was administrated to a 66VO group (group 66VO/FO) as a finishing diet. Hormone-sensitive lipase (HSL) activity was measured in adipose tissue and adipocyte size, and HSL, lipoprotein lipase and liver X receptor gene expression in isolated adipocytes, on which lipolysis and glucose uptake experiments were also performed. Lipolysis was measured after incubation with tumour necrosis factor-α (TNFα), linoleic acid, and two conjugated linoleic acid isomers. Glucose uptake was analysed after TNFα or insulin administration. Our results show that FO replacement increased lipolytic activity and adipocyte cell size. The higher proportion of large cells observed in the 66VO group could be involved in their observed lower response to fatty acid treatments and lower insulin sensitivity. The 66VO/FO group showed a moderate return to the FO conditions. Therefore, FO replacement can affect the morphology and metabolism of gilthead sea bream adipocytes which could potentially affect other organs such as the liver. 相似文献
114.
Lima-Fernandes E Enslen H Camand E Kotelevets L Boularan C Achour L Benmerah A Gibson LC Baillie GS Pitcher JA Chastre E Etienne-Manneville S Marullo S Scott MG 《The EMBO journal》2011,30(13):2557-2568
The tumour suppressor PTEN (phosphatase and tensin deleted on chromosome 10) regulates major cellular functions via lipid phosphatase-dependent and -independent mechanisms. Despite its fundamental pathophysiological importance, how PTEN's cellular activity is regulated has only been partially elucidated. We report that the scaffolding proteins β-arrestins (β-arrs) are important regulators of PTEN. Downstream of receptor-activated RhoA/ROCK signalling, β-arrs activate the lipid phosphatase activity of PTEN to negatively regulate Akt and cell proliferation. In contrast, following wound-induced RhoA activation, β-arrs inhibit the lipid phosphatase-independent anti-migratory effects of PTEN. β-arrs can thus differentially control distinct functional outputs of PTEN important for cell proliferation and migration. 相似文献
115.
116.
Lamia Trabelsi Nour Houda M’sakni Hatem Ben Ouada Hassen Bacha Sadok Roudesli 《Biotechnology and Bioprocess Engineering》2009,14(1):27-31
In this study, the physico-chemical characteristics of extracellular polysaccharides (EPS) produced by Arthrospira platensis were evaluated. Elemental analysis and a bicinchoninic acid (BCA) reaction indicated that the EPS were heteropolysaccharides
that contain carbohydrate (13%) and protein (55%) moieties. Analysis of the infrared spectrum and elemental analysis revealed
the presence of a sulfate group (0.5%). The UV-visible spectrum showed high UV absorption at 190∼230 nm and a shoulder at
260∼280 nm. In addition, this spectrum indicated that EPS can form aggregates with mycosporine-like amino acids and/or scytonemin.
Gas chromatography analysis of the carbohydrate portion of the EPS indicated that it was composed of seven neutral sugars:
galactose (14.9%), xylose (14.3%), glucose (13.2%), frucose (13.2%), rhamnose (3.7%), arabinose (1%), and mannose (0.3%) and
two uronic acids, galacturonic acid (13.5%) and glucuronic acid (0.9%). 相似文献
117.
Lamia Youseff Keith Seymour Haihang You Dmitrii Zagorodnov Jack Dongarra Rich Wolski 《Cluster computing》2009,12(2):101-122
Previous studies have revealed that paravirtualization imposes minimal performance overhead on High Performance Computing
(HPC) workloads, while exposing numerous benefits for this field. In this study, we are investigating the impact of paravirtualization
on the performance of automatically-tuned software systems. We compare peak performance, performance degradation in constrained
memory situations, performance degradation in multi-threaded applications, and inter-VM shared memory performance. For comparison
purposes, we examine the proficiency of ATLAS, a quintessential example of an autotuning software system, in tuning the BLAS library routines for paravirtualized systems. Our results show that the combination of ATLAS and Xen paravirtualization delivers native execution performance and nearly identical memory hierarchy performance profiles
in both single and multi-threaded scenarios. Furthermore, we show that it is possible to achieve memory sharing among OS instances
at native speeds. These results expose new benefits to memory-intensive applications arising from the ability to slim down
the guest OS without influencing the system performance. In addition, our findings support a novel and very attractive deployment
scenario for computational science and engineering codes on virtual clusters and computational clouds.
相似文献
Rich WolskiEmail: |
118.
GALLIGAN Derek C. LAMERS Susanna L. YU Stephanie SHAGRUN Lamia SALEMI Marco MCGRATH Michael S. 《中国科学:生命科学英文版》2009,52(7):651-656
Highly active antiretroviral treatment (HAART) has had a significant impact on survival of individuals with acquired immunodeficiency
syndrome (AIDS); however, with the longer life-span of patients with AIDS, there is increasing prevalence of AIDS dementia
complex (ADC) and other non-AIDS-defining illness, and cardiovascular diseases (CVD) are also common. The influence of these
varied disease processes on HIV-1 DNA concentration in brain tissues has not been thoroughly assessed in the post-HAART era.
The purpose of the current study is to clarify the impacts of ADC and other complications of HIV disease on the viral load
in the brains in AIDS patients with post-HARRT. We examined autopsy specimens from the brains of thirteen patients who died
from complications of AIDS with quantitative polymerase chain reaction (QPCR). All but one patient had received HAART prior
to death since 1995. Two patients died with severe CVD, multiple cerebrovascular atherosclerosis (CVA) throughout the brain
and five patients died with ADC. Six patients had no ADC/CVA. A QPCR was used to measure the presence of HIV-1 DNA in six
brain tissues (meninges, frontal grey matter, frontal white matter, temporal subcortex, cerebellum and basal ganglia). In
the post-HARRT era, for non-ADC/CVA patients, HIV-1 DNA concentration in brain tissues was statistically higher than that
in patients with ADC. In a new finding, two patients who suffered from severe CVD, especially CVA, also had high concentrations
of HIV-1 in brain compartments not showing ADC related changes. To our knowledge, this is the first report of a relationship
between the CVA and HIV-1 viral burden in brain. The current observations suggest that HAART-resistant HIV reservoirs may
survive within ADC lesions of the brain as well as the macrophage rich atherosclerosis, which needs to be confirmed by more
AIDS cases with CVA.
Supported by the National Institutes of Health (Grant Nos. NIH ZMH1 BRB-S and UOI CA66259-09 TDC), National Science Foundation
(Grant No. NSF DMI-0349669), abd Science & Technology Development Program of Shandong Province (Grant No. 2007GG30002003). 相似文献
119.
We have investigated the effect of cholesterol and two abundant phytosterols (sitosterol and stigmasterol) on the voltage-dependent anion-selective channel (VDAC) purified from mitochondria of bean seeds (Phaseolus coccineus). These sterols differ by the degree of freedom of their lateral chain. We show that VDAC displays sensitivity to the lipid-sterol ratio and to the type of sterol found in the membrane. The main findings of this study are: 1), cholesterol and phytosterols modulate the selectivity but only stigmasterol alters the voltage-dependence of the plant VDAC in the range of sterol fraction found in the plant mitochondrial membrane; 2), VDAC unitary conductance is not affected by the addition of sterols; 3), the effect of sterols on the VDAC is reversible upon sterol depletion with 10 μM methyl-β-cyclodextrins; and 4), phytosterols are essential for the channel gating at salt concentration prevailing in vivo. A quantitative analysis of the voltage-dependence indicates that stigmasterol inhibits the transition of the VDAC in the lowest subconductance states. 相似文献
120.
Benguedouar L Boussenane HN Wided K Alyane M Rouibah H Lahouel M 《Indian journal of experimental biology》2008,46(2):112-119
To assess the oxidative stress and mitochondrial dysfunction associated with disease, toxic process and aging, in vivo and in vitro preventive effect of propolis extract against mitochondrial oxidative stress induced by two anticancer drugs (doxorubicin and vinblastin) have been investigated in female wistar rat using liver and heart mitochondria. The results show that doxorubicin and vinblastin altered mitochondrial functions as observed by a decrease in respiratory control value, an activation of swelling and overproduction of superoxide anion. Myocardial tissue from doxorubicin treated rats showed a marked increase in malondialdehyde production, a depletion of reduced glutathione contents and an inhibition of catalase and superoxide dismutase activities. Similar results were also observed in liver tissue. Pretreatment of rats with propolis extract (100 mg/kg/day po) (10(-4) M ip) administered 4 days prior to doxorubicin (20 mg/kg) and/or vinblastin (2 mg/kg) injection, substantially reduced the peroxidative damage in myocardium and hepatic tissues and markedly restored the tissues catalase and SOD activities. The results strongly suggest that propolis extract protects heart and liver tissues from oxidative stress by protecting the mitochondria. 相似文献