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Impact of a training intervention on use of antimicrobials in teaching hospitals

Akter SF, Heller RD, Smith AJ, Milly AF

J Infect Dev Ctries, 2009 Jul 01;3(6):447-51.
PMID: 19762958

BACKGROUND: Antimicrobials are often used inappropriately in paediatric wards of medical college hospitals in Bangladesh. Most of the antimicrobials are prescribed based on clinical grounds-signs and symptoms. This intervention study assessed the effectiveness of a training intervention on antimicrobials prescribing by physicians in paediatric wards of tertiary care level hospitals.
METHODOLOGY: This study was conducted at medical college hospitals in Bangladesh during the period from 1998 through 2000. The pre-intervention survey of antimicrobial use was conducted during 1998 in five hospitals. The post-intervention survey was conducted after the interactive training during the succeeding year in three of the original five hospitals, of which one was the intervention hospital and two control hospitals. A total of 3,466 admitted paediatric patients' treatment charts (2,171 in the pre-intervention and 1,295 in the post-intervention surveys) were reviewed.
RESULTS: The most commonly used antimicrobials were ampicillin, gentamicin, amoxicillin, cloxacillin and ceftriaxone. Appropriate antimicrobial therapy for the most common infectious diseases, pneumonia and diarrhoea, increased by 16.4% and 56.8% respectively in the intervention hospital compared with the two control hospitals and these improvements were significant (p = < 0.001 and p = 0.002, for pneumonia and diarrhoea respectively).
CONCLUSIONS: An interactive, focussed educational intervention, targeted at physicians, appears to have been effective in improving appropriate antimicrobial prescribing for the most common paediatric infectious diseases in a medical college hospital in Bangladesh.
Chlorhexidine hexametaphosphate as a coating for elastomeric ligatures with sustained antimicrobial properties: A laboratory study

Kamarudin Y, Skeats MK, Ireland AJ, Barbour ME

Am J Orthod Dentofacial Orthop, 2020 Nov;158(5):e73-e82.
PMID: 33008710 DOI: 10.1016/j.ajodo.2020.07.027

INTRODUCTION: White spot lesions are a common side effect of orthodontic treatment. This laboratory study aimed to explore the suitability of chlorhexidine hexametaphosphate (CHX-HMP) as a coating for orthodontic elastomeric ligatures to provide sustained chlorhexidine (CHX) release.
METHODS: Dissolution kinetics of CHX-HMP were firstly explored using spectroscopy and a colorimetric phosphate assay. Elastomeric ligatures were categorized into 3 groups-acetone-conditioned, ethanol-conditioned, and as received-and were then immersed in 5 mM CHX-HMP suspension or 5 mM chlorhexidine digluconate solution and rinsed. CHX release was measured over 8 weeks, and the effects of conditioning and immersion on elastomeric force and extension at rupture and surface topography were investigated.
RESULTS: CHX-HMP exhibited a gradual equilibration that had not reached equilibrium within 8 weeks, releasing soluble CHX and a mixture of polyphosphate and orthophosphate. CHX digluconate-treated ligatures showed no CHX release, whereas CHX-HMP-treated ligatures showed varying degrees of release. As received, CHX-HMP-treated ligatures showed a modest release of CHX up to 7 days. Acetone conditioning did not enhance CHX-HMP uptake or subsequent CHX release and caused a deterioration in mechanical properties. Ethanol conditioning enhanced CHX-HMP uptake (6×) and led to a sustained CHX release over 8 weeks without affecting mechanical properties.
CONCLUSIONS: Within the inherent limitations of this in-vitro study, CHX-HMP led to a sustained release of CHX from orthodontic elastomeric ligatures after ethanol conditioning. Conditioned and coated elastomeric ligatures may ultimately find application in the prevention of white spot lesions in orthodontic patients.
Correlation and persistence of hunting and logging impacts on tropical rainforest mammals

Brodie JF, Giordano AJ, Zipkin EF, Bernard H, Mohd-Azlan J, Ambu L

Conserv Biol, 2015 Feb;29(1):110-21.
PMID: 25196079 DOI: 10.1111/cobi.12389

Humans influence tropical rainforest animals directly via exploitation and indirectly via habitat disturbance. Bushmeat hunting and logging occur extensively in tropical forests and have large effects on particular species. But how they alter animal diversity across landscape scales and whether their impacts are correlated across species remain less known. We used spatially widespread measurements of mammal occurrence across Malaysian Borneo and recently developed multispecies hierarchical models to assess the species richness of medium- to large-bodied terrestrial mammals while accounting for imperfect detection of all species. Hunting was associated with 31% lower species richness. Moreover, hunting remained high even where richness was very low, highlighting that hunting pressure persisted even in chronically overhunted areas. Newly logged sites had 11% lower species richness than unlogged sites, but sites logged >10 years previously had richness levels similar to those in old-growth forest. Hunting was a more serious long-term threat than logging for 91% of primate and ungulate species. Hunting and logging impacts across species were not correlated across taxa. Negative impacts of hunting were the greatest for common mammalian species, but commonness versus rarity was not related to species-specific impacts of logging. Direct human impacts appeared highly persistent and lead to defaunation of certain areas. These impacts were particularly severe for species of ecological importance as seed dispersers and herbivores. Indirect impacts were also strong but appeared to attenuate more rapidly than previously thought. The lack of correlation between direct and indirect impacts across species highlights that multifaceted conservation strategies may be needed for mammal conservation in tropical rainforests, Earth's most biodiverse ecosystems.
Evaluating multispecies landscape connectivity in a threatened tropical mammal community

Brodie JF, Giordano AJ, Dickson B, Hebblewhite M, Bernard H, Mohd-Azlan J, et al.

Conserv Biol, 2015 Feb;29(1):122-32.
PMID: 25065425 DOI: 10.1111/cobi.12337

Habitat corridors are important tools for maintaining connectivity in increasingly fragmented landscapes, but generally they have been considered in single-species approaches. Corridors intended to facilitate the movement of multiple species could increase persistence of entire communities, but at the likely cost of being less efficient for any given species than a corridor intended specifically for that species. There have been few tests of the trade-offs between single- and multispecies corridor approaches. We assessed single-species and multispecies habitat corridors for 5 threatened mammal species in tropical forests of Borneo. We generated maps of the cost of movement across the landscape for each species based on the species' local abundance as estimated through hierarchical modeling of camera-trap data with biophysical and anthropogenic covariates. Elevation influenced local abundance of banded civets (Hemigalus derbyanus) and sun bears (Helarctos malayanus). Increased road density was associated with lower local abundance of Sunda clouded leopards (Neofelis diardi) and higher local abundance of sambar deer (Rusa unicolor). Pig-tailed macaque (Macaca nemestrina) local abundance was lower in recently logged areas. An all-species-combined connectivity scenario with least-cost paths and 1 km buffers generated total movement costs that were 27% and 23% higher for banded civets and clouded leopards, respectively, than the connectivity scenarios for those species individually. A carnivore multispecies connectivity scenario, however, increased movement cost by 2% for banded civets and clouded leopards. Likewise, an herbivore multispecies scenario provided more effective connectivity than the all-species-combined scenario for sambar and macaques. We suggest that multispecies habitat connectivity plans be tailored to groups of ecologically similar, disturbance-sensitive species to maximize their effectiveness.
Biosynthesis and characterization of polyhydroxyalkanoate containing high 3-hydroxyhexanoate monomer fraction from crude palm kernel oil by recombinant Cupriavidus necator

Wong YM, Brigham CJ, Rha C, Sinskey AJ, Sudesh K

Bioresour Technol, 2012 Oct;121:320-7.
PMID: 22858502 DOI: 10.1016/j.biortech.2012.07.015

The potential of plant oils as sole carbon sources for production of P(3HB-co-3HHx) copolymer containing a high 3HHx monomer fraction using the recombinant Cupriavidus necator strain Re2160/pCB113 has been investigated. Various types and concentrations of plant oils were evaluated for efficient conversion of P(3HB-co-3HHx) copolymer. Crude palm kernel oil (CPKO) at a concentration of 2.5 g/L was found to be most suitable for production of copolymer with a 3HHx content of approximately 70 mol%. The time profile of these cells was also examined in order to study the trend of 3HHx monomer incorporation, PHA production and PHA synthase activity. (1)H NMR and (13)C NMR analyses confirmed the presence of P(3HB-co-3HHx) copolymer containing a high 3HHx monomer fraction, in which monomers were not randomly distributed. The results of various characterization analyses revealed that the copolymers containing a high 3HHx monomer fraction demonstrated soft and flexible mechanical properties.
Fulltext Lowland biotic attrition revisited: body size and variation among climate change 'winners' and 'losers'

Brodie JF, Strimas-Mackey M, Mohd-Azlan J, Granados A, Bernard H, Giordano AJ, et al.

Proc Biol Sci, 2017 01 25;284(1847).
PMID: 28100818 DOI: 10.1098/rspb.2016.2335

The responses of lowland tropical communities to climate change will critically influence global biodiversity but remain poorly understood. If species in these systems are unable to tolerate warming, the communities-currently the most diverse on Earth-may become depauperate ('biotic attrition'). In response to temperature changes, animals can adjust their distribution in space or their activity in time, but these two components of the niche are seldom considered together. We assessed the spatio-temporal niches of rainforest mammal species in Borneo across gradients in elevation and temperature. Most species are not predicted to experience changes in spatio-temporal niche availability, even under pessimistic warming scenarios. Responses to temperature are not predictable by phylogeny but do appear to be trait-based, being much more variable in smaller-bodied taxa. General circulation models and weather station data suggest unprecedentedly high midday temperatures later in the century; predicted responses to this warming among small-bodied species range from 9% losses to 6% gains in spatio-temporal niche availability, while larger species have close to 0% predicted change. Body mass may therefore be a key ecological trait influencing the identity of climate change winners and losers. Mammal species composition will probably change in some areas as temperatures rise, but full-scale biotic attrition this century appears unlikely.
Attitudes towards diagnostic tests and therapies for dry eye disease

Graham JE, McGilligan VE, Berrar D, Leccisotti A, Moore JE, Bron AJ, et al.

Ophthalmic Res, 2010;43(1):11-7.
PMID: 19829007 DOI: 10.1159/000246573

AIM: The purpose of this study was to survey the attitudes of optometrists and ophthalmologists, located in a number of different countries, towards diagnostic tests and therapies for dry eye disease.
METHODS: A web-based questionnaire was used to survey attitudes using forced-choice questions and Likert scales.
RESULTS: Sixty-one respondents (23 ophthalmologists and 38 optometrists) reported a wide range of patient dry eye symptoms. A large variation in use of diagnostic tests was noted. Patient symptoms and fluorescein staining were reported to be significantly more valuable and more frequently performed than any other test. Artificial tear supplements and improved lid hygiene were the preferred therapeutic options selected by the entire group. The results demonstrated a wide variation in attitudes in relation to satisfaction with the range of available diagnostic and therapeutic options.
CONCLUSIONS: This study indicates that the interest for the issue of dry eye is relatively limited amongst eye professionals, as demonstrated by the poor participation in the questionnaire.
Fulltext Gestational age at time of in utero lipopolysaccharide exposure influences the severity of inflammation-induced diaphragm weakness in lambs

Karisnan K, Mahzabin T, Bakker AJ, Song Y, Noble PB, Pillow JJ, et al.

Am J Physiol Regul Integr Comp Physiol, 2018 04 01;314(4):R523-R532.
PMID: 29212808 DOI: 10.1152/ajpregu.00150.2017

The preterm diaphragm is functionally immature compared with its term counterpart. In utero inflammation further exacerbates preterm diaphragm dysfunction. We hypothesized that preterm lambs are more vulnerable to in utero inflammation-induced diaphragm dysfunction compared with term lambs. Pregnant ewes received intra-amniotic (IA) injections of saline or 10 mg lipopolysaccharide (LPS) 2 or 7 days before delivery at 121 days (preterm) or ∼145 days (term) of gestation. Diaphragm contractile function was assessed in vitro. Plasma cytokines, diaphragm myosin heavy chain (MHC) isoforms, and oxidative stress were evaluated. Maximum diaphragm force in preterm control lambs was significantly lower (22%) than in term control lambs ( P < 0.001). Despite similar inflammatory cytokine responses to in utero LPS exposure, diaphragm function in preterm and term lambs was affected differentially. In term lambs, maximum force after a 2-day LPS exposure was significantly lower than in controls (by ~20%, P < 0.05). In preterm lambs, maximum forces after 2-day and 7-day LPS exposures were significantly lower than in controls (by ~30%, P < 0.05). Peak twitch force after LPS exposure was significantly lower in preterm than in controls, but not in term lambs. In term lambs, LPS exposure increased the proportion of MHC-I fibers, increased twitch contraction times, and increased fatigue resistance relative to controls. In preterm diaphragm, the cross-sectional area of embryonic MHC fibers was significantly lower after 7-day versus 2-day LPS exposures. We conclude that preterm lambs are more vulnerable to IA LPS-induced diaphragm dysfunction than term lambs. In utero inflammation exacerbates diaphragm dysfunction and may increase susceptibility to postnatal respiratory failure.
Gene expression changes in the human fibroblast induced by Centella asiatica triterpenoids

Coldren CD, Hashim P, Ali JM, Oh SK, Sinskey AJ, Rha C

Planta Med, 2003 Aug;69(8):725-32.
PMID: 14531023

The molecular pathways underlying the diverse biological activity of the triterpeniod compounds isolated from the tropical medicinal plant Centella asiatica were studied with gene microarrays and real-time reverse transcription polymerase chain reaction (real-time RT-PCR) to quantify the expression of 1053 human genes in human fibroblasts. Fibroblast cells grown in culture were used as a model system to evaluate the stimulation of wound healing by titrated extract from Centella asiatica (TECA) as well as by the four principal triterpenoid components of Centella. TECA treatment effects the expression of genes involved in angiogenesis and the remodeling of extracellular matrix, as well as diverse growth factor genes. The extent of expression change of TNFAIP6, an extracellular hyaluronan binding protein, was found to be largely dose-dependent, to respond most strongly to the free acids asiatic acid and madecassic acid, and to increase in expression over 48 hours of treatment. These results show that Centella triterpenes evoke a gene-expression response consistent with their prevailing medical uses in the treatment of connective tissue disorders such as wound healing and microangiopathy. The identification of genes modulated by these compounds provides the basis for a molecular understanding of Centella's bioactivity, and opportunities for the quantitative correlation of this activity with clinical effectiveness at a molecular level.
Fulltext Characterization of the highly active polyhydroxyalkanoate synthase of Chromobacterium sp. strain USM2

Bhubalan K, Chuah JA, Shozui F, Brigham CJ, Taguchi S, Sinskey AJ, et al.

Appl Environ Microbiol, 2011 May;77(9):2926-33.
PMID: 21398494 DOI: 10.1128/AEM.01997-10

The synthesis of bacterial polyhydroxyalkanoates (PHA) is very much dependent on the expression and activity of a key enzyme, PHA synthase (PhaC). Many efforts are being pursued to enhance the activity and broaden the substrate specificity of PhaC. Here, we report the identification of a highly active wild-type PhaC belonging to the recently isolated Chromobacterium sp. USM2 (PhaC(Cs)). PhaC(Cs) showed the ability to utilize 3-hydroxybutyrate (3HB), 3-hydroxyvalerate (3HV), and 3-hydroxyhexanoate (3HHx) monomers in PHA biosynthesis. An in vitro assay of recombinant PhaC(Cs) expressed in Escherichia coli showed that its polymerization of 3-hydroxybutyryl-coenzyme A activity was nearly 8-fold higher (2,462 ± 80 U/g) than that of the synthase from the model strain C. necator (307 ± 24 U/g). Specific activity using a Strep2-tagged, purified PhaC(Cs) was 238 ± 98 U/mg, almost 5-fold higher than findings of previous studies using purified PhaC from C. necator. Efficient poly(3-hydroxybutyrate) [P(3HB)] accumulation in Escherichia coli expressing PhaC(Cs) of up to 76 ± 2 weight percent was observed within 24 h of cultivation. To date, this is the highest activity reported for a purified PHA synthase. PhaC(Cs) is a naturally occurring, highly active PHA synthase with superior polymerizing ability.
Fulltext Efficacy of Labisia pumila and Eurycoma longifolia standardised extracts on hot flushes, quality of life, hormone and lipid profile of peri-menopausal and menopausal women: a randomised, placebo-controlled study

Chinnappan SM, George A, Evans M, Anthony J

Food Nutr Res, 2020;64.
PMID: 33061884 DOI: 10.29219/fnr.v64.3665

Background: Interest in herbal medicines and non-hormonal therapies for the treatment of menopausal symptoms has increased since the publication of adverse effects of estrogen replacement therapy. Vasomotor symptoms are the most characteristic and notable symptoms of menopause.
Objective: To investigate the changes in the frequency and severity of hot flush and associated vasomotor symptoms experienced by peri-menopausal and menopausal women supplemented with the herbal formulation (Nu-femme™) comprising Labisia pumila (SLP+®) and Eurycoma longifolia (Physta®) or placebo.
Design: Randomised, double-blind, placebo-controlled, 24-week study enrolled 119 healthy women aged 41-55 years experiencing peri-menopausal or menopausal symptoms and supplemented with Nu-femme™ or placebo. The primary endpoint was comparative changes between treatment groups in the change in the frequency and severity of hot flushes. The secondary objectives were to assess the changes in the frequency and severity of joint pain, Menopause Rating Scale (MRS) and Menopause-Specific Quality of Life (MENQOL) questionnaire domain scores. Concentrations of serum hormone, lipid profile, bone markers, sleep quality and vitality were also studied as secondary objectives.
Results: At week 12, significant (P < 0.01) improvements in hot flush symptoms were observed in Nu-femme™ and placebo groups. Even though there was no significant difference between groups, higher percentage of improvement, 65%, was seen in Nu-femme™ compared to 60% in placebo. Significant improvements (P < 0.001) in MRS and MENQOL scores at weeks 12 and 24 were observed in both groups, respectively. Luteinising hormone and follicle-stimulating hormone levels were significantly reduced (P < 0.05) at weeks 12 and 24, respectively, compared to baseline in the Nu-femme™ group, with no significant changes observed in the placebo group. There were significant (P < 0.05) reductions in serum low-density lipid and triglycerides levels at week 12 in Nu-femme™ group, but no changes seen in placebo group. At the end of week 24, changes in haematology and clinical chemistry parameters remained within normal clinical ranges in both groups.
Conclusion: Herbal formulation consists of L. pumila and E. longifolia (Nu-femme™) may support reduction in hot flushes and improvements in hormone and lipid profile in healthy peri-menopausal and menopausal women.
Fulltext Potential medicinal benefits of Cosmos caudatus (Ulam Raja): A scoping review

Cheng SH, Barakatun-Nisak MY, Anthony J, Ismail A

J Res Med Sci, 2015 Oct;20(10):1000-6.
PMID: 26929767 DOI: 10.4103/1735-1995.172796

Cosmos caudatus is widely used as a traditional medicine in Southeast Asia. C. caudatus has been reported as a rich source of bioactive compounds such as ascorbic acid, quercetin, and chlorogenic acid. Studies have shown that C. caudatus exhibits high anti-oxidant capacity and various medicinal properties, including anti-diabetic activity, anti-hypertensive properties, anti-inflammatory responses, bone-protective effect, and anti-microbial activity. This review aims to present the potential medicinal benefits of C. caudatus from the available scientific literature. We searched PubMed and ScienceDirect database for articles published from 1995 to January 2015. Overall, 15 articles related to C. caudatus and its medicinal benefits are reviewed. All these studies demonstrated that C. caudatus is effective, having demonstrated its anti-diabetic, anti-hypertensive, anti-inflammatory, bone-protective, anti-microbial, and anti-fungal activity in both in vitro and animal studies. None of the studies showed any negative effect of C. caudatus related to medicinal use. Currently available evidence suggests that C. caudatus has beneficial effects such as reducing blood glucose, reducing blood pressure, promoting healthy bone formation, and demonstrating anti-inflammatory and anti-microbial properties. However, human clinical trial is warranted.
Demographic and clinical characteristics of chronic prostatitis: prospective comparison of the University of Sciences Malaysia Cohort with the United States National Institutes of Health Cohort

Lee SW, Cheah PY, Liong ML, Yuen KH, Schaeffer AJ, Propert K, et al.

J Urol, 2007 Jan;177(1):153-7; discussion 158.
PMID: 17162027

PURPOSE: We compared demographic and clinical characteristics of the University of Sciences Malaysia Chronic Prostatitis Cohort to the United States National Institutes of Health Chronic Prostatitis Cohort.
MATERIALS AND METHODS: Participants met the same definition of chronic prostatitis/chronic pelvic pain syndrome. Each participant had extensive demographic, medical history, previous treatment, clinical and laboratory evaluations.
RESULTS: The University of Sciences Malaysia and National Institutes of Health cohorts proved similar in most respects. National Institutes of Health-Chronic Prostatitis Symptom Index total scores, pain and urinary subscores were similar for the 332 University of Sciences Malaysia Chronic Prostatitis Cohort and 488 National Institutes of Health Chronic Prostatitis Cohort participants. Differences included worse quality of life subscore for the University of Sciences Malaysia Chronic Prostatitis Cohort, differences in the location, number of sites, and types of pain/discomfort between the 2 populations, and that the University of Sciences Malaysia participants had received less previous treatment.
CONCLUSIONS: The demographic characteristics and clinical presentation of chronic prostatitis/chronic pelvic pain syndrome proved remarkably similar in these diverse populations. Both cohorts experienced major reduction in their quality of life from chronic pelvic pain and urinary symptoms. Comparison of diverse populations using standard clinical, laboratory and assessment instruments is feasible, and may provide important insights into chronic prostatitis/chronic pelvic pain syndrome and the factors that determine clinical outcome.
Fulltext Publisher Correction: Palm Fruit Bioactives augment expression of Tyrosine Hydroxylase in the Nile Grass Rat basal ganglia and alter the colonic microbiome

Weinberg RP, Koledova VV, Subramaniam A, Schneider K, Artamonova A, Sambanthamurthi R, et al.

Sci Rep, 2020 Feb 13;10(1):2878.
PMID: 32051499 DOI: 10.1038/s41598-020-60010-9

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Fulltext Oil Palm Phenolics Inhibit the In Vitro Aggregation of β-Amyloid Peptide into Oligomeric Complexes

Weinberg RP, Koledova VV, Shin H, Park JH, Tan YA, Sinskey AJ, et al.

Int J Alzheimers Dis, 2018;2018:7608038.
PMID: 29666700 DOI: 10.1155/2018/7608038

Alzheimer's disease is a severe neurodegenerative disease characterized by the aggregation of amyloid-β peptide (Aβ) into toxic oligomers which activate microglia and astrocytes causing acute neuroinflammation. Multiple studies show that the soluble oligomers of Aβ42 are neurotoxic and proinflammatory, whereas the monomers and insoluble fibrils are relatively nontoxic. We show that Aβ42 aggregation is inhibited in vitro by oil palm phenolics (OPP), an aqueous extract from the oil palm tree (Elaeis guineensis). The data shows that OPP inhibits stacking of β-pleated sheets, which is essential for oligomerization. We demonstrate the inhibition of Aβ42 aggregation by (1) mass spectrometry; (2) Congo Red dye binding; (3) 2D-IR spectroscopy; (4) dynamic light scattering; (5) transmission electron microscopy; and (6) transgenic yeast rescue assay. In the yeast rescue assay, OPP significantly reduces the cytotoxicity of aggregating neuropeptides in yeast genetically engineered to overexpress these peptides. The data shows that OPP inhibits (1) the aggregation of Aβ into oligomers; (2) stacking of β-pleated sheets; and (3) fibrillar growth and coalescence. These inhibitory effects prevent the formation of neurotoxic oligomers and hold potential as a means to reduce neuroinflammation and neuronal death and thereby may play some role in the prevention or treatment of Alzheimer's disease.
Influence of antenatal glucocorticoid on preterm lamb diaphragm

Mahzabin T, Pillow JJ, Pinniger GJ, Bakker AJ, Noble PB, White RB, et al.

Pediatr Res, 2017 Sep;82(3):509-517.
PMID: 28388600 DOI: 10.1038/pr.2017.99

BackgroundPregnant women at a high risk of preterm delivery receive glucocorticoids to accelerate fetal lung maturation and surfactant synthesis. However, the effect of antenatal steroids on the developing diaphragm remains unclear. We hypothesized that maternal betamethasone impairs the fetal diaphragm, and the magnitude of the detrimental effect increases with longer duration of exposure. We aimed to determine how different durations of fetal exposure to maternal betamethasone treatment influence the fetal diaphragm at the functional and molecular levels.MethodsDate-mated merino ewes received intramuscular injections of saline (control) or two doses of betamethasone (5.7 mg) at an interval of 24 h commencing either 2 or 14 days before delivery. Preterm lambs were killed after cesarean delivery at 121-day gestational age. In vitro contractile measurements were performed on the right hemidiaphragm, whereas molecular/cellular analyses used the left costal diaphragm.ResultsDifferent durations of fetal exposure to maternal betamethasone had no consistent effect on the protein metabolic pathway, expression of glucocorticoid receptor and its target genes, cellular oxidative status, or contractile properties of the fetal lamb diaphragm.ConclusionThese data suggest that the potential benefits of betamethasone exposure on preterm respiratory function are not compromised by impaired diaphragm function after low-dose maternal intramuscular glucocorticoid exposure.
Fulltext Palm Fruit Bioactives augment expression of Tyrosine Hydroxylase in the Nile Grass Rat basal ganglia and alter the colonic microbiome

Weinberg RP, Koledova VV, Subramaniam A, Schneider K, Artamonova A, Sambanthamurthi R, et al.

Sci Rep, 2019 Dec 09;9(1):18625.
PMID: 31819070 DOI: 10.1038/s41598-019-54461-y

Tyrosine hydroxylase (TH) catalyzes the hydroxylation of L-tyrosine to L-DOPA. This is the rate-limiting step in the biosynthesis of the catecholamines - dopamine (DA), norepinephrine (NE), and epinephrine (EP). Catecholamines (CA) play a key role as neurotransmitters and hormones. Aberrant levels of CA are associated with multiple medical conditions, including Parkinson's disease. Palm Fruit Bioactives (PFB) significantly increased the levels of tyrosine hydroxylase in the brain of the Nile Grass rat (NGR), a novel and potentially significant finding, unique to PFB among known botanical sources. Increases were most pronounced in the basal ganglia, including the caudate-putamen, striatum and substantia nigra. The NGR represents an animal model of diet-induced Type 2 Diabetes Mellitus (T2DM), exhibiting hyperglycemia, hyperinsulinemia, and insulin resistance associated with hyperphagia and accelerated postweaning weight gain induced by a high-carbohydrate diet (hiCHO). The PFB-induced increase of TH in the basal ganglia of the NGR was documented by immuno-histochemical staining (IHC). This increase in TH occurred equally in both diabetes-susceptible and diabetes-resistant NGR fed a hiCHO. PFB also stimulated growth of the colon microbiota evidenced by an increase in cecal weight and altered microbiome. The metabolites of colon microbiota, e.g. short-chain fatty acids, may influence the brain and behavior significantly.
Fulltext Genetic diversity of Eurycoma longifolia inferred from single nucleotide polymorphisms

Osman A, Jordan B, Lessard PA, Muhammad N, Haron MR, Riffin NM, et al.

Plant Physiol, 2003 Mar;131(3):1294-301.
PMID: 12644679 DOI: 10.1104/pp.012492

Eurycoma longifolia Jack. is a treelet that grows in the forests of Southeast Asia and is widely used throughout the region because of its reported medicinal properties. Widespread harvesting of wild-grown trees has led to rapid thinning of natural populations, causing a potential decrease in genetic diversity among E. longifolia. Suitable genetic markers would be very useful for propagation and breeding programs to support conservation of this species, although no such markers currently exist. To meet this need, we have applied a genome complexity reduction strategy to identify a series of single nucleotide polymorphisms (SNPs) within the genomes of several E. longifolia accessions. We have found that the occurrence of these SNPs reflects the geographic origins of individual plants and can distinguish different natural populations. This work demonstrates the rapid development of molecular genetic markers in species for which little or no genomic sequence information is available. The SNP markers that we have developed in this study will also be useful for identifying genetic fingerprints that correlate with other properties of E. longifolia, such as high regenerability or the appearance of bioactive metabolites.
Fulltext Oil palm vegetation liquor: a new source of phenolic bioactives

Sambanthamurthi R, Tan Y, Sundram K, Abeywardena M, Sambandan TG, Rha C, et al.

Br J Nutr, 2011 Dec;106(11):1655-63.
PMID: 21736792 DOI: 10.1017/S0007114511002121

Waste from agricultural products represents a disposal liability, which needs to be addressed. Palm oil is the most widely traded edible oil globally, and its production generates 85 million tons of aqueous by-products annually. This aqueous stream is rich in phenolic antioxidants, which were investigated for their composition and potential in vitro biological activity. We have identified three isomers of caffeoylshikimic acid as major components of oil palm phenolics (OPP). The 2,2-diphenyl-1-picrylhydrazyl assay confirmed potent free radical scavenging activity. To test for possible cardioprotective effects of OPP, we carried out in vitro LDL oxidation studies as well as ex vivo aortic ring and mesenteric vascular bed relaxation measurements. We found that OPP inhibited the Cu-mediated oxidation of human LDL. OPP also promoted vascular relaxation in both isolated aortic rings and perfused mesenteric vascular beds pre-contracted with noradrenaline. To rule out developmental toxicity, we performed teratological studies on rats up to the third generation and did not find any congenital anomalies. Thus, these initial studies suggest that OPP is safe and may have a protective role against free radical damage, LDL oxidation and its attendant negative effects, as well as vascular constriction in mitigating atherosclerosis. Oil palm vegetation liquor thus represents a new source of phenolic bioactives.
Fulltext Positive outcomes of oil palm phenolics on degenerative diseases in animal models

Sambanthamurthi R, Tan Y, Sundram K, Hayes KC, Abeywardena M, Leow SS, et al.

Br J Nutr, 2011 Dec;106(11):1664-75.
PMID: 21736778 DOI: 10.1017/S0007114511002133

It is well established that plant phenolics elicit various biological activities, with positive effects on health. Palm oil production results in large volumes of aqueous by-products containing phenolics. In the present study, we describe the effects of oil palm phenolics (OPP) on several degenerative conditions using various animal models. OPP reduced blood pressure in a NO-deficient rat model, protected against ischaemia-induced cardiac arrhythmia in rats and reduced plaque formation in rabbits fed an atherogenic diet. In Nile rats, a spontaneous model of the metabolic syndrome and type 2 diabetes, OPP protected against multiple aspects of the syndrome and diabetes progression. In tumour-inoculated mice, OPP protected against cancer progression. Microarray studies on the tumours showed differential transcriptome profiles that suggest anti-tumour molecular mechanisms involved in OPP action. Thus, initial studies suggest that OPP may have potential against several chronic disease outcomes in mammals.

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