bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of herbal supplements containing Citrus aurantium and synephrine alkaloids for the management of overweight and obesity: a systematic review
Authors: Onakpoya Igho , Davies Lucy , Ernst Edzard 
Published: November 2011

AbstractNumerous herbal supplements are presently marketed as weight‐loss aids, but the efficacy of most is not proven. One such supplement is the extract of Citrus aurantium (bitter orange). The objective of this systematic review is to critically evaluate the evidence of efficacy for C. aurantium and weight management. Electronic databases, conference proceedings and pertinent journals were searched for relevant RCTs. Bibliographies and our departmental files were searched also. No restrictions on date or language of publication, age of participants or duration of treatment were imposed. Two reviewers independently determined the eligibility of studies, extracted data and evaluated the methodological quality of included studies. Seven studies were identified, of which four met the inclusion criteria. All RCTs had major methodological flaws. Two RCTs reported a marginal to statistically significant reduction in body weight and body fat in participants treated with C. aurantium‐containing supplements, when compared to placebo. One trial reported a statistically significant reduction in body fat only, while the other reported a statistically significant increase in body weight. Adverse events included anxiety, elevated heart rate and musculoskeletal complaints. The evidence of efficacy for C. aurantium and weight management is contradictory and methodologically weak. Until more rigorous RCTs emerge, C. aurantium cannot be recommended as a treatment for weight loss.
The Jamaican root tonics: a botanical reference
Authors: Mitchell Sylvia A 
Published: November 2011

AbstractAn important part of Jamaica's ethnomedical heritage is its root tonics. These tonics are deep decoctions of barks, leaves and roots of forest species, which are consumed mainly to build strength and vitality. The objective of this article has been to gather information on a sample of Jamaican root tonics in order to provide further understanding about these tonics and also to establish a botanical reference to the plants used. Information was elicited by: (1) folk medicine questionnaires and interviews; (2) study of 38 indigenous root tonics; and (3) literature searches for similar Caribbean tonics. Jamaican root tonics are made mainly by men in rural communities. Botanical analysis of 38 indigenous root tonic drinks indicates thatSmilax balbisiana(chainy root; used in 100% of tonics),S. regelii(sarsaparilla; 94.7%), herbs covered by the common name ‘strong back’ which includedDesmodium canum, Cuphea parsonsiaandMorinda royoc(94.6%),Iresine diffusa(nerve wist; 57.9%),Trophis racemosa(ramoon; 57.9%),Alysicarpus vaginalis(medina; 55.3%) andZingiber officinale(ginger; 50.0%) are the most commonly used plants. A total of 24 plants was used in 20–100% of root tonics, with 70 other plant species making up the balance. Between three and 26 plants, with an average of 13.3 plants, were used in each root tonic. Since chainy root is endemic to Jamaica, these root tonics are uniquely Jamaican. Although a wide variety of plants are used in Jamaican root tonics, the method of making the tonics is the same. This is the first scientific documentation of Jamaican root tonics, and an important first step towards validating their efficacy and safety.
The Oligo-Acyl Lysyl Antimicrobial Peptide C
12
K-2β
12
Exhibits a Dual Mechanism of Action and Demonstrates Strong
In Vivo
Efficacy against Helicobacter pylori
Authors: Makobongo Morris O. , Gancz Hanan , Carpenter Beth M. , McDaniel Dennis P. , Merrell D. Scott 
Published: November 2011

ABSTRACT

Helicobacter pylori
has developed antimicrobial resistance to virtually all current antibiotics. Thus, there is a pressing need to develop new anti-
H. pylori
therapies. We recently described a novel oligo-acyl-lysyl (OAK) antimicrobial peptidomimetic, C
12
K-2β
12
, that shows potent
in vitro
bactericidal activity against
H. pylori
. Herein, we define the mechanism of action and evaluate the
in vivo
efficacy of C
12
K-2β
12
against
H. pylori
after experimental infection of Mongolian gerbils. We demonstrate using a 1-
N
-phenylnaphthylamine (fluorescent probe) uptake assay and electron microscopy that C
12
K-2β
12
rapidly permeabilizes the bacterial membrane and creates pores that cause bacterial cell lysis. Furthermore, using nucleic acid binding assays, Western blots, and confocal microscopy, we show that C
12
K-2β
12
can cross the bacterial membranes into the cytoplasm and tightly bind to bacterial DNA, RNA, and proteins, a property that may result in inhibition of enzymatic activities and macromolecule synthesis. To define the
in vivo
efficacy of C
12
K-2β
12
,
H. pylori
-infected gerbils were orogastrically treated with increasing doses and concentrations of C
12
K-2β
12
1 day or 1 week postinfection. The efficacy of C
12
K-2β
12
was strongest in animals that received the largest number of doses at the highest concentration, indicating dose-dependent activity of the peptide (
P
< 0.001 by analysis of variance [ANOVA]) regardless of the timing of the treatment with C
12
K-2β
12
. Overall, our results demonstrate a dual mode of action of C
12
K-2β
12
against the
H. pylori
membrane and cytoplasmic components. Moreover, and consistent with the previously reported
in vitro
efficacy, C
12
K-2β
12
shows significant
in vivo
efficacy against
H. pylori
when used as monotherapy. Therefore, OAK peptides may be a valuable resource for therapeutic treatment of
H. pylori
infection.
Evaluation of Ceftobiprole Activity against a Variety of Gram-Negative Pathogens, Including Escherichia coli, Haemophilus influenzae (β-Lactamase Positive and β-Lactamase Negative), and Klebsiella pneumoniae, in a Rabbit Meningitis Model
Authors: Stucki A. , Cottagnoud M. , Acosta F. , Egerman U. , Läuffer J. , Cottagnoud P. 
Published: November 2011

ABSTRACT

Ceftobiprole medocaril, a new cephalosporin, is highly active against a broad spectrum of Gram-positive and Gram-negative clinical pathogens, including methicillin-resistant
Staphylococcus aureus
(MRSA) and penicillin-resistant pneumococci. In this study, we tested ceftobiprole against various Gram-negative pathogens in a rabbit meningitis model and determined its penetration into the cerebrospinal fluid (CSF). In this animal model, ceftobiprole produced an antibacterial activity similar to that of cefepime against an
Escherichia coli
strain, a
Klebsiella pneumoniae
strain, and a β-lactamase-negative
Haemophilus influenzae
strain. Against a β-lactamase-positive
H. influenzae
strain, ceftobiprole was significantly superior. The penetration of ceftobiprole through inflamed meninges reached about 16% of serum levels compared to about 2% of serum levels through uninflamed meninges.
Generic Vancomycin Enriches Resistant Subpopulations of Staphylococcus aureus after Exposure in a Neutropenic Mouse Thigh Infection Model
Authors: Rodriguez Carlos A. , Agudelo Maria , Zuluaga Andres F. , Vesga Omar 
Published: November 2011

ABSTRACT

Previous studies have shown that “bioequivalent” generic products of vancomycin are less effective
in vivo
against
Staphylococcus aureus
than the innovator compound. Considering that suboptimal bactericidal effect has been associated with emergence of resistance, we aimed to assess
in vivo
the impact of exposure to innovator and generic products of vancomycin on
S. aureus
susceptibility. A clinical methicillin-resistant
S. aureus
(MRSA) strain from a liver transplant patient with persistent bacteremia was used for which MIC, minimum bactericidal concentration (MBC), and autolytic properties were determined. Susceptibility was also assessed by determining a population analysis profile (PAP) with vancomycin concentrations from 0 to 5 mg/liter. ICR neutropenic mice were inoculated in each thigh with ∼7.0 log
10
CFU. Treatment with the different vancomycin products (innovator and three generics; 1,200 mg/kg of body weight/day every 3 h) started 2 h later while the control group received sterile saline. After 24 h, mice were euthanized, and the thigh homogenates were plated. Recovered colonies were reinoculated to new groups of animals, and the exposure-recovery process was repeated until 12 cycles were completed. The evolution of resistance was assessed by PAP after cycles 5, 10, 11, and 12. The initial isolate displayed reduced autolysis and higher resistance frequencies than
S. aureus
ATCC 29213 but without vancomycin-intermediate
S. aureus
(VISA) subpopulations. After 12 cycles, innovator vancomycin had significantly reduced resistant subpopulations at 1, 2, and 3 mg/liter, while the generic products had enriched them progressively by orders of magnitude. The great capacity of generic vancomycin to select for less susceptible organisms raises concerns about the role of therapeutic inequivalence of any antimicrobial on the epidemiology of resistance worldwide.
Pathophysiology of the Rhesus Macaque Model for Inhalational Brucellosis
Authors: Henning Lisa N. , Miller Stephen M. , Pak Dennis H. , Lindsay Amber , Fisher David A. , Barnewall Roy E. , Briscoe Crystal M. , Anderson Michael S. , Warren Richard L. 
Published: November 2011

ABSTRACTThe objective of this study was to characterize the rhesus macaque (RM) as a model for inhalational brucellosis in support of the U.S. Food and Drug Administration's (FDA) Animal Rule. The pathophysiology of chronicBrucella melitensisaerosol infection was monitored in two phases that each occurred over an 8-week time period; dose escalation (8 RMs; targeted doses of 5.0E+03, 5.0E+04, or 5.0E+05 CFU/animal or the unchallenged control) and natural history (12 RMs; targeted dose of 2.50E+05 CFU/animal or the unchallenged control). RMs given an aerosol challenge withB. melitensisdeveloped undulating fevers (6/6 phase I; 8/9 phase II), positive enriched blood cultures (5/10; phase II), and bacterial burdens in tissues starting 14 to 21 days postchallenge (6/6 phase I; 10/10 phase II). In addition, 80% (8/10; phase II) of infected RMs seroconverted 14 to 21 days postchallenge. RMs developed elevations in certain liver enzymes and had an increased inflammatory response by 3 weeks postchallenge as shown by increases in C-reactive protein (6/8) and neopterin (4/8), which correlated with the onset of a fever. As early as 14 days postchallenge, positive liver biopsy specimens were detected (2/8), and ultrasound imaging showed the development of splenomegaly. Finally, histopathologic examination found lesions attributed toBrucellainfection in the liver, kidney, lung, and/or spleen of all animals. The disease progression observed with the RMs in this study is analogous to human brucellosis pathophysiology. Thus, the results from this study support the use of the RM as an animal model for inhalational brucellosis to evaluate the efficacy of novel vaccines and therapeutics againstB. melitensis.
A Protective Epitope in Type III Effector YopE Is a Major CD8 T Cell Antigen during Primary Infection with Yersinia pseudotuberculosis
Authors: Zhang Yue , Mena Patricio , Romanov Galina , Lin Jr-Shiuan , Smiley Stephen T. , Bliska James B. 
Published: November 2011

ABSTRACTVirulence in human-pathogenicYersiniaspecies is associated with a plasmid-encoded type III secretion system that translocates a set of Yop effector proteins into host cells. One effector, YopE, functions as a Rho GTPase-activating protein (GAP). In addition to acting as a virulence factor, YopE can function as a protective antigen. C57BL/6 mice infected with attenuatedYersinia pestisgenerate a dominant H2-Kb-restricted CD8 T cell response to an epitope in the N-terminal domain of YopE (YopE69-77), and intranasal vaccination with the YopE69-77peptide and the mucosal adjuvant cholera toxin (CT) elicits CD8 T cells that are protective against lethal pulmonary challenge withY. pestis. Because YopE69-77is conserved in manyYersiniastrains, we sought to determine if YopE is a protective antigen forYersinia pseudotuberculosisand if primary infection with this enteric pathogen elicits a CD8 T cell response to this epitope. Intranasal immunization with the YopE69-77peptide and CT elicited a CD8 T cell response that was protective against lethal intragastricY. pseudotuberculosischallenge. The YopE69-77epitope was a major antigen (∼30% of splenic CD8 T cells were specific for this peptide at the peak of the response) during primary infection withY. pseudotuberculosis, as shown by flow cytometry tetramer staining. Results of infections withY. pseudotuberculosisexpressing catalytically inactive YopE demonstrated that GAP activity is dispensable for a CD8 T cell response to YopE69-77. Determining the features of YopE that are important for this response will lead to a better understanding of how protective CD8 T cell immunity is generated againstYersiniaand other pathogens with type III secretion systems.
Resolving the genetic structure of striped marlin,Kajikia audax, in the Pacific Ocean through spatial and temporal sampling of adult and immature fish
Authors: Purcell Catherine M. , Edmands Suzanne 
Published: November 2011

Spatial genetic structure in the highly migratory striped marlin ( Kajikia audax ) was examined using nuclear (microsatellite) and mitochondrial (control region sequences) DNA markers. While previous studies on striped marlin were limited by sampling design and sample size, this study employed a multiyear concurrent sampling scheme to collect tissue from seven locations representative of the species’ range in the Pacific: Japan, Hawaii, Southern California, Mexico, Central America, New Zealand, and Australia. Mature and immature specimens were analyzed separately to evaluate life-stage-specific population structure and movements. Microsatellite and sequence results revealed small but significant overall spatial subdivision (FST = 0.0145 and KST = 0.06995, respectively). Pairwise microsatellite analyses (n = 1199) revealed four groups: (1) Japan – Immature Hawaii – Southern California, (2) Mature Hawaii, (3) Mexico – Central America, and (4) Australia – New Zealand. Mitochondrial sequence analysis (n = 451) showed similar patterns; however, no significant differentiation was found between groups 1 and 2. This enhanced resolution of geographic genetic structure is important for understanding the complex migration patterns in this species. Moreover, the consistency among independent genetic studies on striped marlin provides strong support for management of at least three clearly delineated Pacific stocks.
Transcriptomic responses to aluminum stress in soybean roots
Authors: You Jiangfeng , Zhang Hongmei , Liu Ning , Gao Lingling , Kong Lingnan , Yang Zhenming 
Published: November 2011

Aluminum (Al) toxicity is the primary limitation to crop production and plant growth in acid soils. Soybean has multiple mechanisms of Al resistance including the complexing and exclusion of Al in root apices by Al-induced citrate secretion. Microarray analysis is available for the identification of genes in soybean. In the present study, Affymetrix soybean genome array was used to identify the Al-induced differentially expressed genes in Al-resistant genotype Jiyu 70. With a cutoff of >2.0-fold (p < 0.05) between non Al-treated and Al-treated root apices, 561 genes were upregulated and 78 genes were downregulated when roots were exposed to 30 µmol/L AlCl3 for 4 h. Quantitative real-time PCR was used to test the microarray data. The analysis showed that nearly half of the Al-responsive genes were of unknown biological function. A higher proportion of genes related to transcription regulation and cell wall processes were observed in Al-induced up- and downregulated genes, respectively. Some genes homologous to the citrate transporter MATE family gene or C2H2 family transcription factor gene, STOP1, were detected in our analysis. Some genes related to lignin deposition were upregulated, which might be related to Al-induced root elongation inhibition.
Mechanisms and source distances for the input of large woody debris to forested streams in British Columbia, Canada
Authors: Johnston N.T. , Bird S.A. , Hogan D.L. , MacIsaac E.A. 
Published: November 2011

The geomorphic process domain concept predicts consistent associations between stream channel geomorphology and large woody debris (LWD) input mechanisms. We used synoptic surveys at 51 stream reaches adjacent to undisturbed mature or old-growth forests in central and southern British Columbia to test associations between stream geomorphology and the input processes, source distances, physical characteristics, and geomorphic functions of LWD within the bankfull channel. Standing dead tree fall was the dominant input mechanism, but bank erosion was important in low- and medium-gradient channels >3 m bankfull width. Wind-induced inputs (stem breakage and windthrow) were relatively more important in small or steep channels. LWD piece size and source distance varied among delivery processes. LWD originated at ground distances up to 65 m from the streams, but 90% of the LWD at a site originated within 18 m of the channel at 90% of the sites. Statistical models incorporating tree size and stream characteristics (bankfull width, channel type) explained 40%–64% of the variation among sites in the distances from which LWD entered streams. In general, LWD source distances increased with increasing tree height and decreased with increasing stream width; however, the strengths of these relationships were modified by channel type.
Comparing growth and mortality of a spruce budworm (Choristoneura fumiferana) inspired harvest versus a spruce budworm outbreak
Authors: Spence C. Eiry , MacLean David A. 
Published: November 2011

Many current forest management regimes stress emulation of natural disturbance events, e.g., spruce budworm (SBW; Choristoneura fumiferana (Clemens)) outbreaks in a balsam fir (Abies balsamea (L.) Mill.) dominated forest, as the preferred method for ensuring sustainability of forest ecosystems. This study compared a SBW-inspired harvest treatment in 25 plots in northern New Brunswick with an uncontrolled SBW outbreak in 30 plots in the Cape Breton Highlands, Nova Scotia. Stand-level measurements before, during, and after each disturbance indicated similar reduction of living stand volume (70% reduction in emulation harvest versus 83% in SBW outbreak), mortality patterns, and lengths of disturbance (4 years of >10% mortality by density of predisturbance stand). Differences for the harvest treatment included higher cumulative postdisturbance blowdown (43% versus 8% of postdisturbance stand density), conversion to hardwood-dominated stands immediately after the disturbance, and faster growth response (immediate release of all species in the harvest treatment versus decreased balsam fir and white spruce (Picea glauca [Moench] Voss) growth and increased white birch (Betula papyrifera Marshall) growth in the SBW outbreak). There were significant differences in stand dynamics following the two disturbances. Results suggest that instead of emulating SBW disturbances, forest managers should be inspired by the spatial and temporal characteristics of SBW-defoliated stands and use significant key features of them to design harvest plans that satisfy management goals.
Changes in ash tree demography associated with emerald ash borer invasion, indicated by regional forest inventory data from the Great Lakes States
Authors: Pugh Scott A. , Liebhold Andrew M. , Morin Randall S. 
Published: November 2011

The emerald ash borer (EAB) ( Agrilus planipennis Fairmaire) is a nonnative phloem-feeding beetle that was accidentally introduced near Detroit, Michigan, two to three decades ago. North American ash ( Fraxinus spp.) exhibit little or no resistance, and as this insect species expands its range, extensive mortality results. Previous studies of the impacts of EAB, typical of most insect and disease impact studies, utilized data acquired from sites with known infestations and cannot be used to make regional estimates of change on forest land. By contrast, this study investigated the regional impacts of EAB on the affected resource using information from a large-scale forest inventory (Forest Inventory and Analysis program of the US Department of Agriculture, Forest Service) previously implemented to estimate regional forest resources. Results indicate that since 1980, ash has been increasing throughout many of the Great Lakes States but EAB is reversing this trend in recently invaded areas. Within 50 km of the epicenter of the EAB invasion, a major decline was observed after 2004. For growing stock (trees at least 12.7 cm diameter at breast height), average ash volume decreased from 12.7 to 3.2 m3·ha–1and mortality increased from 0.1 to 1.4 m3·ha–1·year–1on timberland between the 2004 and 2009 inventories.
Targeting Tumor-Associated Endothelial Cells: Anti-VEGFR2 Immunoliposomes Mediate Tumor Vessel Disruption and Inhibit Tumor Growth
Authors: Wicki Andreas , Rochlitz Christoph , Orleth Annette , Ritschard Reto , Albrecht Imke , Herrmann Richard , Christofori Gerhard , Mamot Christoph 
Published: November 2011

Abstract
Purpose: Angiogenesis is a key process in tumor progression. By binding VEGF, VEGF receptor-2 (VEGFR2) is a main signaling transducer in tumor-associated angiogenesis. Accordingly, therapeutic approaches against the VEGF/VEGFR2 signaling axis have been designed. However, an efficient and specific chemotherapeutic targeting of tumor-associated endothelial cells has not yet been achieved.
Experimental Design: We have employed anti-VEGFR2 antibodies covalently linked to pegylated liposomal doxorubicin (PLD) to specifically ablate tumor-associated endothelial cells in the Rip1Tag2 mouse model of insulinoma, in the MMTV-PyMT mouse model of breast cancer, and in the HT-29 human colon cancer xenograft transplantation model.
Results: In each model, anti-VEGFR2–targeted immunoliposomes (ILs) loaded with doxorubicin (anti-VEGFR2-ILs-dox) were superior in therapeutic efficacy to empty liposomes, empty anti-VEGFR2-ILs, antibodies alone, and PLD. Efficacy was similar to that of the oral VEGFR1, -2, and -3 inhibitor PTK787. Detailed histopathologic and molecular analysis revealed a strong antiangiogenic effect of anti-VEGFR2-ILs-dox, and the observed antiangiogenic therapy was significantly more efficient in reducing tumor burden in well-vascularized transgenic mouse models as compared with the less-vascularized xenograft model.
Conclusions: Anti-VEGFR2 ILs provide a highly efficient approach to selectively deplete VEGFR2-expressing tumor vasculature. They offer a novel and promising anticancer strategy. Clin Cancer Res; 18(2); 454–64. ©2011 AACR.