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1.
BMC Plant Biol ; 24(1): 49, 2024 Jan 13.
Article in English | MEDLINE | ID: mdl-38216904

ABSTRACT

BACKGROUND: Trees have developed a broad spectrum of molecular mechanisms to counteract oxidative stress. Secondary metabolites via phenolic compounds emblematized the hidden bridge among plant kingdom, human health, and oxidative stress. Although studies have demonstrated that abiotic stresses can increase the production of medicinal compounds in plants, research comparing the efficiency of these stresses still needs to be explored. Thus, the present research paper provided an exhaustive comparative metabolomic study in Dalbergia odorifera under salinity (ST) and waterlogging (WL). RESULTS: High ST reduced D. odorifera's fresh biomass compared to WL. While WL only slightly affected leaf and vein size, ST had a significant negative impact. ST also caused more significant damage to water status and leaflet anatomy than WL. As a result, WL-treated seedlings exhibited better photosynthesis and an up-regulation of nonenzymatic pathways involved in scavenging reactive oxygen species. The metabolomic and physiological responses of D. odorifera under WL and salinity ST stress revealed an accumulation of secondary metabolites by the less aggressive stress (WL) to counterbalance the oxidative stress. Under WL, more metabolites were more regulated compared to ST. ST significantly altered the metabolite profile in D. odorifera leaflets, indicating its sensitivity to salinity. WL synthesized more metabolites involved in phenylpropanoid, flavone, flavonol, flavonoid, and isoflavonoid pathways than ST. Moreover, the down-regulation of L-phenylalanine correlated with increased p-coumarate, caffeate, and ferulate associated with better cell homeostasis and leaf anatomical indexes under WL. CONCLUSIONS: From a pharmacological and medicinal perspective, WL improved larger phenolics with therapeutic values compared to ST. Therefore, the data showed evidence of the crucial role of medical tree species' adaptability on ROS detoxification under environmental stresses that led to a significant accumulation of secondary metabolites with therapeutic value.


Subject(s)
Dalbergia , Humans , Dalbergia/metabolism , Salinity , Plants/metabolism , Antioxidants/metabolism , Photosynthesis
2.
Plant Physiol ; 194(4): 2301-2321, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38048404

ABSTRACT

Field and greenhouse studies attempting to describe the molecular responses of plant species under waterlogging (WL) combined with salinity (ST) are almost nonexistent. We integrated transcriptional, metabolic, and physiological responses involving several crucial transcripts and common differentially expressed genes and metabolites in fragrant rosewood (Dalbergia odorifera) leaflets to dissect plant-specific molecular responses and patterns under WL combined with ST (SWL). We discovered that the synergistic pattern of the transcriptional response of fragrant rosewood under SWL was exclusively characterized by the number of regulated transcripts. The response patterns under SWL based on transcriptome and metabolome regulation statuses revealed different patterns (additive, dominant, neutral, minor, unilateral, and antagonistic) of transcripts or metabolites that were commonly regulated or expressed uniquely under SWL. Under SWL, the synergistic transcriptional response of several functional gene subsets was positively associated with several metabolomic and physiological responses related to the shutdown of the photosynthetic apparatus and the extensive degradation of starch into saccharides through α-amylase, ß-amylase, and α-glucosidase or plastoglobuli accumulation. The dissimilarity between the regulation status and number of transcripts in plants under combined stresses led to nonsynergistic responses in several physiological and phytohormonal traits. As inferred from the impressive synergistic transcriptional response to morpho-physiological changes, combined stresses exhibited a gradually decreasing effect on the changes observed at the molecular level compared to those in the morphological one. Here, by characterizing the molecular responses and patterns of plant species under SWL, our study considerably improves our understanding of the molecular mechanisms underlying combined stress.


Subject(s)
Dalbergia , Dalbergia/genetics , Salinity , Transcriptome/genetics , Phenotype , Metabolomics , Stress, Physiological/genetics
3.
Zhongguo Zhong Yao Za Zhi ; 48(20): 5419-5437, 2023 Oct.
Article in Chinese | MEDLINE | ID: mdl-38114136

ABSTRACT

Curcuma wenyujin, as one of the eight Daodi-herbs in Zhejiang province, is widely used. It has the effects of eliminating stasis and dissipating mass, moving Qi and activating blood, and clearing heart and relieving depression. Modern studies have shown that it has anti-tumor, anti-inflammatory, anti-oxidation, anti-thrombus and liver-protecting effects and mainly contains sesquiterpenoids, monoterpenoids, diterpenoids, and curcumins. This paper reviews the research progress in the chemical constituents and pharmacological effects of C. wenyujin in the last decade, discusses the modern clinical applications combined with the traditional efficacy, and predicts its quality markers(Q-markers) from plant consanguinity, medicinal properties, efficacy, processing and measurability of chemical components based on the theory of Q-markers, so as to provide a reference for the establishment of a scientific quality evaluation system and the research and application of this herb in the future.


Subject(s)
Curcuma , Anti-Inflammatory Agents , Curcuma/chemistry , Liver
4.
BMC Plant Biol ; 22(1): 523, 2022 Nov 10.
Article in English | MEDLINE | ID: mdl-36357840

ABSTRACT

BACKGROUND: The mechanisms of abscisic acid (ABA) and auxin (IAA) in inducing adventitious root (AR) formation, biomass accumulation, and plant development under long-term waterlogging (LT-WL) conditions are largely unexplored. This study aimed to determine the roles of exogenous application of ABA and IAA in two woody plants (Cleistocalyx operculatus and Syzygium jambos) under LT-WL conditions. A pot experiment was conducted using a complete randomized design with two factors: (i) LT-WL and (ii) application of exogenous phytohormones (ABA and IAA) for 120 d. RESULTS: Results revealed that exogenous ABA and IAA promoted LT-WL tolerance in both species. In C. operculatus and S. jambos, plant height, the number of blades, leaf area, and fresh shoot weight were increased by exogenous IAA under LT-WL. However, exogenous ABA affected more the adventitious and primary root in C. operculatus compared to S. jambos. LT-WL decreased drastically the photosynthetic activities in both species, but adding moderate amounts of exogenous ABA or IAA protected the photosynthesis apparatus under LT-WL. Exogenous phytohormones at certain levels decreased the superoxide anion level and malondialdehyde accumulation in plants under LT-WL. Also, the increase of the peroxidases and superoxide dismutase activities by exogenous phytohormones was more marked in C. operculatus compared to S. jambos. Meanwhile, the catalase activity was down-regulated in both species by exogenous phytohormones. Exogenous ABA or IAA positively regulated the jasmonic acid content in ARs under LT-WL. Moderate application of exogenous ABA or IAA in plants under LT-WL decreased the ABA content in the leaves. Lower accumulation of IAA and ABA in the leaves of C. operculatus under LT-WL was positively correlated with a decrease in antioxidant activity. CONCLUSIONS: Lastly, C. operculatus which has greater morphology indexes was more tolerant to waterlogging than S. jambos. Moreover, the adaptive strategies via exogenous ABA were more built around the below-ground biomass indexes particularly in C. operculatus, while exogenous IAA backed the above-ground biomass in both species. Overall, the exogenous hormones applied (spraying or watering) influenced differentially the plant's responses to LT-WL. The phytohormonal profile of plants exposed to waterlogging stress varied depending on the species' tolerance level.


Subject(s)
Abscisic Acid , Syzygium , Indoleacetic Acids , Plant Growth Regulators/pharmacology , Plant Leaves , Plant Roots/physiology
5.
Sci Rep ; 10(1): 20639, 2020 11 26.
Article in English | MEDLINE | ID: mdl-33244131

ABSTRACT

Farnesyl pyrophosphate synthase (FPS) is a key enzyme that catalyzes the formation of farnesyl pyrophosphate, the main initiator for rubber chain initiation in Hevea brasiliensis Muell. Arg. The transcriptional regulatory mechanisms of the FPS gene still not well understood. Here, a WRKY transcription factor designated HbWRKY27 was obtained by screening the latex cDNA library applied the HbFPS1 promoter as bait. HbWRKY27 interacted with the HbFPS1 promoter was further identified by individual Y1H and EMSA assays. HbWRKY27 belongs to group IIe WRKY subfamily which contains a typical WRKY domain and C-X5-CX23-HXH motif. HbWRKY27 was localized to the nucleus. HbWRKY27 predominantly accumulated in latex. HbWRKY27 was up-regulated in latex by ethrel, salicylic acid, abscisic acid, and methyl jasmonate treatment. Transient expression of HbWRKY27 led to increasing the activity of the HbFPS1 promoter in tobacco plant, suggesting that HbWRKY27 positively regulates the HbFPS1 expression. Taken together, an upstream transcription factor of the key natural rubber biosynthesis gene HbFPS1 was identified and this study will provide novel transcriptional regulatory mechanisms of the FPS gene in Hevea brasiliensis.


Subject(s)
Hevea/genetics , Plant Proteins/genetics , Transcription Factors/genetics , Acetates/metabolism , Amino Acid Sequence , Cell Nucleus/genetics , Cyclopentanes/metabolism , Gene Expression Regulation, Plant/genetics , Genes, Plant/genetics , Hevea/metabolism , Latex/metabolism , Oxylipins/metabolism , Plant Growth Regulators/genetics , Promoter Regions, Genetic/genetics , Rubber/metabolism , Nicotiana/genetics , Nicotiana/metabolism , Up-Regulation/genetics
6.
PLoS One ; 13(11): e0206497, 2018.
Article in English | MEDLINE | ID: mdl-30427885

ABSTRACT

Streptomyces species 1-14 isolated from cassava rhizosphere soil were evaluated for their antibacterial efficacy against Fusarium oxysporum f.sp. cubense race 4 (FOC4). Of the 63 strains tested, thirteen exhibited potent antibacterial properties and were further screened against eight fungal pathogens. The strain that showed maximum inhibition against all of the test pathogens was identified by 16S rDNA sequencing as Streptomyces sp. 1-14, was selected for further studies. Through the propagation of Streptomyces sp. 1-14 in soil under simulated conditions, we found that FOC4 did not significantly influence the multiplication and survival of Streptomyces sp. 1-14, while indigenous microorganisms in the soil did significantly influence Streptomyces sp. 1-14 populations. To achieve maximum metabolite production, the growth of Streptomyces 1-14 was optimized through response surface methodology employing Plackett-Burman design, path of steepest ascent determinations and Box-Behnken design. The final optimized fermentation conditions (g/L) included: glucose, 38.877; CaCl2•2H2O, 0.161; temperature, 29.97°C; and inoculation amount, 8.93%. This optimization resulted in an antibacterial activity of 56.13% against FOC4, which was 12.33% higher than that before optimization (43.80%). The results obtained using response surface methodology to optimize the fermentation medium had a significant effect on the production of bioactive metabolites by Streptomyces sp. 1-14. Moreover, during fermentation and storage, pH, light, storage temperature, etc., must be closely monitored to reduce the formation of fermentation products with reduced antibacterial activity. This method is useful for further investigations of the production of anti-FOC4 substances, and could be used to develop bio-control agents to suppress or control banana fusarium wilt.


Subject(s)
Anti-Bacterial Agents/biosynthesis , Biotechnology/methods , Fermentation , Rhizosphere , Streptomyces/growth & development , Streptomyces/metabolism , Musa/microbiology , Soil Microbiology
7.
Aquat Toxicol ; 184: 49-60, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28104549

ABSTRACT

Silver_nanoparticles (AgNPs) have been reported to inhibit specification of erythroid cells and to induce spinal cord deformities and cardiac arrhythmia in vertebrates, but have not been implicated in development of neural crest (NC) and pigment cells in an in vivo model yet. In current study, down-regulated expressions of NC genes pax7 and foxd3, melanophore genes mitfa and dct, and xanthophore gene gch2 in AgNPs-exposed embryos were revealed by microarray, qRT-PCR and whole-mount in situ hybridization (WISH). Then, the down-regulated expressions of melanophore genes mitfa and dct but not xanthophore gene gch2 in AgNPs-exposed embryos were found to be recovered by melanogenesis agonists palmitic acid and dibutyryl cyclic AMP (dbcAMP). Finally, Ag+ chelating and AgNPs coating compound l-cysteine was found to neutralize AgNPs-induced hypopigmentation in AgNPs-exposed embryos, and to recover the down-regulated expressions of both dct and gch2 to nearly normal level in embryos, suggesting that AgNPs-releasing Ag+ might mediate their biological effects on zebrafish pigmentation mostly. This study was firstly to unveil that AgNPs might specifically act up-stream of mitfa and pax7 genes to suppress specification and differentiation of melanophore and xanthophore lineages respectively by their releasing Ag+ during vertebrate embryogenesis.


Subject(s)
Hypopigmentation/chemically induced , Metal Nanoparticles/toxicity , Silver/toxicity , Animals , Embryo, Nonmammalian/drug effects , Embryonic Development/drug effects , Gene Expression Regulation, Developmental/drug effects , Hypopigmentation/physiopathology , In Situ Hybridization , Water Pollutants, Chemical/toxicity , Zebrafish/embryology , Zebrafish Proteins/genetics
8.
Nanotoxicology ; 11(2): 157-167, 2017 03.
Article in English | MEDLINE | ID: mdl-28044463

ABSTRACT

The rapid growth in silver nanoparticles (AgNPs) commercialization has increased environmental exposure, including aquatic ecosystem. It has been reported that the AgNPs have damaging effects on photosynthesis and induce oxidative stress, but the toxic mechanism of AgNPs is still a matter of debate. In the present study, on the model aquatic higher plant Spirodela polyrhiza, we found that AgNPs affect photosynthesis and significantly inhibit Photosystem II (PSII) maximum quantum yield (Fv/Fm) and effective quantum yield (ΦPSII). The changes of non-photochemical fluorescence quenching (NPQ), light-induced non-photochemical fluorescence quenching [Y(NPQ)] and non-light-induced non-photochemical fluorescence quenching [Y(NO)] showed that AgNPs inhibit the photo-protective capacity of PSII. AgNPs induce reactive oxygen species (ROS) that are mainly produced in the chloroplast. The activity of ribulose-1, 5-bisphosphate carboxylase-oxygenase (Rubisco) was also very sensitive to AgNPs. The internalized Ag, regardless of whether the exposure was Ag+ or AgNPs had the same capacity to generate ROS. Our results support the hypothesis that intra-cellular AgNP dissociate into high toxic Ag+. Rubisco inhibition leads to slowing down of CO2 assimilation. Consequently, the solar energy consumption decreases and then the excess excitation energy promotes ROS generation in chloroplast.


Subject(s)
Araceae/drug effects , Metal Nanoparticles/toxicity , Oxidative Stress/drug effects , Photosynthesis/drug effects , Reactive Oxygen Species/metabolism , Silver/toxicity , Araceae/physiology , Araceae/radiation effects , Chlorophyll/metabolism , Energy Transfer , Metal Nanoparticles/chemistry , Photosystem II Protein Complex/metabolism , Silver/chemistry , Sunlight
9.
Aquat Toxicol ; 177: 295-305, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27340786

ABSTRACT

Silver_ nanoparticles (AgNPs), for their attractive antimicrobial properties, have become one of the most commercial nanomaterials used recently. AgNPs are reported to be toxic to blood cells of aquatic organisms and humans, however, few studies related to toxic effects of AgNPs in hematopoiesis using an in vivo model were available. Firstly, microarrays were applied to reveal transcriptional responses of zebrafish embryos to AgNPs at 24h post-fertilization (hpf)in this study, and hemoglobin genes were found to be down-regulated by AgNPs and to be enriched in the top 10 categories by Gene Ontology (GO) analysis. The reduced expressions of hemoglobin were further demonstrated by qRT-PCR detection, whole-mount in situ hybridization, and O-dianisidine staining at transcriptional and translational level. Next, the commitment of mesoderm, specification of hematopoietic progenitor cells and differentiation of erythroids were detected at different developmental stages in AgNPs-exposed embryos, and erythrogenesis were found to be inhibited by AgNPs in developmental-stage-specific and cell-specific manners. Finally, it was pointed out that AgNPs affected erythrogenesis mostly by their particles other than their releasing ions.


Subject(s)
Embryonic Development/drug effects , Erythropoiesis/drug effects , Metal Nanoparticles/toxicity , Silver/toxicity , Water Pollutants, Chemical/toxicity , Animals , Down-Regulation/drug effects , Embryo, Nonmammalian/drug effects , Embryo, Nonmammalian/physiology , Embryonic Development/physiology , Erythropoiesis/genetics , Female , Genetic Markers , Hemoglobins/genetics , Male , Oligonucleotide Array Sequence Analysis , Reverse Transcriptase Polymerase Chain Reaction , Zebrafish
10.
Environ Toxicol Chem ; 33(6): 1398-405, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24619507

ABSTRACT

Silver nanoparticles (AgNPs) are widely used commercially because of their antibacterial properties. Oxidative stress is known to be involved in the toxicity of AgNPs to bacteria, animals, and algae. The authors used Spirodela polyrhiza to investigate whether AgNPs can induce oxidative stress in higher plants. Results showed that there was a dose-dependent increase in levels of reactive oxygen species, superoxide dismutase and peroxidase activity, and the antioxidant glutathione content in 6-nm AgNP treatments. Catalase activity and malondialdehyde content in 6-nm AgNP treatments was significantly higher than the control at silver concentrations of 5 mg L(-1) . Superoxide dismutase and catalase activity and antioxidant glutathione and malondialdehyde content were not significantly different at 10 mg L(-1) of AgNPs (6 nm and 20 nm). Treatment with 20 µg L(-1) Ag(+) (the amount almost equal to 10 mg L(-1) AgNPs released) did not change the reactive oxygen species level or antioxidant enzymes activity. Micron-sized Ag particles had no effect on S. polyrhiza. Transmission electron microscopy showed that, compared with the control, chloroplasts in S. polyrhiza treated with 6-nm and 20-nm AgNPs accumulated starch grains and had reduced intergranal thylakoids. These results clearly indicate that AgNPs are able to cause oxidative stress and affect the chloroplast structure and function of S. polyrhiza, and this effect was not caused by Ag(+) released from particles.


Subject(s)
Antioxidants/metabolism , Araceae/drug effects , Araceae/metabolism , Metal Nanoparticles/toxicity , Reactive Oxygen Species/metabolism , Silver/chemistry , Silver/toxicity , Araceae/enzymology , Culture Media/chemistry , Glutathione/metabolism , Malondialdehyde/metabolism , Oxidative Stress/drug effects , Particle Size , Plant Proteins/metabolism
11.
Mil Med ; 178(6): 696-700, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23756079

ABSTRACT

A challenge facing military caregivers is the presence of multidrug-resistant infection in extremity wounds. Most frequently identified resistant strains are methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae (KP), Pseudomonas aeruginosa (PA), and Acinetobacter baumannii (AB). We adapted an existing osteomyelitis model to simulate an infected extremity wound for antibiotic testing. New Zealand White Rabbits (n = 95) were divided into 6 inoculation groups for infection with MRSA, KP, PA, and AB alone, and in multibacteria infections. Sodium morrhuate was injected into the left tibia to simulate blast wound trauma, then the respective bacteria or combination of pathogens, and finally sterile saline were injected. Colony-forming units for the mono-organism groups showed that AB, KP, or PA alone at 10(7) colony-forming units per mL (CFUs/mL) was effective for rabbit osteomyelitis induction. Colony-forming units for the multiorganism groups showed that the combination of AB (10(7) CFUs/mL)/KP (10(7) CFUs/mL)/PA (10(7) CFUs/mL)/MRSA (10(5) CFUs/mL) yielded a 100% osteomyelitis induction rate. At 8 weeks, however, only one mono-bacterial group and one multibacterial group showed significant radiographic improvement (p < 0.05). The rabbit model of osteomyelitis can be adapted to study infected blast wounds typical of those seen in veterans. To our knowledge, this is the first demonstration of the model simulating multibacterial infections with multidrug-resistant organisms.


Subject(s)
Disease Models, Animal , Drug Resistance, Multiple, Bacterial , Osteomyelitis/microbiology , Wound Infection/microbiology , Animals , Military Personnel , Osteomyelitis/diagnostic imaging , Rabbits , Radiography , Warfare , Wound Infection/diagnostic imaging
12.
Orthopedics ; 35(7): e1046-50, 2012 Jul 01.
Article in English | MEDLINE | ID: mdl-22784898

ABSTRACT

Surgical-site infection is a common form of noscomial infection that can occur in fractures following internal fixation. Treatment of these infections has traditionally included preserving stable implants via debridement and antibiotic administration while the fracture is healing. Recent evidence indicated that this algorithm results in less-than-optimal rates of fracture union and infection eradication.The premise for this study is that bacterial removal from fracture implants using the Versajet Hydrosurgery System (Smith & Nephew, Memphis, Tennessee) method is better compared with the bulb syringe and pressurized pulsatile lavage methods. Thirty-two stainless steel, 4-hole, nonlocking, 3.5-mm fracture plates were incubated with Staphylococus aureus and divided into 4 groups. Eight plates in each group underwent irrigation with 1 L of saline using a bulb syringe lavage, pressurized pulsatile lavage, or the Versajet Hydrosurgery System method. Eight plates underwent no irrigation method and served as a control group. The residual bacterial loads following irrigation were quantitatively cultured. Each of the experimental groups had significantly reduced levels of bacteria adherent to the plate following irrigation compared with the control group (P=.0002). Furthermore, the Versajet Hydrosurgery System was most the effective at bacterial removal, followed by the pressurized pulsatile and bulb syringe lavage techniques (P=.0002 to P=.0012, respectively).Novel approaches to eradicate bacteria from implants, such as hydrosurgery technology, while maintaining rigid stability of healing fracture, may improve clinical outcomes.


Subject(s)
Bacteria/isolation & purification , Debridement/methods , Fractures, Bone/microbiology , Fractures, Bone/surgery , Internal Fixators/microbiology , Sterilization/methods , Therapeutic Irrigation/methods , Humans , Pressure , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/prevention & control , Syringes
13.
Environ Toxicol Chem ; 31(8): 1880-6, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22639346

ABSTRACT

Silver nanoparticles (AgNPs) are commonly used in consumer products for their antibacterial activity. Silver nanoparticles may adversely influence organisms when released into the environment. The present study investigated the effect of AgNPs on the growth, morphology, and physiology of the aquatic plant duckweed (Spirodela polyrhiza). The toxicity of AgNPs and AgNO(3) was also compared. The results showed that silver content in plant tissue increased significantly with higher concentrations of AgNPs and AgNO(3) . Silver nanoparticles and AgNO(3) significantly decreased plant biomass, caused colonies of S. polyrhiza to disintegrate, and also resulted in root abscission. Physiological analysis showed that AgNPs and AgNO(3) significantly decreased plant tissue nitrate-nitrogen content, chlorophyll a (Chl a) content, chlorophyll a/b (Chl a/b), and chlorophyll fluorescence (Fv/Fm). Changes in soluble carbohydrate and proline content were also detected after both AgNO(3) and AgNPs treatment. However, after 192 h of recovery, total chlorophyll content increased, and Fv/Fm returned to control level. Median effective concentration (EC50) values for Chl a and phosphate content showed that AgNO(3) was more toxic than AgNPs (EC50 values: 16.10 ± 0.75 vs 7.96 ± 0.81 and 17.33 ± 4.47 vs 9.14 ± 2.89 mg Ag L(-1) , respectively), whereas dry-weight EC50 values showed that AgNPs were more toxic than AgNO(3) (13.39 ± 1.06 vs 17.67 ± 1.16 mg Ag L(-1) ).


Subject(s)
Araceae/drug effects , Metal Nanoparticles/toxicity , Silver Nitrate/toxicity , Araceae/cytology , Araceae/growth & development , Biomass , Dose-Response Relationship, Drug , Hydrobiology
14.
J Antimicrob Chemother ; 63(2): 357-60, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19060292

ABSTRACT

OBJECTIVES: Staphylococcus aureus is the most common pathogen isolated in osteomyelitis. This study evaluated the efficacies of telavancin (an investigational, rapidly bactericidal lipoglycopeptide with a multifunctional mechanism of action against Gram-positive bacteria), vancomycin and linezolid in a rabbit methicillin-resistant S. aureus (MRSA) osteomyelitis model. METHODS: Localized osteomyelitis was induced in New Zealand White rabbits by percutaneous injection of 10(6) cfu of MRSA clinical isolate 168-1 into the intramedullary cavity. Two weeks post-infection, rabbits with radiographically confirmed, localized proximal tibial osteomyelitis were randomized into four groups (n = 15 per group): untreated controls; vancomycin 30 mg/kg subcutaneously every 12 h; linezolid 60 mg/kg orally every 8 h; and telavancin 30 mg/kg subcutaneously every 12 h. After 4 weeks of antibiotic treatment, animals were left untreated for 2 weeks. Rabbits were then euthanized and the tibias harvested. Bone matrix and marrow from each tibia were cultured and bacterial counts determined. RESULTS: For MRSA isolate 168-1, the MIC was 0.25 mg/L for telavancin, 0.5 mg/L for vancomycin and 0.5 mg/L for linezolid. Tibial cultures were positive for MRSA in 9 of 15 (60%) untreated controls, and 3 of 15 (20%) telavancin-treated, 3 of 15 (20%) vancomycin-treated and 4 of 14 (29%) linezolid-treated rabbits. CONCLUSIONS: Telavancin has comparable efficacy to vancomycin and linezolid in a rabbit model of MRSA osteomyelitis.


Subject(s)
Aminoglycosides/therapeutic use , Anti-Bacterial Agents/therapeutic use , Methicillin-Resistant Staphylococcus aureus/drug effects , Osteomyelitis/drug therapy , Staphylococcal Infections/drug therapy , Acetamides/therapeutic use , Animals , Bone Marrow/microbiology , Colony Count, Microbial , Linezolid , Lipoglycopeptides , Microbial Sensitivity Tests , Osteomyelitis/microbiology , Oxazolidinones/therapeutic use , Rabbits , Random Allocation , Staphylococcal Infections/microbiology , Treatment Outcome , Vancomycin/therapeutic use
15.
Antimicrob Agents Chemother ; 52(5): 1618-22, 2008 May.
Article in English | MEDLINE | ID: mdl-18332175

ABSTRACT

The pharmacokinetics and distribution into bone tissue of ceftobiprole in uninfected New Zealand White rabbits were determined after subcutaneous administration of the prodrug ceftobiprole medocaril. Serum exposure (maximum concentration of the drug in serum, trough concentration, area under the concentration-time curve) to ceftobiprole at 20 and 80 mg/kg was dose proportional, and there was no accumulation of ceftobiprole following repeated (every 6 h [q6h]) injections of the antibiotic. Ceftobiprole titers in the tibial matrix and marrow were 3.2 +/- 1.3 microg/g and 11.2 +/- 6.5 microg/g, respectively, in uninfected animals treated with 20 mg/kg of the antibiotic and 13.4 +/- 7.3 microg/g and 66.3 +/- 43.2 microg/g, respectively, in uninfected animals treated with 80 mg/kg of the antibiotic. No differences in ceftobiprole titers were observed between right and left tibiae for either bone matrix or marrow. The efficacies of 4 weeks of treatment with ceftobiprole (40 mg/kg administered subcutaneously [s.c.] q6h), vancomycin (30 mg/kg administered s.c. q12h), or linezolid (60 mg/kg administered orally q8h) were compared, using a rabbit model of methicillin-resistant Staphylococcus aureus tibial osteomyelitis. After treatment with ceftobiprole, the bacterial titers in all infected left tibiae from evaluable rabbits were below the level of detection, whereas only 73% of infected left tibiae from vancomycin- or linezolid-treated animals had bacterial titers below the level of detection; the mean titers of ceftobiprole were 3 to 5 times higher in infected left tibiae than in uninfected right tibiae. These results indicate that ceftobiprole provided effective parenteral treatment of osteomyelitis in this rabbit model.


Subject(s)
Cephalosporins/pharmacology , Methicillin Resistance , Osteomyelitis/drug therapy , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Animals , Body Weight/drug effects , Cephalosporins/pharmacokinetics , Disease Models, Animal , Microbial Sensitivity Tests , Osteomyelitis/metabolism , Osteomyelitis/microbiology , Rabbits , Staphylococcal Infections/metabolism , Staphylococcal Infections/microbiology , Tibia/drug effects , Tibia/microbiology , Tibia/pathology
16.
J Antimicrob Chemother ; 55(6): 995-1002, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15857944

ABSTRACT

OBJECTIVES: Staphylococcus aureus is the most common organism isolated in osteomyelitis. Methicillin-resistant S. aureus (MRSA) infections are particularly difficult to treat. We evaluated the efficacy of tigecycline and vancomycin with and without rifampicin in a rabbit model of MRSA osteomyelitis. METHODS: A 28 day antibiotic therapy with a subcutaneous injection of tigecycline (14 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily); or subcutaneous administration of vancomycin (30 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily) were compared. Osteomyelitis was induced with an intramedullary injection of 10(6) colony-forming units of MRSA. Infected rabbits were randomly divided into six groups: tigecycline, tigecycline with oral rifampicin, vancomycin, vancomycin with oral rifampicin, and no treatment control and tigecycline bone penetration groups. Treatment began 2 weeks after infection. After 4 weeks of therapy, the rabbits were left untreated for 2 weeks. Rabbits were then euthanized, and the tibias were harvested. The bones were cultured, and bacterial counts of MRSA were performed. RESULTS: Rabbits that received tigecycline and oral rifampicin therapy (n=14) showed a 100% infection clearance. Rabbits treated with tigecycline (n=10) showed a 90% clearance. Rabbits treated with vancomycin and oral rifampicin (n=10) also showed a 90% clearance. Rabbits treated with vancomycin (n=11) showed an 81.8% clearance. Untreated controls (n=15) demonstrated only a 26% clearance. For the tigecycline bone penetration group, the bone concentrations of tigecycline in the infected tibia were significantly higher than the non-infected ones. CONCLUSIONS: Tigecycline may be an effective alternative to vancomycin in the treatment of MRSA osteomyelitis.


Subject(s)
Drug Therapy, Combination/therapeutic use , Minocycline/analogs & derivatives , Osteomyelitis/drug therapy , Rifampin/therapeutic use , Staphylococcal Infections/drug therapy , Vancomycin/therapeutic use , Animals , Bone and Bones/microbiology , Disease Models, Animal , Methicillin Resistance , Minocycline/administration & dosage , Minocycline/adverse effects , Minocycline/therapeutic use , Osteomyelitis/diagnostic imaging , Osteomyelitis/microbiology , Rabbits , Radiography , Rifampin/adverse effects , Staphylococcus aureus/isolation & purification , Tigecycline , Vancomycin/administration & dosage , Vancomycin/adverse effects
17.
Surg Infect (Larchmt) ; 3(3): 283-9, 2002.
Article in English | MEDLINE | ID: mdl-12542929

ABSTRACT

We present a case of systemic fungal infection caused by Apophysomyces elegans in a 50-year-old patient who developed a progressive skin lesion after a motor vehicle crash. Histopathological and mycological examination of the surgical sample showed non-septated hyphae characteristic of mucoraceous fungi. Despite extensive surgical debridement, and parenteral administration of amphotericin B, the patient died of multi-organ failure. Autopsy findings suggested systemic involvement. The fungi recovered from culture had non-apophyseal and globose sporangi, and branched sporaniophores and was identified as Apophysomyces elegans.


Subject(s)
Mucorales , Mucormycosis/complications , Wound Infection/complications , Wounds and Injuries/complications , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Fatal Outcome , Humans , Male , Middle Aged , Mucormycosis/microbiology , Mucormycosis/therapy , Multiple Organ Failure/etiology , Wound Infection/microbiology , Wound Infection/therapy
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