A2B5-positive oligodendrocyte precursor cell transplantation improves neurological deficits in rats following spinal cord contusion associated with changes in expression of factors involved in the Notch signaling pathway.

BACKGROUND: Oligodendrocyte precursor cells (OPCs) are myelinated glial cells of the central nervous system (CNS), able to regenerate oligodendrocytes and myelin. This study aimed to elucidate the effect of A2B5-positive (A2B5+) OPC transplantation in rats with spinal cord contusion (SCC) and to investigate changes in expression of various factors involved in the Notch signaling pathway after OPC transplantation. METHODS: OPCs were obtained from induced pluripotent stem cells (iPSCs) originating from mouse embryo fibroblasts (MEFs). After identification of iPSCs and iPSC-derived OPCs, A2B5+ OPCs were transplanted into the injured site of rats with SCC one week after SCC insult. Behavioral tests evaluated motor and sensory function 7 days after OPC transplantation. Real-time quantitative polymerase chain reaction (RT-qPCR) determined the expression of various cytokines related to the Notch signaling pathway after OPC transplantation. RESULTS: IPSC-derived OPCs were successfully generated from MEFs, as indicated by positive immunostaining of A2B5, PDGFα and NG2. Further differentiation of OPCs was identified by immunostaining of Olig2, Sox10, Nkx2.2, O4, MBP and GFAP. Importantly, myelin formation was significantly enhanced in the SCC+ OPC group and SCI-induced motor and sensory dysfunction was largely alleviated by A2B5+ OPC transplantation. Expression of factors involved in the Notch signaling pathway (Notch-1, Numb, SHARP1 and NEDD4) was significantly increased after OPC transplantation. CONCLUSIONS: A2B5+ OPC transplantation attenuates motor and sensory dysfunction in SCC rats by promoting myelin formation, which may be associated with change in expression of factors involved in the Notch signaling pathway.

[Whole exome sequencing and analysis of a Chinese family with familial pulmonary sarcoidosis].

Objective: To analyze the clinical features and the results of the whole exome sequencing (WES) of a Chinese family containing both pulmonary sarcoidosis patients and healthy members, and to find potent genes and variants that may be involved in the pathogenesis of sarcoidosis. Methods: Three patients with pulmonary sarcoidosis and 1 healthy member was included from a Chinese Han family in the north of China diagnosed in November 2016, which characterized as 2 consecutive generations including 2 males and 1 female, aged from 23 to 69 years old. The proband is Ⅱ-6. Pulmonary sarcoidosis was diagnosed by clinical features, imaging and pathological findings, and clinical data such as family history were collected. Whole blood samples were taken and WES (Illumina NovaSeq S2) was performed. The pathogenicity analysis and gene annotation analysis were performed by ExAC, SIFT, Polyphenv2, Metascape databases. Results: It was found that 27 genes were highly pathogenic in the database filtering result. After gene annotation analysis, we found that ZC3H12A gene can negatively regulate the differentiation of Th17 cells, which may be involved in the onset of pulmonary sarcoidosis. Sanger sequencing confirmed the c.1361 A>G variant in 3 sarcoidosis patients but normal in healthy member. Conclusions: In patients with familial pulmonary sarcoidosis, the genetic background could regulate immune response which is one of the pathogenic mechanisms of sarcoidosis. The whole exome test and gene ontology analysis showed that Ⅱ-2, Ⅱ-6 and Ⅲ-1 pulmonary sarcoidosis patients in this family were all shared the same variant on ZC3H12A gene, which played a pivotal role in differentiation of Th17 cells and is a potent pathogenesis gene in this Chinese pulmonary sarcoidosis family.

Down-regulation of MIAT suppresses osteosarcoma progression by acting as a ceRNA for miR-141-3p to regulate SIX1-mediated PI3K/AKT pathway.

OBJECTIVE: Osteosarcoma (OS) is a frequent bone malignancy. Long non-coding RNA myocardial infarction associated transcript (MIAT) has been reported to be involved in the development of human cancers, including OS. However, the mechanism underlying MIAT in OS progression remains largely unclear. PATIENTS AND METHODS: The expression levels of MIAT and sineoculis homeobox homolog 1 (SIX1) in OS tissues and cells were detected by quantitative real-time polymerase chain reaction and Western blot. Cell viability, apoptosis, migration and invasion of OS cells were determined by MTT, flow cytometry and trans-well assays, respectively. The target interaction among MIAT, miR-141-3p and SIX1 was analyzed by bioinformatics analysis and luciferase reporter assay. Phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT) pathway was evaluated by Western blot. RESULTS: MIAT and SIX1 expression levels were enhanced in OS tissues and cells. Knockdown of MIAT or SIX1 repressed cell viability, migration and invasion but promoted apoptosis in OS cells. Moreover, overexpression of SIX1 reversed the inhibitive role of MIAT silence in OS progression. Furthermore, MIAT could increase SIX1 expression by competitively sponging miR-141-3p. Besides, inhibition of MIAT blocked PI3K/AKT pathway by decreasing SIX1 in OS cells. CONCLUSIONS: MIAT silence suppresses OS progression through inactivating PI3K/AKT signaling by sponging miR-141-3p to regulate SIX1, indicating a novel target for the treatment of OS.

[The role of histone deacetylases in the pathogenesis of idiopathic pulmonary fibrosis and cryptogenic organizing pneumonia].

Objective: To explore the role of histone deacetylases(HDAC) in the pathogenesis of idiopathic pulmonary fibrosis(IPF) and cryptogenic organizing pneumonia(COP). Methods: Fifteen IPF patients [14 males and 1female, age 40-73 years, mean age (59±8) years] and 15 COP patients [5 males and 10 females, age 41-71 years, mean age (59±8) years] from Peking Union Medical College Hospital were recruited from March 2018 to October 2018. Fifteen healthy donors[4 males and 11females, age 43-70 years, mean age (58±6) years] were enrolled as controls. Peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation. The nuclear and cytoplasmic proteins were extracted by Nuclear Extraction Kit. HDAC activity was measured by fluorimetric method. The relations between HDAC activity and clinical parameters were analyzed with SPSS. Results: The HDAC activity of cytoplasmic protein and nuclear protein from patients with IPF were (724±216) nmol/L and (2 309±708) nmol/L, which were higher than that of health controls (409±105) nmol/L and (1 572±611) nmol/L (P<0.01 for both). So as to the HDAC activity of cytoplasmic protein and nuclear protein from patients with COP which were (718±245) nmol/L and (3 310±1 005) nmol/L (P<0.01 for both).The HDAC activity of nuclear protein from COP patients was higher than that from IPF patients (Z=-2.840, P=0.005). The HDAC activity of nuclear protein was negatively correlated with FEV(1) and D(L)CO in IPF patients (r=-0.574, P=0.025; r=-0.583, P=0.029), and negatively correlated with FVC and TLC in COP patients(r=-0.846, P=0.016; r=-0.900, P=0.015). Conclusion: HDAC may be involved in the pathogenesis of COP and IPF.

[The role of B cell activating factor in the differential diagnosis of usual interstitial pneumonia].

Objective: To explore the differential diagnostic role of B cell-activating factor(BAFF) in idiopathic pulmonary fibrosis (IPF) and usual interstitial pneumonia (UIP) associated with autoimmune diseases (AIDs). Methods: Plasma levels of BAFF were measured by ELISA method in 23 patients with AIDs-UIP, 34 patients with IPF, and 21 healthy subjects as control. The correlation between plasma BAFF levels and other clinical results from patients was analyzed. Receiver operating characteristics (ROC) analysis for distinguishing AIDs-UIP from IPF patients was examined and the maximal area under curve (AUC) was found. Results: Plasma levels of BAFF were significantly elevated in AIDs-UIP patients and IPF patients compared to healthy subjects(P<0.001 and P=0.002, respectively). AIDs-UIP patients had higher level of BAFF than IPF patients(P=0.030). Plasma BAFF levels in AIDs-UIP patients were inversely correlated with pulmonary function results, including FVC%(r=-0.435, P=0.040)and TLC%(r=-0.449, P=0.041), as well as DLCO%(r=-0.491, P=0.024). When the cut off value of BAFF was set as 1.5 ng/ml to distinguish AIDs-UIP patients from IPF patients, the sensitivity and the specificity was 64.5% and 90.0%, respectively, and the area under ROC curve reached the maximum of 0.784(P=0.000, 95% CI: 66.3%-90.5%). Conclusions: Plasma BAFF levels were significantly higher and inversely correlated with pulmonary function, reflecting the severity of AIDs-UIP patients. Plasma BAFF levels may be a useful marker for distinguishing AIDs-UIP from IPF.

Resistin-like molecule-ß (RELM-ß) targets airways fibroblasts to effect remodelling in asthma: from mouse to man.

BACKGROUND: RELM-ß has been implicated in airways inflammation and remodelling in murine models. Its possible functions in human airways are largely unknown. The aim was to address the hypothesis that RELM-ß plays a role in extracellular matrix deposition in asthmatic airways. METHODS: The effects of RELM-ß gene deficiency were studied in a model of allergen exposure in mice sensitised and challenged with Aspergillus fumigatus (Af). RELM-ß expression was investigated in bronchial biopsies from asthmatic patients. Direct regulatory effects of RELM-ß on human lung fibroblasts were examined using primary cultures and the MRC5 cell line in vitro. RESULTS: Sensitisation and challenge of wild-type mice with Af-induced release of RELM-ß with a time course coincident with that of procollagen in the airways. Af-induced expression of mRNA encoding some, but not all ECM in the lung parenchyma was attenuated in RELM-ß-/- mice. RELM-ß expression was significantly increased in the bronchial submucosa of human asthmatics compared with controls, and its expression correlated positively with that of fibronectin and α-smooth muscle actin. In addition to epithelial cells, macrophages, fibroblasts and vascular endothelial cells formed the majority of cells expressing RELM-ß in the submucosa. Exposure to RELM-ß increased TGF-ß1, TGF-ß2, collagen I, fibronectin, smooth muscle α-actin, laminin α1, and hyaluronan and proteoglycan link protein 1 (Hapl1) production as well as proliferation by human lung fibroblasts in vitro. These changes were associated with activation of ERK1/2 in MRC5 cells. CONCLUSION: The data are consistent with the hypothesis that elevated RELM-ß expression in asthmatic airways contributes to airways remodelling at least partly by increasing fibroblast proliferation and differentiation with resulting deposition of extracellular matrix proteins.

Effects of sodium butyrate on growth performance, haematological and immunological characteristics of weanling piglets.

The experiment was conducted to study the effects of sodium butyrate (SB) on growth, haematological and immunological characteristics in weanling pigs. A total of 100 male piglets (Duroc×Landrace×Yorkshire) with a body weight of 8.0 ± 0.2 kg weaned at the age of 28 days were randomly assigned to two treatments with five replicates and 10 pigs per replicate. Piglets received a basal diet (control group) or diets supplemented with 1000 mg/kg SB. The feeding trial lasted for 21 days. The results showed that dietary SB significantly decreased (p < 0.05) diarrhoea incidence of weaned piglets, but did not affect (p > 0.05) the average daily feed intake (ADFI), average daily gain (ADG) and feed to gain (F/G). Furthermore, piglets fed dietary SB had higher (p < 0.05) serum concentrations of glucose and triglycerides and lower (p < 0.05) serum concentrations of urea nitrogen, cortisol, D-lactic acid and diamine oxidase when compared with the control group. However, dietary SB did not affect concentrations of serum albumin, total protein, insulin and glucagon (p > 0.05). There were no significant (p > 0.05) treatment effects on serum IgA and IgM, whereas serum IgG concentration and IgA+ cell count in jejunum from pigs fed SB were significantly higher (p < 0.05) than in those given the basal diet. In conclusion, the present study indicated that dietary SB significantly decreased diarrhoea incidence of weaned piglets and increased the efficiency of nitrogen utilization. Also, dietary SB could regulate and enhance the immune function of piglets by increasing the serum IgG concentration and IgA+ cell count in jejunum. Our results suggest that SB may reduce some of the adverse effects of weaning stress and play an important role in maintaining the integrity of intestinal mucosa.

Molecular analysis of intestinal bacterial microbiota of broiler chickens fed diets containing fermented cottonseed meal.

The study was conducted to investigate the effects of dietary inclusion of fermented cottonseed meal (FCM) on the ileal and cecal bacterial microbiota of broiler chickens. A total of 300 newborn yellow-feathered broiler chickens were randomly divided into 2 treatments with 3 replicates each (50 birds per replicate): control and 80 g/kg of FCM group. The feeding trial lasted for 42 d. Ileal and cecal digesta samples were collected from 8 chicks per replicate at 21 and 42 d of age to determine the composition of bacterial microbiota using denaturing gradient gel electrophoresis, cloning, sequencing, and real-time quantitative PCR analysis. The results demonstrated that the microbial composition in the ileum and cecum were considerably affected by the diet. The similarity dendrogram of banding profiles showed a more rapid stabilization of intestinal bacterial microbiota in broilers fed diets supplemented with FCM, compared with that of the birds fed the control diet. No significant difference was observed in total number of bands and Shannon-Weaver index, indicating that FCM had no effects on bacterial diversity. However, enumeration of bacteria in the ileal and cecal contents by quantitative PCR showed an increased (P < 0.05) population of lactobacilli, as well as a decreased (P < 0.05) Escherichia coli number by the dietary inclusion of FCM. In summary, dietary inclusion of FCM did not affect the intestinal microbial diversity but shifted intestinal microbiota, with a more homogenous population and an increased colonization of lactobacilli. The results also support the concept that dietary FCM inclusion could promote the beneficial bacteria in the intestinal tract.

Interleukin-25 promotes basic fibroblast growth factor expression by human endothelial cells through interaction with IL-17RB, but not IL-17RA.

BACKGROUND: Unlike other IL-17 family members, the Th2-derived cytokine IL-25 (IL-17E) induces (promotes) Th2 responses. One or both of the two receptors for IL-25 (IL-17RA, IL-17RB) is expressed on inflammatory cells and tissue structural cells, suggesting that in addition to promoting Th2-type inflammation IL-25 may also act on structural cells at sites of Th2-type inflammation such as in the asthmatic bronchial mucosa to promote remodelling changes. OBJECTIVE: Our previous studies showed elevated expression of IL-25 and IL-17RB immunoreactivity in asthmatic airways with co-localization of the latter to endothelial cells. We therefore hypothesized that IL-25 acts on endothelial cells through this receptor to induce production of the key angiogenic and remodelling cytokine basic fibroblast growth factor (bFGF). METHODS: Polymerase chain reaction (PCR) immunocytochemistry/immunohistochemistry and ELISA were employed to detect expression of IL-17RB, IL-17RA and bFGF by human vascular endothelial cells (HUVEC) and immunoreactivity for IL-25 and bFGF in asthmatic bronchial biopsies. Receptor-blocking antibodies, PCR and an in vitro angiogenesis assay were used to investigate whether IL-25 acts on IL-17RB or IL-17RA to induce bFGF expression and angiogenesis. PCR was also employed to investigate the signalling pathways involved in IL-25-mediated bFGF expression. RESULTS: HUVEC constitutively expressed IL-17RB, IL-17RA and bFGF. Production of the latter was further increased by IL-25, but attenuated after blockade of the IL-17RB, but not the IL-17RA receptor. Neutralization of endogenous VEGF and bFGF completely abrogated IL-25-induced angiogenesis which was also inhibited by blocking IL-17RB, but not IL-17RA. The PI3K-specific inhibitor LY294002 also completely attenuated IL-25-induced bFGF expression. Immunoreactivity for IL-25 and bFGF was elevated in the asthmatic bronchial mucosa and the expression of each correlated with the other. CONCLUSIONS AND CLINICAL RELEVANCE: Our data support the hypothesis that IL-25 contributes to elevated bFGF in asthmatic airways by acting on the endothelial cell IL-17RB receptor through PI3K-signalling pathways. Targeting the pathways might benefit therapy of airways remodelling.

Super-paramagnetic iron oxide nanoparticles for use in extrapulmonary tuberculosis diagnosis.

The limited sensitivity of serological tests for mycobacterial antigens has encouraged the development of a nanoparticle probe specific for the extrapulmonary form of Mycobacterium tuberculosis (Mtb). We developed an innovative probe comprised of super-paramagnetic iron oxide (SPIO) nanoparticles conjugated with Mtb surface antibody (MtbsAb-nanoparticles) to provide ultrasensitive imaging of biomarkers involved in extrapulmonary Mtb infection. MtbsAb-nanoparticles were significantly conjugated with Mtb bacilli. The extent of contrast enhancement reduction on magnetic resonance imaging (MRI) for Mtb and human monocytic THP1 cells was proportional to the concentration of MtbsAb-nanoparticles. When MtbsAb-nanoparticles were intravenously injected into mice bearing Mtb granulomas, the granulomatous site showed a 14-fold greater reduction in signal intensity enhancement on T(2) -weighted MR images compared with an opposing site that received PBS injection. Mtb sAb-nanoparticles represent a new non-invasive technology for the diagnosis of extrapulmonary Mtb.

Type I and II collagen regulation of chondrogenic differentiation by mesenchymal progenitor cells.

Chondrogenic differentiation by mesenchymal progenitor cells (MPCs) is associated with cytokines such as transforming growth factor-beta 1 (TGF-beta1) and dexamethasone. Extracellular matrix (ECM) also regulates the differentiation by MPCs. To define whether ECM plays a functional role in regulation of the chondrogenic differentiation by MPCs, an in vitro model was used. That model exposed to dexamethasone, recombinant human TGF-beta1(rhTGF-beta1) and collagens. The results showed that MPCs incorporated with dexamethasone and rhTGF-beta1 increased proliferation and expression of glycosaminoglycan (GAG) after 14 days. Type II collagen enhanced the GAG synthesis, but did not increase alkaline phosphatase (ALP) activity. When adding dexamethasone and rhTGF-beta1 MPCs increased mRNA expression of Sox9. Incorporation with type II collagen, dexamethasone and rhTGF-beta1, MPCs induced mRNA expression of aggrecan and enhanced levels of type II collagen, and Sox9 mRNA. In contrast, incorporation with type I collagen, dexamethasone and rhTGF-beta1 MPCs reduced levels of aggrecan, and Sox9 mRNA, and showed no type II collagen mRNA. Altogether, these results indicate that type I and II collagen, in addition to the cytokine effect, may play a functional role in regulating of chondrogenic differentiation by MPCs.

MRI and histology of collagen template disc implantation and regeneration in rabbit temporomandibular joint: preliminary report.

INTRODUCTION: We aimed to evaluate regeneration of injured temporomandibular joint (TMJ) discs following reconstituted collagen template implantation in rabbits using contrast-enhanced magnetic resonance imaging (MRI) and to correlate these findings with histology. METHODS: Twenty-four adult rabbits were divided into five groups: group A, partial discectomy without implantation (n = 6); group B, partial discectomy with collagen template implantation (n = 6); group C, partial discectomy with subdermal graft implantation (n = 6); group D, sham operation (n = 4); and group E, control (n = 2). All rabbits received baseline MRI scans before surgery and follow-up MRI studies at 3 months after surgery. All rabbits were sacrificed for histologic analysis after the follow-up MRI. RESULTS: In group A, follow-up MRI showed marked joint effusion in all six injured TMJs, which was accompanied by bony erosion at the tympanic fossa and mandibular condyle. In group B, MRI showed a homogenous low signal intensity in five of six discs, suggestive of regeneration. One disc showed higher signal intensity at its lateral portion than that of the original disc, indicating partial regeneration. MRI of group C depicted a low signal intensity, bandlike regenerative structure in four of the six discs. One disc with partial regeneration demonstrated relatively high signal intensity. The disc in the sixth animal of this group showed no evidence of regeneration. All of the MRI findings were in agreement with the histologic findings. CONCLUSION: TMJ discs can regenerate following implantation of a reconstituted collagen template in discectomied rabbits. Contrast-enhanced MRI can be used to monitor and determine the degree of disc regeneration.

Surfactant and corticosteroid effects on lung function in a rat model of acute lung injury.

OBJECTIVES: To evaluate pulmonary responses to intratracheal administration of surfactant with and without dexamethasone in rats with paraquat-induced lung injury. DESIGN: Prospective, randomized, controlled study. SETTING: University research facility. SUBJECTS: Adult male Sprague Dawley rats. INTERVENTIONS: Rats were anesthetized and underwent a tracheostomy and arterial catheter insertion 3 days after intraperitoneal injection of paraquat (35 mg/kg). The rats were ventilated for 90 mins after sequential designation as controls or as recipients of intratracheal surfactant alone (50 or 100 mg/kg) or surfactant (50 or 100 mg/kg) plus dexamethasone (0.5 mg/kg). MEASUREMENTS AND MAIN RESULTS: Arterial blood gases were determined at 15, 30, 60, and 90 mins. After 90 mins of ventilation, a static pressure-volume curve was performed, and inflammatory cells, total protein content, and cytokines were measured in bronchoalveolar lavage fluid. Postmortem histology was then examined. Treatment with 50 mg/kg dexamethasone/Survanta and 100 mg/kg Survanta with and without dexamethasone significantly increased oxygenation shortly after instillation when compared with the control group, with the response maintained throughout the study period. Static pressure-volume curves showed that the group receiving 100 mg/kg dexamethasone/Survanta had significantly higher lung volumes than the control group. Total cell, neutrophil, and macrophage counts were decreased significantly in the animals treated with 100 mg/kg dexamethasone/Survanta compared with untreated control rats. Total protein recovered from bronchoalveolar lavage fluid in the animals treated with 100 mg/kg Survanta with and without dexamethasone was decreased significantly compared with control animals. The histologic appearance of the lungs was markedly better in the groups treated with surfactant with or without dexamethasone. CONCLUSIONS: Results suggest that the combined administration of high doses of intratracheal surfactant and dexamethasone improves gas exchange, ameliorates lung inflammation, and alleviates lung damage after paraquat-induced lung injury. Surfactant alone and lower doses of surfactant plus dexamethasone had a lesser effect on these measures.

Early colonic carcinoma with extensive lymph node metastases: case report and review of literature.

An 81-year-old woman had an early carcinoma invading focally into the upper submucosa of the middle-transverse colon, which was accompanied by extensive lymph node metastases and resulted in a poor prognosis. Although her tumor was small and flat, a rim of pale yellow-speckled mucosa adjacent to the tumor enabled its earlier detection. To further study the exceptional lymph node metastases we studied the expression of intestinal trefoil factor and sialyl Tn antigen immunohistochemically on the resected specimen. Their simultaneous expression in lymph node metastasis further supports the aggressive nature of this tumor.

Relationship of duodenal ulcer recurrence to gastric metaplasia of the duodenal mucosa and duodenal bulb deformity.

BACKGROUND AND PURPOSE: This study investigated changes in the severity of gastric metaplasia (GM) of the duodenal mucosa before and after ulcer healing and Helicobacter pylori eradication. It also investigated whether deformity of the duodenal bulb affects the severity of GM and the likelihood of ulcer recurrence. METHODS: Eleven patients were consecutively enrolled in this study. They all had duodenal ulcer(s) and H. pylori infection, for which they had received anti-H. pylori triple therapy during the active ulcer stage, and had all undergone serial endoscopic examinations during both the active ulcer and scarring ulcer stages, and at 1 year after ulcer healing. Duodenal biopsies were obtained at each endoscopy to identify the severity of GM. Duodenal ulcers were divided into three types by bulbar shape and GM was classified into four grades of severity. RESULTS: All 11 patients had increased GM severity just after ulcer healing. The 1-year follow-up study revealed that the GM was unchanged in six of eight patients with grade 3 GM severity at the scarring stage, while in the other two it regressed to grade 1 or 2; these two patients suffered ulcer recurrence. A markedly deformed bulb (type III) was found in three patients, of whom two had ulcer recurrence. CONCLUSION: Two characteristic conditions were found in patients with duodenal ulcer recurrence after H. pylori eradication: a markedly deformed bulb with grade 3 GM at the scarring stage, and a change in GM from high to low grade at or around the previous ulcer site after ulcer healing.

Efficacy of linezolid in treatment of experimental endocarditis caused by methicillin-resistant Staphylococcus aureus.

The efficacies of orally (p.o.) dosed linezolid and intravenously (i.v.) dosed vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in rabbits with experimental aortic-valve endocarditis were investigated. After endocarditis was established with a recent clinical MRSA isolate, rabbits were dosed for 5 days with linezolid (p.o., three times a day) at either 25, 50, or 75 mg/kg of body weight or vancomycin (i.v., twice a day) at 25 mg/kg. The 25-mg/kg linezolid group had a high mortality rate and bacterial counts in the valve vegetations that were not different from those of the controls. Linezolid dosed p.o. at 50 and 75 mg/kg and i.v. vancomycin produced statistically significant reductions in bacterial counts compared to those of the untreated controls. The reduced bacterial counts and culture-negative valve rates for the animals treated with linezolid at 75 mg/kg were similar to those for the vancomycin-treated animals. Concentrations of linezolid in plasma were determined at several points in the dosing regimen. These results suggest that the efficacy of linezolid in this infection model is related to trough levels in plasma that remain above the MIC for this microorganism. At the ineffective dose of linezolid (25 mg/kg) the concentration at sacrifice was 0.045 times the MIC, whereas the concentrations of linezolid in plasma in the 50- and 75-mg/kg groups were 2 and 5 times the MIC at sacrifice, respectively. The results from this experimental model suggest that the oxazolidinone linezolid may be effective for the treatment of serious staphylococcal infections when resistance to other antimicrobials is present.