Interactions between SARS coronavirus and its receptor.
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Amino Acid Motifs↗
Biomedical subjects
Fang Li
Publications and source records attributed to Fang Li.
Essential role of c-Jun-NH2-terminal kinase on synergy induction of apoptosis by TRAIL plus ADM in ADM resistant MCF-7/ADM cells.
Combined treatment modalities using tumor necrosis factor related apoptosis-inducing ligand L (TRAIL) and cytotoxic drugs revealed highly additive effects in some tumor cell lines. Little is known about the efficacy and underlying mechanistic effects of the modalities in chemoresistant tumor cells. The purpose of this study is to investigate the possible role of JNK in the synergistic effect in Doxorubicin (Adriamycin, ADM) resistant MCF-7/ADM cells. Here we showed that the JNK pathway was activated slightly by TRAIL in MCF-7/ADM cell lines and was enhanced by the combination of the two treatments. Inhibition of JNK activity by transfection with dominant-negative JNK blocks TRAIL plus ADM induced-apoptosis significantly, and selective stimulation of the JNK pathway sensitizes ADM resistant breast cancer cells to ADM and TRAIL co-treatment through activation of mitochondria-regulated apoptotic pathway. We conclude that the JNK pathway plays an important role in mediating TRAIL plus ADM induced-apoptosis in breast cancer cells.
Anthracenes↗
Changes of land use and of ecosystem service values in Sanjiang Plain, Northeast China.
Agricultural activities, especially reclamation, are considered major threats to the wetland ecosystems in Sanjiang Plain, the largest concentrated area of the freshwater wetlands in China. In the past decades, the area of the cultivated land and its grain production have been increased at the cost of wetlands shrinkage. The large-scale land reclamation severely affected the ecosystems in this region. However, such effects at the regional scale are seldom evaluated quantitatively. We used three datasets of LANDSAT MSS and/or TM imagery to estimate the area changes and the transition of land use types from 1980 to 2000. We also valued changes in ecosystem services delivered by each land category using value coefficients published by Costanza et al. Sensitivity analysis suggested that these estimates were relatively robust. Finally, the contribution of various ecosystem functions was ranked to the overall value of the ecosystem services in this study. According to our estimates, the total annual ecosystem service values in Sanjiang Plain have declined by about 40% between 1980 and 2000 (156284-182572.18 million US dollars in total over 20 years). This substantial decline is largely attributed to the 53.4% loss of wetlands. For individual ecosystem functions, waste treatment, water supply and disturbance regulation account for more than 60% to the total ecological values. During those two decades, the contribution of disturbance regulation, cultural and recreation decreased, while the contribution of water regulation, nutrient cycling, food production, raw materials and climate regulation increased during the same period. We also put forward a few proposals concerning the future land use policy formulation and sustainable ecosystems. They are adjusting the 'food first' agricultural policy, establishing more nature reserves for wetlands, creating systems for the rational use of water, harnessing the degraded cultivated land and encouraging eco-tourism.
Agriculture↗
Role of cGMP in sildenafil-induced activation of endothelial Ca2+-activated K+ channels.
Intracellular cGMP is an important second messenger in endothelial cells. Because Ca(2+)-activated K(+) channels with large conductance (BK(Ca)) have been shown to regulate endothelial cell functions, the aim of the present study was to examine whether sildenafil modulates BK(Ca) activity in cultured human endothelial cells. Changes of the endothelial cell membrane potential were analyzed using the fluorescence dye DiBAC. The patch-clamp technique was used to study BK(Ca) in human endothelial cells of umbilical cord veins (HUVEC). Intracellular Ca(2+) levels were analyzed using Fura-2 fluorescence imaging. Sildenafil caused a dose-dependent (0.05-5 micromol/l) hyperpolarization of the endothelial cells with a maximum at a concentration of 1 micromol/l. A significant increase of BK(Ca) activity was induced by sildenafil (1 micromol/l) perfusion. BK(Ca) open state-probability (NPo) was also increased by the cGMP-analogue 8-bromo-cGMP (0.5 mmol/l), whereas inhibition of the cGMP-dependent kinase (PKG) had no effect on NPo. PKG-inhibition abolished 8-bromo-cGMP induced BK(Ca) activation, and reduced sildenafil induced NPo. Furthermore, sildenafil caused a significant increase of intracellular calcium that was blocked by the BK(Ca) inhibitor iberiotoxin (100 nmol/l). In conclusion sildenafil activates BK(Ca) by a mechanism, which involves cGMP. The activation of the BK(Ca) is responsible for the sildenafil-induced increase of intracellular Ca(2+).
3',5'-Cyclic-GMP Phosphodiesterases↗
Conformational states of the severe acute respiratory syndrome coronavirus spike protein ectodomain.
The severe acute respiratory syndrome coronavirus enters cells through the activities of a spike protein (S) which has receptor-binding (S1) and membrane fusion (S2) regions. We have characterized four sequential states of a purified recombinant S ectodomain (S-e) comprising S1 and the ectodomain of S2. They are S-e monomers, uncleaved S-e trimers, cleaved S-e trimers, and dissociated S1 monomers and S2 trimer rosettes. Lowered pH induces an irreversible transition from flexible, L-shaped S-e monomers to clove-shaped trimers. Protease cleavage of the trimer occurs at the S1-S2 boundary; an ensuing S1 dissociation leads to a major rearrangement of the trimeric S2 and to formation of rosettes likely to represent clusters of elongated, postfusion trimers of S2 associated through their fusion peptides. The states and transitions of S suggest conformational changes that mediate viral entry into cells.
Angiotensin-Converting Enzyme 2↗
Animal origins of the severe acute respiratory syndrome coronavirus: insight from ACE2-S-protein interactions.
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Animals↗
Ultra-sensitive colorimetric method to quantitate hundreds of polynucleotide molecules by gold nanoparticles with silver enhancement.
An ultra-sensitive colorimetric method to quantitate hundreds of polynucleotide molecules by gold nanoparticles with silver enhancement has been developed. The hybridization products from the target polynucleotides with biotin-labeled probes and gold nanoparticle-functioned oligonucleotides were immobilized to microplates via avidin-biotin system, and the absorbance signals of gold nanoparticles were amplified by silver enhance solution. This sandwich colorimetric assay can detect as few as 600 molecules for single-strand oligonucleotides and as few as 6000 molecules for double-strand polynucleotides in a 50 microL reaction system.
Avidin↗
[The application of adenosine stress myocardial perfusion tomographic imaging in detecting coronary artery disease].
OBJECTIVE: To analyze the sensitivity and specificity of adenosine stress myocardial perfusion tomographic imaging for the diagnosis of coronary artery disease (CAD). METHODS: Adenosine was infused intravenously at a rate of 140 microg.kg(-1).min(-1) for 6 minutes. 3 minutes after adenosine infusion, 925 MBq of (99m)Tc-MIBI were injected intravenously. SPECT myocardial imaging acquisition was obtained 1.5 hours after adenosine infusion. If the result was abnormal, rest myocardial perfusion imaging would be performed next day. Coronary angiography was performed in all patients within one week of myocardial imaging. RESULTS: Total 79 cases [(62 +/- 10) years old, 35 men, 44 women] were included in this study. In the 50 cases of CAD patients confirmed by coronary angiography, 44 patients have positive adenosine (99m)Tc-MIBI myocardial perfusion SPECT. Nineteen out of 29 cases without CAD have negative adenosine myocardial perfusion tomographic imaging. The sensitivity and specificity of adenosine myocardial perfusion tomographic imaging for the diagnosis of CAD were 88.0% and 65.5%. The sensitivity of adenosine myocardial perfusion tomographic imaging for diagnosing coronary stenosis in left anterior descending, left circumflex and right coronary artery are 32/40, 21/27 and 31/32. There was no severe adverse side effect during adenosine stress test. CONCLUSION: Adenosine stress myocardial perfusion tomographic imaging is an useful non-interventional method for detecting coronary artery disease.
Adenosine↗
[Study on the optimal ratio of autoskin and alloskin during mixed microskin grafting].
OBJECTIVE: To investigate the influence of different amount of allogeneic microskin in mixed grafting with certain quantity of autologous microskin on wound healing in rats. Methods Male Wistar rats served as alloskin donor rats. Forty female SD rats with full thickness skin defect were enrolled in the study, and they were randomly divided into four groups, i.e. group I (n=10, with allogeneic microskin graft at area expansion rate of 10:3); group II (n=10, with autologous microskin graft at area expansion rate of 10:1); group III (n=10, with mixed grafting of autologous and allogeneic microskin at area expansion rate of 10:1, respectively); group IV (n=10, with mixed grafting of autologous and allogeneic microskin at area expansion rate of 10:1 and 10:3, respectively). The wound healing rate, wound contraction rate and histological changes were observed at the 2, 3 and 4 post graft weeks (PGW). RESULTS: (1) In group I, there was mainly granulation tissue with some de novo epithelial cells appearing at the wound edge along with the rejection of grafted allogenous skin in the rat wound. In group II, there was still some granulation tissue remaining at 2 PGW due to insufficient amount of microskin. However, the wounds in the mixed grafting group appeared almost totally epithelialized. (2) Various amounts of mononuclear inflammatory cell infiltration and different degrees of angiectasis were observed in the dermal layer after the skin grafting in all groups, especially in group II and IV. There was thickening of the epithelial layer in all groups except group I. (3) The wound healing rate decreased obviously along with the development of rejection in group I at 2 to 4 PGWs. The wound healing rate was (55 +/- 26)% in group II, which was obviously lower than that in group III (88 +/- 6)% and in group IV (76 +/- 10)% at 3 PGWs (P < 0.01). (4) The contraction rate of the wound in group IV (69 +/- 7)% was much higher than that in group I (58 +/- 11)% at 3 PGWs (P < 0.05), and there was no difference among all the other groups. CONCLUSION: Wound healing can be obviously accelerated by mixing some autologous microskin with appropriate amount of alloskin. Moreover, certain amount of autologous microskin (expansion rate 10:1) mixed with the same proportion of allogeneic microskin seems to be more beneficial in promoting wound healing.
Animals↗
[Significance of infusion of sodium bicarbonate in amniotic cavity under continuous internal fetal heart rate monitoring for management of fetal distress during labor].
OBJECTIVE: To investigate the effect of infusion of sodium bicarbonate in amniotic cavity and exchange of amniotic fluid for fetus with distress and acidosis. METHODS: The patients included 40 cases of oligohydramnios with mild and serious abnormality of fetal heart rate and amniotic fluid contamination of degree II or more during the labor. The 40 cases had exchange of amniotic fluid with infusion under continuous monitoring. Twenty of them had infusion with 5% sodium bicarbonate into amniotic cavity; the other 20 cases received 5% sodium bicarbonate intravenous in fusion. After the labor all the patients had test of arterial blood gas in umbilical cord and the fetuses were evaluated with Apgar score. RESULTS: (1) the effective rate was 88% in the group of infusion into amniotic cavity and 85% in the group of exchange of amniotic fluid. (2) The arterial blood pH, PO(2), HCO(3)(-), ABE, SBE in the group of amniotic cavity infusion with 5% sodium bicarbonate were all higher than group of IV infusion, however PCO(2) was significantly lower than the group of IV (P < 0.05). CONCLUSION: Infusion into amniotic cavity and exchange of amniotic fluid is effective therapy for fetal distress due to oligohydramnios and can prevent meconium aspiration syndrome; infusion of antacids medicine (5% sodium bicarbonate) into amniotic cavity is effective and safe therapy for fetus with acidosis.
Acidosis↗
[Prolongation of the survival of skin allografts by intravenous injection of neuraminidase-treated donor bone marrow cells in rats].
OBJECTIVE: To optimize the best concentration of neuraminidase (Neu) that enhances the migration of neuraminidase (Neu)-treated donor bone marrow cells (dBMCs) to the liver, and observe the influence of short-term cyclosporin A(CsA) application combined with intravenous injection (i.v.) of Ne treated dBMCs on the survival of skin allografts. METHODS: The experiment consisted of two parts. For selection of an appropriate concentration of Neu, 26 female Wistar rats were randomly divided into four groups. The dBMCs were prepared by routine method and treated with four concentrations (0, 0.5, 1.0, 2.0 U/ml) of Neu at 37 degrees C for 30 min. The untreated and Neu-treated dBMCs were labeled by 99mTc, and injected via the tail veins to female Wistar rats in each group, respectively. After five hours, the radioactivity of various organs collected from sacrificed rats was measured by a gamma counter, and the values were expressed as percentage of total radioactivity of all organs from the same rat. To observe the survival of skin allograft, 23 male Wistar rats were randomly divided into control group, untreated dBMCs group and Neu-treated dBMCs group. All rats in each group were grafted with skin allografts from male Sprague-Dawley (SD) rats. The dBMCs from the same donor without and with Neu treatment by the concentration selected from the above experiment were injected via the tail veins of female Wistar rats in untreated dBMCs group and Neu-treated dBMCs group, respectively. Rats in untreated dBMCs group and Neu-treated dBMCs group received CsA (10 mg/kg) through intraperitoneal injection (i.p.) at 2 and 5 days post-grafting. Neither dBMCs or CsA were given in the control group. The survival of allograft skin in each group was checked and photographed daily after 5 days post operation. RESULTS: When the concentration of Neu was 1.0 U/ml, the percentage of dBMCs in liver was (75.3 +/- 9.8) %, which was obviously higher than that in 0 U/ml group [(58.9 +/- 4.2%)], (P < 0.01), indicating that the optimal concentration of Neu was 1.0 U/ml. The survival time of skin allografts in rats of Neu-treated dBMCs group was prolonged significantly in comparison with that of the rats in dBMCs group without Neu treatment (P < 0.01). The survival time in both dBMCs group and Neu-treated dBMCs group was longer that of control group (P < 0.01), and it was prolonged in Neu-treated dBMCs group compared with that in dBMC group. CONCLUSION: Administration of proper concentration of Neu can increase the affinity of dBMCs to the liver, and promote the Neu-treated dBMCs to migrate to liver. The intravenous injection of Neu-treated dBMCs combined with short-term CsA administration can delay the rejection of skin allografts in rats.
Animals↗
Diagnostic value of single-photon-emission computed tomography in severe central nervous system involvement of systemic lupus erythematosus: a case-control study.
OBJECTIVE: To evaluate the diagnostic value of single-photon-emission computed tomography (SPECT) in severe central nervous system (CNS) involvement of systemic lupus erythematosus (SLE). METHODS: Forty-three patients with SLE, including 22 with CNS-SLE and 21 with non-CNS-SLE, underwent SPECT and magnetic resonance imaging (MRI) examinations. SPECT was repeated 1-2 months after treatment in patients with abnormal findings. RESULTS: SPECT and MRI abnormalities were detected in 20 (90.9%) and 10 (45.5%) of the 22 patients with CNS-SLE, respectively (P < 0.01). For 4 patients with cerebral infarction or hemorrhage, SPECT was equally as sensitive as MRI (100%). For the patients with CNS-SLE with diffuse presentations, SPECT was more sensitive than MRI in revealing abnormalities (16 [88.9%] of 18 patients versus 6 [33.3%] of 18 patients; P < 0.01). In 19 (95.0%) patients, the abnormal SPECT finding manifested as moderate to severe perfusion defect (15 in frontal lobe, 11 in parietal lobe, 11 in basal ganglia, 3 in temporal lobe, and 17 in multiple regions). Although mild perfusion defect was also detected in 4 (19.0%) of the patients with non-CNS-SLE, it only involved a single region and spared the frontal and parietal lobes. Repeated SPECT after treatment showed that perfusion defect had improved significantly or even disappeared in 11 (84.6%) of 13 patients with diffuse CNS-SLE with abnormal findings before treatment. CONCLUSION: Moderate to severe perfusion defect in SPECT involving multiple regions, especially in the frontal and parietal lobes and basal ganglia, in patients with lupus suggests CNS involvement. SPECT is more sensitive than MRI in revealing damage in diffuse CNS-SLE, and is useful in followup, especially for monitoring disease severity and guiding treatment.
Adult↗
SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells.
Viruses require specific cellular receptors to infect their target cells. Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for two divergent coronaviruses, SARS coronavirus (SARS-CoV) and human coronavirus NL63 (HCoV-NL63). In addition to hostcell receptors, lysosomal cysteine proteases are required for productive infection by some viruses. Here we show that SARS-CoV, but not HCoV-NL63, utilizes the enzymatic activity of the cysteine protease cathepsin L to infect ACE2-expressing cells. Inhibitors of cathepsin L blocked infection by SARS-CoV and by a retrovirus pseudotyped with the SARS-CoV spike (S) protein but not infection by HCoV-NL63 or a retrovirus pseudotyped with the HCoV-NL63 S protein. Expression of exogenous cathepsin L substantially enhanced infection mediated by the SARS-CoV S protein and by filovirus GP proteins but not by the HCoV-NL63 S protein or the vesicular stomatitis virus G protein. Finally, an inhibitor of endosomal acidification had substantially less effect on infection mediated by the HCoV-NL63 S protein than on that mediated by the SARS-CoV S protein. Our data indicate that two coronaviruses that utilize a common receptor nonetheless enter cells through distinct mechanisms.
Angiotensin-Converting Enzyme 2↗
The galectin-3 gene promoter binding proteins in the liver of rats 48-h post-treatment with CCl4.
The present study was undertaken to characterize structure-function relationships of the rat galectin-3 gene promoter especially focusing on the promoter binding proteins included in livers injured with CCl4. Transcription start site determination identified a 66-nucleotide-long exon 1 of this gene. Transient expression analysis using a reporter luciferase gene assigned a region between -161 and -15 to the proximal promoter within the 1-kb region flanking the 5'-end of exon 1. The rat galectin-3 gene promoter possesses a Runx2 binding site and inverted repeats of Sp1 binding motifs in separate regions downstream from -117 as structures resembling those of the mouse galectin-3 gene promoter. The -161/-118 region bound two different proteins. One is a novel protein, a rat version of Purbeta that binds to a guanine nucleotide pair at -145 and -144 to modulate constitutive galectin-3 gene transcription. Southwestern blot analysis using the -161/-118 ligand revealed a signal of a 50-kDa protein in liver nuclear extracts from rats 48-h post-treatment with CCl4, but not in those from Ac2F cells and normal rat livers. The inducible nature of this protein suggested its distinctive role in galectin-3 induction in a liver injured with CCl4. E-box and peroxisome proliferator response element-like motifs reside on separate DNA strands from -140 to -135. Contribution of this segment to the regulation of galectin-3 gene transcription under pathological conditions was suggested, since a DNA ligand with the two motifs simultaneously mutagenized at -136 and -137 was not bound by the 50-kDa protein.
Animals↗
Purification, characterization and cDNA cloning of a novel lipopolysaccharide-binding lectin from the shrimp Penaeus monodon.
In invertebrates, C-type lectin plays an important role in innate immunity by mediating the recognition of pathogens to host cells and clearing microinvaders. A few C-type lectins have been identified from shrimps, but none of their gene or protein sequences is known to date. In this paper, a C-type lectin (named PmLec) specific for bacterial lipopolysaccharide was purified from the serum of the shrimp Penaeus monodon. The binding of PmLec to lipopolysaccharide was mainly mediated through the O-antigen. PmLec had a strong hemagglutinating and bacterial-agglutinating activity as well as an opsonic effect that enhances hemocyte phagocytosis. The PmLec cDNA sequence was obtained from the cDNA library of P. monodon by polymerase chain reaction with the degenerated primer designed according to the amino-terminal residue sequence of purified PmLec. A 546-bp open reading frame was found to encode a putative protein comprising 182 amino acids and containing a preceding signal peptide of 17 amino acids. A C-type lectin domain existed in PmLec, but no glycosylation site was found. The recombinant PmLec protein expressed in Escherichia coli also showed the same agglutinating activity and opsonic effect as that of the native protein. This is the first report of a lectin cDNA from the shrimp. PmLec functions as a pattern-recognition protein and an opsonin in the shrimp, and it provides a clue to elucidate the role of lectin in the innate immunity of aquatic invertebrates at the molecular level.
Animals↗
Enhancement of cancer radiation therapy by use of adenovirus-mediated secretable glucose-regulated protein 94/gp96 expression.
Tumor-derived glucose-regulated protein 94 (GRP94/gp96) has shown great promise as a tumor vaccine. However, current protein-based approaches require the availability of large quantities of tumor tissue, which are often not possible. In addition, the efficacy of immunotherapy is often not ideal when used alone. In this study, we explored the therapeutic efficacy of a combined GRP94/gp96-based genetic immunotherapy and radiation therapy strategy in the weakly immunogenic and highly metastatic 4T1 murine mammary cancer model. An adenovirus encoding a modified, secretable form of GRP94 gene (AdsGRP94) was constructed and evaluated in various antitumor experiments. Lethally irradiated, virus-infected cells were used as vaccines. Adenoviral vectors were also injected directly into tumors in conjunction with tumor irradiation. Vaccination with lethally irradiated, AdsGRP94-infected 4T1 cells completely prevented subsequent tumor growth from challenge inoculations of as many as 10(7) cells per mouse. In established tumor models, vaccinations alone had minimal effect on local and metastatic tumor growth. However, when vaccination was combined with radiation therapy and i.t. AdsGRP94 injections, local tumor growth and pulmonary metastasis were markedly inhibited. In some cases, complete tumor regression was observed. In these cases, the mice were resistant to subsequent tumor challenge and remain tumor free up to 10 months after initial therapy. Our results indicate that combined AdsGRP94-based immunotherapy and radiation therapy may be a potentially effective strategy for cancer treatment.
Adenoviridae↗
Reversing chemoresistance in cisplatin-resistant human ovarian cancer cells: a role of c-Jun NH2-terminal kinase 1.
To investigate the role of activation of c-Jun NH2-terminal kinase 1 (JNK1) in mediating cisplatin-induced apoptosis and the possibility of induction of JNK activity in triggering relation to DNA damage and drug resistance. We investigated the difference of cisplatin-induced activation of JNK pathway and H2O2 alteration between cisplatin-sensitive human ovarian carcinoma cell line A2780 and its resistant variant A2780/DDP. JNK, p-JNK protein, and extracellular H2O2 levels were determined in both A2780 and A2780/DDP cells which were transfected with dominant negative allele of JNK and recombinant JNK1 separately. Both A2780 and A2780/DDP were treated with CDDP, the JNK pathway was activated and a prolonged JNK activation was maintained for at least 12 h in A2780, and only a transient activation (3 h) was detected in A2780/DDP in response to cisplatin treatment. Inhibition of JNK activity by transfection with a dominant negative allele of JNK blocked CDDP-induced apoptosis significantly in A2780 cells. Selective stimulation of the JNK pathway by lipofectamine-mediated delivery of recombinant JNK1 led to activation of c-Jun and decrease of extracellular H2O2, as well as apoptosis sensitization to CDDP in A2780/DDP cells. We concluded that JNK pathway might play an important role in mediating cisplatin-induced apoptosis in A2780 cells, and the duration of JNK activation might be critical in determining whether cells survive or undergo apoptosis. The resistance to CDDP can be reversed through activating c-Jun and decreasing extracellular generation of H2O2 by pcDNA3(FLAG)-JNK1-wt transfection in A2780/DDP cells.
Antineoplastic Agents↗
The combined CXCR1/CXCR2 antagonist CXCL8(3-74)K11R/G31P blocks neutrophil infiltration, pyrexia, and pulmonary vascular pathology in endotoxemic animals.
CXC chemokine receptor 2 (CXCR2) antagonism alone can reduce neutrophil infiltration of some inflammatory sites, but the CXCR1 and CXCR2 critically regulate neutrophil responses to Glu-Leu-Arg-CXC chemokines. Herein, we assessed a combined CXCR1/CXCR2 antagonist, CXC chemokine ligand 8(3-74) [CXCL8(3-74)]K11R/G31P, for its ability to blunt neutrophil-influx and ancillary pathology in severe endotoxemia. Guinea pigs challenged via the airways with Escherichia coli lipopolysaccharide (LPS; 5 microg/kg) were given CXCL8(3-74)K11R/G31P (subcutaneously) before or after the onset of symptoms. The airways of the LPS-challenged animals contained high levels of endogenous pyrogens interleukin (IL)-1 and tumor necrosis factor (TNF) at 2-4 h, and the animals developed pyrexia, which peaked at approximately 6 h; strong pulmonary, neutrophilic inflammation; and marked pleural hemorrhagic consolidation, as assessed at approximately 15 h. CXCL8(3-74)K11R/G31P treatment before LPS challenge reduced lung pleural hemorrhagic consolidation and airway neutrophilia by >90% and essentially abrogated the IL-1, TNF, and fever responses. When given 3 or 6 h after LPS, CXCL8(3-74)K11R/G31P reduced pulmonary neutrophilia by up to 85% and pleural hemorrhagic consolidation by 50-85%. The 3-h treatment reduced the 6- to 24-h fever response to background. Delays of 6 or 9 h in beginning treatment had significant effects on the fever decay curve, but only the 6-h treatment had a significant effect on the 24-h fever. These results indicate that combined CXCR1/CXCR2 antagonism can have significant therapeutic effects on pulmonary inflammation and hemorrhage, as well as pyrexia in endotoxemic animals.
Animals↗