DWARF14 is a non-canonical hormone receptor for strigolactone.

Classical hormone receptors reversibly and non-covalently bind active hormone molecules, which are generated by biosynthetic enzymes, to trigger signal transduction. The α/ß hydrolase DWARF14 (D14), which hydrolyses the plant branching hormone strigolactone and interacts with the F-box protein D3/MAX2, is probably involved in strigolactone detection. However, the active form of strigolactone has yet to be identified and it is unclear which protein directly binds the active form of strigolactone, and in which manner, to act as the genuine strigolactone receptor. Here we report the crystal structure of the strigolactone-induced AtD14-D3-ASK1 complex, reveal that Arabidopsis thaliana (At)D14 undergoes an open-to-closed state transition to trigger strigolactone signalling, and demonstrate that strigolactone is hydrolysed into a covalently linked intermediate molecule (CLIM) to initiate a conformational change of AtD14 to facilitate interaction with D3. Notably, analyses of a highly branched Arabidopsis mutant d14-5 show that the AtD14(G158E) mutant maintains enzyme activity to hydrolyse strigolactone, but fails to efficiently interact with D3/MAX2 and loses the ability to act as a receptor that triggers strigolactone signalling in planta. These findings uncover a mechanism underlying the allosteric activation of AtD14 by strigolactone hydrolysis into CLIM, and define AtD14 as a non-canonical hormone receptor with dual functions to generate and sense the active form of strigolactone.

Comparative Analysis of Acanthopanacis Cortex and Periplocae Cortex Using an Electronic Nose and Gas Chromatography-Mass Spectrometry Coupled with Multivariate Statistical Analysis.

Chinese Herbal Medicines (CHMs) can be identified by experts according to their odors. However, the identification of these medicines is subjective and requires long-term experience. The samples of Acanthopanacis Cortex and Periplocae Cortex used were dried cortexes, which are often confused in the market due to their similar appearance, but their chemical composition and odor are different. The clinical use of the two herbs is different, but the phenomenon of being confused with each other often occurs. Therefore, we used an electronic nose (E-nose) to explore the differences in odor information between the two species for fast and robust discrimination, in order to provide a scientific basis for avoiding confusion and misuse in the process of production, circulation and clinical use. In this study, the odor and volatile components of these two medicinal materials were detected by the E-nose and by gas chromatography-mass spectrometry (GC-MS), respectively. An E-nose combined with pattern analysis methods such as principal component analysis (PCA) and partial least squares (PLS) was used to discriminate the cortex samples. The E-nose was used to determine the odors of the samples and enable rapid differentiation of Acanthopanacis Cortex and Periplocae Cortex. GC-MS was utilized to reveal the differences between the volatile constituents of Acanthopanacis Cortex and Periplocae Cortex. In all, 82 components including 9 co-contained components were extracted by chromatographic peak integration and matching, and 24 constituents could be used as chemical markers to distinguish these two species. The E-nose detection technology is able to discriminate between Acanthopanacis Cortex and Periplocae Cortex, with GC-MS providing support to determine the material basis of the E-nose sensors' response. The proposed method is rapid, simple, eco-friendly and can successfully differentiate these two medicinal materials by their odors. It can be applied to quality control links such as online detection, and also provide reference for the establishment of other rapid detection methods. The further development and utilization of this technology is conducive to the further supervision of the quality of CHMs and the healthy development of the industry.

TRPC1/4/5 channels contribute to morphine-induced analgesic tolerance and hyperalgesia by enhancing spinal synaptic potentiation and structural plasticity.

Opioid analgesics remain the mainstay for managing intractable chronic pain, but their use is limited by detrimental side effects such as analgesic tolerance and hyperalgesia. Calcium-dependent synaptic plasticity is a key determinant in opiates tolerance and hyperalgesia. However, the exact substrates for this calcium-dependent synaptic plasticity in mediating these maladaptive processes are largely unknown. Canonical transient receptor potential 1, 4, and 5 (TRPC1, 4, 5) proteins assemble into heteromultimeric nonselective cation channels with high Ca2+ permeability and influence various neuronal functions. However, whether and how TRPC1/4/5 channels contribute to the development of opiates tolerance and hyperalgesia remains elusive. Here, we show that TRPC1/4/5 channels contribute to the generation of morphine tolerance and hyperalgesia. Chronic morphine exposure leads to upregulation of TRPC1/4/5 channels in the spinal cord. Spinally expressed TRPC1, TPRC4, and TRPC5 are required for chronic morphine-induced synaptic long-term potentiation (LTP) as well as remodeling of synaptic spines in the dorsal horn, thereby orchestrating functional and structural plasticity during the course of morphine-induced hyperalgesia and tolerance. These effects are attributed to TRPC1/4/5-mediated Ca2+ elevation in the spinal dorsal horn induced by chronic morphine treatment. This study identifies TRPC1/4/5 channels as a promising novel target to prevent the unwanted morphine tolerance and hyperalgesia.

Canonical Transient Receptor Potential (TRPC) Channels in Nociception and Pathological Pain.

Chronic pathological pain is one of the most intractable clinical problems faced by clinicians and can be devastating for patients. Despite much progress we have made in understanding chronic pain in the last decades, its underlying mechanisms remain elusive. It is assumed that abnormal increase of calcium levels in the cells is a key determinant in the transition from acute to chronic pain. Exploring molecular players mediating Ca2+ entry into cells and molecular mechanisms underlying activity-dependent changes in Ca2+ signaling in the somatosensory pain pathway is therefore helpful towards understanding the development of chronic, pathological pain. Canonical transient receptor potential (TRPC) channels form a subfamily of nonselective cation channels, which permit the permeability of Ca2+ and Na+ into the cells. Initiation of Ca2+ entry pathways by these channels triggers the development of many physiological and pathological functions. In this review, we will focus on the functional implication of TRPC channels in nociception with the elucidation of their role in the detection of external stimuli and nociceptive hypersensitivity.

Efficient ASK-assisted system for expression and purification of plant F-box proteins.

Ubiquitin-mediated protein degradation plays an essential role in plant growth and development as well as responses to environmental and endogenous signals. F-box protein is one of the key components of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, which recruit specific substrate proteins for subsequent ubiquitination and 26S proteasome-mediated degradation to regulate developmental processes and signaling networks. However, it is not easy to obtain purified F-box proteins with high activity due to their unstable protein structures. Here, we found that Arabidopsis SKP-like proteins (ASKs) can significantly improve soluble expression of F-box proteins and maintain their bioactivity. We established an efficient ASK-assisted method to express and purify plant F-box proteins. The method meets a broad range of criteria required for the biochemical analysis or protein crystallization of plant F-box proteins.

CCL2 Potentiates Inflammation Pain and Related Anxiety-Like Behavior Through NMDA Signaling in Anterior Cingulate Cortex.

Previous studies have shown that the C-C motif chemokine ligand 2 (CCL2) is widely expressed in the nervous system and involved in regulating the development of chronic pain and related anxiety-like behaviors, but its precise mechanism is still unclear. This paper provides an in-depth examination of the involvement of CCL2-CCR2 signaling in the anterior cingulate cortex (ACC) in intraplantar injection of complete Freund's adjuvant (CFA) leading to inflammatory pain and its concomitant anxiety-like behaviors by modulation of glutamatergic N-methyl-D-aspartate receptor (NMDAR). Our findings suggest that local bilateral injection of CCR2 antagonist in the ACC inhibits CFA-induced inflammatory pain and anxiety-like behavior. Meanwhile, the expression of CCR2 and CCL2 was significantly increased in ACC after 14 days of intraplantar injection of CFA, and CCR2 was mainly expressed in excitatory neurons. Whole-cell patch-clamp recordings showed that the CCR2 inhibitor RS504393 reduced the frequency of miniature excitatory postsynaptic currents (mEPSC) in ACC, and CCL2 was involved in the regulation of NMDAR-induced current in ACC neurons in the pathological state. In addition, local injection of the NR2B inhibitor of NMDAR subunits, Ro 25-6981, attenuated the effects of CCL2-induced hyperalgesia and anxiety-like behavior in the ACC. In summary, CCL2 acts on CCR2 in ACC excitatory neurons and participates in the regulation of CFA-induced pain and related anxiety-like behaviors through upregulation of NR2B. CCR2 in the ACC neuron may be a potential target for the treatment of chronic inflammatory pain and pain-related anxiety.

TRPC3/6 Channels Mediate Mechanical Pain Hypersensitivity via Enhancement of Nociceptor Excitability and of Spinal Synaptic Transmission.

Patients with tissue inflammation or injury often experience aberrant mechanical pain hypersensitivity, one of leading symptoms in clinic. Despite this, the molecular mechanisms underlying mechanical distortion are poorly understood. Canonical transient receptor potential (TRPC) channels confer sensitivity to mechanical stimulation. TRPC3 and TRPC6 proteins, coassembling as heterotetrameric channels, are highly expressed in sensory neurons. However, how these channels mediate mechanical pain hypersensitivity has remained elusive. It is shown that in mice and human, TRPC3 and TRPC6 are upregulated in DRG and spinal dorsal horn under pathological states. Double knockout of TRPC3/6 blunts mechanical pain hypersensitivity, largely by decreasing nociceptor hyperexcitability and spinal synaptic potentiation via presynaptic mechanism. In corroboration with this, nociceptor-specific ablation of TRPC3/6 produces comparable pain relief. Mechanistic analysis reveals that upon peripheral inflammation, TRPC3/6 in primary sensory neurons get recruited via released bradykinin acting on B1/B2 receptors, facilitating BDNF secretion from spinal nociceptor terminals, which in turn potentiates synaptic transmission through TRPC3/6 and eventually results in mechanical pain hypersensitivity. Antagonizing TRPC3/6 in DRG relieves mechanical pain hypersensitivity in mice and nociceptor hyperexcitability in human. Thus, TRPC3/6 in nociceptors is crucially involved in pain plasticity and constitutes a promising therapeutic target against mechanical pain hypersensitivity with minor side effects.

Quantitative Evaluation of Biceps Brachii Muscle by Shear Wave Elastography in Stroke Patients.

Purpose: The present study aimed to investigate the differences in muscle size and shear wave speed (SWS) values of biceps brachii muscle (BBM) between stroke survivors and healthy controls. Methods: This study comprised 61 stroke survivors and 24 healthy subjects, examined at Guangzhou First People's Hospital within one year. Each participant underwent ultrasonic examinations for recording some specific measurement indicators, including muscle thickness, cross-sectional area (CSA), and shear wave speed (SWS) of BBM. The muscular tension of the paretic arm was scored using the modified Ashworth scale (MAS). These above-mentioned indexes were compared between stroke survivors and healthy controls. Also, the correlations among SWS and MAS scores were assessed. Results: When the lifting arm angle was set for 45°, the CSA and muscle thickness of BBM were obviously decreased in the paretic arms of stroke subjects compared to the non-paretic arms as well as the arms of healthy controls. Moreover, the paretic arms had obviously higher SWS than the non-paretic arms and the healthy arms at 45° or 90°. When the angles of paretic arms were lifted at 90° and 45°, respectively, a positive correlation was established between MAS and SWS. Conclusion: Ultrasonic examination assessing muscle thickness, CSA, and SWS of the BBM could be used as a means of assessment of the paretic arms of stroke survivors.

Transmission of SARS-CoV-2 on Cold-Chain Food: Precautions Can Effectively Reduce the Risk.

The COVID-19 pandemic has generated a new era in the world, also in the food safety. Up to now, there is no evidence to suggest that people can infect COVID-19 via food contaminated by SARS-CoV-2. Here, we analyzed the results of regular SARS-CoV-2 nucleic acid testing of considerable cold-chain food practitioners, cold-chain food surfaces, and their internal or external packaging as well as their associated environments, aiming to explore the risk of cold-chain food being contaminated by SARS-CoV-2 and the probability of people infecting COVID-19 through contaminated cold-chain food in the context of COVID-19 epidemic. This study found that only two batches of cold-chain food were contaminated by SARS-CoV-2, none of the cold-chain food handler were infected due to effective regulatory measures for cold-chain food. Therefore, effective supervision and preventive methods could effectively reduce the transmission risk of SARS-CoV-2 on cold-chain food.

Presynaptic NMDARs on spinal nociceptor terminals state-dependently modulate synaptic transmission and pain.

Postsynaptic NMDARs at spinal synapses are required for postsynaptic long-term potentiation and chronic pain. However, how presynaptic NMDARs (PreNMDARs) in spinal nociceptor terminals control presynaptic plasticity and pain hypersensitivity has remained unclear. Here we report that PreNMDARs in spinal nociceptor terminals modulate synaptic transmission in a nociceptive tone-dependent manner. PreNMDARs depresses presynaptic transmission in basal state, while paradoxically causing presynaptic potentiation upon injury. This state-dependent modulation is dependent on Ca2+ influx via PreNMDARs. Small conductance Ca2+-activated K+ (SK) channels are responsible for PreNMDARs-mediated synaptic depression. Rather, tissue inflammation induces PreNMDARs-PKG-I-dependent BDNF secretion from spinal nociceptor terminals, leading to SK channels downregulation, which in turn converts presynaptic depression to potentiation. Our findings shed light on the state-dependent characteristics of PreNMDARs in spinal nociceptor terminals on modulating nociceptive transmission and revealed a mechanism underlying state-dependent transition. Moreover, we identify PreNMDARs in spinal nociceptor terminals as key constituents of activity-dependent pain sensitization.

HbCOI1 perceives jasmonate to trigger signal transduction in Hevea brasiliensis.

Natural rubber, a strategically essential raw material used in manufacturing throughout the world, is produced from coagulated and refined latex of rubber tree (Hevea brasiliensis). It is known that phytohormone jasmonate (JA) plays an essential role in regulating latex biosynthesis. However, it is unclear how the JA signal is sensed in a rubber tree. Here, we showed that H. brasiliensis CORONATINE-INSENSITIVE 1 (HbCOI1) acts as a receptor that perceives JA to recruit H. brasiliensis JASMONATE ZIM DOMAIN1 (HbJAZ1) for signal transduction. We found that HbCOI1 restores male sterility and JA responses of the coi1-1 mutant in Arabidopsis. The identification of a JA receptor in the rubber tree is essential for elucidating the molecular mechanisms underlying JA-regulated latex biosynthesis. Our results elucidate the mechanism of JA perception in H. brasiliensis and also provide an efficient strategy to identify JA receptors in woody plants.

Nociceptor-localized cGMP-dependent protein kinase I is a critical generator for central sensitization and neuropathic pain.

Patients with neuropathic pain often experience exaggerated pain and anxiety. Central sensitization has been linked with the maintenance of neuropathic pain and may become an autonomous pain generator. Conversely, emerging evidence accumulated that central sensitization is initiated and maintained by ongoing nociceptive primary afferent inputs. However, it remains elusive what mechanisms underlie this phenomenon and which peripheral candidate contributes to central sensitization that accounts for pain hypersensitivity and pain-related anxiety. Previous studies have implicated peripherally localized cGMP-dependent protein kinase I (PKG-I) in plasticity of nociceptors and spinal synaptic transmission as well as inflammatory hyperalgesia. However, whether peripheral PKG-I contributes to cortical plasticity and hence maintains nerve injury-induced pain hypersensitivity and anxiety is unknown. Here, we demonstrated significant upregulation of PKG-I in ipsilateral L3 dorsal root ganglia (DRG), no change in L4 DRG, and downregulation in L5 DRG upon spared nerve injury. Genetic ablation of PKG-I specifically in nociceptors or post-treatment with intervertebral foramen injection of PKG-I antagonist, KT5823, attenuated the development and maintenance of spared nerve injury-induced bilateral pain hypersensitivity and anxiety. Mechanistic analysis revealed that activation of PKG-I in nociceptors is responsible for synaptic potentiation in the anterior cingulate cortex upon peripheral neuropathy through presynaptic mechanisms involving brain-derived neurotropic factor signaling. Our results revealed that PKG-I expressed in nociceptors is a key determinant for cingulate synaptic plasticity after nerve injury, which contributes to the maintenance of pain hypersensitivity and anxiety. Thereby, this study presents a strong basis for opening up a novel therapeutic target, PKG-I, in nociceptors for treatment of comorbidity of neuropathic pain and anxiety with least side effects.

Extracellular matrix protein laminin ß1 regulates pain sensitivity and anxiodepression-like behaviors in mice.

Patients with neuropathic pain often experience comorbid psychiatric disorders. Cellular plasticity in the anterior cingulate cortex (ACC) is assumed to be a critical interface for pain perception and emotion. However, substantial efforts have thus far been focused on the intracellular mechanisms of plasticity rather than the extracellular alterations that might trigger and facilitate intracellular changes. Laminin, a key element of the extracellular matrix (ECM), consists of one α-, one ß-, and one γ-chain and is implicated in several pathophysiological processes. Here, we showed in mice that laminin ß1 (LAMB1) in the ACC was significantly downregulated upon peripheral neuropathy. Knockdown of LAMB1 in the ACC exacerbated pain sensitivity and induced anxiety and depression. Mechanistic analysis revealed that loss of LAMB1 caused actin dysregulation via interaction with integrin ß1 and the subsequent Src-dependent RhoA/LIMK/cofilin pathway, leading to increased presynaptic transmitter release probability and abnormal postsynaptic spine remodeling, which in turn orchestrated the structural and functional plasticity of pyramidal neurons and eventually resulted in pain hypersensitivity and anxiodepression. This study sheds new light on the functional capability of ECM LAMB1 in modulating pain plasticity and identifies a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified cingulate LAMB1/integrin ß1 signaling as a promising therapeutic target for the treatment of neuropathic pain and associated anxiodepression.

Tweety-Homolog 1 Facilitates Pain via Enhancement of Nociceptor Excitability and Spinal Synaptic Transmission.

Tweety-homolog 1 (Ttyh1) is expressed in neural tissue and has been implicated in the generation of several brain diseases. However, its functional significance in pain processing is not understood. By disrupting the gene encoding Ttyh1, we found a loss of Ttyh1 in nociceptors and their central terminals in Ttyh1-deficient mice, along with a reduction in nociceptor excitability and synaptic transmission at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) in the basal state. More importantly, the peripheral inflammation-evoked nociceptor hyperexcitability and spinal synaptic potentiation recorded in spinal-PAG projection neurons were compromised in Ttyh1-deficient mice. Analysis of the paired-pulse ratio and miniature excitatory postsynaptic currents indicated a role of presynaptic Ttyh1 from spinal nociceptor terminals in the regulation of neurotransmitter release. Interfering with Ttyh1 specifically in nociceptors produces a comparable pain relief. Thus, in this study we demonstrated that Ttyh1 is a critical determinant of acute nociception and pain sensitization caused by peripheral inflammation.

[A novel spectral surface plasmon resonance 2-D sensing technique and its applications in DNA microarrays].

The authors have previously proposed a novel refractive index two-dimensional sensing technique named "parallel scan spectral surface plasmon resonance imaging". In the technique, with a line-shaped light illumination, an image acquired with CCD detector could provide both SPR wavelength information and one-dimensional spatial distribution, and then provide one-dimensional distribution of refractive index with further calculation. Thus, two-dimensional distribution of refractive index of the entire sensing area can be obtained with one-dimensional optical line parallel scan. The technique offers advantages of both high sensitivity and high throughput, and could have potential applications in microarray analysis. In the present paper, the authors improve the data processing methods of the technique. The authors use the refractive index of air as a reference to get over the problem of precision of the incident angle. The authors also sense a manually dotted Legionella pneumophila mip DNA probe array with this technique and prove the feasibility of sensing microarrays by this highly sensitive and label-free technique. The relation between the equivalent refractive indices and the concentrations of the dotted Legionella pneumophila mip DNA probes is obtained, which has important reference value for further study.

CCL2-CCR2 Axis Potentiates NMDA Receptor Signaling to Aggravate Neuropathic Pain Induced by Brachial Plexus Avulsion.

Brachial plexus avulsion (BPA) represents the most devastating nerve injury in the upper extremity and is always considered as a sophisticated problem due to its resistance to most standard pain relief medications or neurosurgical interventions. There is also a lack of understanding on the underlying mechanisms. Our study aimed to investigate whether spinal CCL2-CCR2 signaling contributed to the development of neuropathic pain following BPA via modulating glutamate N-methyl-d-aspartate receptor (NMDAR). A rat model of BPA on lower trunk (C8-T1) was established, and the sham- and BPA-operated animals were intrathecally injected with saline, C-C chemokine receptor type 2 (CCR2) inhibitor INCB3344 and NMDAR antagonist DL-AP5 one week postoperatively, the behavioral performance of the treated animals and expressions of C-C motif ligand 2 (CCL2), CCR2, and N-methyl-D-aspartic acid receptor 2B (NR2B) in spinal cord sections of each group were examined. It was shown that BPA injury significantly reduced mechanic withdrawal thresholds the next day after surgery until the end of the observation. Both CCL2 and CCR2 expressions increased in BPA rats compared to those in sham rats. CCL2 was mainly localized in astrocytes, and CCR2 was preferably expressed on astrocytes and neurons. Besides, NMDAR subunit NR2B increased in BPA-operated rats, which was reversed in response to CCR2 and NR2B inhibition. However, these inhibitors didn't change the spinal NMDAR level in sham rats. CCR2 and NMDAR inhibition efficiently alleviated mechanical allodynia caused by BPA either at early or late phase of neuropathic pain. Collectively, CCL2-CCR2 axis is associated with mechanical pain after BPA by elevating NMDAR signaling.

Spinal CCL2 Promotes Pain Sensitization by Rapid Enhancement of NMDA-Induced Currents Through the ERK-GluN2B Pathway in Mouse Lamina II Neurons.

Previous studies have shown that CCL2 (C-C motif chemokine ligand 2) induces chronic pain, but the exact mechanisms are still unknown. Here, we established models to explore the potential mechanisms. Behavioral experiments revealed that an antagonist of extracellular signal-regulated kinase (ERK) inhibited not only CCL2-induced inflammatory pain, but also pain responses induced by complete Freund's adjuvant. We posed the question of the intracellular signaling cascade involved. Subsequent experiments showed that CCL2 up-regulated the expression of phosphorylated ERK (pERK) and N-methyl D-aspartate receptor [NMDAR] subtype 2B (GluN2B); meanwhile, antagonists of CCR2 and ERK effectively reversed these phenomena. Whole-cell patch-clamp recordings revealed that CCL2 enhanced the NMDAR-induced currents via activating the pERK pathway, which was blocked by antagonists of GluN2B and ERK. In summary, we demonstrate that CCL2 directly interacts with CCR2 to enhance NMDAR-induced currents, eventually leading to inflammatory pain mainly through the CCL2-CCR2-pERK-GluN2B pathway.

CCL2 facilitates spinal synaptic transmission and pain via interaction with presynaptic CCR2 in spinal nociceptor terminals.

Previous studies have shown that CCL2 may cause chronic pain, but the exact mechanism of central sensitization is unclear. In this article, we further explore the presynaptic role of CCL2. Behavioral experiments show that intervertebral foramen injection CCR2 antagonists into dorsal root ganglion (DRG) can inhibit the inflammatory pain caused by CCL2 in spinal cord. We raised the question of the role of presynaptic CCR2 in the spinal dorsal horn. Subsequent electron microscopy experiments showed that CCR2 was expressed in the presynaptic CGRP terminal in the spinal dorsal horn. CCL2 can enhance presynaptic calcium signal. Whole-cell patch-clamp recordings showed that CCL2 can enhance NMDAR-eEPSCs through presynaptic effects, and further application of glutamate sensor method proved that CCL2 can act on presynaptic CCR2 to increase the release of presynaptic glutamate. In conclusion, we suggest that CCL2 can directly act on the CCR2 on presynaptic terminals of sensory neurons in the spinal dorsal horn, leading to an increase in the release of presynaptic glutamate and participate in the formation of central sensitization.

The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome.

Multiple organ dysfunction syndrome (MODS) is a major cause of morbidity and mortality in intensive care units. It is being encountered frequently in critically ill patients owing to advancements in organ-specific supportive technologies to survive the acute phase of severe sepsis and shock. It is now believed that MODS is the result of an inappropriate generalized inflammatory response of the host to a variety of acute insults. The pathologic mechanisms of MODS were reviewed, and factors determining the sequence and severity of organ dysfunction were discussed in depth. In the early phase of MODS, circulating cytokines cause universal endothelium injury in organs. In the later phase of MODS, overexpression of inflammatory mediators in the interstitial space of various organs is considered a main mechanism of parenchyma injury. The difference in constitutive expression and the upregulation of adhesion molecules in vascular beds and the density and potency of intrinsic inflammatory cells in different organs are the key factors determining the sequence and severity of organ dysfunction. By activating the intrinsic inflammatory cell in a distant organ, organ dysfunctions are linked in a positive feedback loop through circulating inflammatory mediators. Antagonists targeted at adhesion molecules may alleviate the severity of endothelial damage. And nonsteroidial anti-inflammatory drugs or steroids administered judiciously in the early phase of MODS may retard the progress of multiple organ failure.

[Effects of small volume resuscitation on the hemodynamics and extravascular lung water of septic shock dogs].

OBJECTIVE: To observe the effect of small volume resuscitation by hypertonic-hyperoncotic solution on the hemodynamics and extravascular lung water of septic shock dogs. METHODS: Lipopolysaccharide of E. coli was injected to 24 healthy dogs via femoral vein to induce septic shock. These septic shock dogs were resuscitated with hypertonic salt solutions (HS, 6 ml/kg, n = 6), 6% hydroxyethyl starch in combination with HS (HSS, 6 ml/kg, n=6), normal saline (NS, 100 ml/kg, n=6), and 6% hydroxyethyl starch solutions (HES, 33 ml/kg, n=6), respectively. The changes of hemodynamics and extravascular lung water were observed. RESULTS: After resuscitation, all the solutions improved the hemodynamics of septic shock dogs with significant differences (P<0.05). The effects were superior in HS group and HSS group when compared with in NS group. The extravascular lung water increased in NS group, while no obvious changes were found in the other three groups. CONCLUSIONS: All these four solutions can improve the hemodynamics of septic shock dogs. Small volume hypertonic-hyperoncotic solution has a similar effect in hemodynamics as NS, HS, and HES. Meanwhile, it does not increase the extravascular lung water.