LGCCT: A Light Gated and Crossed Complementation Transformer for Multimodal Speech Emotion Recognition.

Semantic-rich speech emotion recognition has a high degree of popularity in a range of areas. Speech emotion recognition aims to recognize human emotional states from utterances containing both acoustic and linguistic information. Since both textual and audio patterns play essential roles in speech emotion recognition (SER) tasks, various works have proposed novel modality fusing methods to exploit text and audio signals effectively. However, most of the high performance of existing models is dependent on a great number of learnable parameters, and they can only work well on data with fixed length. Therefore, minimizing computational overhead and improving generalization to unseen data with various lengths while maintaining a certain level of recognition accuracy is an urgent application problem. In this paper, we propose LGCCT, a light gated and crossed complementation transformer for multimodal speech emotion recognition. First, our model is capable of fusing modality information efficiently. Specifically, the acoustic features are extracted by CNN-BiLSTM while the textual features are extracted by BiLSTM. The modality-fused representation is then generated by the cross-attention module. We apply the gate-control mechanism to achieve the balanced integration of the original modality representation and the modality-fused representation. Second, the degree of attention focus can be considered, as the uncertainty and the entropy of the same token should converge to the same value independent of the length. To improve the generalization of the model to various testing-sequence lengths, we adopt the length-scaled dot product to calculate the attention score, which can be interpreted from a theoretical view of entropy. The operation of the length-scaled dot product is cheap but effective. Experiments are conducted on the benchmark dataset CMU-MOSEI. Compared to the baseline models, our model achieves an 81.0% F1 score with only 0.432 M parameters, showing an improvement in the balance between performance and the number of parameters. Moreover, the ablation study signifies the effectiveness of our model and its scalability to various input-sequence lengths, wherein the relative improvement is almost 20% of the baseline without a length-scaled dot product.

Design, synthesis, cytotoxicities and DNA cleavage activities of dibenzoxepine and isoquinoline derivatives starting from dehydroabietylamine.

A series of novel hexahydrodibenzoxepine and quinazoline derivatives were designed and synthesized starting from dehydroabietylamine. The cytotoxicities of the compounds against L02 and HepG2 cell lines were investigated. Meanwhile, the plasmid DNA (Escherichia coli) cleavage of several heterocyclic derivatives was studied. These compounds exhibit remarkable activities on plasmid DNA pBR322. Our study provides useful information for developing new and more potent antitumor agents.

A comparative study of antitumor activities and DNA cleavage on a class of dehydroabietylamine derivatives.

A series of novel dehydroabietylamine derivatives containing tricyclic diterpene structures were synthesized. The antitumor activities of these compounds against L02, Hey-1B and HepG2 cells were investigated. Significant activity was discovered forfourteen analogs. Meanwhile these compounds exhibit DNA cleavage activities on plasmid DNA (Escherichia coli), which depend on the Schiff base structure and the substituent of the aromatic moiety. Our findings present further information on the relationship between the chemical structure, biological function and DNA cleavage characteristics.

[Protective effect of Tanreqing injection on acute hepatic injury induced by CCl4 in rats].

OBJECTIVE: To observe the protective effect of Tanreqing injection(TRQ) on carbon tetrachloride-induced acute hepatic injury in rats. METHOD: Rats were randomly divided into the normal group and the model group, and injected subcutaneously with 100% CCl4 5 mL x kg(-1) to establish the single CCl4 infection model, in order to observe the changes in rat liver injury after 3 h and 6 h. Subsequently, the multiple CCl4 infection liver injury model was reproduced by subcutaneously injecting 100% CCl4 (5 mL x kg(-1)), 50% CCl4 olive oil solution (2 mL x kg(-1)) and then 20% CCl4 olive oil solution (2 mL x kg(-1)). At 6 h after the first CCl4 injection, the rats were divided into six groups: the model group, the control group, the diammonium glycyrrhizinate-treated group, and TRQ high, middle and low dose groups. They were injected through caudal veins, while a normal control group was set up. Their weight and liver-body ratio were observed. Hepatic inflammation was observed with HE staining. Assay kits were adopted to detect ALT, AST, T. Bil, D. Bil, CHE, TBA, gamma-GT and Alb. RESULT: According to the single injection model, serum AST and T. Bil of model rats were obviously increased at 6 h after single subcutaneous injection of CCl4, with disordered lobular structure in liver tissues, notable swollen liver cells and remarkable liver injury. According to the results of the multiple injection pharmacological experiment, compared with the normal group, the model group had higher serum ALT, AST, and gamma-GT activities (P < 0. 05), TBA and T. Bil contents (P < 0.05) and lower CHE activity (P < 0.05). HE staining showed disorganized lobular structure in liver tissues and notable ballooning degeneration in liver cells. Compared with the model group, TRQ high and middle dose groups and the diammonium glycyrrhizinate-treated group showed significant charges in serum liver function and inflammation in liver cells. Specifically, TRQ high and middle dose groups were superior to the diammonium glycyrrhizinate-treated group. CONCLUSION: Tanreqing injection has significant protective effect on CCl4-induced acute hepatic injury in rats.

A hybrid with distributed pooling blockchain protocol for image storage.

As a distributed storage scheme, the blockchain network lacks storage space has been a long-term concern in this field. At present, there are relatively few research on algorithms and protocols to reduce the storage requirement of blockchain, and the existing research has limitations such as sacrificing fault tolerance performance and raising time cost, which need to be further improved. Facing the above problems, this paper proposes a protocol based on Distributed Image Storage Protocol (DISP), which can effectively improve blockchain storage space and reduces computational costs in the help of InterPlanetary File System (IPFS). In order to prove the feasibility of the protocol, we make full use of IPFS and distributed database to design a simulation experiment for blockchain. Through distributed pooling (DP) algorithm in this protocol, we can divide image evidence into recognizable several small files and stored in several nodes. And these files can be restored to lossless original documents again by inverse distributed pooling (IDP) algorithm after authorization. These advantages in performance create conditions for large scale industrial and commercial applications.

Synthesis and evaluation of some steroidal oximes as cytotoxic agents: structure/activity studies (I).

The side chain of a compound plays an important role in its biological function. In our studies, we have found that hydroximinosteroid derivatives with different side chains and position of hydroximino on ring A and B displayed remarkable distinct cytotoxicities against a diversity of cancer cell types. Presence of an oxime group on ring B and a hydroxy on ring A or B resulted in a higher cytotoxicity than other structural motifs. In addition, a cholesterol-type side chain at position 17 was required for the biological activity. Our findings provide new evidence showing the relationship between the chemical structure and biological function. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.

Poststroke depression and risk of recurrent stroke: A meta-analysis of prospective studies.

BACKGROUND: Conflicting results have been reported on the association of poststroke depression with recurrent stroke events. This meta-analysis of prospective studies aims to evaluate whether poststroke depression is an independent predictor of stroke recurrence among stroke patients. METHODS: A systematic search of articles in PubMed and Embase databases from their inception to October 2018 was conducted. Prospective studies reporting risk estimates of stroke recurrence by depression status in stroke patients were included and pooled risk ratio (RR) with 95% confidence intervals (CIs) of stroke recurrence was calculated for patients with or without poststroke depression. RESULTS: Six studies with 4648 stroke patients were finally included, and the prevalence of poststroke depression was found to from 15.9% to 40.5%. The pooled adjusted RR for stroke recurrence in patients suffering from poststroke depression was 1.48 (1.22-1.79) in a fixed-effect model. Subgroup analyses indicated that poststroke depression significantly increased stroke recurrence (RR 1.64; 95% CI, 1.28-2.10) among ischemic stroke patients but not in total stroke patients (RR 1.28; 95% CI, 0.96-1.73). CONCLUSIONS: This meta-analysis suggests that poststroke depression may be an independent predictor of stroke recurrence among ischemic stroke patients. Further studies are required to investigate whether treatment of poststroke depression can reduce the risk of stroke recurrence.

[A new method for quick identification for fufang danshen tablets by AOTF-near infrared spectroscopy].

OBJECTIVE: To establish a new method using AOTF-Near infrared spectroscopy for fast identifying Fufang Danshen tablets. METHOD: Near-infrared spectroscopy of Fufang Danshen tablets from different factories and different bacth numbers were collected and the discriminant analysis model (FFDS-C) was established with principal component analysis. This model was applied to predict the the different samples of Fufang Danshn tablets. RESULT: The model can be used to precisely identify Fufang Danshen tablets from other samples. CONCLUSION: The method with low consumption is simple and quick and can be applied to the identification of the Fufang Danshen tablets.

Phosphorus fractionation and bio-availability in Taihu Lake (China) sediments.

Typical sediments from Taihu Lake, a meso-to-hypereutrophic lake, were collected and examined on the basis of P-fractionation by sequential extraction scheme. Sedimentary inorganic phosphorus were fractioned into four forms and the rank order according to the mean concentration of P-fractions in Taihu Lake was NaOH-P > BD-P > HCI-P > NH4Cl-P. The concentrations of BD-P were linearly correlated with the content of active Fe (R2 = 0.96). Also, the linear relationship between the sum of BD-P and NaOH-P and the sum of active Fe and active Al content was observed within the six sediments investigated (R2 = 0.96). Moreover, the bio-available phosphorus (BAP) content was estimated by the sum of NH4 Cl-P, BD-P, and NaOH-P, viz. BAP = NH4 Cl-P + NaOH-P + BD-P. In Taihu Lake, the BAP contents are ranging from 0.10 mg/g dw to 1.25 mg/g dw, and average 0.40 mg/g dw for all sediment samples. The relative contributions of BAP to total sedimentary phosphorus (TP) and inorganic sedimentary phosphorus (IP) range from 18.67% to 50.79% (33.61% on average) and from 52.82% to 82.09% (67.81% on average), respectively.

[Transcutaneous Electrical Stimulation Undergoing Emergency Treatment of Zusanli (ST 36) Is Beneficial to Rescued Organophosphorus Pesticide Poisoning Patients].

OBJECTIVE: To observe the effect of transcutaneous acupoint electrical stimulation (TAES) of Zusanli (ST 36) on gastrointestinal activities in organophosphorus pesticide poisoning (OPP) patients undergoing emergency treatment so as to explore its action in scavenging gastrointestinal toxicant. METHODS: A total of 116 OPP patients were randomly divided into control group and TAES group (n=58 in each group) according to the simple random sampling method. All the patients received comprehensive treatment including gastric lavage, catharsis, oral administration of atropine Pralidoxime Chloride, Omeprazole, etc. For patients of the TAES group, TAES stimulation (30 Hz/60 Hz, 15-20 mA) was applied to bilateral Zusanli (ST 36) for 30 min, 3 times a day till black stool was discharged. The vomiting times after catharsis, the time of the first defecation and black stool discharge, the dosage of atropine and the length of patient stay in hospital were recorded. RESULTS: Of the two 58 cases of OPP patients in the control and TAES groups, 11 (18.9%) and 3 (5.2%) underwent vomiting after catharsis, being significantly lower in the TAES group (P<0.05). Compared with the control group, the time of first defecation and black stool discharge, the dosage of the administrated atropine and the time of hospitalization were significantly lower in the TAES group (P<0.05). CONCLUSION: TAES of ST 36 may lower incidence of emesis, enhance the cathartic effect, promote gastrointestinal poison discharge, reduce total atropine dosage and shorten the hospitalization time in OPP patients, favoring the patient's rehabilitation.

A Meta-analysis Reveals S-1-based Chemotherapy Improves the Survival of Patients With Advanced Gastric Cancer.

The aim of this study was to compare the efficacy and safety of S-1-based therapy versus non-S-1-based therapy in advanced gastric cancer (AGC) patients.Eligible studies stratifying objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) in AGC patients were identified from Embase, Pubmed, Cochrane Library, and China National Knowledge Infrastructure databases. The STATA package (version 11.0) was used to pool the data from the eligible studies.Fifteen studies with 2973 AGC cases, of which 1497 (50.4%) received S-1-based therapy and 1476 (49.6%) received non-S-1-based therapy, were identified in the meta-analysis. AGC patients who had received S-1-based therapy had a higher median OS, median PFS, and ORR than those who had received 5-fluorouracil (FU)-based therapy (OS: hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80-0.98, P = 0.015; PFS: HR 0.88, 95% CI 0.80-0.98, P = 0.016; ORR: OR 1.25, 95% CI 1.08-1.45, P = 0.003, respectively). S-1-based therapy had similar efficacy to capecitabine-based therapy in terms of median OS (HR 1.14, 95% CI 0.91-1.41, P = 0.253), median PFS (HR 1.01, 95% CI 0.82-1.25, P = 0.927), and ORR (OR 0.84, 95% CI 0.63-1.12, P = 0.226). Subgroup analysis for grade 3 to 4 toxicity showed higher incidence of neutropenia (relative risk [RR] = 0.827, P = 0.006), nausea (RR = 0.808, P = 0.040), and lower diarrhea (RR = 1.716, P = 0.012) in 5-FU-based arm, and higher diarrhea (RR = 0.386, P = 0.007) in capecitabine-based arm.S-1-based chemotherapy is favorable to AGC patients with better clinical benefit than 5-FU-based chemotherapy and with equivalent antitumor compare with capecitabine-based therapy.

A short cerebral ischemic preconditioning up-regulates adenosine receptors in the hippocampal CA1 region of rats.

Pharmacologically blocking or stimulating studies have showed the crucial role of adenosine receptors in the protective effect of cerebral ischemic preconditioning (CIP). However, little is know about whether the adenosine receptors are up-regulated in the process. In the present study, changes in expression of adenosine receptors in the CA1 hippocampus after a short CIP in a period of 3 min were investigated in rat four-vessel occluding (4VO) brain ischemic model using immunohistochemistry. The experiments were performed on groups of sham, 4 h, 1, 3, and 7 days (n = 6 in each group) after the CIP. The number and immunostaining density of immunoreactive cells for A1 and A2b adenosine receptors in the CA1 hippocampus were significantly increased after the CIP. For A1 adenosine receptor, the increase occurred in CA1 pyramidal neurons. While for A2b adenosine receptor, the increase occurred in the stratum radiatum of the CA1. The immunoreactive cells for A2b receptor showed distinct morphological characteristics of astrocytes. The increases were consistent in time course (1-7 days) with the development of the ischemic tolerance induced by the CIP. It was concluded that up-regulation of adenosine receptors may also play an important role in the protective effect of CIP.

[Effects of alpha-methyl-(4-tetrazolyl-phenyl) glycine on the induction of hippocampal ischemic tolerance in the rat].

To explore the role of metabotropic glutamate receptor 2/3 mGluR 2/3 in the induction of brain ischemic tolerance (BIT), the influences of mGluR2/3 antagonist alpha-methyl-(4-tetrazolyl-phenyl) glycine (MTPG) on the induction of BIT and expression of glial fibrillary acidic protein (GFAP) in the hippocampus were observed using thionin staining and GFAP immunohistochemical staining in a rat brain ischemic model with four-vessel occlusion (4VO). Fifty-four rats, of which bilateral vertebral arteries were occluded permanently by electrocautery, were divided into 5 groups: (1) sham operated group (n=8): the bilateral carotid common arteries (BCCA) were separated, but the blood flow was not blocked; (2) ischemia group (n=8): the blood flow of BCCA was blocked for 8 min; (3) ischemic preconditioning (IP) group (n=8): the blood flow of BCCA was occluded for 3 min as a cerebral ischemic preconditioning (CIP), and then the rats were exposed to an 8-min brain ischemic insult 24 h after the CIP; (4) MTPG+IP group (n=22): MTPG was administered 20 min before the CIP, then the rats were exposed to an 8-min brain ischemia insult 24 h after the CIP. In order to examine dosage dependency in the effect of MTPG, 4 dosages of MTPG (0.4, 0.2, 0.04 and 0.008 mg) were administered; (5) MTPG+ischemia group (n=8): an ischemic insult for 8 min was given 24 h after the administration of MTPG (0.2 mg). MTPG was injected into the right lateral cerebral ventricle. The results obtained are as follows. (1) Ischemic insult for 8 min increased the histological grade (HG) and reduced the neuronal density (ND) significantly, and also increased the expression of GFAP significantly (P<0.05 vs sham-operated group). (2) In the IP group, the above changes were not observed, indicating that CIP could protect pyramidal neurons against the ischemic insult. (3) The protective effects of CIP were blocked by MTPG, as manifested by the significant increase in HG and decrease in ND in the MTPG+IP group (P<0.05 vs sham-operated group). The changes were dose-dependent. (4) No obvious difference in the HG, ND and expression of GFAP was detected between the groups of MTPG+ischemia and ischemia. The above results indicate that MTPG blocks the induction of BIT induced by CIP, suggesting that mGluR2/3 participates in the induction of BIT.

[Effect of nitric oxide synthase inhibitor L-NAME on the induction of brain ischemic tolerance in rats].

To explore the role of NO in the induction of brain ischemic tolerance (BIT) in vivo, the effect of nitric oxide synthase (NOS) inhibitor L-NAME on the induction of BIT induced by cerebral ischemic preconditioning (CIP) was investigated in the hippocampal CA1 subfield in CIP and ischemic insult models established by rat four-vessel occlusion using brain tissue section and thionine staining methods. Fifty-four male Wistar rats were divided into 6 groups: (1) sham-operated group (n=6): bilateral common arteries were separated without occluding the cerebral blood flow; (2) ischemia group (n=6): an ischemic insult for 10 min was given; (3) CIP+ischemia group (n=6): 3-min CIP was preformed 72 h prior to 10-min ischemic insult; (4) L-NAME group (total n=24, n=6 for each subgroup): L-NAME (5 mg/kg, i.p.) was administered 1 h prior to CIP and 1, 12 and 36 h after CIP, respectively. Other procedures were the same as those for the CIP+ischemia group; (5) L-NAME+L-Arg group (n=6): L-NAME (5 mg/kg, i.p.) and L-Arg (300 mg/kg, i.p.) were administered 1 h prior to CIP, other procedures were the same as those for the L-NAME group; (6) L-NAME+ischemia group (n=6): L-NAME (5 mg/kg, i.p.) was administered 72 h before the 10-min ischemic insult. The results showed that (1)10-min ischemic insult resulted in an increase in the histological grade (indicating a more serious tissue injury) and a decrease in pyramidal neuronal density (P<0.01); (2) the histological grade and neuronal density in hippocampal CA1 in the CIP+ischemia group were similar to those in the sham-operated group (P>0.05); (3) in the L-NAME group, administration of L-NAME brought about an increase in the histological grade and a decrease in neuronal density (P<0.01), suggesting that L-NAME blocked the protection of CIP; (4) the neuronal damage in L-NAME+L-Arg group was slighter than that in the L-NAME group, but still more serious than that in the CIP+ischemia group, suggesting that L-Arg partly reversed the blocking effect of L-NAME; (5) the morphological representations in L-NAME+ischemia group were basically similar to those in the ischemia group. The results mentioned above indicate that NO is involved in the induction of BIT in vivo. The blocking effect of L-NAME administered at 36 h after CIP was obviously weaker than the effects of L-NAME administered 1 h prior to CIP, and 1 or 12 h after CIP. It is suggested that NO is involved in the induction of BIT at an early stage and that the involvement might take place via activating cascades of the events.

Synthesis and antitumour activities of a novel class of dehydroabietylamine derivatives.

Structural modification is still a popular and important route in the forest chemical field for finding novel tricyclic diterpenes with more potential bioactivities and broad bioactive spectra. In this study, a series of dehydroabietylamine derivatives containing tricyclic diterpene structures were synthesised through oxidation in the 7th position of ring B and nitrification in the 12th position of ring C using dehydroabietylamine as the starting material. Structures of the synthesised compounds were confirmed by IR, (1)H-NMR, (13)C-NMR, MS and HRMS. The cytotoxicities of these compounds against PC-3 (human prostate carcinoma cell line) and Hey-1B (human ovarian carcinoma cell line) cells by the MTT assay were investigated. The results showed that the presence of a nitro group at 12th position and a carbonyl group at 7th position resulted in an increase of cytotoxic activity. Our findings present more evidence, showing the relationship between the chemical structure and biological function.

[Expression and clinical significance of GRIM-19 in non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: Gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) is one of the death-related genes. Its overexpression could suppress proliferation and promote apoptosis of tumor cells. This study was to investigate the expression and clinical significance of GRIM-19 in primary non-small cell lung cancer (NSCLC). METHODS: The expression of GRIM-19 in 49 specimens of NSCLC with corresponding adjacent normal lung tissues was examined by immunohistochemistry. The cellular distribution of GRIM-19 was observed under laser scanning confocal microscope. RESULTS: GRIM-19 was dominantly located in the cytoplasm of normal lung cells but enriched in the nuclei of cancer cells. The result was verified by laser scanning confocal microscopy. The positive rate of GRIM-19 was significantly higher in normal lung tissues than in NSCLC (93.8% vs. 55.1%, P<0.05). The protein level of GRIM-19 in NSCLC was reduced by 24.3% of that in normal lung tissues (0.22+/-0.01 vs. 0.29+/-0.02, P<0.05). The positive rates of GRIM-19 were 78.6% in stage I NSCLC, 48.1% in stage II NSCLC, and 12.5% in stages III-IV NSCLC. The expression of GRIM-19 was negatively correlated to clinical stage (rs=-0.428, P<0.05). CONCLUSION: GRIM-19 expression is down-regulated along the clinical development of NSCLC, and transfers from cytoplasm to nucleus.

[The effect of time parameters of cerebral ischemic preconditioning on its protective effect against global cerebral ischemic injury in rats].

AIM: To investigate the effects of the duration of cerebral ischemic preconditioning(CIP) and interval between CIP and the subsequent ischemic insult on the protection of CIP against delayed neuronal death (DND) in the CA1 hippocampus normally induced by brain ischemic insult. METHODS: Four-vessel occlusion cerebral ischemic model of rats (54) was used. The brain of the rats was sectioned and stained with thionin to show DND in the CA1 hippocampus. RESULTS: No DND was found in the hippocampus of the rats subjected to sham operation and CIP, in which 3 min cerebral ischemic preconditioning was performed. Obvious destruction of the CA1 hippocampus was found in brain ischemic insult group, in which histological (HG) was 2-3 in 6 min and 10 min ischemia subgroups and grade 3 in 15 min ischemia subgroup. In CIP + brain ischemic insult group, no obvious neuronal damage was found in 3 min-3d-6 min (CIP for 3 min was followed by a brain ischemic insult for 6 min at an interval of 3 d, the same as the following) and 3 min-3 d-10 min groups, indicating that CIP effectively protected neurons of the CA1 hippocampus against DND normally induced by ischemic insult for 6 or 10 min. However, in 3 min-1 d-10 min and 3 min-3 d-15 min groups, the protective effect of CIP was lower than that in the 3 min-3 d-10 min group. The quantitative analysis of the protective effect of CIP on the CA1 hippocampal neurons showed that there was no significant difference in protecting number and protecting index between 3 min-3 d-6 min and 3 min-3 d-10 min groups (P > 0.05). However, the growth index in 3 min-3 d-10 min group was obvious larger than that in 3 min-3 d-6 min (P < 0.05). CONCLUSION: Although the protective effects of CIP in 3 min-3 d-6 min and 3 min-3 d-10 min groups were similar, the protective effect of CIP in 3 min-3 d-10 min group was sensitively found. Maximal protective potential of CIP could be induced when using the time parameters of 3 min-3 d-10 min to establish the model of global cerebral ischemic tolerance.

[Ischemic tolerance of hippocampus induced by global ischemic preconditioning in rats].

AIM AND METHODS: To investigate the role of the duration of ischemic preconditioning and the interval between the ischemic preconditioning and the following injured ischemia in induction of ischemic tolerance of the hippocampus, using 4 vessel occlusion (4VO) global ischemic model of rats. RESULTS: Ischemia for 6 min resulted in a apparent delayed neuron death (DND) in the hippocampus, while ischemia for 3 min did not cause DND in the hippocampus. Ischemic preconditioning for 3 min could apparently decrease DND caused by ischemia for 6 min followed the preconditioning at intervals of reperfusion 1 or 3 d (P < 0.01), indicating the protective effect of the ischemic preconditioning against the following severe ischemia. However, ischemic preconditioning for 1 min did not produce any apparent protective effect. The DND could not be decreased not only, but increased in a condition of ischemic preconditioning for 5 min followed by 6 min injured ischemia at a interval of 1 d or ischemic preconditioning for 3 min followed by ischemia for 6 min at a interval of 1 h. CONCLUSION: Global ischemic preconditioning could induce tolerance of the hippocampus to ischemic injury. The proper duration of ischemic preconditioning and the interval between the preconditioning and the following injured ischemia might be 3 min and 1 to 3 days, respectively, in the 4VO rat model.

Role of endogenous peroxynitrite in pulmonary injury and fibrosis induced by bleomycin A5 in rats.

AIM: To observe the role of endogenous peroxynitrite (ONOO-) in pulmonary injury and fibrosis induced by bleomycin A5 (BLM-A5) in rats. METHODS: Pulmonary injury and fibrosis of rats were evaluated by testing the level of lipid peroxides (LPO) in out-going pulmonary blood (OPB), and by observing histological changes, including type III and type I collagen changes in lung which were examined with Sirius red staining under polarized light. The peroxynitrite expression was detected by immunohistochemistry for nitrotyrosine (NT), a marker of the peroxynitrite production. RESULTS: (1) The level of LPO was elevated in OPB of rats on d 14 after intratracheal administration of BLM-A5. Thickened alveolar wall and macrophage infiltration were seen, and fibroblasts were near by the interstitial macrophages. Increased amounts of type III collagen and type I collagen were deposited in disoriented fashion. (2) High expression of ONOO- was detected in alveolar epithelial cells and pulmonary interstitial macrophages. (3) The above changes were reduced by aminoguanidine (AG), an inhibitor of nitric oxide synthase (iNOS). CONCLUSION: Endogenous ONOO- mediated BLM-A5-induced pulmonary toxicity. The therapeutic potential of AG for pulmonary injury and fibrosis was realized partly by reducing ONOO- formation.