Recent advances in the protective role of hydrogen sulfide in myocardial ischemia/reperfusion injury: a narrative review.

Hydrogen sulfide (H2S) is recognized to be a novel mediator after carbon monoxide and nitric oxide in the organism. It can be produced in various mammalian tissues and exert many physiological effects in many systems including the cardiovascular system. A great amount of recent studies have demonstrated that endogenous H2S and exogenous H2S-releasing compounds (such as NaHS, Na2S, and GYY4137) provide protection in many cardiovascular diseases, such as ischemia/reperfusion injury, heart failure, cardiac hypertrophy, and atherosclerosis. In recent years, many mechanisms have been proposed and verified the protective role exhibited by H2S against myocardial ischemia/reperfusion injury, and this review is to demonstrate the protective role of exogenous and endogenous H2S on myocardial ischemia/reperfusion injury.

The role of oxygen in cluster headache.

High-flow oxygen inhalation is one of the most effective acute treatments for cluster headache. The therapy was first described for the treatment of cluster headache in 1952 by Horton, and has exhibited some advantages and efficacy compared to other acute medicines. The mechanism is not very clear, but some evidence has demonstrated its relationship to the trigeminovascular system and neuroinflammation. High-flow oxygen inhalation via a non-rebreather mask during cluster headache attacks has been widely recommended. Patients with frequent attacks and/or intolerance to drugs may prefer the oxygen treatment.

A new central post-stroke pain rat model: autologous blood injected thalamic hemorrhage involved increased expression of P2X4 receptor.

Stroke is the leading cause of disability and death in the world. Central post-stroke pain (CPSP), a central neuropathic pain syndrome occurring after cerebral stroke, is a serious problem. But on account of the lack of reliable animal models, the mechanisms underlying CPSP remains poorly understood. To better understand of the pathophysiological basis of CPSP, we developed and characterized a new rat model of CPSP. This model is based on a hemorrhagic stroke lesion with intra-thalamic autologous blood (ITAB) injection in the ventral posterolateral nucleus of the thalamus. Behavioral analysis demonstrated that the animals displayed a significant decrease in mechanical allodynia threshold. We found a significant increase in P2 × 4 receptor expression in microglia in thalamic peri-lesion tissues post-hemorrhage. The mechanical allodynia in rats with CPSP were reversed by blocking P2 × 4 receptors. A significant alleviation of mechanical allodynia was achieved following the administration of adrenergic antidepressants and antiepileptics. Meanwhile, we found a significant decrease in P2 × 4 receptor expression after treatment with these drugs. Taken together, our results suggest that targeting P2 × 4 receptor may be effective in the treatment of CPSP.

Evaluation of the early response and mechanism of treatment of Parkinson's disease with L-dopa using 18F-fallypride micro-positron emission tomography scanning.

The aim of the present study was to investigate the use of 18F-fallypride micro-positron emission tomography (micro-PET) imaging in the evaluation of the early therapeutic efficacy of L-dopa in the treatment of Parkinson's disease (PD) and the underlying mechanism. 18F-fallypride was synthesized and its specific binding with dopamine (DA) receptors in normal mouse brain was studied. Following the establishment of a mouse model of PD, the animals were divided into normal control, PD model and L-dopa treatment groups. General behavior, swimming test, locomotor activity counts, transmission electron microscopy, immunohistochemical analysis, high performance liquid chromatography-electrochemical detection and 18F-fallypride micro-PET imaging were used to study intergroup differences and the correlation between the changes of striatal uptake of 18F-fallypride and the therapeutic efficacy. The general behavioral features of PD model mice were similar to the clinical symptoms of PD patients and were alleviated after treatment. The swimming time, locomotor activity and frequency of standing posture of PD model mice were lower than those of the control mice, but had no difference from those of the control mice after L-dopa treatment. The number of tyrosine hydroxylase-positive neurons and the striatal contents of glutathione peroxidase, superoxide dismutase, DA and its metabolites 3,5-dihydroxyphenylacetic acid and homovanillic acid in the PD group were lower than those in the control group, but were significantly improved following the treatment; the significant reduction in DOPAC/DA and HVA/DA ratios post treatment suggested that the rate of DA metabolism decreased significantly. The striatal malondialdehyde content in the PD group increased compared with that in the control group, but was reduced after L-dopa treatment. Micro-PET imaging indicated that the uptake of 18F-fallypride in the mouse striatum of the PD group was lower than that of the control group and was significantly increased after the treatment. The mechanism of treatment of PD with L-dopa in mice may involve increasing the number of TH-positive cells and DA receptor levels, as well as reducing the rate of DA metabolism; such changes can be noninvasively observed in vitro by 18F-fallypride imaging.

The changes of brainstem auditory evoked potentials (BAEP) after vertebrobasilar artery ischemia in rabbits.

Brainstem auditory evoked potentials (BAEPs) have been used as a valuable neurophysiologic index of neuronal dysfunction in the level of the brainstem. BAEPs are also useful in subdividing evoked potentials into normal, slight, or pronounced in patients with vertebrobasilar insufficiency. We investigated the changes of BAEP after vertebrobasilar artery ischemia in rabbits and its significance in clinical work. A brainstem ischemic model was made by unilateral extracranial occlusion of vertebral artery to monitor BAEPs at 0, 10, 20, 30, 40, 50, and 60 min after occlusion. We found that peak latencies (PL) of I, III, and most notably V were gradually extended. In addition, we observed a significant (P < 0.05) delay of interpeak latencies (IPL) of waves I­III, III­V, and I­V after occlusion. This delay became more significant in IPL I­V 60 min after occlusion. Our results also demonstrate that the amplitude of I and V had no obvious change (P < 0.05). In the rabbit with bilateral extracranial occlusion of vertebral artery, BAEP waveforms disappeared 10 min after occlusion. Our results showed that vertebrobasilar insufficiency caused brainstem ischemia, which induced BAEP abnormity. Taken together, our findings suggest that BAEP has important significance for the clinical diagnosis of vertebrobasilar insufficiency. Therefore, early detection of neuronal change after transient cerebral ischemia is important in initiating treatment within the therapeutic window.

Lack of association between ADRA2B-4825 gene insertion/deletion polymorphism and migraine in Chinese Han population.

OBJECTIVE: The present study aimed to estimate the association between susceptibility to migraine and the 12-nucleotide insertion/deletion (indel) polymorphism in promoter region of alpha(2B)-adrenergic receptor gene (ADRA2B). METHODS: A case-control study was carried out in Chinese Han population, including 368 cases of migraine and 517 controls. Genomic DNA was extracted from blood samples, and DNA fragments containing the site of polymorphism were amplified by PCR. Data were adjusted for sex, age, migraine history and family history, and analyzed using a logistic regression model. RESULTS: There was no association between indel polymorphism and migraine, at either the allele or the genotype level. CONCLUSION: These findings do not support a functional significance of ADRA2B indel polymorphism at position -4825 relative to the start codon in the far upstream region of the promoter in the present migraine subjects.

[Analysis of the parameters about selective anterior fusion of thoracolumbar/lumbar curves in adolescent idiopathic scoliosis].

OBJECTIVE: To establish criteria for AIS of Lenke5 and Lenke6 by an anterior only procedure of the lower curve fusion. METHODS: A retrospective study was conducted between March 1999 and May 2004 to investigate 52 AIS patients of Lenke5 and Lenke6. All the patients were observed 24 years (34 months on average). Many parameters were evaluated. At final assessment, two groups emerged: Group A had satisfactory results (the thoracic curve was reduced) and Group B had just the opposite. RESULTS: Preoperative thoracic curve in group A averaged 33 degrees and 18 degrees after surgery. The lumbar curve averaged 49 degrees before surgery and 21 degrees after surgery. In group B (n = 6), the average thoracic curve was 38 degrees before surgery and 45 degrees after surgery, whereas the lumbar curve averaged 46 degrees before surgery and 25 degrees after surgery. Two of these patients underwent posterior thoracic instrumentation and fusion because of the unreasonable balance. CONCLUSIONS: A successful surgical outcome was dependent on both the flexibility of the thoracic curve and the patients' maturity. The thoracolumbar/lumbar-thoracic (TL/L:T) Cobb ratio in combination with the flexibility of the thoracic curve were the best predictors among the structural indexes.

A recombinant pseudorabies virus encoding the HA gene from H3N2 subtype swine influenza virus protects mice from virulent challenge.

The hemagglutinin (HA) gene of A/Swine/Inner Mogolian/547/2001 (H3N2) swine influenza virus (SIV) was recombined into the genome of pseudorabies virus (PRV) Bartha-K61 vaccine strain, generating a recombinant PRV expressing the HA gene, designated as rPRV-HA. One group of 15 mice was inoculated intranasally (i.n.) with 10(5.0) PFU of rPRV-HA, and another two control groups of mice (15 mice per group) were mock-inoculated or inoculated with Bartha-K61. Mice inoculated with rPRV-HA developed hemagglutination inhibition antibodies 3 weeks post-inoculation. Twenty-eight days post-inoculation, all mice were challenged i.n. with 10(5.0) TCID50 of A/Swine/Heilongjiang/74/2000 (H3N2). No challenge virus was isolated from vaccinated mice, and mild pathological lesions were observed only in lungs following challenge. The results demonstrate that the recombinant rPRV-HA expressing the HA gene from H3N2 SIV can protect mice from heterologous virulent challenge, and may represent a candidate vaccine against SIV.

Protective immunity induced by a recombinant pseudorabies virus expressing the GP5 of porcine reproductive and respiratory syndrome virus in piglets.

Pseudorabies virus (PRV) has been developed as a vaccine vector for expressing foreign immunogens. Porcine reproductive and respiratory syndrome (PRRS), caused by porcine reproductive and respiratory syndrome virus (PRRSV), continues to be a major problem to the pork industry worldwide. Many vaccine strategies have been developed to control the disease but most of them turn out to be unsuccessful. The objective of this research was to explore the feasibility of PRV-based vector vaccine in protection against PRRSV. A live attenuated vaccine-based PRV recombinant expressing the envelope protein GP5 of PRRSV was generated using recombinant DNA techniques. The Bartha-K61-derived recombinant virus, named rPRV-GP5, was shown to express PRRSV GP5 efficiently. Sixteen healthy piglets were assigned to one of four groups (one to four, four pigs per group). Animals in Groups 1 and 2 were each inoculated intramuscularly and intranasally with 10(7.0) PFU of rPRV-GP5 and its parent Bartha-K61, respectively; Group 3 were vaccinated intramuscularly with one-dose of PRRS inactivated vaccine; Group 4 was served as non-vaccinated control. One month later, all animals were all challenged with 10(6.5) TCID(50) of virulent PRRSV CH-1a. All animals in Groups 1 and 3 remained clinically healthy before and after challenge, with only a short period of fever (no more than 41 degrees C and 3 days), mild and gradually improving lung and kidney lesions, and short-term viremia (2 and 3 week, respectively) in spite of no detectable anti-PRRSV antibody before challenge. On the other hand, all animals in the other two groups showed evident clinical signs with higher temperatures (more than 41 degrees C) after challenge, and severe lung, kidney and spleen lesions and extended viremia (4 weeks). The results indicate that the rPRV-GP5 is safe for vaccinates and able to confer significant protection against clinical disease and reduce pathogenic lesions induced by PRRSV challenge in vaccinated pigs.

Construction and characterization of a recombinant pseudorabies virus expressing porcine reproductive and respiratory syndrome virus GP5.

The GP5 gene of porcine reproductive and respiratory syndrome virus (PRRSV) was integrated into the TK gene locus of pseudorabies virus (PRV) vaccine strain Bartha-K61, resulting in a TK- and gE- negative recombinant PRV harboring GP5 gene, designated as rPRV-GP5. The in vitro expression of the GP5 by rPRV-GP5-infected cells was analyzed by single-step growth analysis,Western blot,and indirect immunofluorescence test. It was shown that GP5 gene can be expressed authentically in the cytoplasm of rPRV-GP5-infected cells. Compared to its parental virus, rPRV-GP5 showed no obvious difference regarding viral replication and cytopathogenic effects in several cell cultures. Four PRV-negative sheep immunized intramuscularly with 10(6.0) PFU of rPRV-GP5 were fully protected from challenge with 10(3) LD50 of highly virulent PRV S strain of porcine origin. Ten PRV- and PRRSV-negative piglets given intranasally with 10(7.0) PFU of rPRV-GP5 and challenged intranasally with 10(5.0) TCID50 of virulent PRRSV CH-1a strain at day 63 post-inoculation developed antibodies against PRRSV 3, 5, 14 days post-challenge, as revealed by indirect immunofluorescence test, enzyme-linked immunosorbent assay and virus neutralization test. The results suggest that rPRV-GP5 is capable of inducing anamnestic immune response to PRRS in inoculated animals.

[Expression of truncated gE gene of pseudorabies virus (PRV) and primary application in differential diagnosis of PRV vaccination and infection].

With the application of gE gene deleted pseudarabies virus (PRV) vaccine worldwide, a corresponding differential diagnosis based on gE glycoprotein is needed in the project of PRV eradication. In this study, PRV gE gene without signal and transmembrane region was amplified by PCR and cloned into pGEX-6P-1, generated pGEX-gE. After transformation of BL21 with pGEX-gE, an expressed fusion protein(about 63kD) was identified by SDS-PAGE. The recombinant proteins are produced as inclusion bodies. By changing the inductive conditions, the formation of inclusion bodies was inhibited and tended to increase the percentage of soluble recombinant protein. The antigenic reactivity of the recombinant protein was confirmed by Western blotting with polyclonal antibodies against PRV. Using purified recombinant tgE as antigen, an ELISA was developed to detect sera of PRV infected pigs and sera of pigs immunized with gE-deleted PRV vaccine. The total of 400 serum samples collected from field were comparatively tested with the tgE-ELISA and a commercial competitive ELISA based on monoclonal antibody against gE, the results indicated that the coincidental rate between the two tests is about 94%.