Association between triglyceride-glucose index trajectories and carotid atherosclerosis progression.

BACKGROUND: The triglyceride-glucose (TyG) index has been recognized as being an alternative cardiometabolic biomarker for insulin resistance associated with the development and prognosis of cardiovascular disease (CVD). However, the prospective relationship between baseline and long-term trajectories of the TyG index and carotid atherosclerosis (CAS) progression has yet to be investigated. METHODS: This longitudinal prospective cohort study included 10,380 adults with multiple general health checks at Peking University Third Hospital from January 2011 to December 2020. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The latent class trajectory modeling method was used to analyze the TyG index trajectories over the follow-up. Based on univariate and multivariate Cox proportional hazards analyses, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for the baseline and trajectory of the TyG index. RESULTS: During a median follow-up period of 757 days, 1813 participants developed CAS progression. Each 1-standard deviation (SD) increase in the TyG index was associated with a 7% higher risk of CAS progression after adjusting for traditional CVD risk factors (HR = 1.067, 95% CI 1.006-1.132). Similar results were observed when the TyG index was expressed as quartiles. According to different trajectory patterns, participants were categorized into low-stable, moderate-stable, and high-increasing groups. After multivariate adjustment, the moderate-stable group had a 1.139-fold (95% CI 1.021-1.272) risk of CAS progression. The high-increasing trajectory of the TyG index tended to be associated with CAS progression (HR = 1.206, 95% CI 0.961-1.513). CONCLUSIONS: Participants with higher baseline and moderate-stable trajectory of the TyG index were associated with CAS progression. Long-term trajectories of the TyG index can help to identify individuals at a higher risk of CAS progression who deserve specific preventive and therapeutic approaches.

Exploiting high-quality reconstruction image encryption strategy by optimized orthogonal compressive sensing.

Compressive sensing is favored because it breaks through the constraints of Nyquist sampling law in signal reconstruction. However, the security defects of joint compression encryption and the problem of low quality of reconstructed image restoration need to be solved urgently. In view of this, this paper proposes a compressive sensing image encryption scheme based on optimized orthogonal measurement matrix. Utilizing a combination of DWT and OMP, along with chaos, the proposed scheme achieves high-security image encryption and superior quality in decryption reconstruction. Firstly, the orthogonal optimization method is used to improve the chaotic measurement matrix. Combined with Part Hadamard matrix, the measurement matrix with strong orthogonal characteristics is constructed by Kronecker product. Secondly, the original image is sparsely represented by DWT. Meanwhile, Arnold scrambling is used to disturb the correlation between its adjacent pixels. Following this, the image is compressed and measured in accordance with the principles of compressive sensing and obtain the intermediate image to be encrypted. Finally, the chaotic sequence generated based on 2D-LSCM is used to perform on odd-even interleaved diffusion and row-column permutation at bit-level to obtain the final ciphertext. The experimental results show that this scheme meets the cryptographic requirements of obfuscation, diffusion and avalanche effects, and also has a large key space, which is sufficient to resist brute-force cracking attacks. Based on the sparse and reconstruction algorithm of compressive sensing proposed in this paper, it has better image restoration quality than similar algorithms. Consequently, the compressive sensing image encryption scheme enhances both security and reconstruction quality, presenting promising applications in the evolving landscape of privacy protection for network big data.

Inhibition of corneal neovascularization with the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18 (p-PEDF-SAINT-18) vector in a rat corneal experimental angiogenesis model.

Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonal antibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeability properties. In this study, we demonstrated that the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18(p-PEDF-SAINT-18) has a favorable antiangiogenic effect on corneal NV. Four groups(Group A: 0 µg + 0 µg, B: 0.1 µg + 0.1 µg, C: 1 µg + 1 µg, and D: 10 µg + 10 µg) of bevacizumab + p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus on the temporal side. Then, 1 µgof p-bFGF-SAINT-18 was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. The inhibition of NV was observed and quantified from days 1 to 60. Biomicroscopic examination, western blot analysis and immunohistochemistry were used to analyze the 18-kDa bFGF, 50-kDa PEDF and VEGF protein expression. No inhibition activity for normal limbal vessels was noted. Subconjunctival injection with the combination of bevacizumab and p-PEDF-SAINT-18 successfully inhibited corneal NV.The bFGF and PEDF genes were successfully expressed as shown by western blot analysis,and a mild immune response to HLA-DR was shown by immunohistochemistry. We concluded that the combination of bevacizumab and p-PEDF-SAINT-18 may have more potent and prolonged antiangiogenic effects, making it possible to reduce the frequency of subconjunctival bevacizumab administration combined with a relatively safe profile and low toxicity.

The R93C Variant of PCSK9 Reduces the Risk of Premature MI in a Chinese Han Population.

Background: Dyslipidemia is a common risk factor for premature myocardial infarction (PMI). Our previous work has shown that single-nucleotide polymorphisms (SNPs) of LDLR, APOB, and PCSK9 are associated with dyslipidemia, but how these SNPs correlate with risk for PMI is unknown. Objective: This study aims to evaluate the association between SNPs of LDLR, APOB, and PCSK9 and risk of PMI in Chinese Han population. Methods: Two cohorts were established. In Cohort 1 (413 in the PMI group and 1,239 in the control group), SNPs of APOB, LDLR, and PCSK9 with minor allele frequency (MAF) > 1%, which has been shown to impact the risk of PMI in a Chinese Han population, were thoroughly examined, and gene-environment interactions were analyzed. A model for PMI risk prediction was developed in Cohort 1 and externally validated in Cohort 2 (577 in the PMI group and 270 in the control group). Results: The distribution of the T allele at the PCSK9 R93C variant (rs151193009, C > T) was lower in the PMI group than that in the control group (PMI vs. Control in Cohort 1, 0.8% vs. 2.3%, P adjust < 0.05; in Cohort 2, 1.0% vs. 2.4%, P adjust < 0.05). The T allele at PCSK9 R93C variant (rs151193009, C > T) reduced the risk of PMI by ∼60% regardless of adjusting for confounding factors (in Cohort 1, adjusted odds ratio (OR) 0.354, 95% confidence interval (CI) 0.139-0.900, p = 0.029; in Cohort 2, adjusted OR 0.394, 95% CI 0.157-0.987, p = 0.047). No gene-environment interactions were observed between the R93C variant and diabetes/hypertension/smoking in PMI occurrence in this Chinese Han population. Our model showed good performance in predicting the risk of PMI in Cohort 1 (AUC 0.839, 95% CI 0.815-0.862, p < 0.001) and in an external cohort (AUC 0.840, 95% CI 0.810-0.871, p < 0.001). Conclusions: The PCSK9 R93C variant was associated with significantly reduced risk of PMI in the Chinese Han population, and the model we developed performed well in predicting PMI risk in this Chinese Han population.

Emergence of a Novel Recombinant Pseudorabies Virus Derived From the Field Virus and Its Attenuated Vaccine in China.

The occurrence of pseudorabies (PR) caused by the PR virus (PRV) causes huge economic losses to the pig industry in China. Moreover, the potential threat of PRV to humans' health has received wide attention recently. The prevalence of two PRV genotypes and the application of their corresponding live attenuated vaccines increase the recombination possibility. In the present study, a novel recombinant PRV strain designed as HN-2019 was isolated from one sick piglet in Hunan province, China, its genetic features and pathogenicity were further investigated. The results showed that the glycoprotein E (gE) and gG genes of the HN-2019 strain displayed higher nucleotide homology with PRV classical strains (such as Ea and Fa) compared to others. However, its TK gene with continuous nucleotide deletions shared 100% nucleotide identity with the HB-98 vaccine strain, which was derived from the Ea strain. Moreover, the HN-2019 strain exhibited similar growth characteristics to that of the Ea strain, but its pathogenicity in mice was significantly lower than the latter one. The results above suggested that a naturally recombinant event might occur in the genome of the HN-2019 strain between the PRV classical strain and the HB-98 vaccine strain, which will provide useful guidelines for PRV vaccine design in the future.

Pseudorabies in pig industry of China: Epidemiology in pigs and practitioner awareness.

Pseudorabies virus (PRV) is widely prevalent in China, which can transmit from pigs to other mammals. Moreover, a PRV variant isolated from an acute human encephalitis case was documented recently. It is imperative to investigate PRV epidemiology in pigs, the knowledge regarding pseudorabies (PR) and self-protection behaviors upon working among relevant practitioners including pig farmers, pig cutters, and pork salesman. In the present study, 18,812 pig serum samples and 1,634 tissue samples were collected from Hunan Province during the period of 2020 to 2021 for detecting the presence of PRV gE-special antibody and nucleic acids, respectively. Meanwhile, we conducted a questionnaire survey about PR among these practitioners in China. The results showed that nearly 9% (1,840/20,192) pigs from 161 collected sites (20.17%, 161/797) were seropositive for PRV-gE antibody. Though only 2.33% tissue samples were positive for PRV nucleic acids, all the representative PRV strains were variant. It was learned that most practitioners were frequently injured when working, the injured sites mainly included hand and foot. Among the three transmission routes of PRV, the aerosol transmission route was often overlooked. Moreover, the workers lacked self-protection awareness and were poor conscious about PRV and its potential threat to humans. All the results demonstrate that PRV remains widely spread in pig populations, while the potential threats of PRV in pig industry receive less attention, suggesting that targeted educational programs to these people should be performed.

Trajectories of Lipid Profile and Risk of Carotid Atherosclerosis Progression: A Longitudinal Cohort Study.

BACKGROUND: Early assessment of carotid atherosclerotic plaque characteristics is essential for atherosclerotic cardiovascular disease (ASCVD) risk stratification and prediction. We aimed to identify different trajectories of lipid profiles and investigate the association of lipid trajectories with carotid atherosclerosis (CAS) progression in a large, longitudinal cohort of the Chinese population. METHODS: 10,412 participants aged ≥18 years with ≥2 times general health checkups were included in this longitudinally prospective cohort study at Peking University Third Hospital. We used latent class trajectory models to identify trajectories of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) over follow-up time (757 days, IQR: 388-844 days). RESULTS: Participants with carotid plaque were more likely to be older, male, have higher body mass index, have a higher prevalence of hypertension and diabetes, and have a higher level of blood pressure, TG, TC, and LDL-C, compared with carotid intima-media thickness (cIMT) and normal group. Subjects were trichotomized according to different trajectory patterns into stable, moderate-stable, and elevated-increasing classes. TC ≥ 5.18 mmol/L and moderate-stable class (hazard ratio (HR): 1.416, 95% confidence interval (CI): 1.285-1.559, p: 0.000), TG ≥ 1.70 mmol/L and moderate-stable class (HR: 1.492, 95% CI: 1.163-1.913, p: 0.002), TG ≥ 1.70 mmol/L and elevated-increasing class (HR: 1.218, 95% CI: 1.094-1.357, p: 0.000), LDL-C ≥ 3.36 mmol/L and stable class (HR: 1.500, 95% CI: 1.361-1.653, p: 0.000) were statistically significant associated with CAS progression compared with the reference group. CONCLUSIONS: Borderline elevated baseline lipid (TC, TG, and LDL-C) with stable and elevated-increasing trajectories were associated with CAS progression. Long-term strategies for low-level lipid are beneficial for ASCVD management.

[Effect of noninvasive positive pressure ventilation and high-flow nasal cannula oxygen therapy on the clinical efficacy of coronavirus disease 2019 patients with acute respiratory distress syndrome].

OBJECTIVE: To observe the effect of noninvasive positive pressure ventilation (NIPPV) and high-flow nasal cannula oxygen therapy (HFNC) on the prognosis of patients with coronavirus disease 2019 (COVID-19) accompanied with acute respiratory distress syndrome (ARDS). METHODS: A retrospective study was conducted in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology when authors worked as medical team members for treating COVID-19. COVID-19 patients with pulse oxygen saturation/fraction of inspiration oxygen (SpO2/FiO2, S/F) ratio < 235, managed by medical teams [using S/F ratio instead of oxygenation index (PaO2/FiO2) to diagnose ARDS] from February to April 2020 were included. The patients were divided into NIPPV group and HFNC group according to their oxygen therapy modes. Clinical data of patients were collected, including general characteristics, respiratory rate (RR), fraction of FiO2, SpO2, heart rate (HR), mean arterial pressure (MAP), S/F ratio in the first 72 hours, lymphocyte count (LYM), percentage of lymphocyte (LYM%) and white blood cell count (WBC) at admission and discharge or death, the duration of dyspnea before NIPPV and HFNC, and the length from onset to admission. The differences of intubation rate, all-cause mortality, S/F ratio and RR were analyzed, and single factor analysis and generalized estimation equation (GEE) were used to analyze the risk factors affecting S/F ratio. RESULTS: Among the 41 patients, the proportion of males was high (68.3%, 28 cases), the median age was 68 (58-74) years old, 28 cases had complications (68.3%), and 34 cases had multiple organ dysfunction syndrome (MODS, 82.9%). Compared with HFNC group, the proportion of complications in NIPPV group was higher [87.5% (21/24) vs. 41.2% (7/17), P < 0.05], and the value of LYM% was lower [5.3% (3.4%-7.8%) vs. 10.0% (3.9%-19.7%), P < 0.05], the need of blood purification was also significantly lower [0% (0/24) vs. 29.4% (5/17), P < 0.05]. The S/F ratio of NIPPV group gradually increased after 2 hours treatment and RR gradually decreased with over time, S/F ratio decreased and RR increased in HFNC group compared with baseline, but there was no significant difference in S/F ratio between the two groups at each time point. RR in NIPPV group was significantly higher than that in HFNC group after 2 hours treatment [time/min: 30 (27-33) vs. 24 (21-27), P < 0.05]. There was no significant difference in rate need intubation and hospital mortality between NIPPV group and HFNC group [66.7% (16/24) vs. 70.6% (12/17), 58.3% (14/24) vs. 52.9% (9/17), both P > 0.05]. Analysis of the factors affecting the S/Fratio in the course of oxygen therapy showed that the oxygen therapy mode and the course of illness at admission were the factors affecting the S/F ratio of patients [ßvalues were -15.827, 1.202, 95% confidence interval (95%CI) were -29.102 to -2.552 and 0.247-2.156, P values were 0.019 and 0.014, respectively]. CONCLUSIONS: Compared with HFNC, NIPPV doesn't significantly reduce the intubation rate and mortality of patients with COVID-19 accompanied with ARDS, but it significantly increases the S/F ratio of those patients.

Gene knockdown of the N-methyl-D-aspartate receptor NR1 subunit with subcutaneous small interfering RNA reduces inflammation-induced nociception in rats.

BACKGROUND: Spinal N-methyl-D-aspartate receptors have been demonstrated to play an important role in the facilitation and maintenance of nociception. To avoid adverse effects of blocking N-methyl-D-aspartate receptors in the central nervous system, blocking N-methyl-D-aspartate receptor in peripheral nervous system is an ideal alternative. Transfection of small interfering RNAs (siRNAs) into cells has been revealed to provide potent silencing of specific genes. In this study, the authors examined the effect of subcutaneous injection of siRNA targeting the NR1 subunit of the N-methyl-D-aspartate receptor on silencing NR1 gene expression and subsequently abolishing inflammatory nociception in rats. METHODS: Male Sprague-Dawley rats received intradermal injection of NR1 siRNA and underwent injection of formalin or complete Freund's adjuvant. The flinch response and mechanical hypersensitivity by von Frey filaments were assessed. Then the messenger RNA and protein of NR1 in skin and dorsal root ganglion were analyzed. RESULTS: The results revealed that subcutaneous injection of 1 nmol NR1 siRNA effectively diminished the nociception induced by formalin and complete Freund's adjuvant stimuli and attenuated the level of NR1 messenger RNA and protein in skin and ipsilateral dorsal root ganglion. The antinociception effect and the inhibition of NR1 expression persisted for about 7 days after administration of NR1 siRNA. CONCLUSIONS: The data of this study suggest that NR1 siRNA has potential therapeutic value in the treatment of inflammatory pain induced or maintained by peripheral nociceptor activity and support the potential application of this method to the study of nociceptive processes and target the validation of pain-associated genes.

Inhibition of corneal neovascularization with plasmid pigment epithelium-derived factor (p-PEDF) delivered by synthetic amphiphile INTeraction-18 (SAINT-18) vector in an experimental model of rat corneal angiogenesis.

The use of Synthetic Amphiphile INTeraction-18 (SAINT-18) carrying plasmid pigment epithelium-derived factor (p-PEDF) as an anti-angiogenesis strategy to treat corneal neovascularization in a rat model was evaluated. Four partially dried forms (Group A: 0 microg, B: 0.1 microg, C: 1 microg, D: 10 microg) of a p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus at the temporal side. The 1 microg of plasmid-basic fibroblast growth factor--SAINT-18 (p-bFGF-SAINT-18) (1 microg) was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. Inhibition of neovascularization was observed and quantified from day 1 to day 60. PEDF (50-kDa) and bFGF (18-kDa) protein expression were analyzed by biomicroscopic examination, Western blot analysis, and immunohistochemistry. Gene expression in corneal and conjunctival tissue was observed as early as 3 days after gene transfer and stably lasted for over 3 months with minimal immune reaction. Subconjunctival injection of a highly efficient p-PEDF-SAINT-18 successfully inhibited corneal neovascularization. Successful gene expression of bFGF, PEDF and a mild immune response of HLA-DR were shown by immunohistochemistry staining. We concluded that SAINT-18 was capable of directly delivering genes to the ocular surface by way of subconjunctival injection, and delivered sustained, high levels of gene expression in vivo to inhibit angiogenesis.

Preincisional subcutaneous infiltration of ketamine suppresses postoperative pain after circumcision surgery.

OBJECTIVE: N-methyl-D-aspartate and other glutamate receptors have been shown to present on the peripheral axons of primary afferents, and peripheral injection of N-methyl-D-aspartate-receptor antagonists can suppress hyperalgesia and allodynia. Thus, this study examined postoperative analgesic and adverse effects of local ketamine administered postoperatively. METHODS: Ketamine (0.3%, 3 mL) or saline was subcutaneously infiltrated before incision in a double-blind manner using a sample population of 40 patients undergoing circumcision surgery, equally and randomly assigned to 2 groups based on the treatment. The saline-infiltrated patients also received 9-mg intramuscular ketamine into the upper arm to control for any related systemic analgesic effects. The patients were followed up for 24 hours to determine postoperative analgesia and identify adverse effects. RESULTS: In the ketamine-infiltrated patients, the time interval until first analgesic demand (166 vs. 80 min) was longer and the incidence of pain-free status (pain score=0) during movement (45% vs. 10%) and erection (40% vs. 0%) was significantly higher than for the saline-treated analogs (P<0.05). The dose of ketorolac use and pain score during erection were significant lower in group ketamine patients. No significant differences were noted with respect to the incidence of adverse effects comparing the 2 groups. DISCUSSION: We conclude that preincisional subcutaneous ketamine infiltration can suppress postoperative pain after the circumcision surgery.

Dehydrated form of plasmid expressing basic fibroblast growth factor-polyethylenimine complex is a novel and accurate method for gene transfer to the cornea.

PURPOSE: We describe a novel vector system of nonviral gene transfer into the cornea using a dehydrated form of a plasmid expressing basic fibroblast growth factor-polyethylenimine (p-bFGF-PEI) complex to induce angiogenesis. METHODS: Corneal neovascularization was evaluated in 48 eyes of Sprague-Dawley rats after implantation of a dehydrated form of PEI containing 1 microg green fluorescent protein (p-GFP-PEI; control group), or 10 microg, 1 microg, or 0.1 microg of p-bFGF-PEI introduced by spin vacuum at ambient temperature. Neovascularization was observed and quantified from day 1 to day 45. Eighteen kDa bFGF protein expression was analyzed by Western blot and immunohistochemistry. RESULTS: Limbal vessels began to sprout on day 3 in the p-bFGF-PEI groups. The dehydrated form of the p-bFGF-PEI complex induced dose-dependent corneal neovascularization, which reached a maximum on days 24-30 in the 10 microg bFGF group, days 18-24 in the 1 microg bFGF group, and days 15-21 in 0.1 microg bFGF group, and then regressed progressively. No neovascularization was observed in the GFP group. CONCLUSIONS: The dehydrated form of the p-bFGF-PEI complex is a novel and precise method for controlling the dose, localizing the reagents, and avoiding loss of liquid form during transfection into corneal tissue.

Treatment of empty sella syndrome with ventriculoperitoneal shunt.

A symptomatic empty sella developed in a female patient undergoing bromocriptine therapy for microprolactinoma. Placement of a ventriculoperitoneal shunt dramatically improved the symptoms of headache and blurred vision. The post-operative imaging showed resolution of the empty sella. She was able to resume bromocriptine therapy without recurrence of her previous symptoms and give birth to a baby 20 months later. An MRI 44 months after surgery and on bromocriptine therapy showed no recurrence of the empty sella. We conclude that ventriculoperitoneal shunt may be a simple, and durable treatment for drug induced empty sella and allows resumption of bromocriptine therapy for preexisting microprolactinoma.

In vivo electroporation of proopiomelanocortin induces analgesia in a formalin-injection pain model in rats.

Opioids remain the most efficacious pharmacological agents for various clinical pain syndromes. Recently, various engineered cells capable of secreting opioidergic peptides have been applied to relieve pain in animal models. In vivo gene delivery by viruses encoding endogenous opioids has also been used with success. In this study, we attempted non-viral intrathecal in vivo gene delivery by electroporation to induce analgesia. Thirty Sprague-Dawley rats were used in this study, six in each of five groups. Rats were treated as follows: vehicle without electroporation (group A), vehicle with electroporation (group B), 100 microg of pCMV-hPOMC plasmid without electroporation (group C), or 100 microg of pCMV-hPOMC plasmid with electroporation (group D). Group E was treated with both pCMV-hPOMC plasmid and electroporation, and given naloxone (1mg/kg) 1h before the formalin test. The tail flick, paw withdrawal latency from radiant heat, and formalin test results for each groups were compared. Radioimmunoassay (RIA) and reverse transcription-polymerase chain reaction (RT-PCR) were used to determine the levels of expression of beta-endorphin in the spinal cord. beta-Endorphin expression was localized by immunohistochemistry. A significant decrease in the number of flinches in phase 2 of the formalin test was observed in the group treated with both plasmid and electroporation (group D), whereas the other measures of pain did not differ between groups. RIA and RT-PCR both showed increased expression of beta-endorphin in group D. The expression of beta-endorphin was highest in laminae I and II of the dorsal horn of the spinal cord. We conclude that electroporation successfully delivered intrathecally administered pCMV-hPOMC into the dorsal horn cells of the spinal cord, and induced analgesia in phase 2 of the formalin test in rats.

Neuroprotective synergy of N-methyl-D-aspartate receptor antagonist (MK801) and protein synthesis inhibitor (cycloheximide) on spinal cord ischemia-reperfusion injury in rats.

Thoraco-abdominal aortic surgery requiring temporal cross clamping of the aorta results in a high incidence of paraplegia due to temporary ischemia of the spinal cord. Both excitotoxicity and apoptosis are implicated in the pathogenesis of spinal cord ischemia-reperfusion injury. We propose that the N-methyl-D-aspartate receptor antagonist dizocilpine maleate (MK801) and the protein synthesis inhibitor cycloheximide produce a synergic effect in a rodent model of spinal cord ischemia-reperfusion injury. Injury was induced by 20 min of temporal thoracic aorta occlusion and distal blood volume reduction. After injury, the animals were treated with vehicle, MK801, cycloheximide or MK801 and cycloheximide. Hind limb motor function recovery was better in the MK801 and combined therapy groups than in the control and cycloheximide groups. The mean neuronal survival rate of the control group was 45.3 +/- 3.2% on the 7(th) day after injury. In the MK801 and cycloheximide treatment groups, neuronal survival increased to 62.4 +/- 3.6% and 54.1 +/- 2.4%, respectively. For the combined therapy group, neuronal survival increased to 75.6 +/- 2.5%. The number of apoptotic cells in the control group was 211.4 +/- 8.8 per section on the 7th day after ischemic insult, while apoptosis was significantly reduced in the cycloheximide (96.8 +/- 6.7 cells) and combined (84.8 +/- 8.5 cells) groups. It was unchanged in the MK801 group (209.8 +/- 5.4 cells). These results suggest that combined treatments directed at blocking both N-methyl-D-aspartate receptor-mediated excitotoxic necrosis and caspase-mediated apoptosis might have synergic therapeutic potential in reducing spinal cord ischemia-reperfusion injury.

Intrathecal spinal progenitor cell transplantation for the treatment of neuropathic pain.

Injury to, or dysfunction of, the nervous system can lead to spontaneous pain, hyperalgesia, and/or allodynia. It is believed that the number and activity of GABAergic neurons gradually decreases over the dorsal horn. Glutamic acid decarboxylase (GAD) immunocompetence has been demonstrated on spinal progenitor cells (SPCs) cultivated in vitro. The intrathecal implantation of these cultivated progenitor cells may provide a means of alleviating neuropathic pain. Chronic constriction injury (CCI) of the sciatic nerve was used to induce chronic neuropathic pain in the hind paw of rats. SPCs (1 x 10(6)) were implanted intrathecally on the third day after the CCI surgery. The behavioral response to thermal hyperalgesia was observed and recorded during the 14 days postsurgery. Various techniques were utilized to trace the progenitor cells, confirm the differentiation, and identify the neurotransmitters involved. GAD immunoactivity was revealed for 65% of the cultivated spinal progenitor cells in our study. We also determined that transplanted cells could survive more than 3 weeks postintrathecal implantation. Significant reductions were demonstrated for responses to thermal stimuli for the CCI rats that had received intrathecal SPC transplantation. A novel intrathecal delivery with SPCs reduced CCI-induced neuropathic pain.

Altered synaptophysin expression in the rat spinal cord after chronic constriction injury of sciatic nerve.

Injury to the peripheral nervous system can lead to spontaneous pain, hyperalgesia and allodynia. Previous studies have shown sprouting of Abeta-fibres into lamina II of the spinal cord dorsal horn after nerve injury and the formation of new synapses by these sprouts. Synaptophysin is a presynaptic vesicle protein, useful in the identification of synaptogenesis. Here we investigated whether synaptogenesis as measured by the expression of synaptophysin protein correlates with symptoms of neuropathic pain in rats with a chronic constriction injury (CCI) of the sciatic nerve. We used immunohistochemistry, Western immunoblotting and densitometry to study the distribution of synaptophysin and to quantify relative protein. Synaptophysin was increased in the ipsilateral dorsal horn with a peak level on day 14 and returned to baseline on day 21 post-CCI. Synaptophysin levels temporally correlated with thermal hyperalgesia but not with tactile allodynia. Our results indicate that thermal hyperalgesia in CCI significantly correlates with synaptogenesis within the superficial layers of the dorsal horn.

Shock wave therapy induces neovascularization at the tendon-bone junction. A study in rabbits.

Despite the success in clinical application, the exact mechanism of shock wave therapy remains unknown. We hypothesized that shock wave therapy induces the ingrowth of neovascularization and improves blood supply to the tissues. The purpose of this study was to investigate the effect of shock wave therapy on neovascularization at the tendon-bone junction. Fifty New Zealand white rabbits with body weight ranging from 2.5 to 3.5 kg were used in this study. The right limb (the study side) received shock wave therapy to the Achilles tendon near the insertion to bone. The left limb (the control side) received no shock wave therapy. Biopsies of the tendon-bone junction were performed in 0, 1, 4, 8 and 12 weeks. The number of neo-vessels was examined microscopically with hematoxylin-eosin stain. Neovascularization was confirmed by the angiogenic markers including vessel endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) expressions and endothelial cell proliferation determined by proliferating cell nuclear antigen (PCNA) expression examined microscopically with immunohistochemical stains. The results showed that shock wave therapy produced a significantly higher number of neo-vessels and angiogenesis-related markers including eNOS, VEGF and PCNA than the control without shock wave treatment. The eNOS and VEGF began to rise in as early as one week and remained high for 8 weeks, then declined at 12 weeks; whereas the increases of PCNA and neo-vessels began at 4 weeks and persisted for 12 weeks. In conclusion, shock wave therapy induces the ingrowth of neovascularization associated with early release of angiogenesis-related markers at the Achilles tendon-bone junction in rabbits. The neovascularization may play a role to improve blood supply and tissue regeneration at the tendon-bone junction.

Double-blind parallel comparison of multiple doses of apraclonidine, clonidine, and placebo administered intra-articularly to patients undergoing arthroscopic knee surgery.

OBJECTIVE: This clinical study assessed and compared the potential analgesic and adverse effect of IA apraclonidine with IA clonidine. METHODS: Eighty patients scheduled for arthroscopic knee surgery under general anesthesia were randomized to receive, in a double-blind manner, either IA normal saline (group 1), 50 microg IA apraclonidine (group 2), 150 microg IA apraclonidine (group 3), or 150 microg IA clonidine (group 4), all in a volume of 20 mL subsequent to surgery. Visual analog pain scores (VAS), the duration of analgesia as defined by the time to first demand for supplemental analgesics, the subsequent 24-hour consumption of postoperative supplementary analgesics, and patient adverse effects were evaluated. RESULTS: The patients from groups 3 and 4 demonstrated a longer duration of analgesia and used fewer analgesics in the first postoperative 24 hour period compared with group 1 and 2 patients (P < 0.05). The VAS scores corresponding to the periods 1, 2, and 4 hours postoperatively were significantly lower for group 3 than for group 1 patients. The VAS scores at 1 and 4 hours postoperatively were also lower for group 3 than for group 2 patients (P < 0.05). There was no significant difference in the incidence of side effects among the 4 groups. DISCUSSION: The IA application of 150 microg apraclonidine and 150 microg clonidine provide similar degree of postoperative analgesia following knee arthroscopic surgery without any difference in adverse events.