Stem cells combined with three-dimensional scaffolds for the treatment of osteoporotic bone defects北大核心

BACKGROUND: Stem cells combined with a three-dimensional scaffold have great potential for the treatment of osteoporotic bone defects. OBJECTIVE: To introduce the application of stem cells combined with the three-dimensional scaffold in repairing osteoporotic bone defects. METHODS: A computer-based search of PubMed, Web of Science, Springerlink, Medline, WanFang and CNKI databases was performed for relevant articles published from 2007 to 2017 with “stem cells, scaffold, osteoporosis, bone defects” as key words in English and Chinese, repsectively. Initially, 142 articles were retrieved, and finally 45 articles were included in result analysis. RESULTS AND CONCLUSION: Due to the potential of self-renewal and multilineage differentiation, stem cells can be used to repair or regenerate damaged tissues, which are considered as an ideal cell source for the treatment of diseases in orthopedics. The suitable scaffold can provide a favorable microenvironment for repairing the attachment and growth of the cells related to the bone defect, which can promote the healing without additional side effects. Furthermore, stem cells combined with three-dimensional scaffolds provide a promising clinical application for the treatment of osteoporotic bone defects by regulation of bone metabolism. In addition, gene-modified stem cells with three-dimensional scaffolds bring a huge potential in the treatment of osteoporotic bone defects. In conclusion, the combination of stem cells and three-dimensional scaffolds provides a new approach for the treatment of osteoporotic bone defects, which may be one of the future therapeutic strategies. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

Establishment of an animal model of open tibial fractures with infection in New Zealand rabbits北大核心

BACKGROUND: Open facture is easy to induce infection, which is an urgent problem in clinic. Establishing a reliable animal model of open fracture with infection is of great significance for drug and instrument development and application. OBEJCTIVE: To develop an open fracture with infection model in New Zealand white rabbits, and to identify the available number of bacteria that can cause infection. METHODS: The amount of bacteria was determined by establishing open fracture structure and verifying the concentration of bacterial colonies. Thirty New Zealand white rabbits were randomly divided into control group and four experimental groups, and a transverse fracture at the middle part of tibia was established in all rabbits, followed by the injection of 1 mL of normal saline or 1mL of Staphylococcus aureus suspension at the concentrations of 1×105, 1×106, 5×106, and 1×107 CFU/mL. Afterwards, the optimal concentration of 1 mL of bacteria liquid causing infection was determined by gross observation, body temperature analysis and body mass measurement, white blood cell and C-reactive protein detection, bacterial culture and pathological observation. RESULTS AND CONCLUSION: Rabbits in the 5×106 CFU/mL group were all infected and had higher survival rate. In the 1×105 and 1×106 CFU/mL groups, some rabbits showed no infection. One rabbit died due to infection in the 1×107 CFU/mL group. In summary, the reliable infection model of open fracture can be induced by injected with 1 mL of Staphylococcus aureus at the concentration of 5×106 CFU/mL in New Zealand white rabbits, which can be used as an effective model to guide drugs and instruments related anti-infective research. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

Establishment and validation of a clinical prediction model for severe loss of cervical lordosis after posterior cervical surgery北大核心

BACKGROUND: Current studies only predict the loss of cervical lordosis after cervical surgery through imaging measurement indicators and other indicators at present. There are a few articles summarizing these prediction indicators. This paper establishes a prediction model to summarize these prediction indicators. OBJECTIVE: To investigate the risk variables for severe loss of cervical lordosis following posterior cervical spondylotic myelopathy surgery, as well as to develop and validate the prediction model. METHODS: Retrospective analysis was performed on the cervical spondylotic myelopathy patients who underwent posterior approach of cervical surgery in the Affiliated Hospital of Xuzhou Medical University from January 2015 to January 2020 and met the inclusion criteria. The observation indexes included age, sex, body mass index, surgical technique chosen, the number of operation segments, accumulation of C2 or C7, C2-7 Cobb angle prior to operation, Cobb angle of operation segment, C7 slope angle, sagittal vertical angle of the cervical spine, C2-C7 curvature, extension range of motion, and flexion range of motion. The difference between the cervical spine’s C2-7 Cobb angle before and after surgery (ΔCL) was used to calculate the change in cervical lordosis. Those with ΔCL ≤-10° had significant loss of cervical lordosis, while those with ΔCL >-10° had less severe loss of cervical lordosis. Prediction models were created and validated by doing single-factor and multi-factor analyses on these parameters to identify pertinent risk factors. RESULTS AND CONCLUSION: 117 patients in all, 48 females and 69 males, met the inclusion criteria. The follow-up time ranged from 12 to 26 months. Among these patients, 30 experienced a severe loss of cervical lordosis following surgery, while 87 patients did not have a severe loss of cervical lordosis. Statistical analysis showed that the choice of procedure, whether it involved the C2 or C7 vertebral bodies, the C2-7 Cobb angle, the C7 slope angle, the C2-C7 curvature, and flexion range of motion prior to the procedure were independent risk factors linked to serious loss of cervical lordosis following posterior cervical surgery. Most obviously, whether the surgical segment involved the C2 or C7 segment (OR=3.524, 95% CI:1.127-11.013), and the surgical approach chosen (OR=3.165, 95% CI: 1.013-9.889) were the factors that enhanced the probability of significant postoperative curvature loss. Further foundations were laid for the clinical prediction model (nomogram) and its validation. The model has an excellent capacity for prediction, as evidenced by the C-index of internal validation, which was 0.91, and the C-index of external validation in the validation group, which was 0.87. It is indicated that after posterior cervical surgery, the choice of operation method, whether the operation segment involves the C2 or C7 segment, the preoperative C2-7 Cobb angle, the C7 slope angle, and flexion mobility all are high risks of severe loss of cervical lordosis. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Electroacupuncture for chronic pain in a model of knee arthritis北大核心

BACKGROUND: Acupuncture has been found to be effective for alleviating low back pain and acute pain due to knee arthritis, but its effect on chronic pain is under discussion. OBJECTIVE: To investigate the mechanism underlying electroacupuncture (EA) alleviating chronic pain in a New Zealand rabbit model of knee arthritis. METHODS: (1) Thirty-two New Zealand rabbits were selected, and the knee osteoarthritis model was established by injecting 4% papain into the knee articular cavity of rabbit’s bilateral hind limbs. The model rabbits were randomly divided into four groups (n=8 per group): normal saline plus EA, normal saline plus sham EA, nor-Binaltorphimine (nor-BNI) plus EA, and nor-BNI plus sham EA groups. The dosage of nor-BNI was 1 mg/kg, once daily, for consecutive 3 days. 30-minute EA was given at 2 hours after administration, once daily, until the day the rabbits were killed. Sham EA indicated no given electric current. The behaviors of the lower limbs were evaluated by Basso, Beattie, Bresnahan scores. The rabbits were respectively killed at 1, 3, 5 and 7 days after administration, the spinal cord was separated, and then fixed with formaldehyde. The expression levels of interleukin-17, interleukin-17 receptor A and NR1 in the spinal cord tissues were detected by immunofluorescence. (2) The other 24 New Zealand rabbits were randomly divided into model and control groups (n=12 per group), and the knee osteoarthritis model was established in the former group. Afterwards, the two groups were randomized into two subgroups, followed by given the intrathecal administration of normal saline, or 2 μg interleukin-17 antibody serum dissolved in 10 μL normal saline, once daily, for consecutive 3 days. The behaviors of the lower limbs were evaluated by Basso, Beattie, Bresnahan scores, and the expression levels of p-NR1 and interleukin-17 receptor were detected by western blot assy. RESULTS AND CONCLUSION: The Basso, Beattie, Bresnahan scores in the nor-BNI plus EA group were significantly increased, while the expression levels of interleukin-17, interleukin-17 receptor A and NR1 in the spinal cord tissues were significantly decreased (P < 0.05). The expression level of NRI did not differ significantly between nor-BNI plus EA and nor-BNI plus sham EA groups (P > 0.05). After administration of interleukin-17 antibody serum, the Basso, Beattie, Bresnahan scores in the model group was significantly increased, and the expression levels of interleukin-17 and NR1 in the spinal cord tissues were significantly decreased, but still significantly higher than those in the control subgroups (P < 0.05). These results suggest that chronic pain in knee arthritis is the result of an increase in the expression level of NRI induced by interleukin-17. EA can remarkably improve the pain in the model rabbits of knee arthritis by downregulating interleukin-17 in the spinal cord tissues, rather than interleukin-17 receptor. © 2017, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

The effect of combined treatment with Impella? and landiolol in a swine model of acute myocardial infarction

Cardiogenic shock is associated with a high mortality rate in patients with acute myocardial infarction (AMI). We developed a new treatment approach named heart rest therapy (HRT) for complete revascularization in the early stage of AMI using an ultra-short-acting β-blocker (landiolol) and an Impella(?) left ventricular assist device and verified the effect of this therapy in a swine model. In 18 male pigs, AMI was induced by left anterior descending coronary artery occlusion at the level of the second diagonal branch for 120?min, followed by 240?min of reperfusion. The animals were divided into three groups: group A had no support, group B was supported with the Impella(?), and group C was treated with HRT from 90?min after ischemia to 240?min after reperfusion. Infarct ratio (percentage of the infarct area relative to the area at infarct risk) was significantly reduced in group C (group A 65.38?±?6.07, group B 39.66?±?11.16, group C 21.78?±?7.29), with a significant difference between groups A and B (P?相似文献   

The effect of prenatal diazepam exposure on TNF-α production by rat splenocytes

Prenatal exposure to diazepam and other benzodiazepines (BDZ) has been found to result in a marked reduction of T-lymphocyte proliferation during postnatal development of rats. In search for pathogenic changes underlying this effect, we investigated the mitogen lipopolysaccharide (LPS) and concanavalin A (ConA) stimulated release of tumour necrosis factor (TNF)- by mixed splenocytes of male offspring from Long Evans rats treated with 1.25 mg/kg per day diazepam from gestational day 14 to 20. In response to LPS, TNF- release was found to be significantly lower in mixed splenocytes of two- and four-week-old treated than in control offspring. However, at eight weeks of age, prenatally diazepam-treated animals showed a significantly higher LPS-induced TNF- release than control rats. Since monocytes/macrophages represent a major source of TNF-, additional experiments were performed on purified spleen macrophages and lymphocytes stimulated with LPS. TNF- release was only detectable in supernatants of adherent spleen macrophages and not in supernatants of lymphocytes. Thus, our data indicate that a disturbance in TNF- release from macrophages is involved in the deficient immune response of prenatally diazepam-exposed rats.     

Interferon-γ deficiency reduces neointimal formation in a model of endoluminal endothelial injury combined with atherogenic diet

Interferon (IFN)-γ has been implicated in restenosis, however its precise role in the pathophysiology of neointimal formation following angioplasty is unclear, as it has been shown to both promote and inhibit neointimal formation. Dietary-induced hypercholesterolemia enhances injury-mediated neointimal formation, associated with increased systemic inflammation and serum IFN-γ. This study examined the effect of IFN-γ gene deficiency ((-/-)) on neointimal formation in a mouse model of endothelial injury combined with an atherogenic diet. Neointimal formation was induced via endoluminal endothelial injury of the common iliac arteries of IFN-γ(-/-) and wild-type (WT) C57Bl/6 mice. Histopathological analysis of the arteries was performed at 3 and 6 weeks post-surgery. IFN-γ(-/-) mice demonstrated a significant reduction in neointimal formation at the 3-week time point, compared to their WT counterpart. No significant differences in plasma lipid profile and the extent of re-endothelialization were detected between IFN-γ(-/-) and WT mice, suggesting that the effect of IFN-γ on neointimal formation is due to injury-mediated vessel neointimal responses. In support of the histopathological findings, immunohistochemical analysis revealed a significant reduction in vessel infiltrating macrophages, and neointimal PDGF-B expression, vascular smooth muscle cell composition and cellular proliferation in the IFN-γ(-/-) mice, in comparison to their corresponding WT group at the 3-week time point. In conclusion, the IFN-γ-mediated pathway plays an important role in inflammatory responses and proliferative effects following injury, suggesting that modulation of the IFN-γ pathway would be beneficial in controlling neointimal formation and restenosis.     

Application of recombinant GP III a combined Luminex beads for the detection of HPA-la antibody北大核心CSCD

Objective To generate recombinant GP III a as an alternative source for HPA-la antigen and combine it with Luminex xMAP beads for the detection of HPA-la-specific alloantibody. Methods The full coding region of ITGB3gene was amplified and ligated with pcDNA3. 1. The recombinant plasmid was transfected into CHO cells, andthose with stable expression were screened with G418. Expressed protein was identified and coupled with Luminex xMAP beads, which were then reacted with sera samples. Subsequently, phycoerythrin-labeled anti-species IgGantibody was added to the reaction wells and the median fluorescence was determined on a Luminex-100 analyzer.Results DNA sequencing confirmed that the cloned ITGB3 gene was HPA-laa. The recombinant GP III a was coupledwith Luminex xMAP beads. The sensitivity of Luminex beads assay to detect HPA-la antibody was dilution 1/32 (3. 125 U/mL). The Luminex beads assay could specifically identify the HPA-la antibody from the test sera, and theresults were consistent with that of monoclonal antibody-specific immobilization of platelet antigens (MAIPA)technology. Cross-reactivity was not observed with the samples containing HLA, ABO and other HPA antibodies (HPA-3a and HPA-5b). The results illustrated that to detect HPA antibody with Luminex xMAP beads technology isfeasible. Conclusion Recombinant GP III a was successfully obtained and used to establish a Luminextechnology-based method for the detection of HPA antibodies.     

Effectiveness and safety of rapamycin combined with cd133 antibody stent in preventing vascular restenosis北大核心

BACKGROUND: Drug eluting stents and endothelium stents for clinical treatment of vascular stenosis can lead to delayed endothelialization and restenosis. The authors’ previous in vitro studies have shown a rapamycin eluting stent combined with CD133 antibody can play a synergistic role to offset delayed endothelialization and intimal hyperplasia due to antiproliferative drugs. OBJECTIVE: To observe the efficacy of anti-CD133 antibody applied on a rapamycin eluting stent in the minipig coronary artery injury model. METHODS: Rapamycin-eluting stents, anti-CD133 antibody stents, and anti-CD133 antibody applied on rapamycin-eluting stents were implanted in minipig coronary arteries in the rapamycin group, CD133 antibody group, and rapamycin/CD133 antibody group, respectively. Animal experiments were approved by the Laboratory Animal Ethics Committee of Central Hospital Affiliated to Shenyang Medical College (approval No. 20190017) on March 15, 2019. RESULTS AND CONCLUSION: (1) There were differences in the endothelialization extent in the three groups at 14 days and 1 month after implantation. The stent endothelial coverage of the rapamycin group was lower than that of the CD133 antibody group and the rapamycin/CD133 antibody group. (2) At 3 and 6 months after implantation, the luminal stenosis rate of the rapamycin group and the rapamycin/CD133 antibody group was lower, but there was obvious inflammation in the surrounding tissues of the rapamycin stent, and the CD133 antibody stent could cause obvious intimal hyperplasia and lumen stenosis. (3) It is suggested that rapamycin combined with CD133 antibody stent can achieve early endothelialization in vivo, promote endothelial cell repair, and reduce the inflammation of surrounding tissues after implantation, and its anti-proliferative effect is similar to that of rapamycin stent within 6 months. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Comparative study of traumatic heterotopic ossification in mice induced by Achilles tenotomy combined with skin burn injury and single Achilles tenotomy北大核心

BACKGROUND: At present, Achilles tenotomy model is an animal model mainly used for traumatic heterotopic ossification. However, this method requires a long time to form ectopic bone, and the size of the formed ectopic bone is always small. In addition, this method cannot accurately reproduce the systemic inflammatory state of most traumatic heterotopic ossification cases in clinic practice. OBJECTIVE: To verify the validity of the animal model of traumatic heterotopic ossification induced by Achilles tenotomy combined with skin burn injury, to compare this approach with single Achilles tenotomy, and to evaluate the practicability of the two methods. METHODS: Forty male C57BL/6 mice were randomly divided into two groups: Achilles tenotomy group (control group, n=20) and Achilles tenotomy+30% skin scald on the back group (experimental group, n=20). The survival rate and healing of surgical incisions of the mice in the two groups were recorded. Survival rate and wound healing in the two groups as well as skin recovery of burn injury in the experimental group were recorded. Micro-CT examination and Masson staining of the Achilles tendon was performed 8 weeks after surgery to observe the ectopic bone at the surgical site. Formation of ectopic bone was also observed in the two groups. RESULTS AND CONCLUSION: There was no death and wound infection in the two groups. The skin burn injury in the experimental group recovered well without ulceration. Micro-CT findings indicated that all mice in the experimental group developed traumatic heterotopic ossification, with obvious circular high-density shadow at the surgical site, and the volume of ectopic bone was (2.72±0.04) mm3. In contrast, only 17 mice developed traumatic heterotopic ossification in the control group, and the volume of ectopic bone was (0.65±0.08) mm3. There was a significant difference in the volume of ectopic bone between the two groups (P < 0.05). Masson staining showed that ectopic bone in both groups had bone trabecular and bone marrow structures, but the area of ectopic bone in the experimental group was significantly larger than that in the control group (P < 0.05). To conclude, Achilles tenotomy combined with skin burn injury can effectively induce traumatic heterotopic ossification earlier than single Achilles tenotomy in mice. This combination method has a higher successful rate and can produce larger size of ectopic bone, which can be an ideal method to establish an animal model of traumatic heterotopic ossification. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Analysis of the cause of pregnancy failure with combined MLPA assay for subtelomeric regions and ultrasonography北大核心CSCD

Objective To explore the value of multiplex ligation-dependent probe amplification (MLPA) for thedetection of chromosome abnormalities in miscarriage tissues, and to correlate the result with ultrasoundfindings. Methods A total of 421 cases of spontaneous abortions and fetal deaths were detected with the MLPAmethod. Results Among the 421 samples, 232 (55. 11%) had an abnormal MLPA result. For the 286 cases derivedfrom < 13 weeks pregnancy, 206 (72.03%) were abnormal. For the 49 cases from 14 ~ 19 weeks pregnancy, 14(28. 57%) were abnormal. For the 86 cases derived after 20 weeks pregnancy, 12 (13. 95%) were abnormal. Amongthe 117 cases with abnormal ultrasound findings, 33 cases (28. 21%) had an abnormal MLPA result, 28 out of the33 cases were numerical chromosome abnormality, 4 cases were chromosome microdeletion and/or micro duplication, 1 case had both numerical abnormality and microduplication. For those with abnormal ultrasound findings for the neck region, fetal edematous syndrome, multiple malformations and digestive system, the detection rates forMLPA were 71. 4% , 58. 8% , 37. 8% , and 9.1% , respectively. For those with abnormal finding of cardiacsystem, nervous system, face, skeletal system and urinary system, none was found with positive results of MLPA. Conclusion Numerical chromosomal abnormalities account for the majority of cases with spontaneous abortion.With the increase of gestational age, the occurrence of chromosomal abnormalities gradually declines. Combinedultrasound and MLPA assay can improve the detection rate and accuracy for chromosomal abormalities.     

Bone marrow mesenchymal stem cells combined with acellular dermal matrix for repair of urethral injury北大核心

BACKGROUND: In recent years, the development of tissue engineering provides more choices for the repair of urethral injury. OBJECTIVE: To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) combined with acellular dermal matrix in the repair of urethral injuries. METHODS: Passage 3 BMSCs from New Zealand white rabbits were inoculated on the acellular dermal matrix to construct tissue-engineered urethra grafts. Thirty-six New Zealand rabbits were randomized into three groups (n=12 per group). Experimental group was implanted with BMSCs-acellular dermal matrix complex at urethral injury. Control group was implanted with acellular dermal matrix material at urethral injury. Normal group had neither injury nor treatment. At postoperative 4, 8 and 12 weeks, the repaired urethral tissue was subjected to hematoxylin-eosin staining. At postoperative 12 weeks, immunohistochemical staining and urodynamic study were performed. RESULTS AND CONCLUSION: At postoperative 4 weeks, thin-layer epithelial regeneration was visible in the urethra defect area of the experimental group, and the continuity was better. The urethra mucosa of the control group was discontinuous. At postoperative 8-12 weeks, the urethral epithelial layer in the experimental group became thickened, exhibiting a good continuity with the normal urethral epithelium, thickened mucosa, and smooth and continuous urethral mucosa; the regenerated urethral mucosa of the control group exhibited good continuity, but less regenerated epithelial layers. At postoperative 12 weeks, immunohistochemical results showed the repaired urethra in the experimental group was positive for uroplakin illa, CK AE1/AE3, and α-smooth muscle actm. The maximum urethral pressure in the experimental group showed no significant difference before and after operation, while the postoperative pressure in the control group showed a significant increase (P < 0.05). Overall findings indicate that the combination of BMSCs and acellular dermal matrix has better efficacy than the acellular dermal matrix alone. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

Expression of NOD2 and NLRP3 in the articular cartilage of a rabbit model of osteoarthritis established by arthrorisis using plaster cast北大核心

BACKGROUND: Nucleotide-binding oligomerization domain (NOD)-like receptor plays an important role against inflammatory responses caused by pathogens and non-pathogens, as well as in the initial stage of autoimmune response. Meanwhile, NOD2 and NOD-like receptor protein 3 (NLRP3) are the representative proteins of NOD-like receptor family. OBJECTIVE: To detect the expression of NOD2 and NLRP3 in a rabbit model of osteoarthritis. METHODS: Thirty New Zealand rabbits were randomly divided into six groups (n=5 per group), including five experimental groups (2, 4, 6, 8 and 10 weeks) and one control group. The model of osteoarthritis was established by fixing the left knee joints using plaster cast, and were sacrificed at postoperative 2, 4, 6, 8 and 10 weeks. The controls received no intervention, and were killed at 10 weeks postoperatively. The left distal femur articular cartilage was taken for safranin-fast green staining. The pathological changes were evaluated by Mankin’s scores, and the expression levels of NOD2 and NLRP3 were detected by immunohistochemistry. RESULTS AND CONCLUSION: The Mankin’s scores in the experimental groups were significantly higher than those in the control group (P < 0.01). Moreover, the scores in the experimental groups were significantly increased with time (P < 0.01). The expression levels of NOD2 and NLRP3 in the chondrocytes were also increased with time (P < 0.01). These results indicate that the expresison of NOD2 and NLRP3 in the cartilage cells is positively correlated with the pathological changes of osteoarthritis, which may be through promoting apoptosis in cartilage cells, thus accelerating the development of osteoarthritis. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

Analysis of genetic etiology of a female with 47,XXY syndrome北大核心CSCD

Objective To explore the genetic cause of a female case with intellectual development disorder. Methods Gbanding karyotyping was performed for the patient. Following DNA extraction, the coding sequence of SRY genewas amplified with PCR and subjected to Sanger sequencing. qPCR was used to detect the copy numbers of the SRYgene. Results The karyotype of the patient was 47,XXY. PCR and qPCR analyses of the SRY gene showed a largedeletion with null copy number. Conclusion The female phenotype of the patient is probably due to deletion ofthe SR Y gene on the Y chromosome. This is the first report of 47,XXY female case with deletion of the SRY gene in China.     

Protective effects of N-acetylcysteine on myocardial injury induced by hindlimb ischaemia–reperfusion: a histological study in a rat model

This study evaluated the effects of N-acetylcysteine as a scavenger of radical oxygen species on myocardial injury as a remote organ after skeletal muscle ischaemia–reperfusion. Twenty male Wistar rats were allocated randomly into two experimental groups: ischaemia–reperfusion and ischaemia–reperfusion?+?N-acetylcysteine. All animals underwent 2 h of ischaemia by occlusion of the femoral artery followed by 24 h of reperfusion. Rats treated with N-acetylcysteine were given an intravenous dose of 150 mg/kg, immediately before reperfusion. After the reperfusion period, animals were euthanized and hearts harvested for histopathological analysis under light microscopy. In the ischaemia–reperfusion group, tissues showed histological changes with interstitial oedema, neutrophil infiltration and adhesion of neutrophils to the endothelium, haemorrhage and coagulative necrosis. Histopathologically, there was a significant difference (P?N-acetylcysteine significantly decreased myocardial injury induced by skeletal muscle ischaemia–reperfusion according to our histological findings.     

Long-term restoration of nigrostriatal system function by implanting GDNF genetically modified fibroblasts in a rat model of Parkinson’s disease

The motor behavior and levels of dopamine and its metabolites in the striatum were studied in rats that received a unilateral injection of 6-OHDA and underwent grafting of rat-derived primary fibroblasts that had been genetically modified to express lacZ and human glial cell line-derived neurotrophic factor (GDNF). Rotation behavior tests were performed each week and striatal levels of DA and its metabolites were measured every 4 weeks after grafting of fibroblasts that expressed lacZ, with or without additional transfection of the GDNF transgene. Rats grafted with GDNF-producing fibroblasts showed a significant improvement in motor behavior as determined by the rotation test, with a less pronounced reduction in the levels of dopamine and its metabolites in the striatum as compared with those in the control animals or brain parts. In addition, there was a lower decrease in the number of TH immunoreactive neurons in the substantia nigra ipsilateral to the lesion in rats with GDNF-producing fibroblasts than in rats with lacZ-expressing fibroblasts. These results support the notion that intracerebral grafting of fibroblasts that express GDNF is a potentially useful therapeutic strategy for treating Parkinsons disease.