A novel antibiotic based long-term model of ovine smoke inhalation injury and septic shock

We modified our established and clinically relevant ARDS model of smoke inhalation injury and septic shock by administration of combined antibiotics (AB) such as piperacillin and ciprofloxacin, to more closely mimic the clinical intensive care setting. Twenty-three sheep were subjected to the injury, and allocated to four groups for a 96 h study period: sham (n = 5 non-injured); control (n = 6: injured); AB6h (n = 6: injured, antibiotics started 6 h post-injury); AB12h (n = 6: injured, antibiotics started 12 h post-injury). All sham animals survived 96 h. Control, AB6h, AB12h groups reached criteria of septic shock within 12 h post-injury. All controls died within 36 h. Eighty three percent of AB6h and fifty percent of AB12h survived 96 h. Median survival times were significantly improved in the treated groups compared with the control group: 24 h in control vs. 80.5 h in AB6h, and 65 h in AB12h animals. Combined ciprofloxacin and piperacillin therapy was effective, reduced nitric oxide production and mortality, and will allow future long-term studies in this model.     

Manipulation of anabolic and catabolic responses with bone morphogenetic protein and zoledronic acid in a rat spinal fusion model

Bone fusion involves a complex set of regulated signaling pathways that control the formation of new bone matrix and the resorption of damaged bone matrix at the surgical site. It has been reported that systemically administering a single dose of zoledronic acid (ZA) at the optimal time increases the strength of the bone morphogenetic protein (BMP)–mediated callus. In the present study, we aimed to investigate the effect of BMP-2 and ZA in a rat spinal model. Sixty-seven rats were divided into 6 groups: group I (n = 11) animals were implanted with a carrier alone, group II (n = 12) animals were implanted with a carrier and a subcutaneous injection of ZA was administered 2 weeks after surgery, group III (n = 12) animals were implanted with a carrier containing 1 μg of rhBMP-2, group IV (n = 12) animals were implanted with a carrier containing 1 μg of rhBMP-2 and a subcutaneous injection of ZA was administered 2 weeks after surgery, group V (n = 10) animals were implanted with a carrier containing 3 μg of rhBMP-2, and group VI (n = 10) animals were implanted with a carrier containing 3 μg of rhBMP-2 and a subcutaneous injection of ZA was administered 2 weeks after surgery. The rats were euthanized after 6 weeks, and their spines were explanted and assessed by manual palpation, radiography, high-resolution micro-computerized tomography (micro-CT), and histologic analysis. The fusion rates in group VI (60%) were considerably higher than those in the groups I (0%), II (0%), III (12.5%), IV (20.8%), and V (35%), (P < 0.05). Additionally, the radiographic scores of group VI were higher than those in the other groups, (P < 0.05). In micro-CT analysis, the tissue and bone volumes of the callus were significantly higher in group VI than those in the other groups, (P < 0.05). The trabecular number was significantly higher and the trabecular spacing was significantly lower in group VI than those in the other groups, (P < 0.05). The combination of rhBMP-2 and ZA administered systemically as a single dose at the optimal time was efficacious in our rat spinal fusion model. Our results suggest that this combination facilitates spinal fusion and has potential clinical application.     

Influence of nitric oxide on microcirculation in pancreatic ischemia/reperfusion injury: an intravital microscopic study

Recently, protective effects of nitric oxide donors in pancreatic ischemia/reperfusion (IRI) injury have been described. Their role in post-ischemic microcirculation was previously not investigated. Ischemia reperfusion was induced in an isolated pancreatic tail segment in situ. Animals were randomized to four experimental groups (n=7 animals/group), the control group (CO) received saline as placebo. Treatment groups received either sodium nitroprusside (SN) 5 min before until 2 h after reperfusion, l-arginine (LA) 30 min before reperfusion until 2 h after reperfusion or sodium nitroprusside and l-arginine (SNLA) together. After induction of ischemia (2 h) post-ischemic microcirculation was observed for 2 h by intravital-fluorescence microscopy. Functional-capillary density (FCD), leukocyte adherence in post-capillary venules (LAV) and histological damage were analysed. After reperfusion FCD decreased in all groups (P<0.05). FCD was significantly restored in all groups with administration of nitric oxide donors after reperfusion (P<0.05) as compared to CO without significant difference between the individual nitric oxide donor groups. Leukocyte adherence was significantly increased 1 h and 2 h after reperfusion (P<0.001) as compared to baseline, which was lower in all nitric oxide donor groups. Histological damage in the pancreatic tail-segment was significantly reduced in nitric oxide donor groups (P<0.01). Administration of nitric oxide donors might be useful in ischemia-reperfusion injury of the pancreas by its protective effect on microcirculation and inflammatory reaction.     

Do intramedullary spinal cord changes in signal intensity on MRI affect surgical opportunity and approach for cervical myelopathy due to ossification of the posterior longitudinal ligament?

Some controversy still exists over the optimal treatment time and the surgical approach for cervical myelopathy due to ossification of the posterior longitudinal ligament (OPLL). The aim of the current study was first to analyze the effect of intramedullary spinal cord changes in signal intensity (hyperintensity on T2-weighted imaging and hypointensity on T1-weighted imaging) on magnetic resonance imaging (MRI) on surgical opportunity and approach for cervical myelopathy due to OPLL. This was a prospective randomized controlled study. Fifty-six patients with cervical myelopathy due to OPLL were enrolled and assigned to either group A (receiving anterior decompression and fusion, n = 27) or group P (receiving posterior laminectomy, n = 29). All the patients were followed up for an average 20.3 months (12–34 months). The clinical outcomes were assessed by the average operative time, blood loss, Japanese Orthopedic Association (JOA) score, improvement rate (IR) and complication. To determine the relevant statistics, we made two factorial designs and regrouped the data of all patients to group H (with hyperintensity on MRI, n = 31), group L (with hypointensity on MRI, n = 19) and group N (no signal on MRI, n = 25), and then to further six subgroups as well: AH (with hyperintensity on MRI from group A, n = 15), PH (with hyperintensity on MRI from group P, n = 16), AL (with hypointensity on MRI from group A, n = 10), PL (with hypointensity on MRI from group P, n = 9), AN (no signal intensity on MRI from group A, n = 12) and PN (no signal intensity on MRI from group P, n = 13). Both hyperintensity on T2-weighted imaging and hypointensity on T1-weighted imaging had a close relationship with the JOA score and IR. The pre- and postoperative JOA score and postoperative IR of either group H or group L was significantly lower than that of group N (P < 0.05), regardless of whether the patients had received anterior or posterior surgery. On the other hand, both the JOA score and IR of subgroup AH were higher than those of subgroup PH at 1 week, 6 and 12 months postoperatively (P < 0.05), as well as between subgroup AL and PL; but in group N, there was no difference between the subgroup AN and PN (P > 0.05). In conclusion, regardless of hyperintensity on T2-weighted imaging or hypointensity on T1-weighted imaging in patients with OPLL, severe damage to the spinal cord is indicated. Surgical treatment should be provided before the advent of intramedullary spinal cord changes in signal intensity on MRI. The anterior approach is more effective than posterior approach for treating cervical myelopathy due to OPLL characterized by intramedullary spinal cord changes in signal intensity on MRI.     

A porcine collagen-derived matrix as a carrier for recombinant human bone morphogenetic protein-2 enhances spinal fusion in rats

Background contextRecombinant bone morphogenetic proteins (rhBMPs) have been used successfully in clinical trials. However, large doses of rhBMPs were required to induce adequate bone repair. Collagen sponges (CSs) have failed to allow a more sustained release of rhBMPs. Ongoing research aims to design carriers that allow a more controlled and sustained release of the protein. E-Matrix is a injectable scaffold matrix that may enhance rhBMP activity and stimulate bone regeneration.PurposeThe purpose of this study was to test E-Matrix as a carrier for rhBMPs in a CS and examine its feasibility in clinical applications by using a rat spinal fusion model.Patient sampleA total of 80 Lewis rats aged 8–16 weeks were divided into nine groups.Study design/settingRat spinal fusion model.Outcome measuresRadiographs were obtained at 4, 6, and 8 weeks. The rats were sacrificed and their spines were explanted and assessed by manual palpation, high-resolution microcomputed tomography (micro-CT), and histologic analysis.MethodsGroup I animals were implanted with CS alone (negative control); Group II animals with CS containing 10 μg rhBMP-2 (positive control); Group III animals with CS containing 3 μg rhBMP-2; Group IV animals with CS containing 3 μg rhBMP-2 and E-Matrix; Group V animals with CS containing 1 μg rhBMP-2; Group VI animals with CS containing 1 μg rhBMP-2 and E-Matrix; Group VII animals with CS containing 0.5 μg rhBMP-2; Group VIII animals with CS containing 0.5 μg rhBMP-2 and E-Matrix; and Group IX animals with CS and E-Matrix without rhBMP-2.ResultsRadiographic evaluation, micro-CT, and manual palpation revealed spinal fusion in all rats in the BMP-2 and E-Matrix groups (IV, VI, and VIII) and high-dose BMP-2 groups (II and III). Four spines in the 3 μg rhBMP-2 group (V) fused, and one spine in the 0.5 μg rhBMP-2 group (VII) exhibited fusion. No spines were fused in Groups I (CS alone) and IX (E-Matrix alone). The volume of new bone in the area between the tip of the L4 transverse process and the base of the L5 transverse process in Group IV was equivalent to the volumes observed in Group II.ConclusionE-matrix enhances spinal fusion as a carrier for rhBMP-2 in a rat spinal fusion model. The results of this study suggest that E-Matrix as a growth factor carrier may be applicable to spinal fusion and may improve rhBMP-2's activity at the fusion site.     

大鼠脊髓损伤后一氧化氮合酶基因表达的变化

目的　探讨大鼠脊髓损伤后3种类型一氧化氮合酶（NOS）mRNA表达的变化规律。方法　成年SD大鼠36只,随机分为种类6组,每组6只大鼠。建立大鼠脊髓压迫伤模型,以逆转录-聚合酶链反应（RT-PCR）法测定伤段脊髓组织神经型（nNOS）、诱导型（iNOS）及内皮型（eNOS）一氧化氮合酶的mRNA表达情况。结果　脊髓压迫伤后nNOSmRNA及NOSRNA表达增强,伤后6h达到高峰0.633±0.012、1.236±0.207;iNOSmRNA表达亦增高,但在伤后24h才达到高峰1.043±0.049。结论　脊髓损伤后NOSmRNA的表达增强,但不同类型的NOSmRNA变化规律不同,增强或抑制不同NOSmRNA的表达可能减轻脊髓继发性损伤。     

The relationship between varicocele and semen nitric oxide concentrations

We investigated the relationship between seminal plasma nitric oxide (NO) concentrations and conventional semen parameters in patients with varicocele. Semen samples were obtained from infertile patients with varicocele (n=55) and from normal controls (n=48). The mean NO concentration in the seminal plasma of patients with varicocele was significantly higher than that of the controls (P < 0.01). A significant negative correlation was noted between NO and sperm motility (r=−0.29, P=0.003), NO and sperm concentration (r=−0.26, P=0.008) and NO and normal morphology (normal %) (r=−0.25, P=0.01). It was concluded that increased NO production may influence sperm production, motility and morphology in patients with varicocele. Received: 21 February 2000 / Accepted: 20 June 2000     

比较局麻与全麻对病人血清NOS及NO浓度的影响

目的　比较局麻与全身麻醉对手术病人血清一氧化氮合酶 (NOS)和一氧化氮 (NO)的影响。方法　根据不同麻醉方法将 2 0例颌面外科手术病人分为局麻组 (A组 )和静吸复合全麻组 (B组 ) ,每组 10例 ,在麻醉诱导前、手术切皮和手术开始后 1h抽取静脉血 3ml,分别测定血清NOS和NO浓度。结果　A组血清NOS及NO含量在切皮和术中 1h与术前比较显著增高 (P <0 0 5 ) ,B组血清NOS及NO含量在切皮和术中 1h与术前比较无显著增高 (P >0 0 5 ) ;在切皮和术中 1hB组NOS及NO含量比A组显著降低 (P <0 0 5 )。结论　静吸复合麻醉能明显抑制NOS的活性 ,降低NO的生成     

Níveis de óxido nítrico mais elevados estão associados à atividade da doença em pacientes egípcios com artrite reumatoide

BackgroundOxidative stress generated within inflammatory joints can produce autoimmune phenomena and joint destruction. Radical species with oxidative activity, including reactive nitrogen species, represent mediators of inflammation and cartilage damage.ObjectivesTo assess serum nitric oxide as a marker of oxidative stress in Egyptian patients with rheumatoid arthritis and its relation to disease activity.Methods80 patients with rheumatoid arthritis were divided into 2 groups, according to the DAS‐28 score: Group I: 42 patients with disease activity, and Group II: 38 patients with no disease activity. Forty age‐ and sex‐matched individuals were included as control group (Group III). Routine laboratory investigations were done, and nitric oxide was measured using Elisa. Hand plain radiographies were done for radiological status scoring using the Sharp method.ResultsA comparison between nitric oxide in all three groups showed a highly significant difference (p < 0.001), significantly higher levels were obtained among rheumatoid arthritis patients in comparison to controls, and higher levels were obtained in patients with active disease (mean ± SD 82.38 ± 20.46) in comparison to patients without active disease (35.53 ± 7.15). Nitric oxide in Group I showed a significant positive correlation with morning stiffness (r = 0.45), arthritis (r = 0.43), platelet count (r = 0.46), erythrocyte sedimentation rate (r = 0.83), C‐reactive protein (r = 0.76) and Disease Activity Score (r = 0.85). Nitric oxide showed a significant positive correlation (r = 0.43) with hand radiographies (Sharp score) in Group I.ConclusionThere are increased levels of nitric oxide in the serum of patients with rheumatoid arthritis. Nitric oxide correlates significantly with disease activity, inflammatory markers and radiological joint status.     

Comparative study of different transplantation methods of adipose tissue-derived stem cells in the treatment of erectile dysfunction caused by cavernous nerve injury

We aimed to compare intracavernosal injection (ICI), tail vein injection (IV), and periprostatic injection (PPI) of adipose-derived stem cells (ADSCs) for their ability to improve erectile function in cavernous nerve injury-induced erectile dysfunction (CNIED) rats and to explore the possible mechanism. Eighty-four male SD rats were divided into the sham group (n = 6), BCNI group (bilateral CN crush injury, n = 6), PBS-ICI group (n = 6), PBS-IV group (n = 6), PBS-PPI group (n = 6), ADSC-ICI group (n = 18), ADSC-IV group (n = 18) and ADSC-PPI group (n = 18). ADSCs were labelled with 5-ethynyl-2′-deoxyuridine (EdU), and six rats each in the ADSC-ICI group, ADSC-IV group, and ADSC-PPI group were sacrificed 2, 7, and 28 days after injection. EdU-labelled ADSCs were tracked by immunofluorescence staining. The intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio, neuronal nitric oxide synthase (nNOS)-positive nerve fibres in the dorsal penile nerve and the smooth muscle/collagen ratio in the cavernosum between groups were also evaluated. ADSCs can significantly improve erectile function through ICI or IV. The two are similar in efficacy and superior to PPI. The mechanism may be that after CN injury, ADSCs are recruited to around the MPG and secrete a variety of neurotrophic factors that promote the repair of the CN, thereby improving erectile function.     

脊髓急性损伤时NO、IL-8、IL-6的表达及意义

目的 :研究脊髓急性损害早期白细胞介素 -8(IL 8) ,白细胞介素 -6(IL 6) ,一氧化氮 (NO)及一氧化氮合酶 (NOS)的变化。方法 :76例脊髓急性损害病人 ,根据Franked分类 ,分完全截瘫 (FrankedA)组 ,不完全截瘫 (FrankedB ,C和D)组 ,以ELISA法 ,硝酸还原酶法分别测IL 8、IL 6、NO、NOS的值 ,以健康体检人员作对照。结果 :IL 8、IL 6的值完全截瘫者和不完全截瘫者都显著升高 (P <0 .0 5 ) ,NO、NOS的值完全截瘫者和不完全截瘫者都显著降低 (P <0 .0 5 )。结论 :脊髓急性损害早期IL 8、IL 6显著升高 ,NO、NOS显著降低 ,脊髓急性损害早期IL 8、IL 6、NO参与了脊髓继发性损害。     

Preservation of Endothelium Nitric Oxide Release by Pulsatile Flow Cardiopulmonary Bypass When Compared With Continuous Flow

The aim of this work is to analyze endothelium nitric oxide (NO) release in patients undergoing continuous or pulsatile flow cardiopulmonary bypass (CPB). Nine patients operated under continuous flow CPB, and nine patients on pulsatile flow CPB were enrolled. Plasma samples were withdrawn for the chemiluminescence detection of nitrite and nitrate. Moreover the cellular component was withdrawn for the detection of nitric oxide synthase (NOS) activity in the erythrocytes, and an estimation of systemic inflammatory response was carried out. Significant reduction in the intraoperative concentration with respect to the preoperative was observed only under continuous flow CPB for both nitrite and NO_x (nitrite + nitrate) concentration (P = 0.010 and P = 0.016, respectively). Significant difference in intraoperative nitrite concentration was also observed between the groups (P = 0.012). Finally, erythrocytes showed a certain endothelial NOS activity, which did not differ between the groups, and no differences in the inflammatory response were pointed out. The significant reduction of NO₂^‐ concentration under continuous perfusion revealed the strong connection among perfusion modality, endothelial NO release, and plasmatic nitrite concentration. The similar erythrocyte eNOS activity between the groups revealed that the differences in blood NO metabolites are mainly ascribable to the endothelium release.     

Experiences of laparoscopic liver resection including lesions in the posterosuperior segments of the liver

Background  There is a growing interest in laparoscopic liver resection because of its minimal invasiveness, the increased experience with laparoscopic procedures, and the advances of the laparoscopic devices. The authors describe their experience with laparoscopic liver resection, including its use for lesions in the posterosuperior segments of the liver (segments 1, 7, and 8, and the superior part of segment 4). Methods  A retrospective analysis was performed for the clinical data of 128 patients who underwent laparoscopic liver resection between January 2004 and December 2007. The patients were classified into two groups according to the location of the lesion: the anterolateral (AL) group (n = 92) and the posterosuperior (PS) group (n = 36). Results  The study enrolled 76 men and 52 women with a mean age of 57 years. The indications for resection were hepatocellular carcinoma (n = 57), hepatolithiasis (n = 39), liver metastasis from colorectal cancer (n = 21), and benign liver tumor (n = 11). There were no differences between the groups in terms of preoperative patient demographic characteristics or indications for liver resection. Major liver resection was performed more frequently for the PS group than for the AL group (p < 0.001). The mean operative time and the rate of intraoperative transfusion were significantly greater in the PS group than in the AL group (p = 0.009 and 0.015, respectively). However, the mean postoperative hospital stay and the complication rate were similar in the two groups (p = 0.345 and 0.733, respectively). Four patients underwent conversion to open hepatectomy (3.1%), with no difference in the rate of conversion between the two groups (p = 0.323). The complication rate was 18%, and all the patients were managed conservatively without the need for additional surgery. Conclusions  Laparoscopic liver resection, including that for lesions in the posterosuperior part of the liver, is technically feasible and safe. This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A060299).     

-Arginine given after ischaemic preconditioning can enhance cardioprotection in isolated rat hearts

Objective: Ischaemic or pharmacological preconditioning with -arginine has been reported to be insufficient for optimal cardioprotection. The ability of nitric oxide (NO) to enhance ischaemic preconditioning was assessed, and the role of -arginine-induced ischaemic preconditioning in myocardial protection was determined. Methods: Isolated rat hearts were prepared and divided into six groups: control hearts (control, n=6) were perfused without global ischaemia at 37°C for 160 min; global ischaemia hearts (GI, n=6) were subjected to ischaemia for 20 min and reperfusion for 120 min; ischaemic preconditioned hearts (IP, n=6) received 2 min of zero-flow global ischaemia followed by 5 min reperfusion, before 20 min of global ischaemia; -arginine hearts (ARG, n=6) received 1 mmol/l -arginine for 5 min, before 20 min of global ischaemia; ischaemic preconditioning plus nitro- -arginine methyl ester hearts (IP+ -NAME, n=6) received 2 min of ischaemic preconditioning and 5 min reperfusion with 3 mmol/l -NAME in Krebs–Henseleit buffer, before 20 min of global ischaemia; and ischaemic preconditioning plus -arginine hearts (IP+ARG, n=6) received 2 min of ischaemic preconditioning and 5 min reperfusion with 1 mmol/l -arginine in Krebs–Henseleit buffer. Haemodynamic parameters and coronary flow were recorded continuously. Nitrites and nitrates (NOx) were measured 5 and 60 min after reperfusion, and infarct size was also determined. Results: In the IP+ARG group, significant amelioration and preservation of left ventricular peak developed pressure and coronary flow was observed compared with the GI, IP, ARG and IP+ -NAME groups. Infarct size in the IP+ARG group was reduced significantly compared with that in the GI, IP, ARG and IP+ -NAME groups. Significant preservation of NOx was observed during reperfusion in the IP+ARG group compared with the GI group. Conclusions: Inhibition of NO synthase with -NAME had little impact on ischaemic preconditioning, suggesting that endogenous NO is not a major mediator of ischaemic preconditioning. Nevertheless, enhancement of the effects of ischaemic preconditioning can be achieved with -arginine, a precursor of NO, improving post-ischaemic functional recovery and infarct size in the isolated rat heart.     

Up-regulation of endothelin (ETA and ETB) receptors and down-regulation of nitric oxide synthase in the detrusor of a rabbit model of partial bladder outlet obstruction

Bladder outlet obstruction (BOO) is associated with altered bladder structure and function. Endothelin-1 (ET-1) has mitogenic and potent contractile properties. There are two ET receptors: ET_A and ET_B. Nitric oxide synthase (NOS) is the enzyme responsible for the synthesis of nitric oxide (NO) which is involved in smooth muscle relaxation. We investigated whether there are any changes in the density of ET-receptors and NOS in the detrusor and bladder neck in a rabbit model of BOO. Partial BOO was induced in adult male New Zealand White rabbits. Sham operated age-matched rabbits acted as controls. After six weeks the urinary bladders were excised and detrusor and bladder neck sections incubated with radioligands for ET-1, ET_A and ET_B receptors and with [³H]–l-NOARG (a ligand for NOS). NADPH histochemistry was also performed. BOO bladder weights were significantly increased (P=0.002). ET-1 binding and ET_A receptor binding sites were significantly increased in the BOO detrusor smooth muscle (P=0.04, P=0.03 respectively) and urothelium (P=0.002, P=0.02 respectively). ET_B receptor binding sites were also significantly increased in the BOO detrusor smooth muscle (P=0.04). However, there was no change in the BOO bladder neck. NOS was significantly decreased in the detrusor smooth muscle (P=0.003) and urothelium (P=0.0002). In the bladder neck NOS was also significantly reduced in the urothelium (P=0.003). NADPH staining was decreased in the detrusor and bladder neck. The up-regulation of ET receptors along with the down-regulation of NOS in the detrusor may contribute to the symptoms associated with BOO. Since ET-1 has a mitogenic role, especially via its ET_A receptors, the increase in ET_A receptors may also be involved in detrusor hyperplasia and hypertrophy in BOO. ET antagonists may therefore have a role in the treatment of patients with BOO. Received: 24 March 1999 / Accepted: 25 June 1999     

一氧化氮对大鼠前列腺增殖/凋亡的影响

目的 探讨一氧化氮（NO）对大鼠前列腺上皮增殖／凋亡的影响。方法 20只成年雄性SD大鼠随机分为3组，第一组为正常对照组（6只），第二、三组皮下注射一氧化氮合酶（NOS）抑制剂L-NAME（各7只），注射剂量分别为50mg／kg，2次／d及100mg／kg，2次／d。2周后观察各组大鼠前列腺重量和组织学变化，Ki-67免疫染色及TUNEL染色测定前列腺上皮细胞的增殖和凋亡指数，免疫组织化学染色及逆转录-聚合酶链反应（RT-PCR）法检测NOS3种亚型的蛋白及mRNA表达情况。结果 3组大鼠的前列腺重量差异无统计学意义（P〉0．05）；与第一组相比，第二、三组大鼠前列腺上皮细胞萎缩较明显。Ki-67及TUNEL染色显示上皮和间质细胞增殖率明显降低，上皮细胞凋亡率明显升高（P〈0．05），NOSl和NOS3蛋白及mRNA表达水平显著下降。3组NOS2表达均不明显。结论 NO可能影响前列腺细胞增殖及凋亡，在BPH的发病机理中具有重要作用。     

The efficacy of rhBMP-2 versus autograft for posterolateral lumbar spine fusion in elderly patients

Few studies have specifically examined the outcomes following rhBMP-2 usage in patients 65 years and older. The purpose of this retrospective study is to evaluate the efficacy of rhBMP-2 with allograft versus autograft for posterolateral lumbar fusion in patients 65 years and older. One hundred twenty-seven patients were divided into three groups based on fusion material and age. Subjects in group A (n = 34) consisted of patients 65 years and older who received rhBMP-2 and allograft. Group B (n = 52) was composed of patients under 65 years of age with rhBMP-2 and allograft. Subjects in group C (n = 41) were 65 years and older with autograft use. A comparison was made of fusion rate, fusion time (noticed, solid), clinical outcome, VAS, perioperative complications and revision rate between each group. The fusion rate and fusion time were similar in groups A and C; however, these were lower than that observed in group B. Clinical outcomes were similar amongst the groups. There were no significant differences in VAS and perioperative complication rate between groups A and C. In patients 65 years and older, rhBMP-2 with allograft may lead to acceptable fusion rates and fusion times, good clinical outcomes and reduced perioperative complications. The combination of rhBMP-2 with allograft yields equivalent outcomes as autograft in elderly patients undergoing instrumented posterolateral lumbar fusion. Additionally, when compared to patients under 65 years of age undergoing posterolateral lumbar fusion, the use of rhBMP-2 was not sufficient to overcome all aspects of the age-related weakened osteoinductive capacity encountered in elderly patients.     

Antitumor necrotic factor agent promotes BMP-2-induced ectopic bone formation

Etanercept (ETN), which is a recombinant human soluble tumor necrosis factor (TNF) receptor that inhibits TNF activity, is effective in the treatment of rheumatoid arthritis. We investigated the effect of ETN on recombinant human bone morphogenetic protein-2 (rhBMP-2)-induced ectopic bone formation in vivo. A block copolymer composed of poly-d,l-lactic acid with random insertion of p-dioxanone and polyethylene glycol (PLA–DX–PEG polymer) was used as the delivery system. Polymer discs (6 mm, 30 mg) containing 5 μg rhBMP-2 were implanted into the left dorsal muscle pouch of mice (n = 50). In the systemic administration groups (n = 5 per group), ETN was subcutaneously injected (25 mg/human = 12.5 μg/mouse) twice per week in a dose-dependent manner (placebo, 12.5 × 10⁻³, 12.5 × 10⁻¹, 12.5, 125 μg), whereas a single dose of ETN (placebo, 12.5 × 10⁻³, 12.5 × 10⁻¹, 12.5, 125 μg) was embedded in each rhBMP-2 polymer disc in the local administration groups (n = 5 per group). Three weeks after implantation, the mice were killed and the implants were analyzed. Implants in the optimally dosed groups had increased radiodensity, which was consistent with a significant increase in bone mineral content of the ossicles. Bone histomorphology revealed a significant increase in bone volume/total volume, number of osteoblasts, osteoblast surface/bone surface, and a significant decrease in the number of osteoclasts, osteoclast surface/bone surface in the optimal dosed systemic and locally administered groups. These data suggest that the optimal dose of ETN, administered either systemically or locally, enhanced the bone-inducing capacity of BMP with no apparent adverse systemic effects.     

衰老对大鼠阴茎海绵体NOS I的表达和NOS活性的影响

目的 :探讨衰老对大鼠阴茎海绵体一氧化氮合酶Ⅰ (NOSⅠ)mRNA、蛋白的表达和NOS活性的影响。　方法 :30只雄性SD大鼠按不同月龄分为成年组、老年组和衰老组 ,应用Western印迹、RT PCR方法分别检测不同年龄组阴茎海绵体NOSⅠ蛋白及mRNA的表达 ;用紫外分光光度计测定不同年龄组阴茎海绵体NOS的活性。　结果 :成年组NOSⅠ 蛋白的表达量最高 ,老年组和衰老组显著降低 ,分别为成年组的 75 .6 %和 6 1.2 % ;NOSⅠmRNA的表达与蛋白表达的变化一致 ;老年组NOS活性与成年组差异无显著性 (P >0 .0 5 ) ,衰老组NOS活性明显降低 ,是成年组的70 .4 % ,并且差异非常显著 (P <0 .0 1)。　结论 :衰老引起NOSⅠ 蛋白及mRNA的表达降低和NOS活性的显著降低 ,可能是老年性阴茎勃起功能障碍的主要机制之一。