Curcumin attenuates the expression and secretion of RANTES after spinal cord injury in vivo and lipopolysaccharide-induced astrocyte reactivation in vitro

Curcumin has been proposed for treatment of various neuroinflammatory and neurodegenerative conditions, including post-traumatic inflammation during acute spinal cord injury (SCI). In this study, we examined whether curcumin anti-inflammation involves regulation of astrocyte reactivation, with special focus on the injury-induced RANTES (regulated on expression normal T-cell expressed and secreted) from astrocytes in acute SCI. Male Sprague-Dawley (SD) rats were subjected to impact injury of the spinal cord followed by treatment with curcumin (40 mg/kg i.p.). RANTES and inducible nitric oxide synthase expression as well as RANTES-positive astrocytes were all induced by injury accompanied by the elevation of lipid peroxidation, and attenuated by the curcumin treatment. In primary cultured rat astrocytes challenged with lipopolysaccharide (LPS) to mimic astrocyte reactivation following SCI, LPS induces robust increase of RANTES expression and the effect was also reduced by 1 μM curcumin treatment. Furthermore, cortical neurons cultured with astrocyte conditioned medium (ACM) conditioned with both LPS and curcumin (LPS-curcumin/ACM), which characteristically exhibited decreased RANTES expression when compared with ACM from astrocytes treated with LPS alone (LPS/ACM), showed higher level of cell viability and lower level of cell death as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction activity assay and lactate dehydrogenase release assay, respectively. Knockdown of RANTES expression by siRNA (siRANTES) shows reduced RANTES expression and release from LPS-reactivated astrocytes, and ACM obtained from this condition (LPS-siRANTES/ACM) becomes less cytotoxic as compared with the LPS-ACM. Therefore, curcumin reduction of robust RANTES production in reactivated astrocytes both in vitro and in vivo may contribute to its neuroprotection and potential application in SCI.     

Collagen IV significantly enhances migration and transplantation of embryonic stem cells: involvement of α2β1 integrin-mediated actin remodeling

Embryonic stem (ES) cell transplantation represents a potential means for the treatment of degenerative diseases and injuries. As appropriate distribution of transplanted ES cells in the host tissue is critical for successful transplantation, the exploration of efficient strategies to enhance ES cell migration is warranted. In this study we investigated ES cell migration under the influence of various extracellular matrix (ECM) proteins, which have been shown to stimulate cell migration in various cell models with unclear effects on ES cells. Using two mouse ES (mES) cell lines, ESC 26GJ9012-8-2 and ES-D3 GL, to generate embryoid bodies (EBs), we examined the migration of differentiating cells from EBs that were delivered onto culture surfaces coated with or without collagen I, collagen IV, Matrigel, fibronectin, and laminin. Among these ECM proteins, collagen IV exhibited maximal migration enhancing effect. mES cells expressed α2 and β1 integrin subunits and the migration enhancing effect of collagen IV was prevented by RGD peptides as well as antibodies against α2 and β1 integrins, indicating that the enhancing effect of collagen IV on cell migration was mediated by α2β1 integrin. Furthermore, staining of actin cytoskeleton that links to integrins revealed well-developed stress fibers and long filopodia in mES cells cultured on collagen IV, and the actin-disrupting cytochalasin D abolished the collagen IV-enhanced cell migration. In addition, pretreatment of undifferentiated or differentiated mES cells with collagen IV resulted in improved engraftment and growth after transplantation into the subcutaneous tissue of nude mice. Finally, collagen IV pretreatment of osteogenically differentiated mES cells increased osteogenic differentiation-like tissue and decreased undifferentiation-like tissue in the grafts grown after transplantation. Our results demonstrated that collagen IV significantly enhanced the migration of differentiating ES cells through α2β1 integrin-mediated actin remodeling and could promote ES cell transplantation efficiency, which may be imperative to stem cell therapy.     

Functional pectoralis minor muscle flap transplantation for reconstruction of thumb opposition: an anatomic study and clinical applications

In this report, we present the results of an anatomic study on the dimensions of the pectoralis minor muscle and its neurovascular supply in 10 adult human cadavers, in attempt to evaluate the feasibility of microsurgical transplantation of a part of the muscle for thumb opposition reconstruction. A series of five patients consequently underwent thenar reconstruction with the pectoralis minor muscle flap from December 2004 to October 2006. The transferred muscle was reinnervated with the third lumbrical branch of the ulnar nerve. Follow-up assessment showed that the patients recovered functional opposition of carpometacarpal joint with 24 degrees of pronation, and a muscle power with M4 to M5. All patients were satisfied with the appearance of reconstructed thenar eminence. We recommend this new technique for thenar and opposition reconstruction in patients who have severe loss of thenar muscles, injury to the median nerve, and wish to improve the appearance of thenar eminence.     

Noninvasive Pancreatic Cystic Neoplasms can be Safely and Effectively Treated by Limited Pancreatectomy

Background Appropriate management of cystic lesions of the pancreas is controversial. Major pancreatectomies (pancreaticoduodenectomy or distal pancreatectomy with splenectomy) are the commonly used procedures, even though most cystic lesions are noninvasive neoplasms. We tested the adequacy of limited pancreatectomies in the treatment of pancreatic cystic lesions. Methods Data from 109 patients who underwent surgical resection of a pancreatic cystic lesion at National Taiwan University Hospital from 2001 to 2007 were retrospectively reviewed. Major pancreatomies (n = 79) constituted pancreaticoduodenectomy and total/distal pancreatectomies, while other resection procedures (n = 30) represented limited pancreatectomies. Clinicopathologic features were compared between the major and limited groups. Results There were no statistically significant differences in sex, age, presence of symptoms, cyst diameter, minor or major treatment complications, or pancreatic leakage between the two groups. Cystic lesions located in the neck/body/tail rather than in the head/uncinate process were significantly more often treated with limited pancreatectomy (P = .02). Both groups had similar pathologic distribution of cystic lesions, with the exception of nine invasive neoplasms. The latter were treated with major pancreatectomy. No recurrence was noted in 100 patients with noninvasive cystic neoplasms after major or limited pancreatectomy. Conclusions Noninvasive pancreatic cystic neoplasms can be safely and effectively treated by limited pancreatectomy.     

The acceptance and feasibility of breast cancer screening in the East

Breast cancer, traditionally a disease prevalent among women in the West, has become an increasing disease burden in the East. In Hong Kong, breast cancer is the number one incident cancer in women. In Asian countries, due to the lower incidence rate, population screening is still controversial. Most screening programs are not population-based, and are either self-financed privately or partially subsidized by the government. Since the first government-subsidized screening program was set up in 1991 in Hong Kong, numerous private and government health centres for women have been set up. A dedicated private Breast Care Centre was set up at the Hong Kong Sanatorium and Hospital (HKSH) in 1999. Over an 8-year period from October 1999 to September 2006, 14,596 women were screened, of whom 11,408 were asymptomatic. This study aims to produce the first report on breast screening experience in the largest cohort of asymptomatic Chinese women in the private sector. An overall malignancy detection rate of 2.3 per 1000 screens and a recall rate of 9.2% were found. Despite culture differences and differences in breast characteristics (denser and smaller breasts), breast screening is feasible and acceptable in the East.     

A Prospective Evaluation of Intracorporeal Laparoscopic Small Bowel Anastomosis during Gastric Bypass

Background: We evaluated the safety and feasibility of performing a laparoscopic intracorporeal end-toside small bowel anastomosis using a stapling technique as part of a Roux-en-Y gastric bypass operation (RYGBP). Methods: 80 consecutive patients who underwent RYGBP with laparoscopic jejunojejunostomy were evaluated. Operative time and intraoperative and postoperative complications directly related to the jejunojejunostomy anastomosis were recorded. Results: All 80 laparoscopic jejunojejunostomy procedures were successfully performed without conversion to laparotomy. Mean operative time was longer for the first 40 laparoscopic RYGBP than for the last 40 RYGBP (32±18 min vs 21±14 min, respectively, p<0.05). Intraoperative complications were staple-line bleeding (2 patients) and narrowing of the anastomosis (1 patient). Postoperative complications were four small bowel obstructions: technical narrowing at jejunojejunostomy site (2 patients), angulation of the afferent limb (1 patient), and food impaction at the jejunojejunostomy anastomosis (1 patient). These four patients underwent successful laparoscopic re-exploration and creation of another jejunojejunostomy proximal to the original anastomosis. There were no small bowel anastomotic leaks. The median time to resuming oral diet was 2 days. Conclusions: Laparoscopic jejunojejunostomy as part of the RYGBP operation is a safe and technically feasible procedure. Postoperative small bowel obstruction is a potential complication, which can be prevented by avoiding technical narrowing of the afferent limb.     

Nephrogenic adenoma associated with cytomegalovirus infection of the ureter in a renal transplant patient: presentation as ureteral obstruction

Nephrogenic adenoma (NA), a rare benign lesion of the urinary tract, is widely accepted to be a metaplastic reaction due to urothelial injury. It mainly occurs in the urinary bladder and rarely in the ureter. Renal transplant recipients are prone to the development of NA. However in those patients, NA was diagnosed exclusively in the bladder. Herein, we present the – to our knowledge – first case of NA involving a transplanted ureter. A 42-year-old female kidney transplant recipient suffered hematuria, oliguria, and acute renal failure and presented with ureteral obstruction and hydronephrosis of the renal transplant. To our surprise, evidence of cytomegalovirus (CMV) infection of the NA was demonstrated using special immunohistochemical staining. The findings in this case raise the possibility that CMV infection, as an irritant of the ureteral epithelium, may be an etiological factor of NA. Received: 5 November 1999 Revised: 7 August 2000 Accepted: 20 November 2000     

Resveratrol neuroprotective effects during focal cerebral ischemia injury via nitric oxide mechanism in rats

BACKGROUND: Our prior study showed that resveratrol could suppress infarct volume and exert neuroprotective effect on rats subjected to focal cerebral ischemia (FCI) injury. Recently, it has been reported in some literature that resveratrol protects the spinal cord, kidney, and heart from ischemia-reperfusion injury through upregulation of nitric oxide (NO). Therefore, this study was designed to investigate the role of nitric oxide on the neuroprotective mechanisms of resveratrol on rats after FCI injury. METHODS: The FCI injury was induced by the middle cerebral artery (MCA) occlusion for 1 hour and then a 24-hour reperfusion followed in the anesthetized Long-Evans rats. Resveratrol was intravenously injected after 1 hour MCA occlusion. RESULTS: Treatment of resveratrol (0.1 and 1 microg/kg) decreased the lactate dehydrogenase (LDH) in plasma and malondialdehyde (MDA) in FCI injury brain tissue, whereas the level of NO in plasma was increased. In addition, resveratrol downregulated protein and mRNA expression of inducible nitric oxide synthase (iNOS), and upregulated protein and mRNA expression of endothelial nitric oxide synthase (eNOS), while the expression of protein and mRNA of neuronal nitric oxide synthase (nNOS) was unchanged. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, the nonselective NOS inhibitor) or L-N(5)-(1-iminoethyl)-ornithine (L-NIO, the eNOS selective inhibitor) completely blocked the effect of resveratrol in decreasing infarction volumes. CONCLUSIONS: This study demonstrated the important role of NO in the neuroprotective effect of resveratrol in FCI injury.     

Long-term results of transpedicle body augmenter in treating burst fractures

Background:

Short-segment fixation alone to treat thoracolumbar burst fractures is common but it has a 20-50% incidence of implant failure and rekyphosis. A transpedicle body augmenter (TpBA) to reinforce the vertebral body via posterior approach has been reported to prevent implant failure and increase the clinical success rate in treating burst fracture. This article is to evaluate the longterm results of short-segment fixation with TpBA for treatment of thoracolumbar burst fractures.

Materials and Methods:

Patients included in the study had a single-level burst fracture involving T11-L2 and no distraction or rotation element with limited neurological deficit. Patients in the control group (n = 42) were treated with short-segment posterior instrumentation alone, whereas patients in the augmented group (n = 90) were treated with a titanium spacer designed for transpedicle body reconstruction. The followup was 48-101 months. The radiographic and clinical results were evaluated and compared by Student''s t test and Fisher''s exact test.

Results:

The blood loss, operation time and hospitalization were similar in both the groups. The immediate postoperative anterior vertebral restoration rate of the augmented group was similar to that of the control group (97.6% ± 2.4% vs. 96.6% ± 3.2%). The final anterior vertebral restoration was greater in the augmented group than in the control group (93.3% ± 3.4% vs. 62.5% ± 11.2%). Immediate postoperative kyphotic angles were not significantly different between the groups (3.0° ± 1.8° vs. 5.1° ± 2.3°). The final kyphotic angles were less in the augmented group than the control group (7.3° ± 3.5° vs. 20.1° ± 5.4°). The augmented group had less (P < 0.001) implant failure [0% (n=0) vs. 23.8% (n=10)] for the control group) and more patients (P < 0.001) with no pain or minimal or occasional pain (Grade P1 or P2) than the control group [90.0% (n=81) vs. 66.7% (n=28)]. All patients in the augmented group and 39 (92.8%) patients in the control group experienced neurological recovery to Frankel Grade E. Three patients in the control group had improvement to Frankel Grade D from Frankel Grade C, but later had deterioration to Frankel Grade C because of loosening and dislodgement of the implant.

Conclusion:

Posterior body reconstruction with TpBA can maintain kyphosis correction and vertebral restoration, prevent implant failure and lead to better clinical results.     

Is Surgery Indicated for Patients with Symptomatic Nonfunctioning Pancreatic Neuroendocrine Tumor and Unresectable Hepatic Metastases?

Background Patients with advanced pancreatic neuroendocrine tumor, even in the presence of unresectable hepatic metastases, have survival usually measured in years than in months. Theoretically, we would have reason to resect symptomatic primary pancreatic neuroendocrine tumors from these patients palliatively. However, the effect and feasibility of removing symptomatic primary pancreatic neuroendocrine tumor in patients with unresectable hepatic metastases has never been addressed. Methods In 2000, we instituted a prospective study to resect symptomatic primary tumors and treat unresectable hepatic metastases by lanreotide and hepatic artery embolization in patients with definite tissue proof of pancreatic neuroendocrine tumor. Results Thirteen patients were included in this study; seven patients underwent pancreaticoduodenectomy, and six underwent distal pancreatectomy and splenectomy. There were no operative deaths. Eight of thirteen patients had no radiologic evidence of disease progression. The other five patients had disease progression by their 6-month follow-up; they underwent hepatic artery chemoembolization or chemotherapy. One patient died of multiple lung and bone metastases 80 months after operation, and one patient died of continuous progression of liver metastases 18 months after operation. Telephone interviews of 11 patients who survived revealed that 10 reported improved quality of life after resection of symptomatic primary pancreatic neuroendocrine tumor and one patient reported no change. Conclusions We suggest that symptomatic primary pancreatic neuroendocrine tumors should be resected even when unresectable hepatic metastases are found at diagnosis because of the relatively low risk of pancreatic surgery, effective elimination of symptoms caused by primary tumors, and slow progression of hepatic metastases under lanreotide and hepatic artery embolization.