The effect of intrastriatal single injection of GDNF on the nigrostriatal dopaminergic system in hemiparkinsonian rats: behavioral and histological studies using two different dosages

Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-beta superfamily and acts as a neurotrophic factor for the nigrostriatal dopamine (DA) system. Although previous studies have shown that pretreatment with GDNF could prevent degenerative changes of nigrostriatal DA system by DA neurotoxin 6-hydroxydopamine (6-OHDA), it is not really known whether GDNF can induce recovery of nigrostriatal DA system after partial lesioning by 6-OHDA. Substantia nigra has been commonly chosen as injection site for GDNF but a limited number of studies have used striatum as injection site where neural transplantation is commonly performed. Unilateral intrastriatal administration of 6-OHDA was performed in Sprague-Dawley rats to create partial lesion of the nigrostriatal DA system. These hemiparkinsonian model rats received a 10- or 100-microg single injection of human recombinant GDNF into the same portion of the striatum 4 weeks after 6-OHDA treatment. Both animals that received a 10- or 100-microg single injection of GDNF showed decreased apomorphine-induced rotation at 2 weeks after injection. More potent and prolonged functional recovery was observed in animals receiving 100 microg of GDNF than in those receiving 10 microg of GDNF. Tyrosine hydroxylase (TH) immunocytochemistry revealed that TH positive DA fiber density in the striatum and the number of DA cell bodies in the substantia nigra were greater in animals receiving 10 or 100 microg of GDNF than those receiving saline. These immunocytochemical results have also shown that 100 microg of GDNF was more potent than 10 microg of GDNF. These morphological and functional results indicate that GDNF treatment 4 weeks after 6-OHDA lesioning could induce recovery of nigrostriatal DA system. Striatum was a good site for GDNF administration for hemiparkinsonian rats and a single injection of 100 microg of GDNF was more potent than 10 microg of GDNF.     

Nicotinamide phosphoribosyltransferase delays cellular senescence by upregulating SIRT1 activity and antioxidant gene expression in mouse cells

Senescent cells accumulate in tissues of aged animals and deteriorate tissue functions. The elimination of senescent cells from aged mice not only attenuates progression of already established age‐related disorders, but also extends median lifespan. Nicotinamide phosphoribosyltransferase (NAMPT), the rate‐limiting enzyme in mammalian NAD⁺ salvage pathway, has shown a protective effect on cellular senescence of human primary cells. However, it still remains unclear how NAMPT has a protective impact on aging in vitro and in vivo. In this study, we found that primary mouse embryonic fibroblast (MEF) cells undergo progressive decline of NAMPT and NAD⁺ contents during serial passaging before becoming senescent. Furthermore, we showed that constitutive Nampt over‐expression increases cellular NAD⁺ content and delays cellular senescence of MEF cells in vitro. We further found that constitutive Nampt over‐expression increases SIRT1 activity, increases the expression of antioxidant genes, superoxide dismutase 2 and catalase and promotes resistance against oxidative stress. These findings suggest that Nampt over‐expression in MEF cells delays cellular senescence by the mitigation of oxidative stress via the upregulation of superoxide dismutase 2 and catalase gene expressions by SIRT1 activation.     

Balloon-Occluded Retrograde Transvenous Obliteration for Gastric Varices: A Feasibility Study

Purpose: To evaluate the clinical feasibility of balloon-occluded retrograde transvenous obliteration (BORTO) for gastric varices. Methods: BORTO was performed in 14 patients with gastric varices due to liver cirrhosis. The gastric varices were confirmed by endoscopy, and their feeding and draining veins were identified by contrast-enhanced computed tomography (CT) and angiography. A 6 Fr Simmons-shaped balloon catheter was inserted into the gastrorenal shunt. The balloon was inflated, and 5% ethanolamine oleate iopamidol was infused slowly through the catheter. Patients were followed up with endoscopy and enhanced CT at 1 week, 1, 3, and 6 months after the procedure and every 6 months thereafter. Results: The gastric varices completely disappeared in 12 of 14 patients and was partially resolved in the remaining 2 patients. Neither a recurrence nor an aggravation of gastric varices were found. No major complications were experienced. Conclusion: BORTO is a safe and effective treatment for gastric varices. Received: 0/00/00/Accepted: 0/00/00     

Ribbon enchephalo-duro-arterio-myo-synangiosis for moyamoya disease

In patients with advanced moyamoya disease, reconstructive surgery alone may not prevent the deterioration of blood flow in the territory of the anterior cerebral artery. These types of surgery include superficial temporal artery-to-middle cerebral artery anastomosis and encephalo-duro-arterio-myo-synangiosis (EDAMS). Bilateral encephalo-duro-arterio-synangiosis (EDAS) gradually reduced the transient ischemic attacks in one of our patients who experienced motor weakness in the left extremities. After surgery, however, persistent bilateral attacks still occurred in the patient's legs. In a subsequent maneuver, we inserted the pedicle of the galea on both sides into the interhemispheric fissure, which induced marked vascularization in the territory of the anterior cerebral artery, and the attacks disappeared. Since then, we have combined this “ribbon” technique with EDAMS to treat eight patients with moyamoya disease. Postoperative angiograms showed widespread collateral circulation on the ischemic brain surface in six patients undergoing ribbon EDAS or EDAMS. Postoperative measurements of cerebral blood flow revealed improved circulation in the frontal region in four patients. The clinical results were excellent in six patients, and good in one, and we lost follow-up in one. The ribbon EDAMS procedure is effective on moyamoya disease with symptomatic cerebral ischemia of the anterior circulation.     

Proliferative potential of malignant glioma cells before and after interstitial brachytherapy.

The viability of tumor cells in radionecrotic tissue after interstitial brachytherapy (BRTX) was evaluated using immunohistochemical markers of proliferative potential in primary and recurrent tumors. Tumor specimens from 30 patients with malignant gliomas (14 anaplastic astrocytomas, 16 glioblastomas) taken before and after BRTX were examined using MIB-1 monoclonal antibody. Histological examination of specimens obtained by craniotomy or stereotactic biopsy after BRTX revealed tumor recurrence in 18 patients and radionecrosis in 12 patients including two with pure radionecrosis and 10 with a mixture of both tumor and radionecrosis. The MIB-1 index of the tumors with radionecrosis was 7.6 +/- 5.5%, and that of the primary tumors was 17.0 +/- 11.2%, showing a significant difference (p < 0.05). There was no significant difference between the MIB-1 index of the primary tumors with local recurrence after BRTX and the primary tumors which underwent radionecrosis. Although morphologically viable tumor cells were found in the radionecrotic tissue, BRTX causes a reduction in the proliferative potential of these tumor cells.