BACKGROUND The role of epacl, an exchange protein activated by cAMP. in melanoma migration is largely unknown. Heparan sulfate (HS), a major ECM, and syndecan2, a HS-binding protein on the cell surface, play important roles in regulating such migration. Synde- can2, when activated, translocates to lipid-rich plasma microdomains, known as lipid rafts. We thus examined the role of epacl in HS production and syndecan2 transloca¬tion in melanoma migration. METHODS SK-MF.L-2, a human melanoma cell line, and migration assays with Boyden cham¬bers were employed. RESULTS Activation of Epacl adenoviral Epacl overexprcssiotl or HpMeOPT, at) Epac-specif- ic cAMP analog, significantly increased cell migration in a time- and dose-dependent manner. Epacl also increased HS production by 2-fold, and the removal of HS abol¬ished Epacl-induced migration. Epacl also increased expression of N-deacetylase/N- sulfotransferase-1 (NDST-1), a key synthetic enzyme for HS. Sucrose gradient frac¬tionation showed that Epacl increased syndecan2 translocation to rafts. In addition, disruption of rafts with lipid depletion abolished Epacl-induced migration. SUMMARY Epacl increased migration in malignant melanoma through HS production and syn- decan2 translocation to rafts.

We present here a rare case of coronary artery bypass grafting through a left thoracotomy after substernal gastric interposition for esophageal cancer. A 58-year-old man, who had undergone esophagectomy and substernal gastric interposition 11 years previously, was admitted for cerebral infarction from which he made a good recovery without any complication. At this time, the patient was diagnosed as having coronary artery disease on electrocardiogram. Cardiac catheterization revealed triple vessel disease. Coronary artery bypass grafting to the left anterior descending artery and obtuse marginal branch through a left thoracotomy was performed using a radial artery Y-graft under femorofemoral bypass. The aorta was cross-clamped and the heart was arrested with antegrade cold cardioplegic solution for the distal anastomosis of the left anterior descending artery and the obtuse marginal branch which was embedded within the myocardium. The postoperative angiography showed good coronary flow. Left thoracotomy approach provides a good exposure of the left coronary artery. This approach, therefore, is advocated as an alternative method for cases requiring coronary artery bypass but in which median sternotomy is difficult, such as the present case. The appropriate procedure for the site of thoracotomy, supporting methods, choice of graft, and the site of graft anastomosis should be selected in each patient.

BACKGROUNDThe role of epacl, an exchange protein activated by cAMP. in melanoma migration is largely unknown. Heparan sulfate (HS), a major ECM, and syndecan2, a HS-binding protein on the cell surface, play important roles in regulating such migration. Synde- can2, when activated, translocates to lipid-rich plasma microdomains, known as lipid rafts. We thus examined the role of epacl in HS production and syndecan2 transloca¬tion in melanoma migration. METHODSSK-MF.L-2, a human melanoma cell line, and migration assays with Boyden cham¬bers were employed.RESULTSActivation of Epacl adenoviral Epacl overexprcssiotl or HpMeOPT, at) Epac-specif- ic cAMP analog, significantly increased cell migration in a time- and dose-dependent manner. Epacl also increased HS production by 2-fold, and the removal of HS abol¬ished Epacl-induced migration. Epacl also increased expression of N-deacetylase/N- sulfotransferase-1 (NDST-1), a key synthetic enzyme for HS. Sucrose gradient frac¬tionation showed that Epacl increased syndecan2 translocation to rafts. In addition, disruption of rafts with lipid depletion abolished Epacl-induced migration.SUMMARYEpacl increased migration in malignant melanoma through HS production and syn- decan2 translocation to rafts.

Every year, an estimated 180 000 babies in the Western Pacific Region are infected by hepatitis B, 13 000 by syphilis and 1400 by HIV through mother-to-child transmission.1 These infections can be largely prevented by antenatal screening, treatment and timely vaccination for newborns. Despite challenges in controlling each disease, major achievements have been made. National immunization programmes have reduced the regional hepatitis B prevalence from over 8% in 1990 to 0.93% among children born in 2012. In addition, HIV testing and treatment have helped keep the regional prevalence of HIV infections at 0.1%. In contrast, the number of maternal syphilis cases is still high in the Western Pacific Region, with an estimated 45 million cases in 2012. Elimination of mother-to-child transmission of these infections cannot be achieved through vertically applied programming and require using and augmenting to the shared Maternal, Newborn and Child Health platform to coordinate, integrate and enable cost efficiencies for these elimination efforts. The Regional Framework for Triple Elimination of Mother-to-Child Transmission of HIV, Hepatitis B and Syphilis in Asia and the Pacific 2018–2030 offers such a coordinated approach towards achieving the triple elimination of mother-to-child transmission of HIV, hepatitis B and syphilis and provides guidance for decision-makers, managers and health professionals working in programmes addressing maternal, newborn and child health, HIV, hepatitis, sexually transmitted infections and immunization.

In this study, we examined the feasibility of using subzonal cell injection with electrofusion for interspecies somatic cell nuclear transfer (iSCNT) to produce sei whale embryos and to improve their developmental capacity by investigating the effect of osmolarity and macromolecules in the culture medium on the in vitro developmental capacity. Hybrid embryos produced by the electrofusion of fetal whale fibroblasts with enucleated porcine oocytes were cultured in modified porcine zygote medium-3 to examine the effects of osmolarity and fetal serum on their in vitro developmental capacity. More than 66% of the whale somatic cells successfully fused with the porcine oocytes following electrofusion. A portion (60~81%) of the iSCNT whale embryos developed to the two- to four-cell stages, but no embryos were able to reach the blastocyst stage. This developmental arrest was not overcome by increasing the osmolarity of the medium to 360 mOsm or by the addition of fetal bovine or fetal whale serum. Our results demonstrate that sei whale-porcine hybrid embryos may be produced by SCNT using subzonal injection and electrofusion. The pig oocytes partly supported the remodeling and reprogramming of the sei whale somatic cell nuclei, but they were unable to support the development of iSCNT whale embryos to the blastocyst stage.
Animals ; Cloning, Organism/*veterinary ; Culture Media ; Embryo, Mammalian ; Karyotyping ; Nuclear Transfer Techniques/*veterinary ; *Oocytes ; Swine/*embryology ; Whales/*embryology

STUDY DESIGN: Experimental animal study. PURPOSE: To evaluate pain-related behavior and changes in nuclear factor-kappa B (NF-kB), receptor activator of NF-kB (RANK), and ligand (RANKL) in dorsal root ganglia (DRG) after combined sciatic nerve compression and nucleus pulposus (NP) application in rats. OVERVIEW OF LITERATURE: The pathological mechanisms underlying pain from lumbar-disc herniation have not been fully elucidated. RANKL are transcriptional regulators of inflammatory cytokines. Our aim was to evaluate pain-related behavior and RANKL expression in DRG after sciatic-nerve compression and application of NP in rats. METHODS: Mechanical hyperalgesia and RANKL expression were assessed in three groups of rats: NP+sciatic nerve compression (2 seconds), sham-operated, and controls (n=20 each). Mechanical hyperalgesia was measured every other day for 3 weeks using von Frey filaments. RANKL expression in L5 DRGs was examined at five and ten days after surgery using immunohistochemistry. RESULTS: Mechanical hyperalgesia was observed over the 12-day observation period in the NP+nerve compression group, but not in the control and sham-operated animal groups (p<0.05). RANKL immunoreactivity was seen in the nuclei of L5 DRG neurons, and its expression was significantly upregulated in NP+nerve compression rats compared with control and sham-operated rats (p<0.01). CONCLUSIONS: The exposure of sciatic nerves to mechanical compression and NP produces pain-related behavior and up-regulation of RANKL in DRG neurons. RANKL may play an important role in mediating pain after sciatic nerve injury with exposure to NP.
Animals ; Cytokines ; Diagnosis-Related Groups ; Ganglia, Spinal* ; Hyperalgesia ; Immunohistochemistry ; Negotiating ; Neurons ; NF-kappa B ; RANK Ligand* ; Rats* ; Sciatic Nerve* ; Up-Regulation

STUDY DESIGN: Experimental animal study. PURPOSE: To evaluate pain-related behavior and changes in glial activity in the spinal dorsal horn after combined sciatic nerve compression and nucleus pulposus (NP) application in rats. OVERVIEW OF LITERATURE: Mechanical compression and inflammation caused by prostaglandins and cytokines at disc herniation sites induce pain. Structural changes and pain-associated cytokines in the dorsal root ganglia and spinal dorsal horn contribute to prolonged pain. Glial cells in the spinal dorsal horn may also function in pain transmission. METHODS: The sciatic nerve was compressed with NP for 2 seconds using forceps in the NP+nerve compression group; the sham-operated group received neither compression nor NP; and the control group received no operation. Mechanical hyperalgesia was measured for 3 weeks using von Frey filaments. Glial activity in the spinal dorsal horn was examined 7 days and 14 days postsurgery using anti-glial fibrillary acidic protein and anti-Ionized calcium binding adaptor molecule-1 antibodies to detect astrocytes and microglia, respectively. RESULTS: Mechanical hyperalgesia was detected throughout the 14-day observation in the NP+nerve compression group, but not in control or sham-operated groups (p<0.05). Both astrocytes and microglia were significantly increased in the spinal dorsal horn of the NP+nerve compression group compared to control and sham groups on days 7 and 14 (p<0.05). CONCLUSIONS: Nerve compression with NP application produces pain-related behavior, and up-regulates astrocytes and microglia in the spinal dorsal horn, suggesting that these glia may be related to pain transmission.
Animals ; Antibodies ; Astrocytes ; Calcium ; Cytokines ; Ganglia, Spinal ; Horns ; Hyperalgesia ; Inflammation ; Microglia ; Neuroglia ; Prostaglandins ; Rats* ; Sciatic Nerve* ; Spinal Cord* ; Surgical Instruments ; Up-Regulation*

PURPOSE: Opioids improve pain from knee and hip osteoarthritis (OA) and decrease the functional impairment of patients. However, there is a possibility that opioids induce analgesia and suppress the physiological pain of OA in patients, thereby inducing the progression of OA changes in these patients. The purpose of the current study was to investigate the possibility of progressive changes in OA among patients using opioids. MATERIALS AND METHODS: Two hundred knee or hip OA patients were evaluated in the current prospective, randomized, active-controlled study. Patients were randomized 1:1:1 into three parallel treatment groups: loxoprofen, tramadol/acetaminophen, and transdermal fentanyl groups. Medication was administered for 12 weeks. Pain scores and progressive OA changes on X-ray films were evaluated. RESULTS: Overall, pain relief was obtained by all three groups. Most patients did not show progressive OA changes; however, 3 patients in the transdermal fentanyl group showed progressive OA changes during the 12 weeks of treatment. These 3 patients used significantly higher doses than others in the transdermal fentanyl group. Additionally, the average pain score for these 3 patients was significantly lower than the average pain score for the other patients in the transdermal fentanyl group. CONCLUSION: Fentanyl may induce progressive changes in knee or hip OA during a relatively short period, compared with oral Non-Steroidal Anti-Inflammatory Drugs or tramadol.
Aged ; Aged, 80 and over ; Analgesics, Opioid/*adverse effects/therapeutic use ; Disease Progression ; Female ; Fentanyl/*adverse effects/therapeutic use ; Humans ; Male ; Middle Aged ; Osteoarthritis, Hip/*drug therapy/radiography ; Osteoarthritis, Knee/*drug therapy/radiography ; Pain/drug therapy

PURPOSE: Bupivacaine is commonly used for the treatment of back pain and the diagnosis of its origin. Nonunion is sometimes observed after spinal fusion surgery; however, whether the nonunion causes pain is controversial. In the current study, we aimed to detect painful nonunion by injecting bupivacaine into the disc space of patients with nonunion after anterior lumbar interbody fusion (ALIF) surgery for discogenic low back pain. MATERIALS AND METHODS: From 52 patients with low back pain, we selected 42 who showed disc degeneration at only one level (L4-L5 or L5-S1) on magnetic resonance imaging and were diagnosed by pain provocation on discography and pain relief by discoblock (the injection of bupivacaine). They underwent ALIF surgery. If the patients showed low back pain and nonunion 2 years after surgery, we injected bupivacaine into the nonunion disc space. Patients showing pain relief after injection of bupivacaine underwent additional posterior fixation using pedicle screws. These patients were followed up 2 years after the revision surgery. RESULTS: Of the 42 patient subjects, 7 showed nonunion. Four of them did not show low back pain; whereas 3 showed moderate or severe low back pain. These 3 patients showed pain reduction after injection of bupivacaine into their nonunion disc space and underwent additional posterior fixation. They showed bony union and pain relief 2 years after the revision surgery. CONCLUSION: Injection of bupivacaine into the nonunion disc space after ALIF surgery for discogenic low back pain is useful for diagnosis of the origin of pain.
Back Pain ; Bupivacaine* ; Diagnosis ; Humans ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Low Back Pain* ; Magnetic Resonance Imaging ; Methods ; Spinal Fusion ; Spine